Glossary of terms

• A1C test is a blood test that assesses a person's average level of blood glucose over a 3 month period.  Because glucose attaches to hemoglobin the 3 month lifetime of red blood cells can be used as a buffer of blood glucose.  
• ABA is the:
  
• American Bankers Association.  
• American Board of Anesthesiology. 
• Abacavir is a nucleoside reverse transcriptase inhibitor, an ARV is antiretroviral treatments for H.I.V. infection, such as abacavir. 
  medication, branded as Ziagen, which is used in the prevention and constraint of AIDS is acquired auto-immune deficiency syndrome, a pandemic disease caused by the HIV.  It also amplifies the threat of tuberculosis.   Initially deadly, infecting and destroying the T-lymphocytes of the immune system, it can now be treated with HAART to become a chronic disease.  And with an understanding of HIV's mode of entry into the T-cells, through its binding to CCR5 and CD4 encoded transmembrane proteins, AIDS may be susceptible to treatment with recombinant DNA to alter the CCR5 binding site, or with drugs that bind to the CCR5 cell surface protein preventing binding by the virus.  Future optimization of drug delivery may leverage nanoscale research (May 2016).  .  It is a WHO is World Health Organization a United Nations organization. 
  essential medicine.  Its use is problematic in about 6% of the patient base.  Pharmacogenomics studies how genes affect a person's response to drugs so as to develop personalized drug treatment plans, tailored to a person's specific phenotype.  The process optimizes the treatment process but there are barriers to its deployment:
  • Large scale clinical trials may test 20,000 individuals, but if a toxic response impacts only 0.1% of them there would only be 20 cases found which is often too few to identify the cause of the response.  Instead a process for capturing adverse drug reactions after approval and marketing must be used along with the ability to take a blood sample in these cases.  
  • Simplified studies on a subset of individuals that have the target allele should be cheaper but are unattractive to pharmaceutical companies which typically want to maximize their target market (Aug 2016).  
  • F.D.A. has not required genomic testing for most drug developments.  
  • Health care providers are being slow to use pharmacogenomics.  Often third-party payers are unwilling to reimburse the tests. 
    
  • Transportation to centralized laboratories for genomic testing causes delays which makes some drug therapy applications impractical.  An alternative solution would be to have a patient's EHR contain their genome sequence for immediate genomic implications.  
  allows these patients to be identified and treated with an alternative ARV. 
  
• ABIGAIL is Geisinger's patient experience standards, after founder Abigail Geisinger:
  
• Accountable
• Befriend
• Inform
  
• Genuine
  
• Acknowledge
  
• Involve
  
• Listen
  
• ABL is a gene on human chromosole 22.  In the majority of cases of CML is chronic myelogenous leukemia.  It is a leukemia characterized by the unregulated growth of myeloid cells in the bone marrow.  The growth is encouraged by the cellular signalling system (gene change that generates a faulty tyrosine kinase) being locked on.  Visual methods allowed Dr. Janet Rowley's team to recognize that most CML includes the Philadelphia chromosome.  It encodes the chimeric always on tyrosine kinase protein seen only in CML.  Targeted treatments such as Gleevec block the pathway for the tyrosine kinase. 
  part of ABL is coppied into a merged chromosome with part of BCR is a gene on chromosome 22 which normally codes the breakpoint cluster region protein which is a GTPase-activating protein for RAC1 and CDC42.  In many cases of CML part of the BCR gene gets translated onto an additional Philadelphia chromosome along with part of gene ABL from chromosome 9. 
  from chromosome 9, in a transformation initially noted by Dr. Janet Rowley and colleagues and called the Philadelphia chromosome is a chromosome fragment generated by a mutation copying bits of chromosome 9 including part of gene BCR and part of gene ABL from chromosome 22.  In the majority of cases of CML Philadelphia chromosome is present and generates an aways on tyrosine kinase signalling protein which causes vast proliferation of white blood cells.  Since the protein is aberrant blocking its production pathway with drugs such as Gleevec stop the excessive white blood cell production. 
  .  
• ABS is an asset-backed security defined as backed by nonconforming loans rather than Fannie Mae is the coloquial name for the FNMA which is:
  • The federal national mortgage association, a GSE.  It was made a publically traded company by the HUD act of 1968 to remove its debt from the federal budget.  
  • In 1970 FNMA was authorized to purchase conventional mortgages.  FHLMC was setup to ensure competition for FNMA in this task. 
    
  • In 1981 FNMA issued its first designated MBS. 
    
  • In 1992 the Democratic Congress and President Bush established HCDA which gave FNMA affordable housing goals set annually by HUD with Congressional approval.  
  • In 1999 the Clinton administration put pressure on FNMA to expand loans to low and moderate income borrowers.  FNMA took on additional subprime risk. 
    
  • In 2000 HUD placed anti-predatory lending rules on the affordable housing goals, but these constraints were dropped in 2004.  In effect they just pushed mortgage originators to Wall Street finance. 
    
  • Once mortgage originators started to use warehouse loans, the GSEs lost visibility and control of origination.  
  • The GSEs purchased AAA mortgages from commercial banks.  Many of these classifications were fraudulent leaving the GSEs with bad debt.  In 2008 to maintain the stability of the global economy the George W. Bush administration seized the GSEs and placed them in conservatorship under the FHFA, ensuring they could not collapse.  
  • In 2010 FNMA's stock was delisted from the NYSE.  They still trade over-the-counter. 
    
  or Freddie Mac quality loans used in original MBS is mortgage backed security, a bond backed by the monthly payments homeowners make on their residences.  It was initially developed by Lew Ranieri at Salomon Brothers. 
  or CMO is a:
  
  • Chief medical officer or a
    
  • Care maintenance organization or in finance a
    
  • Collateralized mortgage obligation.  The collateralized mortgage obligation was invented by Larry Fink (BlackRock) and team while they were at First Boston in 1983.  The key innovation was that the risk in these contracts was more predictable than in an MBS due to the presence of a trust that guaranteed payments to the bond holders.  The risk was separated into tranches with different credit ratings and yields.  The structure was used by the banking and securities companies to finance the subprime housing boom. 
    
  . 
  
• Abulia is an incapacity to generate voluntary actions. 
  
• ACA is the Patient Protection and Affordable Care Act amended by the Health Care and Education Reconciliation is a fast-track Senate procedure defined in title III of the CBIC act.  In response to a stagnant economy and President Nixon's spending controls it was hoped this process would help with acting rapidly on the rising budget deficit and increasing entitlement spending.  The process is constrained by Senate rules that limit its use to provisions that deal with government tax and spending activities, but not policy:
  • Senators can object to a reconciliation bill if they see the rules being broken & ask for the parliamentarian to judge if a provision of a bill fails the rules. 
    
  • If the parliamentarian judges the proposal does fail the rules, the bill must be passed by 60 votes to overcome the objections, rather than a simple majority of the Senate or the provision must be stripped from the bill. 
    
  Act of 2010 (Obama care).  In part it is designed to make the health care system costs grow slower.  It aims to do this by: increasing competition between insurers and providers, offering free preventative services to limit the development of serious illnesses, constraining patients' use of expensive services, constraining the growth of payments to Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  providers and piloting new ways for PCP is a Primary Care Physician.  PCPs are viewed by legislators and regulators as central to the effective management of care.  When coordinated care had worked the PCP is a key participant.  In most successful cases they are central.  In certain Medicare ACO models (Pioneer) PCPs are committed to achieve meaningful use requirements.  Working against this is the: replacement of diagnostic skills by technological solutions, low FFS leverage of the PCP compared to specialists, demotivation of battling prior authorization for expensive treatments. 
  s to manage patient care to keep patients away from costly E.D. is emergency department.  Pain is the main reason (75%) patients go to an E.D.  It has traditionally been part of an acute care hospital but recently is being deployed standalone as a catchment funnel to the owning hospital.  The EMTALA legislation requires E.D. treatment to stabilize every person seeking treatment by most hospitals.  Unreimbursed care is supported from federal government funds.  E. D. profitability has been helped by hospitals contracting with 3rd party companies who are able to improve margins through surprise billing.  The standalone E.D. competes with the positioning and brand power of lower cost urgent care clinics.  Commercial nature of care requires walk-ins to register to gain access to care.  With the focus on treatment of pain, E.D.s are a major distributor of opioids (5% of opioid prescriptions) and a major starting point of addiction in patients but are cutting back (Jun 2016). 
  s.  It funds these changes with increased taxes on the wealthy is schematically useful information and its equivalent, schematically useful energy, to paraphrase Beinhocker.  It is useful because an agent has schematic strategies that can utilize the information or energy to extend or leverage control of the cognitive niche.   .  It follows an architecture developed by Heritage Action's Butler, Moffit, Haislmaier extended by White House OMB is the Office of Management and Budget.  It:
  • Creates and promotes the President's federal budget and hence indirectly his priorities. 
    
  • Has the power to advance or constrain federal regulation as many proposed rules must be signed off by the O.M.B. (OIRA) before they are issued.  The rules it can constrain include those relating to:
  • Energy
  • Environmental standards
  • Labor protections
  • Food safety
  • All administration policies affect the budget directly or indirectly so they are constrained by the O.M.B. 
    
  health policy advisor Ezekiel Emanuel & architect Jeanne Lambrew.  The Obama administration drafting team included: Bob Kocher; allowing it to integrate ideas from: Dartmouth Institute's Elliot Fischer (ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness, improving the provision of primary care to a large group of Medicare patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV business.  The ACA regulates qualification to be a Medicare ACO.  Individual organizations within a Medicare shared savings ACO continue to submit their own claims and are paid by Medicare for FFS.  But the ACO is eligible for shared savings.  Within the shared savings program the CMS innovation center has setup advanced payment ACOs.  As an alternative to shared savings, in a Pioneer ACO, over time 50% of the FFS payments flow directly to the ACO as a bundled payment.  CMS has established quality measures for ACOs for Medicare.  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination. 
  
  • CMS initiated its Physician Group Practice Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
    
  • CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
  • CMS has developed APMs which include ACOs, and advanced APMs where the ACOs must be risk bearing. 
    
  • CMMI accepts providers' proposals to test various payment systems including shared savings and partial capitation.  
  • Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
  ).  The ACA did not include a Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  buy in (May 2016).  The law includes:
• Alterations, in title I is ACA quality affordable care for all Americans.  It mandates community rating & essential health benefits.  It includes:
  • Subtitle A: Immediate improvements in health care for all Americans. 
    
  • Subtitle B: Immediate actions to preserve and expand coverage. 
    
  • Subtitle C: Quality health insurance coverage for all Americans.  Which reforms the health insurance markets and prohibits preexisting condition exclusions and forms of health status discrimination.  
  • Subtitle D: Available coverage choices for all Americans. 
    
  • Subtitle E: Affordable coverage choices for all Americans. 
    
  • Subtitle F: Shared responsibility for health care which mandates individuals and employers to pay for insurance.  
  • The employer mandate requires employers with more than 50 full-time workers to offer most of their employees insurance or face penalties. 
    
  , to how health care is paid for and who is covered.  This has been altered to ensure
  
• Americans with preexisting conditions get health insurance cover - buttressed by mandating community rating mandates health insurers charge the same price to people of the same age living in the same geographic area. 
  and
  
• That they are constrained by the individual mandate to have insurance but the requirement was supported by subsidies for the poor (those with incomes between 100 & 400% of the federal poverty line is based on the Johnson War on Poverty valuation of $3000 as the relative needed income.  It was justified using Mollie Orshansky's modelling of the price of food to limit hunger.  It was adopted as an official US poverty line in August 1969 and has remained unchanged except for adjustments for price inflation.  ).  
• Children, allowed to, stay on their parents insurance until 26 years of age. 
  
• Medicare solvency improvements. 
  
• Medicaid is the state-federal program for the poor.  Originally part of Lyndon Johnson's 1965 Bill, eligibility and services vary by state.  Less than 10 percent of Medicaid recipients, those in long-term care including nursing homes where 64% are dependent on Medicaid, use one-third of all Medicaid spending which is a problem.  The ACA's Medicaid expansion program, made state optional by the SCOTUS decision, was initially taken up by fifty percent of states.  As of 2016 it covers 70 million Americans at a federal cost of $350 billion a year.  In 2017 it pays for 40% of new US births. 
  expansion, in title II is ACA role of public programs.  It includes:
  • Subtitle A: Improved access to Medicaid. 
    
  • Subtitle B: Enhanced support for children's health insurance program. 
    
  • Subtitle C: Medicaid and CHIP enrolment simplification. 
    
  • Subtitle D: Improvements to Medicaid services. 
    
  • Subtitle E: New options for states to provide long-term services and support. 
    
  • Subtitle F: Medicaid prescription drug coverage. 
    
  • Subtitle G: Medicaid disproportionate share hospital (DSH) payments.  
  • Subtitle H: Improved coordination for dual eligibles. 
    
  • Subtitle I: Improving the quality of Medicaid for patients and providers
    
  • Subtitle J: Improvements to the Medicaid and CHIP payment and access commission (MACPAC)
    
  • Subtitle K: Protections for American Indians and Alaska natives. 
    
  • Subtitle L: Maternal and child health services. 
    
  : to poor with incomes below 138% of the federal poverty line; an expansion which was subsequently constrained by the Supreme Court's ruling making expansion an optional state government decision. 
  
• Hospital Readmissions have become a source of increased revenue for hospitals.  But with government interested in reducing the US health care cost curve ACA's HRRP (pay-for-performance), BPCI and CTI and Interact discharge initiative have all increased the focus on unnecessary readmissions.  Now the end-to-end process is under scrutiny with hospitals reengineering discharge (RED) and PAC providers using RAI and TCN. 
  Reduction Program (HRRP is the Hospital Readmissions Reduction Program of the ACA.  It imposes payment penalties on high readmitting IPPS hospitals.  Such hospitals with higher than expected readmissions rates will receive reduced Medicare payments for all Medicare discharges relating to three medical conditions: heart failure, acute myocardial infarction, and pneumonia.  The reductions will be driven by an adjustment factor of 1% in 2013, 2% in 2014, and 3% subsequently. 
  ) which was enforced by CMS is the centers for Medicare and Medicaid services.   mandated rules finalized in 2011 and effected starting Oct 2012.  
• Medical home models are primary care architectures which deliver: patient-centered, accessible, coordinated, comprehensive care of high quality and safety (Dec 2015).  The models have been made more significant due to Affordable Care Act payment reform requirements.  The goal is to reduce treatment costs and improve population health by reengineering of the traditional silo'd provider network.  See PCMH. 
  .  
• Community transformation grants support the transformation of low income stressed neighborhoods to improve their lifestyles and health. 
  
• Qualifications for ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness, improving the provision of primary care to a large group of Medicare patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV business.  The ACA regulates qualification to be a Medicare ACO.  Individual organizations within a Medicare shared savings ACO continue to submit their own claims and are paid by Medicare for FFS.  But the ACO is eligible for shared savings.  Within the shared savings program the CMS innovation center has setup advanced payment ACOs.  As an alternative to shared savings, in a Pioneer ACO, over time 50% of the FFS payments flow directly to the ACO as a bundled payment.  CMS has established quality measures for ACOs for Medicare.  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination. 
  
  • CMS initiated its Physician Group Practice Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
    
  • CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
  • CMS has developed APMs which include ACOs, and advanced APMs where the ACOs must be risk bearing. 
    
  • CMMI accepts providers' proposals to test various payment systems including shared savings and partial capitation.  
  • Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
  s.  Organizations must:
  
• Establish a formal legal structure with shared governance which allows the ACO to distribute shared savings is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  payments to participating providers and suppliers. 
  
• Participate in the MSSP is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  for three or more years. 
  
• Have a management structure. 
  
• Have clinical and administrative systems. 
  
• Include enough PCP is a Primary Care Physician.  PCPs are viewed by legislators and regulators as central to the effective management of care.  When coordinated care had worked the PCP is a key participant.  In most successful cases they are central.  In certain Medicare ACO models (Pioneer) PCPs are committed to achieve meaningful use requirements.  Working against this is the: replacement of diagnostic skills by technological solutions, low FFS leverage of the PCP compared to specialists, demotivation of battling prior authorization for expensive treatments. 
  s to care for Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  FFS is fee-for-service payment.  For health care providers the high profits were made in hospitalizations, imaging and surgery.  Due to its inducing excessive treatment activity it may be replaced by FFV bundled payment.   patient population (> 5000) assigned to the ACO. 
  
• Be accountable for the quality and cost of care provided to the Medicare FFS patient population. 
  
• Have defined processes to promote: Evidence-based medicine is evidence based medicine where explicit and judicious use of current best practice evidence is used in making decisions about the care of patients.  There are differences in the application to individuals and populations.  Still the goal was to replace subjective use of basic and clinical research with:
  
  • Prioritization of clinical trial results to build conclusions. 
    
  • Adoption of processes that translated epidemiological methods to physician decision making. 
    
  • Widely used but innapropriate procedures were abandoned.  
  • There is now explicit evaluation of evidence of effectiveness before issuing practice guidelines.  A rational for adoption is required.  
  • HHS appointed USPSTF to develop evidence based recommendations.  
  , Patient-centeredness, Quality reporting, Cost management, Coordination of care aims to transfer information between the patient and each care participant as required and establish accountability by defining who is responsible for each care delivery activity, the extent of that responsibility and when that responsibility will be transferred to other care participants or the patient and family.  Successful care coordination requires face-to-face interactions.  It also requires aligned incentives (ACO, Bundled payments).  AHRQ defines quality measures for care coordination.  The situation is usually complex and adaptive due to the interactions of all the providers, settings, the patients' preferences, and the number of physical health problems, treatments, and the patients' social situation.  The potentially exponential increase in complexity as the number of these factors present increases leads to patient hot spots requiring explicit proactive coordination of care.  It is argued that care coordination must include six specific activities:
  1. Determination and updating of care coordination needs: Needs assessment should identify preferences and goals, current situation and past history.  It needs to be updated periodically and after new diagnosis and other changes in health or functional status. 
     
  2. Creation and updating of proactive plan of care
     
  3. Communication
  4. Facilitation of transitions: typical transition problems are detailed by Project Boost.  A challenging issue with transitions is what to do when there is no resource to take over the coordination role in the handoff. 
     
  5. Connection to community resources: Community resources are any service or program outside the health care system that may support a patient's health and wellness. 
     
  6. Alignment of resources with population needs: need to see the system-level, assess the needs of populations to identify and address gaps in services.  
  ; 
• Demonstrate it meets HHS is the U.S. Department of Health and Human Services.   patent-centeredness criteria including use of patient and caregiver assessments and individualized care plans outline the patient's current and long-term needs and goals for care, identifies coordination needs, and addresses potential gaps.  This is consistant with the biopsychosocial model.  It also clarifies how the patient will reach the goals and who is responsible for implementing each part of the plan.  HL7's FHIR has defined a CarePlan resource.  .  
• CMMI is the center for Medicare and Medicaid Innovation.  It is a test bed for new ways of financing and delivering care.  It allowed Congress to institutionalize innovation sending a signal to providers that they would be participating in CMS driven programs that could become mainstream.  It funds evaluations of innovative health care models.  Under the ACA if the HHS secretary finds any of its projects would reduce Medicare spending without harming the quality of care the projects may be expanded nationwide.  The CBO estimates the CMMI will save $34 billion between 2016 and 2026.  CMMI projects include:
  • Medicare will make a bundled payment for hip and knee replacement surgery (CJR) and 90 days of follow-up care forcing hospitals to work closely with doctors, nursing homes and home health agencies.  
  • New ways to pay for prescription drugs, medical devices, cancer care (OCM).  
  • HHS secretary has invoked his 3021 authority to institute DPP. 
    
  Medicare payment experimentation.  
• Requirements that pharmaceutical companies must report payments made to physicians (Sunshine Act is the physician payments sunshine act of 2010.  It is:
  • Section 6002 of the ACA.  
  • It requires pharmaceutical and medical device companies to release details of payments to doctors and US teaching hospitals.  
  ). 
  
• A requirement that chain restaurants must report calorie counts on their menus. 
  
• ACA title I is ACA is the Patient Protection and Affordable Care Act amended by the Health Care and Education Reconciliation Act of 2010 (Obama care).  In part it is designed to make the health care system costs grow slower.  It aims to do this by: increasing competition between insurers and providers, offering free preventative services to limit the development of serious illnesses, constraining patients' use of expensive services, constraining the growth of payments to Medicare providers and piloting new ways for PCPs to manage patient care to keep patients away from costly E.D.s.  It funds these changes with increased taxes on the wealthy.  It follows an architecture developed by Heritage Action's Butler, Moffit, Haislmaier extended by White House OMB health policy advisor Ezekiel Emanuel & architect Jeanne Lambrew.  The Obama administration drafting team included: Bob Kocher; allowing it to integrate ideas from: Dartmouth Institute's Elliot Fischer (ACO).  The ACA did not include a Medicare buy in (May 2016).  The law includes:
  • Alterations, in title I, to how health care is paid for and who is covered.  This has been altered to ensure
    
  • Americans with preexisting conditions get health insurance cover - buttressed by mandating community rating and
    
  • That they are constrained by the individual mandate to have insurance but the requirement was supported by subsidies for the poor (those with incomes between 100 & 400% of the federal poverty line).  
  • Children, allowed to, stay on their parents insurance until 26 years of age. 
    
  • Medicare solvency improvements. 
    
  • Medicaid expansion, in title II: to poor with incomes below 138% of the federal poverty line; an expansion which was subsequently constrained by the Supreme Court's ruling making expansion an optional state government decision. 
    
  • Hospital Readmissions Reduction Program (HRRP) which was enforced by CMS mandated rules finalized in 2011 and effected starting Oct 2012.  
  • Medical home models.  
  • Community transformation grants support the transformation of low income stressed neighborhoods to improve their lifestyles and health. 
    
  • Qualifications for ACOs.  Organizations must:
    
  • Establish a formal legal structure with shared governance which allows the ACO to distribute shared savings payments to participating providers and suppliers. 
    
  • Participate in the MSSP for three or more years. 
    
  • Have a management structure. 
    
  • Have clinical and administrative systems. 
    
  • Include enough PCPs to care for Medicare FFS patient population (> 5000) assigned to the ACO. 
    
  • Be accountable for the quality and cost of care provided to the Medicare FFS patient population. 
    
  • Have defined processes to promote: Evidence-based medicine, Patient-centeredness, Quality reporting, Cost management, Coordination of care; 
  • Demonstrate it meets HHS patent-centeredness criteria including use of patient and caregiver assessments and individualized care plans.  
  • CMMI Medicare payment experimentation.  
  • Requirements that pharmaceutical companies must report payments made to physicians (Sunshine Act). 
    
  • A requirement that chain restaurants must report calorie counts on their menus. 
    
  quality affordable care for all Americans.  It mandates community rating mandates health insurers charge the same price to people of the same age living in the same geographic area. 
  & essential health benefits are the minimum mandated set of benefits that insurers must cover under the ACA.  These include:
  • Mental health care,
  • Emergency services,
    
  • maternity and newborn care,
    
  • prescription drugs;
    
  .  It includes:
• Subtitle A: Immediate improvements in health care for all Americans. 
  
• Subtitle B: Immediate actions to preserve and expand coverage. 
  
• Subtitle C: Quality health insurance coverage for all Americans.  Which reforms the health insurance markets and prohibits preexisting condition exclusions and forms of health status discrimination.  
• Subtitle D: Available coverage choices for all Americans. 
  
• Subtitle E: Affordable coverage choices for all Americans. 
  
• Subtitle F: Shared responsibility for health care which mandates individuals and employers to pay for insurance.  
• The employer mandate requires employers with more than 50 full-time workers to offer most of their employees insurance or face penalties. 
  
• ACA title II is ACA is the Patient Protection and Affordable Care Act amended by the Health Care and Education Reconciliation Act of 2010 (Obama care).  In part it is designed to make the health care system costs grow slower.  It aims to do this by: increasing competition between insurers and providers, offering free preventative services to limit the development of serious illnesses, constraining patients' use of expensive services, constraining the growth of payments to Medicare providers and piloting new ways for PCPs to manage patient care to keep patients away from costly E.D.s.  It funds these changes with increased taxes on the wealthy.  It follows an architecture developed by Heritage Action's Butler, Moffit, Haislmaier extended by White House OMB health policy advisor Ezekiel Emanuel & architect Jeanne Lambrew.  The Obama administration drafting team included: Bob Kocher; allowing it to integrate ideas from: Dartmouth Institute's Elliot Fischer (ACO).  The ACA did not include a Medicare buy in (May 2016).  The law includes:
  • Alterations, in title I, to how health care is paid for and who is covered.  This has been altered to ensure
    
  • Americans with preexisting conditions get health insurance cover - buttressed by mandating community rating and
    
  • That they are constrained by the individual mandate to have insurance but the requirement was supported by subsidies for the poor (those with incomes between 100 & 400% of the federal poverty line).  
  • Children, allowed to, stay on their parents insurance until 26 years of age. 
    
  • Medicare solvency improvements. 
    
  • Medicaid expansion, in title II: to poor with incomes below 138% of the federal poverty line; an expansion which was subsequently constrained by the Supreme Court's ruling making expansion an optional state government decision. 
    
  • Hospital Readmissions Reduction Program (HRRP) which was enforced by CMS mandated rules finalized in 2011 and effected starting Oct 2012.  
  • Medical home models.  
  • Community transformation grants support the transformation of low income stressed neighborhoods to improve their lifestyles and health. 
    
  • Qualifications for ACOs.  Organizations must:
    
  • Establish a formal legal structure with shared governance which allows the ACO to distribute shared savings payments to participating providers and suppliers. 
    
  • Participate in the MSSP for three or more years. 
    
  • Have a management structure. 
    
  • Have clinical and administrative systems. 
    
  • Include enough PCPs to care for Medicare FFS patient population (> 5000) assigned to the ACO. 
    
  • Be accountable for the quality and cost of care provided to the Medicare FFS patient population. 
    
  • Have defined processes to promote: Evidence-based medicine, Patient-centeredness, Quality reporting, Cost management, Coordination of care; 
  • Demonstrate it meets HHS patent-centeredness criteria including use of patient and caregiver assessments and individualized care plans.  
  • CMMI Medicare payment experimentation.  
  • Requirements that pharmaceutical companies must report payments made to physicians (Sunshine Act). 
    
  • A requirement that chain restaurants must report calorie counts on their menus. 
    
  role of public programs.  It includes:
• Subtitle A: Improved access to Medicaid is the state-federal program for the poor.  Originally part of Lyndon Johnson's 1965 Bill, eligibility and services vary by state.  Less than 10 percent of Medicaid recipients, those in long-term care including nursing homes where 64% are dependent on Medicaid, use one-third of all Medicaid spending which is a problem.  The ACA's Medicaid expansion program, made state optional by the SCOTUS decision, was initially taken up by fifty percent of states.  As of 2016 it covers 70 million Americans at a federal cost of $350 billion a year.  In 2017 it pays for 40% of new US births. 
  . 
  
• Subtitle B: Enhanced support for children's health insurance program. 
  
• Subtitle C: Medicaid and CHIP is:
  
  • The Children's Health Insurance Program started in 1997 as part of the BBA as SCHIP.  It provides health insurance coverage for children in families with income below 200 percent of the poverty line.  The coverage is focused on care specialized for children including: developmental delays, chronic conditions including asthma and obesity.  CHIP's funding must be iteratively re-authorized by Congress.  CHIP is financed federally, but states must enroll eligible children.  In many states one agency administers CHIP and Medicaid.  CHIP is leveraged by families that have employer based insurance with costly premiums, so the families only cover the adults.  
  • Clonal Hematopoiesis of Indeterminate Potential, where stem cells develop a somatic mutation cluster pair often found in leukemia, which is expressed in white blood cells they produce.  The mutation clusters give these stem cells a competitive advantage and they accumulate over time.  The white blood cells form inflammatory plaques.  CHIP increases with age, increasing the risk of dying, of clot fragment induced heart attacks and stroke, over the subsequent 10 years by 54%
    
  enrolment simplification. 
  
• Subtitle D: Improvements to Medicaid services. 
  
• Subtitle E: New options for states to provide long-term services and support. 
  
• Subtitle F: Medicaid prescription drug coverage. 
  
• Subtitle G: Medicaid disproportionate share hospital (DSH is disproportionate share hospital ACA program providing federal government Medicare compensation for a provider treating indigent patients. 
  ) payments.  
• Subtitle H: Improved coordination for dual eligibles. 
  
• Subtitle I: Improving the quality of Medicaid for patients and providers
  
• Subtitle J: Improvements to the Medicaid and CHIP payment and access commission (MACPAC)
  
• Subtitle K: Protections for American Indians and Alaska natives. 
  
• Subtitle L: Maternal and child health services. 
  
• ACC is either the
  
• Anterior cingulate cortex which:
• Is a central focus of empathy is the capability to relate to another person from their perspective.  It is implemented by spindle neurons.  It is context dependently mediated by estrogen.  It develops over time: Piaget's preoperational stage includes rudimentary empathy, Theory of mind supports the development; initially feeling someone's pain as one integrated being, then for them and eventually as them.  In adults, when someone else is hurt the anterior cingulate cortex, amygdala & insula activates projecting [scapegoating] to the vmPFC.  If the pain is physical the PAG activates and motor neurons for the area where the other person was injured.  The intertwining of the ACC amygdala & insula in adults results in attribution of fault even when there is none which can make it hard to step in and actually help.  But in seven-year-olds the activation is concrete: PAG and sensory & motor cortexes with minimal coupling to the rudimentary vmPFC.  In older children the vmPFC is coupled to limbic structures.  Ten to twelve year olds abstract empathy to classes of people.  By adolescence the vmPFC is coupled to theory of mind regions and intentional harm induces disgust via the amygdala.  Sapolsky explains adolescent boys are utilitarian and tend to accept inequality more than girls do.  But both sexes accept inequality as the way it is.  Sociopaths do not develop empathy.   supporting people relating to other's pain.  This is dependent on oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening outgroup.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant which is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
  . 
  
• In non-human mammals it processes interoceptive signals indicate the body's internal state: Pain, Fatigue; seconds to minutes before.  The interoceptive 'networks' project to brain regions that implement social emotions. 
  .  The ACC focuses the internal signals into high level 'gut intuitions.'  Pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Pain is the main reason people visit the ED in the US.   catches the ACC's attention. 
  
• Performs discrepancy detection from the outcome that was predicted - at a high level.  The ACC cares about the meaning of what is predicted. 
  
• If the ACC has been convinced that a pain killer placebo has inhibited pain signals, the ACC will stay silent about actual pain that is signalled from interoceptive networks.  
• The ACC will signal: physical pain, emotional pain, metaphorical pain, anxiety is manifested in the amygdala mediating inhibition of dopamine rewards.  Major anxiety results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women. 
  , disgust is a universal human emotion.  Pinker notes it has its own facial expression and is codified in food taboos.  The mind must be associated with the proximate environment and parents minimize the risk for their omnivorous children by teaching them what foods to eat and what to avoid.  The children's minds are initially receptive to trying all foods but their brains subsequently lock in on the foods they have experienced.  These parental choices are affected by schematic influence on what has been beneficial.  Adolescent's brain developments undermine these constraints enabling intergroup transfers.  Disgust is modulated by the insula cortex which projects signals to the amygdala. 
  , embarrassment, social exclusion especially in adolescence in humans supports the transition from a juvenile configuration, dependent on parents and structured to learn & logistically transform, to adult optimized to the proximate environment.  And it is staged encouraging the adolescents to escape the hierarchy they grew up in and enter other groups where they may bring in: fresh ideas, risk taking; and alter the existing hierarchy: Steve Jobs & Steve Wozniak, Bill Gates & Paul Allen.  It marks the beginning of Piaget's formal operational stage of cognitive development.  The limbic, autonomic and hormone networks are already deployed and functioning effectively.  The frontal cortex has to be pruned: winning neurons move to their final highly connected positions, and are myelinated over time.  The rest dissolve.  So the frontal lobe does not obtain its adult configuration and networked integration until the mid-twenties when prefrontal cortex control becomes optimal.  The evolutionarily oldest areas of the frontal cortex mature first.  The PFC must be iteratively customized by experience to do the right thing as an adult.  Adolescents:
  • Don't detect irony effectively.  They depend on the DMPFC to do this, unlike adults who leverage the fusiform face area.  
  • Regulate emotions with the ventral striatum while the prefrontal cortex is still being setup.  Dopamine projection density and signalling increase from the ventral tegmentum catalyzing increased interest in dopamine based rewards.  Novelty seeking allows for creative exploration which was necessary to move beyond the familial pack.  Criticisms do not get incorporated into learning models by adolescents leaving their risk assessments very poor.  The target of the dopamine networks, the adolescent accumbens, responds to rewards like a gyrating top - hugely to large rewards, and negatively to small rewards.  Eventually as the frontal regions increase in contribution there are steady improvements in: working memory, flexible rule use, executive organization and task shifting.  And adolescents start to see other people's perspective. 
    
  • Drive the cellular transformations with post-pubescent high levels of testosterone in males, and high but fluctuating estrogen & progesterone levels in females.  Blood flow to the frontal cortex is also diverted on occasion to the groin.  
  • Peer pressure is exceptionally influential in adolescents.  Admired peer comments reduce vmPFC activity and enhance ventral striatal activity.  Adults modulate the mental impact of socially mean treatment: the initial activation of the PAG, anterior cingulate, amygdala, insula cortex; which generate feelings of pain, anger, and disgust, with the VLPFC but that does not occur in adolescents.  
  • Feel empathy intensely, supported by their rampant emotions, interest in novelty, ego.  But feeling the pain of others can induce self-oriented avoidance of the situations. 
    
  ; as one and the same.  The ACC's abnormalities being associated with major depression is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult;. 
  
• Has a bridging role between the empathetic and self-interested pain monitor.  Sapolsky notes the ACC is essential for learning fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
  and conditioned avoidance by observation alone through an intermediate step of shared representation of self.  He concludes "At its core the ACC is about self-interest, with caring about the other person in pain as an add-on." 
  
• American College of Cardiology
  
• ACE is
  
• An acute care episode.  CMS is the centers for Medicare and Medicaid services.   has used an ACE demonstrator to explore the value of bundled payments is where the purchaser disburses a single predefined payment to cover certain combinations of hospital, physician, post-acute, or other services performed during an episode of care relating to a particular condition (unlike capitation).  This bundling is assumed to allow the value delivery system to optimize around low cost high quality long term health care.  With one bundled payment physicians & hospitals must coordinate care and reduce the unit costs to remain profitable.  And to avoid taking on risk of expensive complications physicians & hospitals are incented to standardize and focus on quality.  This optimization is dependent on quantifying the value of the outcome of the episode of care.  Previously FFS payments induced excessive treatment activity.  Bundled payment is included in CMS ACE demonstrations and BPCI initiatives.  There are significant impacts on IT. 
  
  1. It is argued that effective pricing of the bundle requires marketing data which must be extracted from the historic transaction base.  
  2. Billing and payment systems must be updated to handle the receipt and distribution of the bundled payments. 
     
  3. Care delivery must be re-architected to reduce costs and improve quality. 
     
  4. Monitoring sensors can be used to feed reports to ensure re-architected operations conform.  
  .  The demonstrator covered 37 cardiac is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   and orthopedic is the treatment of the musculoskeletal system which supports multi-cell animals and allows them to move about: including correcting deformities, breaks, tears, compression, tendonitis, disc failures, misalignment, fusion to treat damaged discs. 
  procedures including: bypass surgery, hip replacements, pacemakers, and cardiac stents is a small wire cage that can be inserted into an artery to prop it open.  They were introduced as an alternative to bypass surgery in the 1990s.  Stents are expensive.  Medicare payments vary depending on what kind of stent is used and how many, but are generally in the range $10,000 to $17,000 in 2015.   Double blind trials show that stents have no effect on chest pain relief (Nov 2017)
  ; in 11 hospitals.  It saved $319 per person, across over 12,000 cases, on average.  
• Angiotensin-converting-enzyme. 
  
• ACE inhibitor is angiotensin-converting-enzyme inhibitor.  They help relax blood vessels and are used to treat hypertension and CHF is congestive heart failure which occurs when the heart is unable to generate enough blood flow to meet the body's demands.  There are two main types: failure due to left ventricular dysfunction and abnormal diastolic function increasing the stiffness of the left ventricle and decreasing its relaxation.  Treatments include: digoxin; .  
• ACHC is the accreditation commission for health care.  It is recognized by the federal government for:
• HHA is home health agency. 
  accreditation along with the CHAP is the community health accrediation program, one of three federally recognized HHA focused programs along with those provided by the Joint Commission and ACHC. 
  and the Joint Commission, JC or JCAHO is a nonprofit that accredits more than 19,000 health care organizations and programs in the United States. 
  
  • Home health care: The JC is one of three groups (JC, CHAP, ACHC) recognized by the federal government as accreditors of HHAs.  The JC requires its accredited HHAs receive payment from Medicare.  To become accredited an HHA must undergo detailed reviews and onsite visits, including direct observation of patient caregiving, every three years. 
    
  • Hospitals: In 1965 the federal government decided that a hospital that met joint commission accreditation met the Medicare conditions of participation.  MIPPA removed the joint commission's accreditation authority requiring it to submit accreditations to CMS which subsequently determines the granting of accreditation. 
    
  • Rehabilitation: Joint Commission accreditation is an alternative to CARF certification for rehabilitation.  
  .  
• ACI is advanced care information. 
  
• ACID transactions are Atomic, Consistent, Isolated and Durable, allowing the user of the transaction a simple operating paradigm.  In particular if the transaction fails there are no ramifications outside of the local transaction. 
  
• ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness is a health care oriented employer based strategy for reducing health care costs and encouraging wellbeing.  Wellbeing has traditionally been a focus of public health.  , improving the provision of primary care to a large group of Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV is fee-for-value payment.  It may be a bundled payment for a set of services provided by a group of doctors and facilities, or full capitation.  In each case the risk has shifted from the payer to the providers of care. 
  business.  The ACA is the Patient Protection and Affordable Care Act amended by the Health Care and Education Reconciliation Act of 2010 (Obama care).  In part it is designed to make the health care system costs grow slower.  It aims to do this by: increasing competition between insurers and providers, offering free preventative services to limit the development of serious illnesses, constraining patients' use of expensive services, constraining the growth of payments to Medicare providers and piloting new ways for PCPs to manage patient care to keep patients away from costly E.D.s.  It funds these changes with increased taxes on the wealthy.  It follows an architecture developed by Heritage Action's Butler, Moffit, Haislmaier extended by White House OMB health policy advisor Ezekiel Emanuel & architect Jeanne Lambrew.  The Obama administration drafting team included: Bob Kocher; allowing it to integrate ideas from: Dartmouth Institute's Elliot Fischer (ACO).  The ACA did not include a Medicare buy in (May 2016).  The law includes:
  • Alterations, in title I, to how health care is paid for and who is covered.  This has been altered to ensure
    
  • Americans with preexisting conditions get health insurance cover - buttressed by mandating community rating and
    
  • That they are constrained by the individual mandate to have insurance but the requirement was supported by subsidies for the poor (those with incomes between 100 & 400% of the federal poverty line).  
  • Children, allowed to, stay on their parents insurance until 26 years of age. 
    
  • Medicare solvency improvements. 
    
  • Medicaid expansion, in title II: to poor with incomes below 138% of the federal poverty line; an expansion which was subsequently constrained by the Supreme Court's ruling making expansion an optional state government decision. 
    
  • Hospital Readmissions Reduction Program (HRRP) which was enforced by CMS mandated rules finalized in 2011 and effected starting Oct 2012.  
  • Medical home models.  
  • Community transformation grants support the transformation of low income stressed neighborhoods to improve their lifestyles and health. 
    
  • Qualifications for ACOs.  Organizations must:
    
  • Establish a formal legal structure with shared governance which allows the ACO to distribute shared savings payments to participating providers and suppliers. 
    
  • Participate in the MSSP for three or more years. 
    
  • Have a management structure. 
    
  • Have clinical and administrative systems. 
    
  • Include enough PCPs to care for Medicare FFS patient population (> 5000) assigned to the ACO. 
    
  • Be accountable for the quality and cost of care provided to the Medicare FFS patient population. 
    
  • Have defined processes to promote: Evidence-based medicine, Patient-centeredness, Quality reporting, Cost management, Coordination of care; 
  • Demonstrate it meets HHS patent-centeredness criteria including use of patient and caregiver assessments and individualized care plans.  
  • CMMI Medicare payment experimentation.  
  • Requirements that pharmaceutical companies must report payments made to physicians (Sunshine Act). 
    
  • A requirement that chain restaurants must report calorie counts on their menus. 
    
  regulates qualification to be a Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  ACO.  Individual organizations within a Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  shared savings is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  ACO continue to submit their own claims and are paid by Medicare for FFS is fee-for-service payment.  For health care providers the high profits were made in hospitalizations, imaging and surgery.  Due to its inducing excessive treatment activity it may be replaced by FFV bundled payment.  .  But the ACO is eligible for shared savings is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  .  Within the shared savings program the CMS is the centers for Medicare and Medicaid services.   innovation center is the CMS Innovation Center.  It was created by the ACA to test new models of health care delivery and payment including the Pioneer ACO and the Advance Payment ACO.  It also offers technical support to providers to improve the coordination of care and share lessons learned and best practices.  In 2016 Andy Slavitt proposed testing a new Medicare part B drug pricing rule, which was furiously resisted by PhRMA and blocked by Representative Skimkus collection of 242 Representative's signatures. 
  has setup advanced payment ACOs is a CMS Innovation center has developed a model of an ACO for physician-owned and rural providers participating in the Shared Savings Program who would benefit from additional start-up resources to build the necessary infrastructure, such as new staff or information technology systems.  .  As an alternative to shared savings, in a Pioneer ACO is a CMS Innovation Center initiative to support ACOs in providing more coordinated care to beneficiaries (individuals and populations) at lower cost to Medicare.  It leverages the ACA shared savings program and tests an alternative 'pioneer ACO' model.  Pioneers are assumed to be organizations with experience offering coordinated, patient-centered care, and operating in ACO-like arrangements.  A first performance period Jan 1 2012 - 2014 tests a shared savings and shared losses payment arrangement with higher levels of reward and risk than in the shared savings program.  In year three Pioneer ACOs that have showed savings over the first two years can move to a population based payment model.  Two alternative payment models were added which allow pioneer ACOs more flexibility in the speed at which they assume financial risk.  Pioneers must also commit to having greater than 50% of primary care providers meet meaningful use of certified EHRs for receipt of payments through Medicare and Medicaid EHR Incentive Programs.  Pioneers must have > 15000 beneficiaries enrolled in original FFS part A and part B Medicare.  Organizations were selected using these criteria. 
  , over time 50% of the FFS payments flow directly to the ACO as a bundled payment is where the purchaser disburses a single predefined payment to cover certain combinations of hospital, physician, post-acute, or other services performed during an episode of care relating to a particular condition (unlike capitation).  This bundling is assumed to allow the value delivery system to optimize around low cost high quality long term health care.  With one bundled payment physicians & hospitals must coordinate care and reduce the unit costs to remain profitable.  And to avoid taking on risk of expensive complications physicians & hospitals are incented to standardize and focus on quality.  This optimization is dependent on quantifying the value of the outcome of the episode of care.  Previously FFS payments induced excessive treatment activity.  Bundled payment is included in CMS ACE demonstrations and BPCI initiatives.  There are significant impacts on IT. 
  
  1. It is argued that effective pricing of the bundle requires marketing data which must be extracted from the historic transaction base.  
  2. Billing and payment systems must be updated to handle the receipt and distribution of the bundled payments. 
     
  3. Care delivery must be re-architected to reduce costs and improve quality. 
     
  4. Monitoring sensors can be used to feed reports to ensure re-architected operations conform.  
  .  CMS is the centers for Medicare and Medicaid services.   has established quality measures for ACOs for Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  .  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination aims to transfer information between the patient and each care participant as required and establish accountability by defining who is responsible for each care delivery activity, the extent of that responsibility and when that responsibility will be transferred to other care participants or the patient and family.  Successful care coordination requires face-to-face interactions.  It also requires aligned incentives (ACO, Bundled payments).  AHRQ defines quality measures for care coordination.  The situation is usually complex and adaptive due to the interactions of all the providers, settings, the patients' preferences, and the number of physical health problems, treatments, and the patients' social situation.  The potentially exponential increase in complexity as the number of these factors present increases leads to patient hot spots requiring explicit proactive coordination of care.  It is argued that care coordination must include six specific activities:
  1. Determination and updating of care coordination needs: Needs assessment should identify preferences and goals, current situation and past history.  It needs to be updated periodically and after new diagnosis and other changes in health or functional status. 
     
  2. Creation and updating of proactive plan of care
     
  3. Communication
  4. Facilitation of transitions: typical transition problems are detailed by Project Boost.  A challenging issue with transitions is what to do when there is no resource to take over the coordination role in the handoff. 
     
  5. Connection to community resources: Community resources are any service or program outside the health care system that may support a patient's health and wellness. 
     
  6. Alignment of resources with population needs: need to see the system-level, assess the needs of populations to identify and address gaps in services.  
  . 
  
• CMS initiated its Physician Group Practice in health care is physician group practice a CMS demonstrator program that led to the promotion of ACOs. 
  Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
  
• CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
• CMS has developed APM is alternative payment model, Medicare's risk based payments to organizations set up as ACOs.  It includes track 1 ACOs which are not risk bearing.  APMs have to report various measures to CMS.  s which include ACOs, and advanced APM is a CMS regulated group of APMs that effectively uses FFV.  The list includes: Risk-bearing ACOs, Comprehensive end stage renal disease care, Comprehensive primary care plus, Oncology care model. 
  s where the ACOs must be risk bearing. 
  
• CMMI is the center for Medicare and Medicaid Innovation.  It is a test bed for new ways of financing and delivering care.  It allowed Congress to institutionalize innovation sending a signal to providers that they would be participating in CMS driven programs that could become mainstream.  It funds evaluations of innovative health care models.  Under the ACA if the HHS secretary finds any of its projects would reduce Medicare spending without harming the quality of care the projects may be expanded nationwide.  The CBO estimates the CMMI will save $34 billion between 2016 and 2026.  CMMI projects include:
  • Medicare will make a bundled payment for hip and knee replacement surgery (CJR) and 90 days of follow-up care forcing hospitals to work closely with doctors, nursing homes and home health agencies.  
  • New ways to pay for prescription drugs, medical devices, cancer care (OCM).  
  • HHS secretary has invoked his 3021 authority to institute DPP. 
    
  accepts providers' proposals to test various payment systems including shared savings is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  and partial capitation is a global payment for all care for a patient during a specified time period.  It forces the provider of care to take a high risk.  Managing the risk implies successful population health management. 
  .  
• Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
• ACOG is the American Congress of Obstetricians and Gynecologists. 
  
• ACR is the American College of Radiology.  It is HHS is the U.S. Department of Health and Human Services.  's PAMA is the Protecting Access to Medicare Act of 2014.  It includes:
  • Delays of the SGR cut to Medicare until March 2015 ('doc fix').  The delay is partly funded with cuts to Medicare's funding of SNF, lab tests, physician and other provider services.  The rest is offset by moving Medicare sequester cuts from 2025 to 2024.  This SGR cut has been iteratively delayed for 10 years and was finally removed in 2015. 
  • Helps states establish CCBHCs through section 223 the Excellence in Mental Health Act demonstration program.  This stipulated that CCBHCs may receive an enhanced Medicaid reimbursement rate based on their anticipated cost of care. 
    
  • Directs HHS to develop VBP and readmissions strategies for SNFs
  • Directs HHS to: Develop, Promote the use by ordering and furnishing agents of, Make the interfaces public of; rules for imaging services appropriateness criteria.  The rules held in a radiology CDSS will remove the need for pre-authorization of the procedure. 
    
  • Enhances clinical diagnostic laboratory tests coverage, payment rates;
  • Alters end stage renal disease payments, audits;
  applicable imaging services are advanced diagnostic imaging services for which appropriate use criteria apply.   appropriate use criteria are those:
  
  • Which assist ordering and furnishing professionals in making the most appropriate treatment decision per condition for this individual
    
  • Developed or endorsed by national medical specialty societies or other provider led entities.  For imaging services this is the ACR. 
    
  standards body. 
  
• Acrophonic principle where each shape of a mnemonic leveraged a word that began with the corresponding consonant.  This
  This page discusses the impact of random events which once they occur encourage a particular direction forward for a complex adaptive system (CAS). 
  
  frozen accident resulted in the names and representations of the alphabetic characters we now use as the Greeks and Phoenicians turned them into modern letters.  Greek and Roman letters have distorted Semitic names of the two dozen images that gave our letters their shape, name and pronunciation of their first consonant:
• 'A' when rotated 90 degrees looks like the ox head that it initially represented - aleph (ox). 
  
• 'b' is the outline of a house termed beth in Semitic languages include Arabic, Amharic and Hebrew.  They have an unusual morphology that emphasizes consonants.  The designers of Proto-Sinaitic writing exploited this building a representation of an abstract consonant grid that only required about two dozen shapes in the consonant lexicon.  They also used the acrophonic priciple to leverage mnemonics. 
  .  It became the Greek beta.  
  
• 'I' is a goad (lamd). 
  
• 'k' is a hand with outstretched fingers (kaf). 
  
• 'm' symbolizes waves (mayyuma). 
  
• 'n' is a snake (nahasu).  
• 'R' is a head (res). 
  
• ACTH is adrenocorticotropic hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  which stimulates the adrenal glands are endocrine glands, situated above the kidneys, that produce: adrenaline, aldosterone and cortisol. 
  to release glucocorticoids are corticosteroids which bind the glucocorticoid receptor.  They decrease excitability of prefrontal cortical neurons.  They have adverse effects in fetal/infant development having organizational effects on fetal brain construction and decreasing levels of: growth factors, neurons, synapses; resulting in an adult brain that is more sensitive to environmental triggers of depression and anxiety.  Glucocorticoids affect gene control structures and induce epi-genetic changes.  They have been found associated with high sodium chloride consumption (May 2017). 
  . 
  
• Action potentials are the actively generated waves of voltage change was formulated by Julius Bernstein to describe the generation and propagation of an action potential along a neuron's cell membrane.  It elegantly established how a resting potential of -70 millivolts was maintained until the selective permeability of the membrane is broken down briefly (0 millivolts) during the action potential, utilizing energy stored in concentration gradients of ions. 
  across the neuron's, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  membrane, formed from a lipid (fat) bilayer which creates a barrier between aqueous (water soluble) media.  In AWF a key property of membranes - their providing a catalytic environment and supporting the suspension of enzymatically active proteins within the membrane; is simulated with a Workspace list where 'active' structures can be inserted and codelets can detect and act on the structure's active promise configured as an association in the Slipnet.   that
  Flows of different kinds are essential to the operation of complex adaptive systems (CAS). 
  Example flows are outlined.  Constraints on flows support the emergence of the systems.  Examples of constraints are discussed. 
  
  flow down a neuron, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  's axon, a long extension of a neuron which has a membrane constructed to support the uni-directional flow of action potential from the dendritic tree and cell body to the synaptic terminals.  .  Helmholtz noted that while they propagate far more slowly than electrical transmissions action potentials do not attenuate.  Lord Adrian showed the action potential to be an all-or-nothing signal, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  .  Consequently Adrian extended the neuron doctrine is cell theory applied to the brain.  Anatomist Santiago Cajal developed ground breaking strategies to view individual neurons and concluded that nerve cells (neurons) are the fundamental building blocks and signalling units of the brain.  
  • Looking at newborn brains helped Cajal to see individual neurons because there were less present than in mature animals. 
    
  • Using Golgi's silver stain only 1% of neurons are stained but that 1% is fully stained revealing the full anatomy of single neurons.  This allowed Cajal to develop observations which he used to formulate the four principles of the neuron doctrine:
  1. Neuron is the fundamental structural and functional element of the brain with the dendrites and axon having different roles. 
     
  2. The terminals of one neuron's axon communicate with the dendrites of other neurons via specialized sites that include a small gap.  
  3. Connection specificity argues that neurons only form synapses and communicate with certain targets to construct a neural circuit.  Typically a single neuron makes contact with dendrites of many target cells, allowing broad dissemination of information. 
     
  4. Dynamic polarization Cajal argued was provided by signals only traveling in one direction in a neural circuit. 
     
  from anatomy to function demonstrating:
• Sensitivity is indicated by the frequency of transmission of action potentials. 
  
• Anatomy indicates the meaning of the signal.  Hodgkin and Huxley's ionic hypothesis proposes the mechanism for generating action potentials that can propagate long distances within a given neuron.  Extending Bernstein's membrane hypothesis about breakdown of the resting potential (-70 millivolts) Hodgkin and Huxley's studies on squid giant axons showed that the action potential was actively generated by transport of sodium ions into the cell (+40 millivolts) and then potassium ions out to restore the resting potential. 
  completed the characterization of the action potential. 
  
• Activation function provides an artificial neural network node with its output given a set of inputs with a weight and bias.  Typical activation functions are the sigmoid function generates an s curve.  It is f(x) = 1/(1+exp(-x)).  It is a simple function that may be selected for classifying a novel instance x as belonging to a particular class within the training data in machine learning.  The hyperplane (bias + x(t) weight) = 0 forms the decision boundary.  The orientation of the decision boundary is determined by the vector weight.  The bias shifts the decision boundary by a constant amount.  The sigmoid function is one activation function for use with neural networks which does not suffer unstable convergence (like the linear activation function), or produce a limiting binary output (like a binary function).  One effective alternative to selecting a direct sigmoid function is to apply a class conditional density estimation and Bayes rule to form the classifier. 
  and the hyperbolic tangent.  The Rectified linear function is given by f (z) = max (0, x)
  often works better in practice for DNN are representational models that achieve high performance on difficult pattern recognition problems in vision and speech.  But they need specialized training methods such as greedy layerwise pre-training or HF optimization.  s. 
  
• Active sites, on the external surface of folded proteins, a relatively long chain (polymer) of peptides.  Shorter chains of peptides are termed polypeptides.   present amino acids are the building blocks of proteins.  The 20 main variants differ by the nature of their side chain.  Some are positively charged, others negatively charged.  Some are water seeking while others are fat seeking.  The genetic code mapping of DNA base pair triplets thus specifies the primary sequence of amino-acids in any protein polymer. 
  which become catalytic structures, an infrastructure amplifier.  .  
• Activity based cost accounting identifies the process based flow of activities used to perform a task and the cost of each activity to effectively apportion costs. 
  
• AD is Anno Domini also referred to as common era (CE).  
• Ada refers to Ada Byron, Countess of Lovelace and, in deference to her memory, is the name of a computer programming language used in developing military systems during the late 1970s and beyond. 
  
• ADA is either the Americans with Disabilities Act of 1990 or a label for the gene that encodes the enzyme, a protein with a structure which allows it to operate as a chemical catalyst and a control switch. 
  adenosine deaminase. 
  
• Adair three-circles model is a tool for leadership aims to develop plans and strategies which ensure effective coordination to improve the common good of the in-group.  John Adair developed a leadership methodology based on the three-circles model. 
  described in Effective Leadership.  It argues an effective team has distinct but interacting:
• Individual needs - which must be supported by the leader to ensure the team member's self-motivation is not undermined. 
  
• Group needs - Each member's social emotions are emotions that are induced in response to other people's signals, are implemented by specific brain regions including: Prefrontal cortex, Insula cortex, Anterior cingulate cortex, Amygdala; receive lots of projections from interoceptive networks.  Sapolsky asserts in the moments just before we prioritize a consequential act the process is less rational and autonomous than we assume.  There are many significant signals from the prior seconds to minutes that effect social emotions:
  
  • Our brains respond subliminally to skin color very quickly: Amygdala activates, Fusiform face area activates; prior to the conscious stream activating the anterior cingulate and DLPFC which then inhibit the amygdala. 
    
  • Social dominance is culture independent and accurately subliminally assessed after a 40-millisecond exposure.  Stable status relations activate the ventromedial prefrontal cortex and DLPFC, while a dynamic situation also activates the amygdala.  
  • People who are subliminally judged attractive by the medial orbitofrontal cortex are considered kinder, smarter and more honest.  They are given more breaks. 
    
  • Faces and eyes in particular are most important subliminal cues.  They are monitored by the fusiform.  People respond more appropriately under the subliminal influence of eyes. 
    
  • Olfactory sensors send more direct projections to the limbic network than other sensory networks.  Pheromones signal fear activating the amygdala. 
    
  • Observing pain responses in others results in empathy even among young children. 
    
  • Words are important emotional signals providing unconscious priming of social responses.  Kahneman & Tversky demonstrated how the phrase '95% survival rate' is found to be a more acceptable choice than '5% death rate'.  Sapolsky notes that prosocial word priming fosters cooperation with antisocial word priming doing the opposite.  
  • Cultural objects such as visible: flags, team badges; subliminally modify in-group outgroup decisions. 
    
  • The presence of women in a situation alters the responses of men: Increased risk-taking, more focus on luxuries, increased aggression; in circumstances where conflict is already encouraged but not when status is achieved prosocially.  
  • Physical environment shapes behavior as demonstrated by Philip Zimbardo and leveraged in broken windows policing.  
  • Bodily adjustments to sensory structures introduce adaptive complexity, with the brain being influenced to become more sensitive and alter the sensor networks to make some more sensitive.  But these adaptations also vary culturally.  Collectivist cultures focus on a visual scene's surrounding contextual information while people from individualistic cultures focus on the focal object!   
  are supported by being part of a cohesive group or organization performing a worthwhile task. 
  
• Task needs - A task that is to big for an individual, which is agreed to be valuable and achievable by the group within expected timescales.  Tasks can be seen to be valuable to the organization when they are clearly derived from the corporate Hoshin - Hoshin (direction) Kanri (management) is a planning process which was popularized by Professor Kaoru Ishikawa which helped align goals and objectives across an organization.  It argues:
  1. Focus on a few breakthrough ideas.  As a method to focus an organization on lean management it can be used to drive cost cutting.  However, if the measures are poor the results can undermine the operation of an effective system, as at Laguna Honda Hospital.  
     
  2. Cascade of goals and strategies is developed by top down and bottom up discussions allowing detail to be added along with alignment and buy in.  In Japan, lifelong employment supported this process.  The individual focused merit ratings used in Western management practice undermines the process in Deming's view (deadly disease 3). 
     
  3. The goals, strategies and success measures should be rigorously documented.  In the original paper and fax processes in Japan each goal, its strategies, measures and resources were documented in a planning table.  The whole activity became coordinated by a house of quality.  In AWF the planning table is replaced by a bullet point infinite labelled goal in the execution schematic plan with a structured status block allowing easy visualization of the goal network. 
     
  4. Regular review process based on a Shewhart cycle.  
  . 
  
• Adaptation in evolutionary biology argues that the human genome and phenotypes developed during the relatively long period when our ancestors were hunter-gatherers.  These biologists argue we can best understand ourselves by observing the remaining hunter-gatherer tribes including the Hadza. 
  is a trait that increased the number of surviving offspring in an
  This page reviews the implications of reproduction initially generating a single child cell.  The mechanism and resulting strategic options are discussed. 
  
  organism's ancestral lineage.  In
  Terrence Deacon explores how constraints on dynamic flows can induce emergent phenomena which can do real work.  He shows how these phenomena are sustained.  The mechanism enables the development of Darwinian competition. 
  
  Deacon's conception of evolution an adaptation is the realization of a set of constraints on candidate mechanisms, and so long as these constraints are maintained, other features are arbitrary.  
• Adaptive walk is a
  This web page reviews opportunities to find and capture new niches based on studying fitness landscapes using complex adaptive system (CAS) theory. 
  
  fitness landscape search strategy that picks its direction of search randomly, and then selects for ascending steps, and backtracks if it starts to descend.  It gets trapped in local maxima and must be augmented with other strategies, such as a short random jump is a fitness landscape search strategy that picks its direction of search randomly, and jumps a random distance in that direction. It is risky since it can jump into danger where the searcher may die. 
  . 
  
• Adaptive web supports the agents writing and using the dark webs is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   by:
  
• Leveraging unstructured HTML documents to allow clusters of related information to be juxtaposed.  
• Allowing source data to be private to a particular agent or shared and jointly edited within a team. 
  
• Allowing the writers to define streams of information (signals) within the source HTML. 
  
• Supporting the linkage of the signals to other streams of information deployed into specific dark webs. 
  
• Genetic operations can be applied to the source data.  Key items are labelled.  They are prioritized.  But they should never be deleted from the source documents. 
  
• Transforming the streams of information as they are gathered for deployment into target dark webs.  Aspects like checklist are signals which remind the reader of highly significant aspects of a process.  They are designed to be consulted at a point in the process where forgetting about the aspect will have a significantly detrimental effect.  Often the processes are being used to respond to failures in the regular operation.  Atul Gawande argues that effective use of checklists is vital to coping with situations that are complex. 
  and glossary references can be augmented with details.  Changes in one area of the dark web can be signalled in other pages. 
  
• Constraining which dark webs the information streams will deploy too.  
  
• Addcltag is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies the AWF is the adaptive web framework.   tag are structures which are used by the dark web generator to filter the current source stream.  Once a start tag for the current case selector is detected the source data is merged into the HTML template.  This continues until a terminating end tag for the current case selector is detected.  The generator becomes a filter of the source. 
  that marks the start and end of the checklist are signals which remind the reader of highly significant aspects of a process.  They are designed to be consulted at a point in the process where forgetting about the aspect will have a significantly detrimental effect.  Often the processes are being used to respond to failures in the regular operation.  Atul Gawande argues that effective use of checklists is vital to coping with situations that are complex. 
  definition source stream.  It is also the identifier that must be prepended to checklist are signals which remind the reader of highly significant aspects of a process.  They are designed to be consulted at a point in the process where forgetting about the aspect will have a significantly detrimental effect.  Often the processes are being used to respond to failures in the regular operation.  Atul Gawande argues that effective use of checklists is vital to coping with situations that are complex. 
  entry names in the source documents and hence the target dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   checklist page.  For example:
  
• The command triple addcltag 'id' = 'cl' tells the generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  to include items from the checklist page (identified to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  by the filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command addcltext is a filter file command which describes to the dark web generator the source file from which the checklist description is loaded.  If this command is not present in the filter file no hover substitution will be performed. 
  ) that have names starting with 'cl_'. 
  
• Addcltext is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which describes to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  the source file from which the checklist are signals which remind the reader of highly significant aspects of a process.  They are designed to be consulted at a point in the process where forgetting about the aspect will have a significantly detrimental effect.  Often the processes are being used to respond to failures in the regular operation.  Atul Gawande argues that effective use of checklists is vital to coping with situations that are complex. 
  description is loaded.  If this command is not present in the filter file no hover substitution will be performed. 
  
• Addgitst is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which describes to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  the file name prefix that when appended with a Git is a source control system created to support the development of the Linux operating system.  Linus Torvalds was not happy with the source control systems that he and the other Linux developers used so he designed and developed Git.  AWF uses Git as a way to share the HTML sources and istrings library files of group developed dark webs. 
  branch name is an AWF Git workflow based on the SPIMWF where:
  • Branches are long lived and associated with individual participants in the shared plan development. 
    
  • Only the Integration Manager has to understand Git terminal tools or perform merges and fix conflicts. 
    
  • All other team members use AWFCE's Git integration facilities to gitpull the latest sources, add and commit edits, and then gitpush the updates back to their own branch of a source repository that is accessible by the intrgration manager. 
    
  and .htm will match a page of the git status web frame.  This allows the <rhlgitsourcestatus is a filter file command which specifies the name of the report html web page in the Git status frame that will be generated by the dark web generator for this shared source maintainer.  With 'gitsourcestateweb' activated and an html source stream that includes the key word <rhlgitsourcestatus> a report will be generated detailing the current merge state of the master and other branches of the shared and maintainer repositories. 
  > generation process to use Git memo information from the branch page in reporting the merge state of the branch in the Git source maintainer's master branch. 
  
• Addglkey is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies that an item with the key specified from an additional included glossary stream (addglstream is a filter file command which specifies a path and file name of a source file containing glossary items delineated by the AWF tag that marks the start and end of the glossary definition source stream.  A number of streams can be included.  The first should have a key 'file0', the second 'file1' etc.  If an addglstream statement is used in a filter file:
  
  • No glossary items should be declared in the source file containing the basic glossary source within start and end tags.  
  • The basic glossary page should include the target <gltarget> which the merged and sorted glossary items will be deployed into. 
    
  ) should be merged into the target glossary stream. 
  
• Addglstream is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies a path and file name of a source file containing glossary items delineated by the AWF is the adaptive web framework.   tag are structures which are used by the dark web generator to filter the current source stream.  Once a start tag for the current case selector is detected the source data is merged into the HTML template.  This continues until a terminating end tag for the current case selector is detected.  The generator becomes a filter of the source. 
  that marks the start and end of the glossary definition source stream.  A number of streams can be included.  The first should have a key 'file0', the second 'file1' etc.  If an addglstream statement is used in a filter file:
  
• No glossary items should be declared in the source file containing the basic glossary source within start acts as a start operon initiating the sourcing of an AWF stream, by the dark web generator from the current schematic structure being traversed, when the:
  
  • Tag label value matches the case selector being actioned by the generator, and  
    
  • The generator's target path does not include any of the exclusion terms of the form -<exclusion pathname fragment>. 
    
  • There are two visible forms deployed into the visual editor text stream: the list form (see '(cxpradjames2 -randd -open)' within an HTML unnumbered list with two path exclusion terms) and the start of body text form (see '(cxpradjames1)' within yellow highlights - cut and paste the highlighted line and one above and below and then change the selector value to the string you require); and a low level html comment form (see 'start tag paral' in the linked example within an html inclusion of a Perl code stream and hence the html comment follows a Perl comment '#' character) deployed into the raw HTML tag stream. 
    
  and end tags acts as a terminator of an AWF stream as long as the:
  • Tag label value matches the case selector being actioned by the dark web generator. 
    
  .  
• The basic glossary page should include the target <gltarget> which the merged and sorted glossary items will be deployed into. 
  
• Addgltag is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies the AWF is the adaptive web framework.   tag are structures which are used by the dark web generator to filter the current source stream.  Once a start tag for the current case selector is detected the source data is merged into the HTML template.  This continues until a terminating end tag for the current case selector is detected.  The generator becomes a filter of the source. 
  that marks the start and end of the glossary definition source stream.  It is also the identifier that must be prepended to glossary entry names in the source documents and hence the target dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   glossary page.  For example:
  The command triple addgltag 'id' = 'gl' tells the generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  to include items from the glossary page (identified to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  by the filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command addgltext is a filter file command which describes to the dark web generator the source file from which the glossary description is loaded.  If this command is not present in the filter file no hover substitution will be performed.  ) that have names starting with 'gl_'. 
• Addgltext is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which describes to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  the source file from which the glossary description is loaded.  If this command is not present in the filter file no hover substitution will be performed.  
• Addstatelink is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which connects the same execution plan are lists of strategies.  Each strategy is numbered with a unique infinite label. 
  page in two dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.  s together providing a mechanism to construct a network of 'open' dark webs.  The command specifies that when generating the target page matching the 'key' any http name associated strategy should have an execution link are http references deployed by the dark web generator from each http id associated infinite labelled execution plan goal, via its primary resource to an equivalent page and goal in another dark web.  The links are deployed in response to the filter file command addstatelink. 
  . 
  
• The command triple addstatelink 'fwpwcxprad.htm' = 'http://localhost:3000/fwpwcxprad.htm' would add execution links from the generating page in the target dark web to the same page in another dark web via the internal web server. 
  
• Addstatepref is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies the prefix used by the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  execution plan are lists of strategies.  Each strategy is numbered with a unique infinite label. 
  monitored region is a part of a child execution plan that has a link from the 'update' or 'PDCA' keyword within a strategy's status description in the associated parent execution plan.  With appropriate filter file settings (addstatepref, addstatetag, statecase, statefile, statelist) the dark web generator will monitor changes to the region starting at the infinite label for the strategy in the child plan and each line following it until a higher labeled strategy is detected.  Any changes within the region will be indicated by linking the parent's status description 'done' keyword to a status file description and changing the 'done' link status to unused. 
  state change processor to help it reconstruct the child execution plan filenames in conjunction with the statelist is a filter file command which associates a list of child execution plan case selectors with a parent execution plan's state dark web page.   data items and '.htm'.  
  
• Addstatetag is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which specifies the AWF is the adaptive web framework.   tag are structures which are used by the dark web generator to filter the current source stream.  Once a start tag for the current case selector is detected the source data is merged into the HTML template.  This continues until a terminating end tag for the current case selector is detected.  The generator becomes a filter of the source. 
  that defines the file name appended string used to name an execution plans are lists of strategies.  Each strategy is numbered with a unique infinite label. 
  associated execution state dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   page.  For example the command triple addstatetag 'id' = 'st' tells the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  to name any state is a filter file command which associates a state dark web page with its parent execution plan.  For example with an addstatetag 'id' of 'st' the statefile 'prefixparentcasest.htm' = 'prefixparentcase.htm' requests the dark web generator to create the 'prefixparentcasest.htm' file and provide state links to it about the monitored regions in the child execution plans. 
  dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   page it associates with a parent execution plan 'parentplan.htm' with the dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   page name 'parentplanst.htm'. 
  
• Addsumtext is a filter file contains filter statements that alter the merge process executed by the dark web generator.  In particular it describes:
  • Dontunload filters statement (dontunload 'filters' = 't').  By default the statements are unloaded. 
    
  • Map statements which replace a link found in the active source stream with the mapped equivalent (mapf '../web/awfbur01.html' = 'awfbur01.html'). 
    
  • Purge statements which remove the HTML link structure from the active source stream (purge 'http://www.reinventures.com' = 't').  The purge will only be executed if the right hand side of the command equates to true in Perl.  
  • Region dominance statements, which request the dark web generator to replace the regular stream source tagged with the identified start and end stream tag names with a replacement with the same name in the merge stream (region '<stream name>' = 'dom') from a source file with a 'dom' suffix to the file name.  For example:
    
  • The source file awffwbusitdom.html would be dominant to AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'anhp1' and end tag 'anhp1'. 
    
  • If the file awffwbusitdom.htm is created and includes an HTML stream identified by 'anhp1' its source will be included instead of the recessive source once the filter file includes the statement:
  • region 'anhp1' = 'dom'
  • Region co-dominance statements, which request the dark web generator to prepend an additional stream identified in the statements to the regular stream being deployed at the html name specified.  For example:
  • The source file awffwbusitext.html would be co-dominant with the AWF provided source file awffwbusit.html.  
  • The file awffwbusit.htm includes the sub-stream tagged with start tag 'sgen132' and end tag 'sgen132'. Within this stream is HTML named 'Impact_of_socio-cultural_complexity'. 
    
  • If the file awffwbusitext.htm is created and includes an HTML stream identified by 'dsgen132Impact_of_socio-cultural_complexity' start and end tags its source will be included immediately before the HTML source named 'Impact_of_socio-cultural_complexity', once the filter file includes the ordered pair of statements:
  • regionexttnlist 'sgen132' = 't'
  • regionexthnlist 'sgen132' = 'Impact_of_socio-cultural_complexity'
    
  • Glossary mouse over text source file statement (addgltext 'hover' = 'html/awfhelphomeplan.html').  When a glossary reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the glossary item details. 
    
  • Glossary HTML tag start string statement (addgltag 'id' = 'gl').  
  • Glossary target file statement (glfile 'name' = '<target glossary page name>').  
  • Glossary source file (addglstream 'file0' = '<path to>/<glossary source file>')
  • Glossary element (addglkey 'gl_Hoshin' = '1') with key gl_Hoshin will be included from addglstream file1. 
    
  • Checklist mouse over text source file statement (addcltext 'hover' = 'html/awfhelphomeplan.html').  Checklists are structured lists that conform to Atul Gawande's description in The Checklist Manifesto.  When a checklist reference is detected in the source stream it is enhanced so that in the target HTML file on a mouse over JavaScript will display the checklist item details. 
    
  • Checklist HTML tag start string statement (addcltag 'id' = 'cl').  
  • Checklist target file statement (clfile 'name' = 'awfhcl.htm'). 
    
  • State link generation statements (addstatelink 'awffwpwcxprad.htm' = 'http://localhost:3000/openstage/randd/randmgr/awffwpwcxprad.htm') which link one dark web to another via an execution link. 
    
  • Summary item text source file statement (addsumtext 'hover' = 'html/awfhelphomeplan.html').  On mouse over items specified in sumfile descriptions will display the summary information, which occurs after the summary heading and before the next heading, from the source file. 
    
  • Statements of each summary source file to include in summary mouse over (sumfile 'pwhp' = 'awfhpwhp.htm').  
  • Name list statement (namelist 'name' = 'nam').  
  • Statefile commands which allow a dark web execution plan to include a strategy status description, and for the dark web to be associated via an execution link with the dark web containing the delegates implementation actions. 
    
  • Strategy contents list statement (lablist 'name' = 'cxp'). 
  • Strategy label priority statement (labpr '1.1.0.1' = '1').
  • Link error report suppression statement (linkerror 'usetext' = 't').  
  • Setup shared source developer Git status web report generation with (gitstateweb '<web file name>' = 't')
  • Setup shared source maintainer Git status web report generation with (gitsourcestateweb 'web file name>' = 't')
  • Setup indicator of names of Git status web pages with (addgitst 'id' = '<Git status page file name prefix>')
    
  command which describes to the dark web generator is a Perl script, typically launched as a child process within the configuration editor, by clicking 'generate web', which executes frame configuration file instructions merging the configuration variables with an HTML template file to generate target web pages.  The configuration instructions can be tailored by filters from the configuration file specified filter file. 
  the source file from which the summary text descriptions are the lines of HTML between the Summary heading and the next heading in a source stream. 
  are loaded.  If this command is not present in the filter file no hover substitution will be performed. 
  
• Adenocarcinoma is a cancer of mucus is used to cover tissues that are exposed.  It is made from mucins.  Mucous membranes may secrete mucus to generate a robust barrier. 
  -secreting glands.  It can occur thoughout the body including the lungs affects 200,000 Americans each year.  Inflammation is a driver of lung cancer spread (Aug 2017).  All these cancers are carcinomas.  There are two main hystological types:
  • Non-small-cell carcinomas are of three sub-types:
  • Adenocarcinomas (40% of lung cancers) are typically peripherally situated and mostly induced by smoking.
    
  • Squamous-cell carcinomas (30% of lung cancers) arise in the large bronchi an are highly correlated with smoking. 
    
  • Large-cell carcinomas (5 to 10% of lung cancers).
    
  • Small-cell carcinomas.
    
  , where 40% of cancers are adenocarcinomas.  Genes ERBB2 is a gene, often termed HER2, that encodes RTK erbB-2, a proto-oncogene. 
  and VEGF is vascular endothelial growth factor, a signalling protein used by cells to stimulate angiogenesis.   are often amplified in this cancer. 
  
• ADHD is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation. 
    
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
    
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    
  • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
  • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    
  • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
  • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
  • Dopamine is removed from the synapse by a reuptake transporter DAT. 
    
  response profiles to temporal discounting tasks are abnormal for ADHD sufferers.  Imaging studies show differences in the brains of ADHD sufferers.  Stimulants have been found to have a calming effect on ADHD sufferers.  Causally associated factors include:
• Family history
• Genetics
• May be influenced by high doses of Tylenol during pregnancy (Sep 2016). 
  
• Environmental factors - a consistant daily schedule, praise for good behavior, clear bondaries, enough sleep and limiting distractions are all part of behavioral therapy for ADHD.  
  
• CNS developmental is a phase during the operation of a CAS agent.  It allows for schematic strategies to be iteratively blended with environmental signals to solve the logistical issues of migrating newly built and transformed sub-agents.  That is needed to achieve the adult configuration of the agent and optimize it for the proximate environment.  Smiley includes examples of the developmental phase agents required in an emergent CAS.  In situations where parents invest in the growth and memetic learning of their offspring the schematic grab bag can support optimizations to develop models, structures and actions to construct an adept adult.  In humans, adolescence leverages neural plasticity, elder sibling advice and adult coaching to help prepare the deploying neuronal network and body to successfully compete. 
  problems.   
• Adjacent possible. 
  
• Adolescence in humans supports the transition from a juvenile configuration, dependent on parents and structured to
  The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
  
  learn & logistically transform, to
  In a post disruption environment there is a race to capture network effects.  Once the network effects have been obtained the winner will ensure further advantage until the next round of disruption. 
  
  adult optimized to the proximate environment.  And it is staged encouraging the adolescents to escape the hierarchy they grew up in and enter other groups where they may bring in: fresh ideas, risk taking; and alter the existing hierarchy: Steve Jobs & Steve Wozniak, Bill Gates & Paul Allen.  It marks the beginning of Piaget's formal operational stage of cognitive development.  The limbic supports emotional circuits: Amygdala, Hippocampus, Septum, Habenula, Mammillary bodies; all of which signals the midbrain through the hypothalamus. The broad interconnections of these regions with a part of the frontal lobe suggested to Walle Nauta that it (ventromedial prefrontal cortex) is a quasi-member of the limbic network.  , autonomic and hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  
  This page discusses the effect of the network on the agents participating in a complex adaptive system (CAS).  Small world and scale free networks are considered. 
  
  networks are already deployed and functioning effectively.  The frontal cortex of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  has to be pruned: winning neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  move to their final highly connected positions, and are myelinated is the fatty insulating material deployed by Schwann cells & oligodendrocytes, both types of glial cells, around axons to improve their conduction rate.  In humans it is still occurring 25 years after birth.  It has great impact on long axons, in neurons that project over long distances, where it helps brain inter-region signalling.  The long development time of myelination allows for the later myelinated brain regions to be particularly shaped by the proximate environment. 
  over time.  The rest dissolve, programmed cell death is a signal initiated DNA controlled process which results in eukaryotic cells self-destructing.  .  So the frontal lobe does not obtain its adult configuration and networked integration until the mid-twenties when prefrontal cortex (PFC) is
  
  • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
  control becomes optimal.  The evolutionarily oldest areas of the frontal cortex mature first.  The PFC is prefrontal cortex which is:
  • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
  must be iteratively customized by experience to do the right thing as an adult.  Adolescents:
• Don't detect irony effectively.  They depend on the DMPFC is dorsomedial prefrontal cortex which is:
  • A major agent of the sense of self and theory of mind in human adults. 
    
  • It participates in altruism.  
  to do this, unlike adults who leverage the fusiform is a region of the brain which supports advanced mechanisms of shape recognition and implements the early stages of reading.  Subliminal priming with words did not depend on the shape of the word.  The fusiform gyrus was able to process the abstract identity of a word without caring if it was upper or lower case.   While high up in the cortex it can operate below the level of conscious experience.  It contributes to social emotions with:
  
  • Its face area being more activated by faces with in-group skin color.  
  • It activating when shown pictures of cars in automobile aficionados. 
    
  • It activating when shown pictures of birds in birdwatchers; since it really recognizes examples of items from an individual's emotionally salient categories. 
    
  face area.  
• Regulate emotions are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   with the ventral striatum is a region within the basal ganglia.   It is a target of the tegmentostriatal dopamine pathway.  It has been captured by brain imaging assigning values to subliminal symbols experimentally associated with winning (highly valued) and losing (low valuation) money.  During adolescence, prior to the deployment of the prefrontal cortex, the ventral striatum helps balance/control emotional decision making. 
  while the prefrontal cortex is still being setup.  Dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation. 
    
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
    
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    
  • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
  • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    
  • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
  • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
  • Dopamine is removed from the synapse by a reuptake transporter DAT. 
    
  projection density and signalling, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  increase from the ventral tegmentum is part of the tegmentum which contains dopamine long system cell bodies (high levels of D(2)).  Their axons branch extensively and reach many areas including: Mesolimbic to the limbic system: amygdala, hippocampus; Tegmentostriatal to the nucleus accumbens, Mesocortical to the forebrain including the prefrontal cortex.  The terminals are fairly evenly distributed through out layers 1 - 6.  So dopamine can modulate input and output excitatory and inhibitory transmissions.  If a rodent wins a fight on his home territory, there are long-lasting increases in levels of testosterone receptors enhancing pleasurable effects.  The lateral ventral tegmental area is now known to be one of two large adrenergic pathways, along with the locus ceruleus.  During child birth the ventral tegmentum deploys more oxytocin receptors increasing its sensitivity to the neuropeptide.  
  catalyzing, an infrastructure amplifier.   increased interest in dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation. 
    
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
    
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    
  • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
  • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    
  • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
  • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
  • Dopamine is removed from the synapse by a reuptake transporter DAT. 
    
  based
  Read Montague explores how brains make decisions.  In particular he explains how:
  

  • Evolution can create indirect abstract models, such as the dopamine system, that allow
    
  • Life changing real-time decisions to be made, and how
    
  • Schematic structures provide encodings of computable control structures which operate through and on incomputable, schematically encoded, physically active structures and operationally associated production functions. 
  rewards.  Novelty seeking allows for creative exploration which was necessary to move beyond the familial pack.  Criticisms do not get incorporated into learning models by adolescents leaving their risk, is an assessment of the likelihood of an independent problem occurring.  It can be assigned an accurate probability since it is independent of other variables in the system.  As such it is different from uncertainty. 
  assessments very poor.  The target of the dopamine networks are categorized anatomically into three key types:
  • Ultra-short systems,
    
  • Intermediate length systems,
    
  • Long systems. 
    
  , the adolescent accumbens is a region of the basal forebrain rostral to the preoptic area and immediately adjacent to the septum.  The nucleus accumbens was closely associated with the limbic system and plays an important role in reinforcement.  If a rodent wins a fight on his home territory, there are long-lasting increases in levels of testosterone receptors enhancing pleasurable effects.  When prairie voles first mate, epi-genetic state changes are induced in the accumbens to support pair-bonding.  The accumbens projects to brain regions associated with movement.  The major pathways of dopaminergic neurons begin in the substantia nigra and the ventral tegmental area.  The amygdala projects back to the accumbens.  The tegmentostriatal system begins in the ventral tegmental area and projects to the nucleus accumbens.  The nucleus accumbens includes high levels of D1, D2 and D3 dopamine receptors located on the spine & shafts of dendrites of excitatory cells reduce the transfer of excitation from the dendrites to the cell bodies, so only especially strong excitatory inputs get through to the cell body to elicit excitation.  It also has D4 dopamine receptors which are highly variable.  The accumbens responds differently to rewards depending on maturity: In juveniles all reward levels result in the same response activity level, During adolescence the accumbens responds to small rewards negatively, and large rewards hugely, In adults the rewards result in measured scaled positive responses.  Chronic stress depletes dopamine from the nucleus accumbens biasing humans towards depression.  , responds to rewards like a gyrating top - hugely to large rewards, and negatively to small rewards.  Eventually as the frontal regions increase in contribution there are steady improvements in: working memory is a dominant function of the dorsolateral prefrontal cortex and the areas it connects with.  Prefrontal neurons implement an active memory continuing to fire after the signal is gone for potentially dozens of seconds from the inferior temporal cortex (multi-sensory integration area) and lower level sensory neurons characterized by Hubel & Weisel, while the short-term memory task continues.  If the prefrontal cortex gets distracted the memory is lost from consciousness.  Earl Miller argues the prefrontal cortex implements the rules that decide which working memory neurons will fire (Spring 2017). 
  , flexible rule use, executive organization and task shifting.  And adolescents start to see other people's perspective. 
  
• Drive the cellular transformations with post-pubescent high levels of testosterone is a hormone secreted by the testes in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  Testosterones effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
  in males, and high but fluctuating estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The levels of each type of receptor is independently regulated.  Different receptor variants are associated with:
  • Higher rates of anxiety among women
  • Higher rates of antisocial behavior and conduct disorder in men
  & progesterone is a steroid hormone.  It:
  • Rarely directly effects areas of the brain.  Instead it is converted into other sterioids which have different actions in different brain areas. 
    
  • Increases maternal aggression in concert with estrogen by increasing oxytocin release in certain brain regions.  However, on its own progresterone decreases aggression and anxiety.  It decreases anxiety by entering neurons where it is converted to allopregnanolone which binds to GABA receptors increasing their sensitivity to GABA. 
    
  levels in females.  Blood flow to the frontal cortex is also diverted on occasion to the groin.  
• Peer pressure is exceptionally influential in adolescents is Robert Trivers theory to explain the allocation of parental resources to various offspring, from the implications of genetics on the family.  Observing that children want to take more than what their parents want to give Trivers concluded a parent should aim to transfer resources depending on the relative benefits to each child and the costs, since each child has the same percentage of the parent's genes.  But each child shares only fifty percent of their genes with their siblings so should aim to get resources until the benefit to the others is twice the cost to the child.  And the parent may keep back some resources for allocation to further planned offspring.  A variety of conflicts ensue:
  • In the womb the fetus tries to capture nutrients from the mother at the expense of future children.  It ties up the mother's insulin to increase the blood sugar available to it and placing the mother at risk of diabetes.  Fathers can assist their offspring in this 'fight with the mother' by supplying imprinted genes that help the offspring capture resources. 
    
  • At birth mothers must decide whether to let the baby die.  This practice is cross cultural but is considered a depravity by present Western culture.  That is probably due to the West having captured a majority of the world's resources for centuries.  
  • Infants use cuteness to encourage parental investment.  A mother's attachment delays until it is clear that the baby will live.  
  • Infants cry to demand milk.  Until weaned the mother won't ovulate limiting her future reproductive potential. 
    
  • Young children are in conflict with their father over access to their mother. 
    
  • Children are in a position to develop paradoxical tactics to push for more resource allocation. 
    
  • Older children may have sexual conflicts with their parents, especially their fathers.  Fathers compete with sons for sexual partners in many societies.  But this competition is not for their mother.  
  • Adult children may conflict with their parents over allocation of family resources.  This has led to murder. 
    
  • Parents attempt to train children to assist the parent's social interests.  The implication is that children are wary of their parent's suggestions and typically pay more attention to the advice of their peer group according to Judith Harris.  
  • Parents sell or trade their children.  The price paid for a daughter will likely depend on her virginity.  Hence fathers take an interest in their daughters' sexuality.  
  .  Admired peer comments reduce vmPFC is ventromedial prefrontal cortex which is:
  • Focused on the impact of emotion on decision making
    
  • A participant in limbic system operations 
  • Many human behaviors involve interactions between the vmPFC, the limbic system & the dorsolateral prefrontal cortex.  Part of decision making is for the limbic system to internally simulate (often with the help of the sympathetic nervous system) what alternative outcomes of a decision will feel like with the results of these somatic marker analyses being reported to the vmPFC.  
    
  • Damage to the vmPFC results in bad decision making: Poor judgement in choosing friends & partners, Failure to respond to negative feedback; because they can't feel the issues. 
    
  activity and enhance ventral striatal is a region within the basal ganglia.   It is a target of the tegmentostriatal dopamine pathway.  It has been captured by brain imaging assigning values to subliminal symbols experimentally associated with winning (highly valued) and losing (low valuation) money.  During adolescence, prior to the deployment of the prefrontal cortex, the ventral striatum helps balance/control emotional decision making. 
  activity.  Adults modulate the mental impact of socially mean treatment: the initial activation of the PAG is periaqueductal gray, an ancient core brain structure that projects pain sensations to the amygdala.  , anterior cingulate is the cingulate gyrus, a rich club hub.  Contains many sub-parts:
  
  • The anterior cingulate cortex ACC:
  • Is a central focus of empathy supporting people relating to other's pain.  This is dependent on oxytocin. 
    
  • In non-human mammals it processes interoceptive signals.  The ACC focuses the internal signals into high level 'gut intuitions.'  Pain catches the ACC's attention. 
    
  • Performs discrepancy detection from the outcome that was predicted - at a high level.  The ACC cares about the meaning of what is predicted. 
    
  • If the ACC has been convinced that a pain killer placebo has inhibited pain signals, the ACC will stay silent about actual pain that is signalled from interoceptive networks.  
  • The ACC will signal: physical pain, emotional pain, metaphorical pain, anxiety, disgust, embarrassment, social exclusion especially in adolescence; as one and the same.  The ACC's abnormalities being associated with major depression. 
    
  • Has a bridging role between the empathetic and self-interested pain monitor.  Sapolsky notes the ACC is essential for learning fear and conditioned avoidance by observation alone through an intermediate step of shared representation of self.  He concludes "At its core the ACC is about self-interest, with caring about the other person in pain as an add-on." 
    
  • The midcingulate cortex was formerly judged part of the 'emotional' limbic system in MacLean's discredited triune brain model. 
    
  , amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  , insula cortex is part of the cerebral cortex folded deep within the lateral sulcus.  It includes: anterior, posterior insula; and is overlaid by the operculum.  It is assumed to participate in consciousness where it has been linked to emotion, salience & body homeostasis functions:
  
  • Perception,
    
  • Motor control: Hand-&-eye motor movement, Swallowing, Gastric motility, Speech articulation;
    
  • Self-awareness,
    
  • Inter-personal experiences: Disgust at smells, contamination & mutilation which generate visceral responses, that are projected to the amygdala; binding physical and moral aspects of purity (Macbeth effect)
    
  • Homeostatic regulation of the sympathetic network, parasympathetic network, and immune system.   
  ; which generate feelings of pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Pain is the main reason people visit the ED in the US.  , anger is an emotion which protects a person who has been cheated by a supposed friend.  When the exploitation of the altruism is discovered, Steven Pinker explains, the result is a drive for moralistic aggression to hurt the cheater. 
  , and disgust is a universal human emotion.  Pinker notes it has its own facial expression and is codified in food taboos.  The mind must be associated with the proximate environment and parents minimize the risk for their omnivorous children by teaching them what foods to eat and what to avoid.  The children's minds are initially receptive to trying all foods but their brains subsequently lock in on the foods they have experienced.  These parental choices are affected by schematic influence on what has been beneficial.  Adolescent's brain developments undermine these constraints enabling intergroup transfers.  Disgust is modulated by the insula cortex which projects signals to the amygdala. 
  , with the VLPFC is ventrolateral prefrontal cortex
  but that does not occur in adolescents.  
• Feel empathy is the capability to relate to another person from their perspective.  It is implemented by spindle neurons.  It is context dependently mediated by estrogen.  It develops over time: Piaget's preoperational stage includes rudimentary empathy, Theory of mind supports the development; initially feeling someone's pain as one integrated being, then for them and eventually as them.  In adults, when someone else is hurt the anterior cingulate cortex, amygdala & insula activates projecting [scapegoating] to the vmPFC.  If the pain is physical the PAG activates and motor neurons for the area where the other person was injured.  The intertwining of the ACC amygdala & insula in adults results in attribution of fault even when there is none which can make it hard to step in and actually help.  But in seven-year-olds the activation is concrete: PAG and sensory & motor cortexes with minimal coupling to the rudimentary vmPFC.  In older children the vmPFC is coupled to limbic structures.  Ten to twelve year olds abstract empathy to classes of people.  By adolescence the vmPFC is coupled to theory of mind regions and intentional harm induces disgust via the amygdala.  Sapolsky explains adolescent boys are utilitarian and tend to accept inequality more than girls do.  But both sexes accept inequality as the way it is.  Sociopaths do not develop empathy.   intensely, supported by their rampant emotions, interest in novelty, ego.  But feeling the pain of others can induce self-oriented avoidance of the situations. 
  
• Adrenal glands are endocrine glands, situated above the kidneys provides multiple vital functions.  It: Produces renin which supports negative feedback, Removes excess organic molecules from the blood, Regulates electrolytes in the blood, Maintains pH homeostasis, Regulates fluid balance, Regulates blood pressure, Reabsorbs water, glucose (SGLT2) and amino acids.  Kidney function is monitored with the GFR.  Kidneys can fail acutely or chronically.  Kidneys are affected by a variety of cancers including: advanced kidney cancer, von Hippel Landau; some of which are induced by PFAS.    Multiple myeloma, type 2 diabetes, TB and drug treatments for MDR TB place a strain on the kidneys and can induce failure.  , that produce: adrenaline, aldosterone and cortisol is a glucocorticoid produced in the adrenal cortex of the adrenal glands.  It:
  
  • Stimulates
    
  • Gluconeogenesis to increase production of blood sugar
    
  • Metabolism of fats, proteins and carbohydrates
    
  • Suppresses the immune system.  
  • Decreases bone formation
    
  . 
  
• ADT is admit, discharge, transfer, a backbone HIS Health care information systems.  There were traditionally four backbone services:
  • ADT,
  • Financial,
    
  • Scheduling,
  • Acuity (EDIS);
    
  allowing the sharing of patient information with other health care providers.  It has a corresponding HL7 is health level 7 (name implying focused on application level protocols in health care).  It includes a variety of standards: Arden Syntax, RIM, CDA, CCOW, claims attachments, FHIR, SPL and messaging and has developed a EHR system functional model providing a standardized description of the functions provided.  The formation of HL7 messaging communications streams has a relatively high overhead.  HL7 version 2 is generally deployed.  The version 2 messaging standardizes health care data interchange with messages originally based on character delimited '|' segments (containing character delimited '^' composite fields (containing character delimited '&' subcomponents) in a non XML structure interchanged widely over a secure network stack.  The first field in a message segment is the 3 character segment name.  HL7 is generally transmitted over MLLP.  HL7 v2 has been extended with an XML encoding.  HL7 v2 messages have to be augmented to transmit over TCP/IP.  The US Government mandate that licenced recipients of HL7 messages understand all aspects of the information transferred.  That is point-to-point specific since each sender has their own interpretation of what information goes in what HL7 fields.  The usual solution to this situation and rule is (1) an interface engine placed between the two points which maps the sender's information from the fields it uses for transmission to the recipients interpretation of HL7 field usage and (2) a lot of testing to show the mappings are correct and reliable.  Because of the impact of changing the interpretation of use of HL7 (on all the interface engines of point connected partners) operational adjustments to HL7 are difficult.  Version 3 of HL7 adopts a different strategy.  It introduces a Meta model (RIM) of the data and so when adopted changes the strategies available for interconnection.  It is XML based.  But the operational difficulty of switching to version 3 has left most systems tied to version 2.   message that reports a status change for a patient.  
• Advance payment ACO is a CMS is the centers for Medicare and Medicaid services.   Innovation center is the CMS Innovation Center.  It was created by the ACA to test new models of health care delivery and payment including the Pioneer ACO and the Advance Payment ACO.  It also offers technical support to providers to improve the coordination of care and share lessons learned and best practices.  In 2016 Andy Slavitt proposed testing a new Medicare part B drug pricing rule, which was furiously resisted by PhRMA and blocked by Representative Skimkus collection of 242 Representative's signatures. 
  has developed a model of an ACO for physician-owned and rural providers participating in the Shared Savings is the Medicare Shared Savings Program.  The program began in 2012 with 3 year term contracts.  ACO Physician groups and hospitals are eligible to participate but there must be primary care physicians in the ACO.  Participating ACOs must serve > 5000 Medicare beneficiaries.  The potential for a bonus payment is based on Medicare cost savings and quality metrics.  Two payment models are available.  Only one has downside risk involved.  CMS included 'robust' quality measures to monitor the quality of care provided and beneficiary satisfaction (see fact sheet 'Improving Quality of Care for Medicare Patients: Accountable Care Organizations'). 
  Program who would benefit from additional start-up resources to build the necessary infrastructure, such as new staff or information technology systems.  
• Advanced APM is a CMS is the centers for Medicare and Medicaid services.   regulated group of APM is alternative payment model, Medicare's risk based payments to organizations set up as ACOs.  It includes track 1 ACOs which are not risk bearing.  APMs have to report various measures to CMS.  s that effectively uses FFV is fee-for-value payment.  It may be a bundled payment for a set of services provided by a group of doctors and facilities, or full capitation.  In each case the risk has shifted from the payer to the providers of care. 
  .  The list includes: Risk-bearing ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness, improving the provision of primary care to a large group of Medicare patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV business.  The ACA regulates qualification to be a Medicare ACO.  Individual organizations within a Medicare shared savings ACO continue to submit their own claims and are paid by Medicare for FFS.  But the ACO is eligible for shared savings.  Within the shared savings program the CMS innovation center has setup advanced payment ACOs.  As an alternative to shared savings, in a Pioneer ACO, over time 50% of the FFS payments flow directly to the ACO as a bundled payment.  CMS has established quality measures for ACOs for Medicare.  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination. 
  
  • CMS initiated its Physician Group Practice Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
    
  • CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
  • CMS has developed APMs which include ACOs, and advanced APMs where the ACOs must be risk bearing. 
    
  • CMMI accepts providers' proposals to test various payment systems including shared savings and partial capitation.  
  • Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
  s, Comprehensive end stage renal disease care, Comprehensive primary care plus, Oncology care model. 
  
• Advanced kidney cancer - There are expected to be 61,560 new cases of kidney cancer includes any cancer initiated in the kidney.  In adults the most common form is an RCC.  In children Wilms tumors are most common.  Transitional cell cancer is the other common form.  It develops in the renal pelvis and ureter in adults. 
  in the US is the United States of America.   and 14,080 deaths in 2015.  Drug treatments have increased survival from 10 - 12 months to up to 30.  Exact causes are unknown but risk factors are: smoking, obesity is a disorder where the brain is induced to require more eating, often because of limits to the number of fat cells available to report satiation (Jul 2016).  It is associated with: metabolic syndrome including inflammation, cancer (Aug 2016), high cholesterol, hypertension, type-2-diabetes and heart disease.  It is suspected that this is contributing to the increase in maternal deaths in the US (Sep 2016).  Obesity is a complex condition best viewed as representing many different diseases, which is affected by the: Amount of brown adipose tissue (Oct 2016), Asprosin signalling by white adipose tissue (Nov 2016), Genetic alleles including 25 which guarantee an obese outcome, side effects of some pharmaceuticals for: Psychiatric disorders, Diabetes, Seizure, Hypertension, Auto-immunity; Acute diseases: Hypothyroidism, Cushing's syndrome, Hypothalamus disorders; State of the gut microbiome.  Infections, but not antibiotics, appear associated with childhood obesity (Nov 2016). 
  , high blood pressure is high blood pressure.  It is directly associated with death rate due to pressure induced damage to the left ventricle and in general to cardiovascular diseases.  Treated with antihypertensives: Diuretics, Calcium channel blockers, Angiotensin receptor blockers or Beta blockers.  , genetic mutations and heredity.  
• Adverse drug reactions result from various causes of drug treatments including:
• Individual pharmacogenomics studies how genes affect a person's response to drugs so as to develop personalized drug treatment plans, tailored to a person's specific phenotype.  The process optimizes the treatment process but there are barriers to its deployment:
  • Large scale clinical trials may test 20,000 individuals, but if a toxic response impacts only 0.1% of them there would only be 20 cases found which is often too few to identify the cause of the response.  Instead a process for capturing adverse drug reactions after approval and marketing must be used along with the ability to take a blood sample in these cases.  
  • Simplified studies on a subset of individuals that have the target allele should be cheaper but are unattractive to pharmaceutical companies which typically want to maximize their target market (Aug 2016).  
  • F.D.A. has not required genomic testing for most drug developments.  
  • Health care providers are being slow to use pharmacogenomics.  Often third-party payers are unwilling to reimburse the tests. 
    
  • Transportation to centralized laboratories for genomic testing causes delays which makes some drug therapy applications impractical.  An alternative solution would be to have a patient's EHR contain their genome sequence for immediate genomic implications.  
  differences altering the metabolic processing chain of each drug. 
  
• Pharmacists' miss-understanding handwritten prescriptions. 
  
• Patient's miss-interpreting their treatment instructions. 
  
• Complex interactions of multiple drugs being taken by a patient. 
  
• Underlying illnesses, especially of the liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
  & kidneys provides multiple vital functions.  It: Produces renin which supports negative feedback, Removes excess organic molecules from the blood, Regulates electrolytes in the blood, Maintains pH homeostasis, Regulates fluid balance, Regulates blood pressure, Reabsorbs water, glucose (SGLT2) and amino acids.  Kidney function is monitored with the GFR.  Kidneys can fail acutely or chronically.  Kidneys are affected by a variety of cancers including: advanced kidney cancer, von Hippel Landau; some of which are induced by PFAS.    Multiple myeloma, type 2 diabetes, TB and drug treatments for MDR TB place a strain on the kidneys and can induce failure.   altering the metabolism and clearing of drugs in the body. 
  
• AF is atrial fibrillation, an abnormal heart rhythm: rapid, irregular.  It:
• Can lead to blood clots or coagulation is formation of a clot:
  • Platlets become activated, adhere and aggregate supported by
  • Fibrin polymerization, deposition and maturation.  
  , stroke is when brain cells are deprived of oxygen and begin to die.  750,000 patients a year suffer strokes in the US.  85% of those strokes are caused by clots.  There are two structural types: Ischemic and hemorrhagic.  Thrombectomy has been found to be a highly effective treatment for some stroke situations (Jan 2018). 
  , CHF is congestive heart failure which occurs when the heart is unable to generate enough blood flow to meet the body's demands.  There are two main types: failure due to left ventricular dysfunction and abnormal diastolic function increasing the stiffness of the left ventricle and decreasing its relaxation.  Treatments include: digoxin; , dementia is a classification of memory impairment, constrained feelings and enfeebled or extinct intellect.  The most common form for people under 60 is FTD.  Dementia has multiple causes including: vascular disease (inducing VCI) including strokes, head trauma, syphilis and mercury poisoning for treating syphilis, alcoholism, B12 deficiency (Sep 2016), privation, Androgen deprivation therapy (Oct 2016), stress, Parkinson's disease and prion infections such as Alzheimer's disease, CJD and kuru.  The condition is typically chronic and treatment long term (Laguna Honda ward) and is predicted by Stanley Prusiner to become a major burden on the health system.  It appears to develop faster in women than men.   and other complications.  
• Fibrillations allow blood to pool in the heart chambers and form small clots which can then lodge in small arteries and block blood flow. 
  
• Has become much more common being induced by endemic diseases: hypertension is high blood pressure.  It is directly associated with death rate due to pressure induced damage to the left ventricle and in general to cardiovascular diseases.  Treated with antihypertensives: Diuretics, Calcium channel blockers, Angiotensin receptor blockers or Beta blockers.  , obesity is a disorder where the brain is induced to require more eating, often because of limits to the number of fat cells available to report satiation (Jul 2016).  It is associated with: metabolic syndrome including inflammation, cancer (Aug 2016), high cholesterol, hypertension, type-2-diabetes and heart disease.  It is suspected that this is contributing to the increase in maternal deaths in the US (Sep 2016).  Obesity is a complex condition best viewed as representing many different diseases, which is affected by the: Amount of brown adipose tissue (Oct 2016), Asprosin signalling by white adipose tissue (Nov 2016), Genetic alleles including 25 which guarantee an obese outcome, side effects of some pharmaceuticals for: Psychiatric disorders, Diabetes, Seizure, Hypertension, Auto-immunity; Acute diseases: Hypothyroidism, Cushing's syndrome, Hypothalamus disorders; State of the gut microbiome.  Infections, but not antibiotics, appear associated with childhood obesity (Nov 2016). 
  and type-2-diabetes is the leading cause of blindness, limb amputations and kidney failure.  Insulin and glucose levels are regulated by the pancreas, liver, muscle, brain and fat.  Diabetes occurs when the insulin level is insufficient to regulate the glucose in the system.  Increased fat levels in obesity demand more insulin overloading the pancreas.  Persistent high glucose levels are also toxic to the pancreas beta cells.  High glucocorticoid levels have been associated with type 2 diabetes.  There are genetic risk factors since siblings of someone with the disease have three times the baseline risk (about 50% of the risk of getting type 2 diabetes is genetic).  The inheritance is polygenic.  More than 20 genes have been identified as risk factors, but that is too few to account for the 50% weighting so many more will be identified.  Of those identified so far many are associated with the beta cells.  The one with the strongest relative risk is TCF7L2.  The disease can be effectively controlled through a diligent application of treatments and regular checkups.  Doctors are monitored for how under control their patients' diabetes is (Sep 2015).  Treatments include:
  • Metformin - does not change the course of pre-diabetes - if you stop taking it, it is as if it hasn't been taken. 
    
  • Diet
  • Exercise
  . 
  
• Cocoa reduces risk of AF (May 2017)
• Treatments include: digoxin is a WHO essential medicine for treating heart conditions including: AF, atrial flutter and CHF.  It typically makes the heart beat more strongly, slowly and regularly.  But in one patient in ten a gut bacterium, Eggerthella lenta with two specific gene variants, inactivates the digoxin.  Digoxin was initially isolated from the foxglove, Digitalis lanata. 
  ;
  
• AFDC is Aid to Families with Dependent Children program, created by the SSA is the social securities act of 1935 was part of the second New Deal.  It attempted to limit risks of old age, poverty and unemployment.  It is funded through payroll taxes via FICA and SECA into the social security trust funds.  Title IV of the original SSA created what became the AFDC.  The Social Security Administration controls the OASI and DI trust funds.  The funds are administered by the trustees.  The SSA was amended in 1965 to include:
  • Title V is Maternal and child health services. 
    
  • Title XVIII is Medicare.  
  , that ran from 1935 to 1996 when it was replaced by TANF.  The values provided declined over the years. 
  
• Affective facial display is a face expressing strong emotions are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   as interpreted by an observer's brain.  In:
• Adult observers this activates that amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  and subsequently the vmPFC is ventromedial prefrontal cortex which is:
  • Focused on the impact of emotion on decision making
    
  • A participant in limbic system operations 
  • Many human behaviors involve interactions between the vmPFC, the limbic system & the dorsolateral prefrontal cortex.  Part of decision making is for the limbic system to internally simulate (often with the help of the sympathetic nervous system) what alternative outcomes of a decision will feel like with the results of these somatic marker analyses being reported to the vmPFC.  
    
  • Damage to the vmPFC results in bad decision making: Poor judgement in choosing friends & partners, Failure to respond to negative feedback; because they can't feel the issues. 
    
  as they become habituated to the emotional content. 
  
• Adolescents the vmPFC responds less allowing the amygdala's activation to keep growing. 
  
• Aflatoxins are a family of complex aromatic toxins and carcinogens produced by certain Aspergillus molds.  They are amongst the most carcinogenic substances known.  They are metabolized in the liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
  to reactive intermediates that mutate p53 is a tumor suppressor which improves the specificity of transcription's DNA binding and promotes the transcriptional activity of E2F.  P53's activity is controlled by phosphorylation by cyclin Cdk complexes allowing indirect control of the cell cycle.  Among the many genes controlled by p53 are cyclin genes, genes for an inhibitor of cyclin-dependent kinases (Cdk), and the bax gene, which promotes apoptosis.  p53 can thus promote cell proliferation.  It can drive cells into apoptosis.  But it can also stop cell proliferation by arresting the cell cycle.  Normally there is a dynamic balance between proliferation of cells and their death.  In cancer proliferation may become unregulated due to oncogenic mutations or over expression of key regulatory signalling G proteins such as Ras.  Mutations of the p53 suppressor gene are the most frequent suppressor gene mutations in human cancers.  Elephants like humans, have a relatively low buildup of cancer with age.  Elephant's cells have twenty copies of p53 gene pairs which ensure cells with damaged DNA go into apoptosis blocking cancer onset. 
  .  They are regularly found in improperly stored commodities such as chillis, peanuts, rice and wheat.  And they flow through the food distribution system when contaminated food is processed.  Animals fed on contaminated food can pass aflatoxin transformation products into the food chain.  They have been found in feed stock, eggs, milk products and meat.  The most toxic aflatoxin can permeate the skin. 
  
• African savanna is the environment where hunter-gatherers primarily
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  evolved.  Its grassland supported large herbivores that could be hunted.  Clumps of trees & rocks supported places to hide from large carnivores.  Streams and paths add to the signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  enabling orientation. 
  
• Plans are interpreted and implemented by agents.  This page discusses the properties of agents in a complex adaptive system (CAS). 
  It then presents examples of agents in different CAS.  The examples include a computer program where modeling and actions are performed by software agents.  These software agents are aggregates. 
  The participation of agents in flows is introduced and some implications of this are outlined. 
  
  Agent. 
• Aggregation is when a number of actions become coordinated and operate together.  In the adaptive web framework's
  This page describes the Adaptive Web framework (AWF) test system and the agent programming framework (Smiley) that supports its operation. 
  Example test system statements are included.  To begin a test a test statement is loaded into Smiley while Smiley executes on the Perl interpreter. 
  Part of Smiley's Perl code focused on setting up the infrastructure is included bellow. 
  The setup includes:
  

  • Loading the 'Meta file' specification,
    
  • Initializing the Slipnet, and Workspaces and loading them
    
  • So that the Coderack can be called. 

  The Coderack, which is the focus of a separate page of the Perl frame then schedules and runs the codelets that are invoked by the test statement structures. 
  
  Smiley, codelets become coordinated by their relative position in the deployment cascade.  The cascade's dynamics are dependent on the situation, the operating codelets responses to that situation and the grouping, in Copycat grouping codelets can group two or more bonded Workspace objects (WSO) together.  In effect grouping adjusts the system to reflect the presence of a chemically active molecule in the molecules local environment. 
  of
  Plans emerge in complex adaptive systems (CAS) to provide the instructions that agents use to perform actions.  The component architecture and structure of the plans is reviewed. 
  
  schematic strings they are
  This page describes the Smiley infrastructure that supports the associative binding of schematic strings to codelets defined in the Meta file and Slipnet. 
  The infrastructure supporting the associations is introduced. 
  The role of Jeff Hawkins neocortical attributes is discussed. 
  Relevant Slipnet configurations are included. 
  The codelets and supporting functions are included. 
  
  associated with.  The aggregate affect is a phenotype is the system that results from the controlled expression of the genes.  It is typically represented by a bacterial cell or the body of a multi-cell animal or plant.  The point is that the genes provide the control surface and the abstract recipe that has been used to generate the cell.   the adaptive
  Plans are interpreted and implemented by agents.  This page discusses the properties of agents in a complex adaptive system (CAS). 
  It then presents examples of agents in different CAS.  The examples include a computer program where modeling and actions are performed by software agents.  These software agents are aggregates. 
  The participation of agents in flows is introduced and some implications of this are outlined. 
  
  agent. 
  
• AHA is the American_hospital association. 
  
• AHP is association health plan:
• Allow small businesses and individuals in particular professions, trades or interest groups to join associations that offer insurance to members. 
  
• Are a form of MEWA is a multiple-employer welfare arrangement which is state regulated. 
  
  
• AHRQ is the Agency for Healthcare Research and Quality.  It provided the definition of a medical home are primary care architectures which deliver: patient-centered, accessible, coordinated, comprehensive care of high quality and safety (Dec 2015).  The models have been made more significant due to Affordable Care Act payment reform requirements.  The goal is to reduce treatment costs and improve population health by reengineering of the traditional silo'd provider network.  See PCMH. 
  (PCMH is patient centered medical homes:
  • Describes a reorganization of the health care delivery system to focus on the patient and care giver supported by EHR infrastructure and some form of process management which will be necessary to coordinate interventions by each of the functional entities resources to treat the patients specific problems.   The disadvantage of a PCMH is the administrative and technology cost needed to support its complex processes.  The PCMH
    
  • Was promoted as a way to incent more PCP which had been seen as a low reward role by medical students.  HCI3 argues this use of PCMH is flawed.  PCMH is driven by the medical home models of the ACA.  In this model the PCMH is accountable for meeting the vast majority of each patients physical and mental health care needs including prevention and wellness, acute care, and chronic care.  It is focused on treating the whole person.  It is tasked with coordinating the care across all elements of the health care system, including transitions and building clear and open communications.  It must ensure extended access and availability of its services and patients preferences about access.  It must continuously improve quality by monitoring evidence-based medicine and clinical decision support tools.  Many argue that to be effective it must be connected to a 'medical neighborhood'.  The PCMH brings together the specialized resources and infrastructure required to develop and iteratively maintain the care plans and population oriented system descriptions that are central to ACA care coordination. 
    
   
  ) as both a place and a model of the organization of primary care consists of providing accessible, comprehensive, longitudinal, and coordinated care in the context of families and community.  Interpreting the meaning of many streams of information and working together with the patient to make decisions based on the fullest understanding of this information relative to the patient's values and preferences is key to PCP providing value. 
  that delivers core functions of primary health care. 
  
• AIDA - activities that initially create awareness and then interest, desire and subsequently action.  
• AIDS is acquired auto-immune deficiency syndrome, a pandemic disease caused by the HIV is human immunodeficiency virus, an RNA retrovirus which causes AIDS.  It infects T-lymphocytes destroying the host's immune system. 
  .  It also amplifies the threat of tuberculosis, consumption or otherwise TB, is mostly an airborn bacterial lung infection, but it can also infect the brain, kidneys and other parts of the body.  The only vaccine is still the BCG.  The deployment of antibiotics during the 1940s allowed effective treatment: Streptomycin.  Diagnostic tools for TB are insufficient.  And because TB grows slowly in walled off pockets in the lungs it takes many months of treatment for antibiotics to eradicate the infection.  TB benefits from compromised hosts and has benefited from HIV/AIDS.  TB is also leveraging the plasmids that now carry immunity to all current antibiotics.  In 2016 it is estimated to latently infect two billion people.  9.6 million worldwide became infected in 2014.  1.5 million people will die from TB in 2016.  Deaths from the disease have fallen drastically since 2000.  TB has been halted or reversed in 16 of the 22 countries: India (Sep 2016, Infection base estimate increased Oct 2016), Vietnam, Indonesia; that have the majority of cases.  But it is still the infectious disease causing the most deaths world-wide.  Nano scale drug delivery has the potential to push back on TB and is being actively researched (May 2016).   .   Initially deadly, infecting and destroying the T-lymphocytes are a type of leukocyte.  They appear mainly in the lymphatic network.  Their are various types:
  • B cells which make antibodies that bind to pathogens, and activate the complement system.  When malignant these cells can produce multiple myeloma. 
    
  • Natural killer cells can kill body cells that do not display MHC class 1 molecules, or do display stress markers including MIC-A. 
    
  • T cells including CD4+ helper cells, Cytotoxic T cells, Gamma 5 T cells; 
    
  of the immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  , it can now be treated with HAART is highly active ARV therapy using a combination of at least three drugs that supress HIV replication. 
  to become a chronic disease.  And with an understanding of HIV's mode of entry into the T-cells, through its binding to CCR5 is a gene that encodes the CD195 cell membrane receptor.  The receptor is part of the target cell binding strategy of HIV.  Phase shift mutations of CCR5 have provided immunity to AIDS. 
  and CD4 is a gene that encodes a cell surface glycoprotein called CD4.  It is expressed on the surface of T-lymphocytes.  It is part of the binding target strategy of HIV. 
  encoded transmembrane proteins, AIDS may be susceptible to treatment with recombinant DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  to alter the CCR5 binding site, or with drugs that bind to the CCR5 cell surface protein preventing binding by the virus.  Future optimization of drug delivery may leverage nanoscale research (May 2016).  
• Akinetic mutism is an inability to generate spontaneous verbal reports.  Repetition is often still possible.  
• Aleksander's Axioms were proposed by Aleksander & Dunmall to define a minimal set of material preconditions for a conscious biological or non-biological agent.  These axioms are:
1. Depiction - Internal perceptual states depict the external world and the self 
   
2. Imagination - internal state that imagines depiction
   
3. Attention is the focusing of our mental resources onto a specific piece of information.  Attention uses valuations assigned to each potential object of thought by the basal ganglia. 
   
   
4. Planning - imagines future actions and selects among the alternatives
   
5. Emotion - affective states that evaluate planned actions and prioritize for selection
   
• All-or-nothing measures set is used by Geisinger because it closely matches the wants and needs of patients to slow chronic disease progression and prevent additional diseases and their impacts by delivery of optimal treatment, and drives care givers to achieve all goals.  It also provides a sensitive scale for measuring improvements.  Not all patients will achieve every measure, but the set encourages the patient, their family, the PCP is a Primary Care Physician.  PCPs are viewed by legislators and regulators as central to the effective management of care.  When coordinated care had worked the PCP is a key participant.  In most successful cases they are central.  In certain Medicare ACO models (Pioneer) PCPs are committed to achieve meaningful use requirements.  Working against this is the: replacement of diagnostic skills by technological solutions, low FFS leverage of the PCP compared to specialists, demotivation of battling prior authorization for expensive treatments. 
  and specialists to engage and develop a shared understanding. 
  
• Allele, one of multiple alternative forms of a schematic sequence with the same address on a
  Plans emerge in complex adaptive systems (CAS) to provide the instructions that agents use to perform actions.  The component architecture and structure of the plans is reviewed. 
  
  schematic string. 
  
• Alpha-synuclein is a protein found mainly in the presynaptic, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
  terminals of neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  .  It is important in maintaining the supply of synaptic vesicles - it interacts with tubulin.  It simultaneously binds to phospolipids of the plasma membrane and to synaptobrevin is a component of the core SNARE complex that drives fusion of membranes in exocytosis.  -2 becoming a chaperone.  It is encoded by the SNCA gene.  It is a major constituent of Parkinson's disease corresponds to the breakdown of certain interneurons in the brain.  It is not fully understood why this occurs.  Dopamine system neuron breakdown generates the classical symptoms of tremors and rigidity.  In some instances an uncommon LRRK2 gene mutation confers a high risk of Parkinson's disease.  In rare cases Italian and Greek families are impacted in their early forties and fifties resulting from a single letter mutation in alpha-synuclein which alters the alpha-synuclein protein causing degeneration in the substantia nigra.  But poisoning from MPTP has also been shown to destroy dopamine system neurons.  Paraquat has also been linked to Parkinson's disease.  Parkinson's disease does not directly kill many sufferers.  But it impacts swallowing which encourages development of pneumonia through inhaling or aspirating food.  And it undermines balance which can increase the possibility of falls.  Dememtia can also develop. 
  Lewy bodies are protein clumps that are a pathological mark of Parkinson's disease and Lewy body dementia.  A major component of the clumps is alpha-synuclein.  .  Knockout mice with targeted inactivation of the expression of alpha-synuclein show impaired spatial learning and working memory.  
• Alpha helix provides a structural building block (a helical tube) that can be conserved and used by
  Richard Dawkin's explores how nature has created implementations of designs, without any need for planning or design, through the accumulation of small advantageous changes. 
  
  natural selection. 
• Alphabet is a writing process where representational signals (letters and graphemes is a series of one or more letters that maps onto a phoneme in the target language.  The grapheme 'tt' in 'button' maps to the phoneme 't'.  Dehaene notes that English has an extensive set of:
  
  • Simple frequently used graphemes including 't', 'k' and 'a'. 
    
  • Simple but less frequent graphemes including 'b', 'm', 'f'. 
    
  • Irregular ones including 'i', 'o'. 
    
  • Complex graphemes including 'un', 'ch', 'ough', 'oi' and 'au.'   The human visual system treats learned graphemes as units.  
  ) refer to speech sounds (phonemes are the smallest speech units explicitly representing discrete speech sounds.  The phoneme 't' is a part of Tuna, stop and foot. 
  ) rather than meanings.  Dehaene asserts the principle probably emerged in small groups of people on the fringes of mainstream society.  The first example is Proto-Sinaitic is the earliest alphabetic writing system.  It dates from 1700 BC in the Sinai Peninsula.  It used shapes from Egyptian characters but used them to represent sounds of the Semitic language.  This allowed for a dramatic reduction in the required number of symbols used: two dozen were enough to represent all the existing speech sounds. 
  .  Alphabets allow for a drastic reduction in the number of signs required to be learnt. 
  
• ALS is amyotrophic lateral sclerosis which selectively destroys motor neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  . 
  
• Alternative quality contract (AQC) is:
  
• A 2009 payment arrangement developed by Blue Cross Blue Shield of Massachusetts.  It was developed to support change.  It differs from capitation is a global payment for all care for a patient during a specified time period.  It forces the provider of care to take a high risk.  Managing the risk implies successful population health management. 
  in including upside measures for patient safety, appropriateness of care and patient satisfaction.  Its key components are:
• Integration across the care continuum
• Accountability for performance measures for ambulatory and inpatient care.  Includes a 10% incentive for performing. 
  
• Performance measures are selected that are: Nationally accepted, Vary across providers, Include sufficient data on provider being measured, measured at the level that can influence the outcome. 
  
• Global payment for all medical services with health status adjustment and with margin retention. 
  
• Five year contract to create a sustained partnership 
• Altruism, is the property that since kin share genes
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  natural selection will improve the replicator is Richard Dawkin's name for the genotype since it has the evolutionary goal of surviving long enough to reproduce its schematic plan effectively.  The action of genetic operators means that the results of successful reproduction may be different to the parental genotypes and phenotypes (Dawkin's vehicle). 
  's selfish goals, Richard Dawkins's postulate described in 'The Selfish Gene' that genes are self-interested, meaning they include strategies for their agent's which promote the genes survival and replication.  Families will act altruistically to one another since they include a percentage of shared genes, allowing kin selection.  All other situations are viewed as competitive. 
  by supporting the survival of such relatives.  Improving the chances of survival of non-kin is hard to explain with a gene preservation theory.  Why help a competitive gene?  Trivers explanation of reciprocal altruism benefits another organism at a cost to the behaver.  It is differentiated from kin altruism, by Williams and Trivers, since it can apply between unrelated individuals.  It can be induced by natural selection when there is mutual survival benefit in group activities and cheating can be detected and discouraged.  Humans, leveraging the cognitive niche, can particularly easily, build an evolved amplifier, through sharing information at little cost and significant benefit.  But African savanna hunters similarly gain from sharing large game meat with other un-related altruistic group members since the meat would otherwise spoil before it could be eaten. 
  shows the special conditions under which it can occur. 
  
• Alzheimer's disease is a dementia is a classification of memory impairment, constrained feelings and enfeebled or extinct intellect.  The most common form for people under 60 is FTD.  Dementia has multiple causes including: vascular disease (inducing VCI) including strokes, head trauma, syphilis and mercury poisoning for treating syphilis, alcoholism, B12 deficiency (Sep 2016), privation, Androgen deprivation therapy (Oct 2016), stress, Parkinson's disease and prion infections such as Alzheimer's disease, CJD and kuru.  The condition is typically chronic and treatment long term (Laguna Honda ward) and is predicted by Stanley Prusiner to become a major burden on the health system.  It appears to develop faster in women than men.   which correlates with deposition of amyloid plaques in the neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  .  As of 2015 there are 5 million Alzheimer's patients in the USA is the United States of America.  .  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI is mild behavioral impairment, a proposed early diagnosis for dementia.  It recognizes and measures something that some experts say is often overlooked: Sharp changes in mood and behavior can precede the memory and thinking problems of dementia.  But there is a risk of over diagnosis which could leave many people unnecessarily fearful about their futures and seeking more tests.  And the diagnosis could affect insurance premiums.  To imply MBI the symptoms must last for more than six months and be a fundamental change in behavior.  
  ) and memory and thinking problems (MCI is mild cognitive impairment, a sense of memory loss despite normal performance on memory tests.  It is often associated with Alzheimer's disease. 
  ).  Variants include: late-onset sporadic; with risk factors - ApoE4 is a gene variant which produces the E4 variant of APOE.  It is a risk-factor for late-onset sporadic Alzheimer's disease.  Being homozygote for E4 does not imply getting Alzheimer's but does increase the risk 20 fold.  ApoE2 may reduce the risk of Alzheimer's.  It appears that ApoE4 differentially affects women.  Apoe4 is known to be broken down into fragments which impare mitochondrial operation.  It also promotes amyloid plaque buildup.  Therapies are being developed based on small molecules which reshape ApoE4 to be more like ApoE3 reducing the breakdown.   
  , presenilin is a gene which encodes the amyloid precursor protein.  John Hardy of UCL followed a family with a history of Alzheimer's disease who inherited the gene with a mutation that supported amyloidosis.  , androgen deprivation therapy lowers the levels of male sex hormones.  These hormones stimulate the growth of prostrate cancer cells.  But the treatment: Bicalutamide, Lupron; is associated with increased rates of: Depression (Apr 2016), Dementia (Oct 2016) including Alzheimer's disease (Dec 2015).   (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria are the energy molecule generating production functions of eukaryotic cells.  They are vestigial blue-green bacteria with their own DNA and infrastructure.  Unlike stand-alone bacteria they also use the eukaryotic host DNA and infrastructure for some functions.  The high energy molecules are nucleotides with a high energy phosphate bond.  The most used high energy molecule is Adenosine-tri-phosphate.   to support neuron, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  operation; It is initiated by an increasingly leaky blood-brain barrier and the innate immune response has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  to subsequent infections (May 2016).  The Alzheimer's pathway follows:
• Plaques form and set off the formation of tangled thread-like tau protein.
• Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
• BACE inhibitors block an enzyme needed to form amyloid. 
  
• The Tau tangles kill nerve cells.  LMTX is leucomethylthioninium salts, a second generation tau aggregation inhibitor manufactured by TauRx Therapeutics. 
  is a drug treatment targeted at these tangles. 
  
• The brain becomes inflamed resulting in the killing of many more nerve cells. 
  
• AMA is the American Medical Association. 
  
• AMC is Academic medical center.  They perform education, research and patient care.  They include one or more health professions schools, such as a medical school and a hospital.  The major AMCs are represented by the United HealthSystem Consortium.   The costly strategies of the AMCs and increased difficulty of finding enough targeted patients for research studies (Aug 2017) is forcing integration with larger hospital systems is the owner of a set of hospitals and other owned infrastructure and employer of direct staff.  .  AMCs offer researchers clinical research support: Virus vectors (Nov 2017);
  
• AMD is age related macular degeneration is a disease that results in progressive and complete blindness.  It includes: AMD which has two forms dry and wet. 
  which is the leading cause of vision loss and blindness among Americans over 65.  It is associated with a damaging buildup of drusen pigments in the dry form is the slow destruction of foveal vision.  It is caused by a buildup of drusen pigments due to a failure of the aging cellular infrastructure to remove these metabolic waste products.  The pigments inhibit the flow of oxygen from the choroid blood supply through Bruch's membrane to the RPE and photo-receptor cells.  The drusen damage the RPE causing this layer of the macular to thin.  Over a decade this results in deterioration of perception in the fovea.  In about 20% of sufferers the reduced flows across the RPE result in development of more blood vessels which anomalously push through Bruch's membrane causing the far more rapidly destructive wet macular degeneration.  Dry macular degeneration can be detected using an Amsler grid and confirmed with OCT. 
  and additionally, blood vessels in the wet form is an age related, rapidly irreversible, destruction of foveal vision.  It occurs in 20% of AMD and can damage the retina within a 12 month period.  It is due to aberrant blood vessel development in the choroid, pushing through the RPE and disrupting it.  Treatments using locally deployed VEGF and POGF receptor blockers inhibit the problematic angiogenesis.  .  It is associated with a variety of genetic mutations.  Using HapMap is a genomics project of 2000 scientists in six countries project managed by Francis Collins, which mapped the various haplotypes.  By leveraging the clustering of SNPs in neighborhoods of the genes and knowledge of the boundaries of the neighborhoods you can identify all the SNPs without spending huge amounts of money or laboratory time to test for every one.  HapMap was designed to define the boundaries of the neighborhoods to allow these shortcuts in genome analysis reducing the amount of work by a factor of 40. 
  data it was realized that two gene variations on separate chromosomes, both involved in inflammatory response carry high risk for this disease.  These two genetic factors along with smoking and obesity is a disorder where the brain is induced to require more eating, often because of limits to the number of fat cells available to report satiation (Jul 2016).  It is associated with: metabolic syndrome including inflammation, cancer (Aug 2016), high cholesterol, hypertension, type-2-diabetes and heart disease.  It is suspected that this is contributing to the increase in maternal deaths in the US (Sep 2016).  Obesity is a complex condition best viewed as representing many different diseases, which is affected by the: Amount of brown adipose tissue (Oct 2016), Asprosin signalling by white adipose tissue (Nov 2016), Genetic alleles including 25 which guarantee an obese outcome, side effects of some pharmaceuticals for: Psychiatric disorders, Diabetes, Seizure, Hypertension, Auto-immunity; Acute diseases: Hypothyroidism, Cushing's syndrome, Hypothalamus disorders; State of the gut microbiome.  Infections, but not antibiotics, appear associated with childhood obesity (Nov 2016). 
  infer 80 percent of the risk.  Treatments can thus target the inflammatory response.  Ranibizumab is a MAB fragment that blocks VEGF binding driven blood vessel formation.  It is marketed under the trade name Lucentis. 
  blocks the VEGF is vascular endothelial growth factor, a signalling protein used by cells to stimulate angiogenesis.   stimulated growth of blood vessels that occur in the wet form. 
• AMI is acute myocardial infarction which means that some of the heart muscle has died from a blocked blood supply.  AMI is hard to measure.  Nanosensors offer a possibility (May 2016).   
• Amino-acids are the building blocks of proteins, a relatively long chain (polymer) of peptides.  Shorter chains of peptides are termed polypeptides.  .  The 20 main variants differ by the nature of their side chain.  Some are positively charged, others negatively charged.  Some are water seeking while others are fat seeking.  The genetic code, the mapping of DNA base triplet sequences, such as AAA and AAT, to amino-acids (AAA maps to the amino-acid lysine for example) and transcription termination sequences (TGA maps to stop transcription for example) that has currently evolved. 
  mapping of DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  base, a nucleotide base is the side chain purine (A or G) or pyrimidine (T or C).  A is a natural pair for T.  G pairs naturally with C.  These bases have multiple uses in cells including energy transfer, second messenger signalling as well as genetic data storage, transcription and translation.  Deacon argues that the multiple uses are significant to the emergence of evolution. 
  pair triplets thus specifies the primary sequence of amino-acids in any protein polymer. 
  
• Amok is a Malay word describing the homicidal actions occasionally performed by lonely Indochinese men who have suffered a loss of love, money or face.  The syndrome occurs across cultures is how we do and think about things, transmitted by non-genetic means as defined by Frans de Waal.  CAS theory views cultures as operating via memetic schemata evolved by memetic operators to support a cultural superorganism.  Evolutionary psychology asserts that human culture reflects adaptations generated while hunting and gathering.  Dehaene views culture as essentially human, shaped by exaptations and reading, transmitted with support of the neuronal workspace and stabilized by neuronal recycling.  Sapolsky argues that parents must show children how to transform their genetically derived capabilities into a culturally effective toolset.  He is interested in the broad differences across cultures of: Life expectancy, GDP, Death in childbirth, Violence, Chronic bullying, Gender equality, Happiness, Response to cheating, Individualist or collectivist, Enforcing honor, Approach to hierarchy; illustrating how different a person's life will be depending on the culture where they are raised.  Culture:
  • Is deployed during pregnancy & childhood, with parental mediation.  Nutrients, immune messages and hormones all affect the prenatal brain.  Hormones: Testosterone with anti-Mullerian hormone masculinizes the brain by entering target cells and after conversion to estrogen binding to intracellular estrogen receptors; have organizational effects producing lifelong changes.  Parenting style typically produces adults who adopt the same approach.  And mothering style can alter gene regulation in the fetus in ways that transfer epigenetically to future generations!  PMS symptoms vary by culture. 
    
  • Is also significantly transmitted to children by their peers during play.  So parents try to control their children's peer group.  
  • Is transmitted to children by their neighborhoods, tribes, nations etc. 
    
  • Influences the parenting style that is considered appropriate. 
    
  • Can transform dominance into honor.  There are ecological correlates of adopting honor cultures.  Parents in honor cultures are typically authoritarian. 
    
  • Is strongly adapted across a meta-ethnic frontier according to Turchin.  
  • Across Europe was shaped by the Carolingian empire. 
    
  • Can provide varying levels of support for innovation.  
  • Produces consciousness according to Dennet. 
    
  .  An amok man responds autonomously and can't be reasoned with.  But Steven Pinkers explains it is:
  
• An emotional are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   result of lengthy brooding over failure, 
• Carefully planned as a means of deliverance from an unbearable situation
• Cognitive is the ability to orchestrate thought and action in accordance with internal goals according to Princeton's Jonathan Cohen. 
  - It is triggered by an idea, rather than some immediate stimulus or tumor
  
• I am not an important or "big man." 
  
• I possess only my personal sense of dignity
• My life has been reduced to nothing by an intolerable insult which means  
  
• I have nothing to lose except by life, which is nothing, so I trade my life for yours, as your life is favored. 
  
• I will kill many of you which will rehabilitate myself in the eye of the group (amok) of which I am a member even though I might be killed in the process. 
  
• Amortized loans include interest & repayment of principal in the monthly payment.  No lump-sum payment is left when the loan matures.  Varying the number of payments helped limit the size of the monthly payment. 
  
• Amputation is a surgical technique to remove damaged body parts.  The regular method was developed by the 1800s and leaves considerable scope for increasing support for bionic devices: rebuilding agonist antagonist muscle group feedback etc. 
  
• Amygdala contains > 12 distinct areas: Central is a relatively ancient evolved part of the amygdala which processes 'innate' fears.  It projects to the BNST to raise the heart rate and blood pressure in preparation for fight and flight. 
  , Lateral is the basolateral amygdala, a relatively recently evolved part of the amygdala which learns stimuli to fear and then signals the central amygdala.  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH and BDNF encouraging the building of new dendrites and synapses. 
  .  It receives simple signals from the lower parts of the brain: pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Pain is the main reason people visit the ED in the US.   from the PAG is periaqueductal gray, an ancient core brain structure that projects pain sensations to the amygdala.  ; and abstract complex information from the highest areas: Disgust is a universal human emotion.  Pinker notes it has its own facial expression and is codified in food taboos.  The mind must be associated with the proximate environment and parents minimize the risk for their omnivorous children by teaching them what foods to eat and what to avoid.  The children's minds are initially receptive to trying all foods but their brains subsequently lock in on the foods they have experienced.  These parental choices are affected by schematic influence on what has been beneficial.  Adolescent's brain developments undermine these constraints enabling intergroup transfers.  Disgust is modulated by the insula cortex which projects signals to the amygdala. 
  from the insula cortex is part of the cerebral cortex folded deep within the lateral sulcus.  It includes: anterior, posterior insula; and is overlaid by the operculum.  It is assumed to participate in consciousness where it has been linked to emotion, salience & body homeostasis functions:
  
  • Perception,
    
  • Motor control: Hand-&-eye motor movement, Swallowing, Gastric motility, Speech articulation;
    
  • Self-awareness,
    
  • Inter-personal experiences: Disgust at smells, contamination & mutilation which generate visceral responses, that are projected to the amygdala; binding physical and moral aspects of purity (Macbeth effect)
    
  • Homeostatic regulation of the sympathetic network, parasympathetic network, and immune system.   
  .  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  .  It has high levels of D(1) dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation. 
    
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
    
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    
  • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
  • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    
  • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
  • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
  • Dopamine is removed from the synapse by a reuptake transporter DAT. 
    
  receptors.  During extreme fear the amygdala drives the hippocampus is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
  into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus is a relatively ancient evolved part of the amygdala which processes 'innate' fears.  It projects to the BNST to raise the heart rate and blood pressure in preparation for fight and flight. 
  projects to the BNST is the bed nucleus of the stria terminalis.  It receives 'innate fear' signals from the central amygdala.  It projects to: Parts of the hypothalamus that initiate the hormonal stress response, Midbrain and brain-stem networks that activate the sympathetic nervous system and inhibit the parasympathetic.  Winning in competition induces the addition of testosterone receptors increasing the sensitivity of the BNST to the hormone.  That will lead to reduced fear and increased confidence. 
  .  It signals the locus ceruleus and its projections determine the brain's global orientation concerning events in the external world and within the viscera.  It is signalled by the amygdala.  Such a hypothesis of central noradrenergic neuron function has been generated by observations of locus ceruleus unit discharge in untreated, awake, behaviorally responsive rats and monkeys.  These studies reveal the locus ceruleus units to be highly responsive to a variety of non-noxious sensory stimuli and that the responsiveness of these units varies as a function of the animal's level of behavioral vigilance.  Increased neuronal activity in the locus ceruleus is associated with unexpected sensory events in the subject's external environment, while decreased noradrenergic activity is associated with mediating tonic vegetative behaviors.  Sapolsky argues that arousal spread through the locus ceruleus to many brain regions, particularly the cortex, increases the intensity of what is sensed. 
  .  The amygdala:
  
• Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger is an emotion which protects a person who has been cheated by a supposed friend.  When the exploitation of the altruism is discovered, Steven Pinker explains, the result is a drive for moralistic aggression to hurt the cheater. 
  into aggression and when impaired it impacts the ability to detect angry facial expressions.  
• Participates in disgust is a universal human emotion.  Pinker notes it has its own facial expression and is codified in food taboos.  The mind must be associated with the proximate environment and parents minimize the risk for their omnivorous children by teaching them what foods to eat and what to avoid.  The children's minds are initially receptive to trying all foods but their brains subsequently lock in on the foods they have experienced.  These parental choices are affected by schematic influence on what has been beneficial.  Adolescent's brain developments undermine these constraints enabling intergroup transfers.  Disgust is modulated by the insula cortex which projects signals to the amygdala. 
  
• Perceives fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
  promoting stimuli.  In PTSD is post-traumatic stress disorder, an induced level of stress that is so troubling to the brain that it avoids processing it, change that is necessary if the stress is to be dissipated by the normal brain processes.  The hippocampus loses volume.  The amygdala increases in volume and is hyperactive.  As a result it remains in a heightened state, resulting in fear of recall and further stress.  It is now being realized that PTSD can be introduced into patients by traumatic treatment regimens such as ICU procedures.  Traumatic head injuries, seen in athletes and soldiers can be reflected in PTSD and can subsequently become associated with prion based dementia.   sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size refers to lasting changes to the brain that occur throughout the life span of the organism.  Many aspects of the brain can be altered into adulthood.  Almost anything in the nervous system can change in response to sustained stimulus.  And in a different environment the changes will often reverse.  The changes include:
  • The strength of dendritic input alters due to genetic, neural and hormonal signals
  • Hebb notes that memories require strengthening of preexisting synapses.  Glutamate responsive neurons' post synaptic dendritic spines have two types of receptor: non-NMDA and NMDA.  NMDA channels are responsible for this strengthening mechanism.  LTP then occurs to prolong the increase in excitability of the synapse. 
    
  • The LTP operation results in calcium diffusion which triggers new spine formation in adjacent parts of the dendrite.  Eventually that can stimulate dentrite growth enabling more neurons to connect. 
    
  • Short term stress promotes hippocampal LTP.  
  • Sustained stress promotes:
    
  • Hippocampal & frontal cortex  LTD & suppresses LTP.  Subsequent reductions in NCAM then reduce dendrite and synapse density. 
    
  • Amygdala LTP and suppresses LTD boosting fear conditioning.  It increases BDNF levels and expands dendrites in the BLA. 
    
  • Depression and anxiety reduce hippocampal dendrite and spine number by reducing BDNF. 
    
  • The axon's conditions for
    
  • Initiating an action potential. 
    
  • Progesterone boosts GABA-ergic neurons response to GABA decreasing the excitability of other neurons over a period of hours. 
    
  • Duration of a neuron's refractory period.  Testosterone shortens the refractory period of amygdala and amygdala target neurons over a period of hours. 
    
  • Synaptic connections being constantly removed and recreated
  • Synapses being created or destroyed.  Stimulation generates additional dendritic spines which become associated with a nearby axon terminal and within weeks a synapse forms.  The synapse then contributes calcium diffusion through LTP triggering more spine formation.  When dendritic spines recede synapses disappear. 
    
  • Cortical maps change to reflect alterations in the inputs and outputs from the body. 
    
  • Birth of brain cells in many areas of adult brains: the hippocampus (where 3% are replaced each month) and olfactory bulb and lesser amounts in the cortex. 
    
  • Restructuring after brain damage including axonal plasticity.  Distant rerouting of axons is observed but no mechanism has been identified yet. 
    
  • Vision is plastic in predators, where the eyes are moved during final development.  Dehaene argues for neuronal recycling supporting reading.  
  over a period of months.  Fear is processed by the lateral nucleus is the basolateral amygdala, a relatively recently evolved part of the amygdala which learns stimuli to fear and then signals the central amygdala.  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH and BDNF encouraging the building of new dendrites and synapses. 
  which serves as the input from various senses, and the central nucleus is a relatively ancient evolved part of the amygdala which processes 'innate' fears.  It projects to the BNST to raise the heart rate and blood pressure in preparation for fight and flight. 
  which outputs to the brain stem includes: medulla, raphe, pons, substantia nigra, ventral tegmental area, pituitary, superior colliculi, cerebellum, thalamus (LGN), basal ganglia including caudate nucleus and striatum; amygdala, hypothalamus, nucleus accumbens; (central grey - freezing, lateral hypothalamus is essential to many operations of the body.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, and similar body operations.  Its (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).   - blood pressure, activates paraventricular hypothalamus is essential to many operations of the body.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, and similar body operations.  Its (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).   => crf -> hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  adjustments). 
  
• Has lots of receptors is NR3C1 a receptor deployed in several forms, to which cortisol and other glucocorticoids bind.  It regulates transcription of genes controlling development, metabolism and immune response.  The unbound receptor resides in the cytosol.  Gene/environment interactions have been identified:
  • One variant of the gene for the MR receptor in the presence of childhood abuse produces an amydala that is hyperactive to threat.  
  • The GR receptor's activity is modified by FKBP5.  Once FKBP5 variant in the presence of childhood abuse is associated with: aggression, hostility, PTSD, hyperreactivity of the amygdala to threat. 
    
  for and is highly sensitive to glucocorticoids are corticosteroids which bind the glucocorticoid receptor.  They decrease excitability of prefrontal cortical neurons.  They have adverse effects in fetal/infant development having organizational effects on fetal brain construction and decreasing levels of: growth factors, neurons, synapses; resulting in an adult brain that is more sensitive to environmental triggers of depression and anxiety.  Glucocorticoids affect gene control structures and induce epi-genetic changes.  They have been found associated with high sodium chloride consumption (May 2017). 
  .  Stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  
  • The short term response to the stressor
    
  • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
    
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    
  • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    
  • Activates the integration between the thalamus and amygdala. 
    
  • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
    
  • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    
  • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    
  • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    
  • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention. 
    
  • During depression, stress inhibits dopamine signalling. 
    
  • Strategies for stress reduction include: Mindfulness. 
    
  inhibits the GABA is gamma-Aminobutyric acid which is:
  • An inhibitory neurotransmitter in the central nervous system of mammals.  It binds to pre- and postsynaptic neuron receptors that induce the opening of potassium and chloride ion channels, or G-protein receptor transformations. 
    
  interneurons in the basolateral amygdala (BLA is the basolateral amygdala, a relatively recently evolved part of the amygdala which learns stimuli to fear and then signals the central amygdala.  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH and BDNF encouraging the building of new dendrites and synapses. 
  ) allowing the excitatory glutamate releasing neurons to excite more. 
  
• Is sensitive to unsettling/uncertain social situations where it promotes anxiety is manifested in the amygdala mediating inhibition of dopamine rewards.  Major anxiety results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women. 
  .  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA is the basolateral amygdala, a relatively recently evolved part of the amygdala which learns stimuli to fear and then signals the central amygdala.  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH and BDNF encouraging the building of new dendrites and synapses. 
  supports rejecting an unacceptable offer, as allowed in the Ultimatum Game is an economic game involving two players: One makes an offer about how to split a pot of money.  If the offer is rejected neither party gets any money.  The other player can accept or reject the offer.  Rationality implies that any offer should be accepted by the recipient.  Instead recipients are keenly aware of being unfairly treated.  The longer the amygdala responds to the offer the more likely it is to be rejected.  The rejection is mentally costly and must be encouraged by a dopaminergic reward, fueled by the amygdala and insula.  When the offer is rejected the first player feels dissed, subordinated - especially if the result is shared with others, undermining status & reputation.  Sapolsky notes that:
  
  • People with damaged amygdalae are unusually generous because the BLA normally injects learned implicit distrust and vigilance into social decision making.  
  • People given testosterone before the game become more generous.  Sapolsky notes the effect demands fancy neuroendocrine wiring. 
    
  • People from small-scale, non-Western cultures were less trusting and punished more.  Joseph Henrich found three variables predicted how the play executed: Market integration, Community size, Religion; where large communities need ways to make strangers trustworthy.  Communities that trade are also more likely to act fairly and punish unfairness.  Sapolsky asserts that market interactions represent an impoverishment of human reciprocity with the total transaction having to be judged and occur in an instant.  Small-scale cultures are more practiced at the nuanced judgements about their long term neighbors. 
    
  • Chimps can be trained to play the game.  Max Planck Institute's Michael Tomasello found no evidence of chimp requirements for fairness.  But De Waal & Brosnan found chimps will be fair but only if they see a downside in being unfair.  Primates seem to reflect the same hypocritical strategies underneath any reciprocal altruism that humans display. 
    
  , by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus has all the main inputs to the cortex passing through it.  It is massively supplied with return innervations from the cortical regions it routes too.  It does not stand on the route of the main exits from the cortex.  The parafascicular nucleus of the rat thalamus contains relatively high levels of D5 dopamine receptors.  For human vision the primary system connects to the neocortex via a small part of the thalamus the LGN.   of outgroup skin color.  The amygdala subsequently tips social emotions are emotions that are induced in response to other people's signals, are implemented by specific brain regions including: Prefrontal cortex, Insula cortex, Anterior cingulate cortex, Amygdala; receive lots of projections from interoceptive networks.  Sapolsky asserts in the moments just before we prioritize a consequential act the process is less rational and autonomous than we assume.  There are many significant signals from the prior seconds to minutes that effect social emotions:
  
  • Our brains respond subliminally to skin color very quickly: Amygdala activates, Fusiform face area activates; prior to the conscious stream activating the anterior cingulate and DLPFC which then inhibit the amygdala. 
    
  • Social dominance is culture independent and accurately subliminally assessed after a 40-millisecond exposure.  Stable status relations activate the ventromedial prefrontal cortex and DLPFC, while a dynamic situation also activates the amygdala.  
  • People who are subliminally judged attractive by the medial orbitofrontal cortex are considered kinder, smarter and more honest.  They are given more breaks. 
    
  • Faces and eyes in particular are most important subliminal cues.  They are monitored by the fusiform.  People respond more appropriately under the subliminal influence of eyes. 
    
  • Olfactory sensors send more direct projections to the limbic network than other sensory networks.  Pheromones signal fear activating the amygdala. 
    
  • Observing pain responses in others results in empathy even among young children. 
    
  • Words are important emotional signals providing unconscious priming of social responses.  Kahneman & Tversky demonstrated how the phrase '95% survival rate' is found to be a more acceptable choice than '5% death rate'.  Sapolsky notes that prosocial word priming fosters cooperation with antisocial word priming doing the opposite.  
  • Cultural objects such as visible: flags, team badges; subliminally modify in-group outgroup decisions. 
    
  • The presence of women in a situation alters the responses of men: Increased risk-taking, more focus on luxuries, increased aggression; in circumstances where conflict is already encouraged but not when status is achieved prosocially.  
  • Physical environment shapes behavior as demonstrated by Philip Zimbardo and leveraged in broken windows policing.  
  • Bodily adjustments to sensory structures introduce adaptive complexity, with the brain being influenced to become more sensitive and alter the sensor networks to make some more sensitive.  But these adaptations also vary culturally.  Collectivist cultures focus on a visual scene's surrounding contextual information while people from individualistic cultures focus on the focal object!   
  against outgroups unless restrained by the frontal lobe of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
  
• Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure is the outcome of the dopamine reward system, argues UCSF professor Robert Lustig.  He, like the early Christians, contrasts [addiction oriented] pleasure with serotonin driven happiness & contentment. 
  . 
  
• Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
  
• Uses but is not directly involved in vision. 
  
• Amyloidosis is the accumulation of badly folded proteins.  The miss-folding makes them insoluble and so they deposit in the organs and tissues of the body.  The kidney provides multiple vital functions.  It: Produces renin which supports negative feedback, Removes excess organic molecules from the blood, Regulates electrolytes in the blood, Maintains pH homeostasis, Regulates fluid balance, Regulates blood pressure, Reabsorbs water, glucose (SGLT2) and amino acids.  Kidney function is monitored with the GFR.  Kidneys can fail acutely or chronically.  Kidneys are affected by a variety of cancers including: advanced kidney cancer, von Hippel Landau; some of which are induced by PFAS.    Multiple myeloma, type 2 diabetes, TB and drug treatments for MDR TB place a strain on the kidneys and can induce failure.   and heart are most often affected.  Often the problem is that two protein, a relatively long chain (polymer) of peptides.  Shorter chains of peptides are termed polypeptides.   subunits fail to bind together.  Once the protein becomes insoluble it becomes inaccessible to the proteases that would otherwise break it down.  Sometimes prions is a protein with the unusual property of having two highly stable configurations.  DNA generally encodes only one of the stable configurations of the prion.  The other form once present converts the rest of the local prion to its configuration which is very stable.  The generation of prions and their configuration shifts are used by neurons to represent long term state. 
  are viewed as participating in amyloidosis.  However in at least some neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  prion re-folding appears to provide long term state transitions for memory.  
• ANA is the American nurses association. 
  
• Anal cancer is very rare.  The cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).   typically develops in the squamous cells of the anus.  It has been associated with HPV is human papillomavirus which causes cancer of the cervix in women and is also associated with anal cancer. 
  .  It is distinct from colon cancer is a major hereditary cancer also called colorectal cancer.  It follows a slow, many yearlong, progression from a benign polyp to a localized cancer to an invasive one.  Two bacteria: Bacteroides fragilis, Escherichia coli variant; from the gut microbiome have been implicated in the early stages of tumor induction (Feb 2018).  It is often associated with Ras mutations and the high risk allele TCF7L2.  30 to 50% of colon cancers have KRAS mutations.  Intensive medical surveillance and removal of polyps can be lifesaving for those at high risk.  Types of colon cancer include the single gene mutation hereditary: FAP, HNPCC; . 
  
• Anchor and adjust is a behavior broadly adopted by human
  Plans are interpreted and implemented by agents.  This page discusses the properties of agents in a complex adaptive system (CAS). 
  It then presents examples of agents in different CAS.  The examples include a computer program where modeling and actions are performed by software agents.  These software agents are aggregates. 
  The participation of agents in flows is introduced and some implications of this are outlined. 
  
  agents to inductively
  The agents in complex adaptive systems (CAS) must model their environment to respond effectively to it.  Samuel modeling is described as an approach. 
  
  model the operation of a
  This page introduces the complex adaptive system (CAS) theory frame.  The theory is positioned relative to the natural sciences.  It catalogs the laws and strategies which underpin the operation of systems that are based on the interaction of emergent agents. 
  John Holland's framework for representing complexity is outlined.  Links to other key aspects of CAS theory discussed at the site are presented. 
  
  CAS network.  Using patterns of past flow rates, the agents select a model that seems to match and anchor to that.  When the actual operation diverges from the anchor model, the agents continue to leverage the model, but make adjustments to account for the differences.  If a characteristic of the network, such as increased demand, has changed the model and adjustments will generate more divergence.  In a network with buffer pools and time delays, the anchor and adjust strategy ensures both overshooting and undershooting. 
  
• Androgen deprivation therapy lowers the levels of male sex hormones are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  .  These hormones stimulate the growth of prostrate cancer is cancer of the prostate gland.  Genomics detected several common DNA variants associated with increased risk of prostate cancer.  Dr. Francis Collins explains that a cluster of these risk variants lies in a stretch of 1 million DNA base pairs on chromosome 8.  The cluster contains seven or more risk variants, each of which can raise the risk of prostate cancer by 10 to 30%.  The high risk variants occur more frequently in African-American men than European or Asians.  African-Americans die from prostate cancer at more than twice the rate of Europeans.  Research in mice may explain a link between obesity and prostate cancer (Jan 2018).  The average diagnosis is at age 66.  Worldwide in 2012 there were 1.1 million cases from which 307,000 died.  A common life-saving (Feb 2017) treatment is androgen deprivation therapy, but it has worrying side effects.  Various classically defined types of cancer can occur.  The most common is adenocarcinoma associated with the epithelial gland cells that generate seminal fluid.  Epithelial cell differentiation potency makes these significant cancer agents.  Other very rare types of cancer that can start in the prostate are:
  • Sarcomas
  • Small cell carcinomas
  • Neuroendocrine tumors
  • Transitional cell carcinomas
    
  cells.  But the treatment: Bicalutamide, Lupron; is associated with increased rates of: Depression is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; (Apr 2016), Dementia is a classification of memory impairment, constrained feelings and enfeebled or extinct intellect.  The most common form for people under 60 is FTD.  Dementia has multiple causes including: vascular disease (inducing VCI) including strokes, head trauma, syphilis and mercury poisoning for treating syphilis, alcoholism, B12 deficiency (Sep 2016), privation, Androgen deprivation therapy (Oct 2016), stress, Parkinson's disease and prion infections such as Alzheimer's disease, CJD and kuru.  The condition is typically chronic and treatment long term (Laguna Honda ward) and is predicted by Stanley Prusiner to become a major burden on the health system.  It appears to develop faster in women than men.   (Oct 2016) including Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It is initiated by an increasingly leaky blood-brain barrier and the innate immune response to subsequent infections (May 2016).  The Alzheimer's pathway follows:
  • Plaques form and set off the formation of tangled thread-like tau protein.
  • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
  • BACE inhibitors block an enzyme needed to form amyloid. 
    
  • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    
  • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    
  (Dec 2015).  
• Androgens are a class of steroid hormones including testosterone is a hormone secreted by the testes in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  Testosterones effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
  , androstenedione and dihydrotestosterone.  They are precursors of estrogens is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The levels of each type of receptor is independently regulated.  Different receptor variants are associated with:
  • Higher rates of anxiety among women
  • Higher rates of antisocial behavior and conduct disorder in men
  . 
  
• Anemia is a decrease in the number of red blood cells or the amount of hemoglobin the the blood.  There are various types: Fanconia anemia is a recessive disease where the bone marrow fails to produce red and white cells.  PGD has been used to select for embryos that do not have the Fanconi mutation and are a transplantation match for a suffering sibling, and that would result in a baby whose umbilical cord can be used to generate stem cell bone marrow for transplant to a sibling already born with the anemia. 
  , Iron-deficiency anemia is anemia caused by lack of iron.  It is generally caused by loss of blood, insufficient dietary iron, poor absorption of iron. 
  , Pernicious anemia is an autoimmune disease with a deficiency in red blood cells due to a lack of intrinsic factor limiting absorbtion of vitamin B12.  The cells in the stomach that make intrinsic factor are damaged by the autoimmune attack by antibodies to intrinsic factor. 
  , Sickle-cell anemia is a recessive single gene disease where the sufferer's hemoglobin causes the red blood cells to distort.  It is a side effect of the evolved protection from malaria provided by sickle cell trait.  Potential treatments include gene therapy and drugs that block the sickling of red blood cells.  Carrier screening was undermined by there being no effective prenatal test limiting the benefit of the information and because the white doctors were not trusted by their black patients.  In the future iPS cells could have the problem mutations replaced with ex vivo gene therapy. 
  ;
  
• Anesthesia is the temporary removal of sensation.  It can be local, regional renders a large area of the body insensitive by blocking transmission of nerve impulses between a part of the body and the spinal chord. 
  or general induces a deep sleep that suppresses breathing and vigilance and often requires a breathing tube.  This is far more risky than sedation.  Researchers are actively looking at the impacts on children under three years old including SmartTots since:
  • Studies of children have found an association between learning problems and multiple exposures to anesthesia early in life. 
    
  • Experiments in young monkeys have shown that commonly used anesthetics and sedatives can kill brain cells, diminish learning and memory and cause behavior problems. 
    
  . 
  
• Anesthesiology is a four year accredited residency is the apprenticeship of a medical or nursing graduate with a practitioner (attending), usually performed at a teaching hospital: Brigham & Women's, Cottage Health System, El Camino Hospital, Johns Hopkins, LSU Health Sciences Center, Rush University Medical Center, Stanford University Medical Center; skilled in the specialized techniques required for consistent success in diagnosis and treatment, or treatment execution, of medical conditions.  A first year resident is also called an intern.  Christensen, Grossman & Huang note the difficulty of presenting all the necessary case types to a resident during the limited period of the apprenticeship.  The difficulty of matching graduates with desired residency slots intrigued Al Roth who helped mitigate the problem with efficient market tools deployed by NRMP.  Docphin provides web access to categorized research information used during residency. 
  including a one year medical or surgical internship, and three years of anesthesiology training.  This includes specialized testing in anesthesia is the temporary removal of sensation.  It can be local, regional or general. 
  as well as tests of physiology, pathophysiology, pharmacology and other medical sciences.  There is a board exam at the completion of residency to obtain certification as an anesthesiologist is a physician who has completed an accredited residency program in anesthesiology and is trained in anesthesia and perioperative medicine. 
  .  Practices as an anesthesiology specialist.  
• Anesthesiologist is a physician who has completed an accredited residency is the apprenticeship of a medical or nursing graduate with a practitioner (attending), usually performed at a teaching hospital: Brigham & Women's, Cottage Health System, El Camino Hospital, Johns Hopkins, LSU Health Sciences Center, Rush University Medical Center, Stanford University Medical Center; skilled in the specialized techniques required for consistent success in diagnosis and treatment, or treatment execution, of medical conditions.  A first year resident is also called an intern.  Christensen, Grossman & Huang note the difficulty of presenting all the necessary case types to a resident during the limited period of the apprenticeship.  The difficulty of matching graduates with desired residency slots intrigued Al Roth who helped mitigate the problem with efficient market tools deployed by NRMP.  Docphin provides web access to categorized research information used during residency. 
  program in anesthesiology is a four year accredited residency including a one year medical or surgical internship, and three years of anesthesiology training.  This includes specialized testing in anesthesia as well as tests of physiology, pathophysiology, pharmacology and other medical sciences.  There is a board exam at the completion of residency to obtain certification as an anesthesiologist.  Practices as an anesthesiology specialist.   and is trained in anesthesia is the temporary removal of sensation.  It can be local, regional or general. 
  and perioperative medicine is the care of a patient prior to and after surgery. 
  . 
  
• Anesthetist is used to describe anesthesia is the temporary removal of sensation.  It can be local, regional or general. 
  providers without the qualification of physician.  Often these are CRNA is a certified registered nurses trained in anesthesia.  s. 
  
• Anger is an emotion are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   which protects a person who has been cheated by a supposed friend.  When the exploitation of the altruism benefits another organism at a cost to the behaver.  It is differentiated from kin altruism, by Williams and Trivers, since it can apply between unrelated individuals.  It can be induced by natural selection when there is mutual survival benefit in group activities and cheating can be detected and discouraged.  Humans, leveraging the cognitive niche, can particularly easily, build an evolved amplifier, through sharing information at little cost and significant benefit.  But African savanna hunters similarly gain from sharing large game meat with other un-related altruistic group members since the meat would otherwise spoil before it could be eaten. 
  is discovered, Steven Pinker explains, the result is a drive for moralistic provides rules for identifying right from wrong.  It develops in stages with children using play to work out rules of appropriate behavior.  Kohlberg's 1950s experiments using children led him to conclude moral judgement is a cognitive process that develops in three stages.  Sapolsky raises issues with the framework: Its a model, It does not apply to other cultures, Intuition & emotion are as significant as cognition, Moral reasoning doesn't predict moral actions; and notes the capacity of the frontal cortex to regulate emotions and behavior is far more predictive.  The marshmallow test, performed on three to six year olds, actually predicted their subsequent SAT scores at high school, social success and lack of aggression, and forty years on more PFC activation during a frontal task and a lower BMI!  Jonathan Haidt argues people's moral decisions are rationalizations rather than using reasoning. 
  aggression to hurt the cheater. 
  
• Angiogenesis is the formation of new blood vessels from existing vessels.  It is important in growth, development and wound healing.  To become malignant many tumors is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).   stimulate angiogenesis. 
  
• Angioplasty involves inserting a catheter is a thin tube that can be inserted into the body.  , inflating a balloon to expand a narrowed artery, and inserting a stent is a small wire cage that can be inserted into an artery to prop it open.  They were introduced as an alternative to bypass surgery in the 1990s.  Stents are expensive.  Medicare payments vary depending on what kind of stent is used and how many, but are generally in the range $10,000 to $17,000 in 2015.   Double blind trials show that stents have no effect on chest pain relief (Nov 2017)
  to keep the area propped open.  Christensen argues angioplasty should be part of a radically lower cost business which should
  US healthcare is ripe for disruption.  Christensen, Grossman and Hwang argue that technologies are emerging which will support low cost business models that will undermine the current network.  Applying complex adaptive system (CAS) theory to these arguments suggests that the current power hierarchy can effectively resist these progressive forces. 
  
  disrupt the solution business of the general hospital. 
• Angiotensin receptor blockers block hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  (angiotensin II) from causing the contraction of muscles surrounding blood vessels and so stop the blood vessels contracting, lowering blood pressure. 
  
• Anosognosia is unawareness of a major deficit, including paralysis. 
  
• Anterior insula is a rich club hub are areas of the brain which are highly connected to other club hubs: Ventral anterior insula, Dorsal anterior cingulate cortex, Posterior orbitofrontal cortex, Parahippocampal gyrus, Temporal pole. 
  within the insula cortex is part of the cerebral cortex folded deep within the lateral sulcus.  It includes: anterior, posterior insula; and is overlaid by the operculum.  It is assumed to participate in consciousness where it has been linked to emotion, salience & body homeostasis functions:
  
  • Perception,
    
  • Motor control: Hand-&-eye motor movement, Swallowing, Gastric motility, Speech articulation;
    
  • Self-awareness,
    
  • Inter-personal experiences: Disgust at smells, contamination & mutilation which generate visceral responses, that are projected to the amygdala; binding physical and moral aspects of purity (Macbeth effect)
    
  • Homeostatic regulation of the sympathetic network, parasympathetic network, and immune system.   
  .  It is anatomically subdivided by sulci into gyri.  It includes a direct projection from the: thalamus has all the main inputs to the cortex passing through it.  It is massively supplied with return innervations from the cortical regions it routes too.  It does not stand on the route of the main exits from the cortex.  The parafascicular nucleus of the rat thalamus contains relatively high levels of D5 dopamine receptors.  For human vision the primary system connects to the neocortex via a small part of the thalamus the LGN.  's ventral medial nucleus, central nucleus of the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  .  The anterior insula projects into the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  .  It includes spindle neurons are also termed von Economo neurons and are:
  • Found only in: Primates, Whales, Dolphins, Elephants;
  • Present in the: Insula, Anterior cingulate - focused on empathy; integrating and repurposing these basic facilities into high level capabilities such as moral disgust. 
    
  • First neurons destroyed by FTD. 
    
  . 
  
• Anti-Kickback Statute of the SSA is the social securities act of 1935 was part of the second New Deal.  It attempted to limit risks of old age, poverty and unemployment.  It is funded through payroll taxes via FICA and SECA into the social security trust funds.  Title IV of the original SSA created what became the AFDC.  The Social Security Administration controls the OASI and DI trust funds.  The funds are administered by the trustees.  The SSA was amended in 1965 to include:
  • Title V is Maternal and child health services. 
    
  • Title XVIII is Medicare.  
  criminally prohibits giving a kickback for a Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  or Medicaid is the state-federal program for the poor.  Originally part of Lyndon Johnson's 1965 Bill, eligibility and services vary by state.  Less than 10 percent of Medicaid recipients, those in long-term care including nursing homes where 64% are dependent on Medicaid, use one-third of all Medicaid spending which is a problem.  The ACA's Medicaid expansion program, made state optional by the SCOTUS decision, was initially taken up by fifty percent of states.  As of 2016 it covers 70 million Americans at a federal cost of $350 billion a year.  In 2017 it pays for 40% of new US births. 
  service referral links a doctors patient to an additional service as part of a treatment proposal.  The regulations are state based so the mechanism is geography dependent.  Referral services will be key to providers managing their revenue base.  
  .  
• Antibiotics are compounds which kill bacteria, molds, etc.  Sulfur dye stuffs were found to be effective antibiotics.  The first evolved antibiotic discovered was penicillin.  Antibiotics are central to modern health care supporting the processes of: Surgery, Wound management, Infection control works to prevent healthcare-associated infections.  It monitors & supports associated hospital processes: Anti-microbial surfaces, Barrier clothing, Cleaning, Disinfection, Hand washing: North shore; Patient access during epidemics, Sterilization; to contain cross infection.  The CDC provides support: Ebola process; and works closely with the primary biocontainment unit at Emory University Hospital. 
  ; which makes the development of antibiotic resistance results from plasmids and R factors: NDN1; which encode resistance properties for otherwise lethal antibiotics.  World leaders hope cooperation can preserve the power of last resort antibiotics: Carbapenems, Colistin (Oct 2016).  Worrying trends include: CRE (May 2016), C. diff. (May 2015), MDR & XDR TB; resulting in increased risk of sepsis and death.  The World Bank estimates full resistance would reduce the global economy in 2050 by between 1.1 and 3.8%. 
  worrying.  Antibiotics are:
• Economically is the study of trade between humans.  Traditional Economics is based on an equilibrium model of the economic system.  Traditional Economics includes: microeconomics, and macroeconomics.  Marx developed an alternative static approach.  Limitations of the equilibrium model have resulted in the development of: Keynes's dynamic General Theory of Employment Interest & Money, and Complexity Economics.  Since trading depends on human behavior, economics has developed behavioral models including: behavioral economics.   problematic to develop and sell. 
  
• Congress enacted GAIN is generating antibiotic incentives now act of 2012 which grants manufacturers an extended exclusive period to sell newly approved antibiotics.  It was an attempt by Congress to encourage pharmaceutical companies to invest in antibiotics, which would be likely to be held back from the market, as last resort solutions for antibiotic resistant infections.   to encourage development of new antibiotics.  But it has not developed any market-entry award scheme, which seems necessary to encourage new antibiotic R&D. 
  
• Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  has required hospitals and SNF is skilled nursing facility. 
  s to execute plans to ensure correct use of antibiotics & prevent the spread of drug-resistant infections.  
• C.D.C. is the HHS's center for disease control and prevention based in Atlanta Georgia.  
  is acting to stop the spread of resistant infections and reduce unnecessary use of antibiotics.  
  
• F.D.A. Food and Drug Administration. 
  has simplified approval standards.  It is working with industry to limit use of antibiotics in livestock. 
  
• BARDA is the biomedical advanced research and development authority, an HHS ASPR office responsible for procurement and development of vaccines, drugs, therapies and diagnostic tools for public health emergencies. 
  is promoting public-private partnerships to support promising research.
  
• Impacting the microbiome, the trillions of bacteria and viruses that live inside higher animals' guts, on their skin etc.  These bacteria and viruses seem to play a role in: immune responses, digesting food, making nutrients, controlling mental health and maintaining a healthy weight.  The signals from the gut microbiota are relayed by major nerve fibers: vagus; to the central nervous system.  The symbiotic relationship must be actively managed.  In the human gut: Barriers are setup: Mucus secretions form a physical constraint and provide sites for bacteriophages to anchor and attack pathogenic bacteria; Symbiont tailored nourishment: Plant-heavy food creates opportunities for fibre specialists like Bacteroides thetaiotaomicron; is provided, Selective binding sites are provided, Poisons are deployed against the unwelcome, and Temperature, acidity and oxygenation are managed.    High throughput sequencing allows the characterization of bacterial populations inside guts.  Beginning at birth, as they pass down the birth canal infants are supplied with a microbiome from their mothers.  If they are borne via cesarean they never receive some of the key bacteria from their mothers.  A variety of diseases may be caused by changes in the microbiome:
  • Eczema can be related to changes in the skin microbiome. 
    
  • Obesity can be induced by changes to the gut microbiome. 
    
  of the recipient.  Stool banking is a solution  (Sloan-Kettering stool banking).  
• Associated with obesity is a disorder where the brain is induced to require more eating, often because of limits to the number of fat cells available to report satiation (Jul 2016).  It is associated with: metabolic syndrome including inflammation, cancer (Aug 2016), high cholesterol, hypertension, type-2-diabetes and heart disease.  It is suspected that this is contributing to the increase in maternal deaths in the US (Sep 2016).  Obesity is a complex condition best viewed as representing many different diseases, which is affected by the: Amount of brown adipose tissue (Oct 2016), Asprosin signalling by white adipose tissue (Nov 2016), Genetic alleles including 25 which guarantee an obese outcome, side effects of some pharmaceuticals for: Psychiatric disorders, Diabetes, Seizure, Hypertension, Auto-immunity; Acute diseases: Hypothyroidism, Cushing's syndrome, Hypothalamus disorders; State of the gut microbiome.  Infections, but not antibiotics, appear associated with childhood obesity (Nov 2016). 
  , although evidence suggests childhood obesity relates to the infections not the antibiotic treatments (Nov 2016). 
  
• Monitored globally by W.H.O. is World Health Organization a United Nations organization. 
  
  
• Regulated in the US is the United States of America.   by the F.D.A. Food and Drug Administration. 
  who promote voluntary labeling by industry to discourage livestock fattening (Dec 2013).  
• Customer demands have more effect - Perdue shifts to no antibiotics in premier chickens (Aug 2015). 
  
• Antibiotic resistance results from plasmids and R factors provide bacteria with a way to transfer parts of their DNA complement with one another.  The effect is to ensure that useful mutations can become rapidly distributed within a population of bacteria.  : NDN1 is New Delhi metallo-beta-lactamase 1 plasmid which provides bacterial populations globally with total current antibiotic resistance. 
  ; which encode resistance properties for otherwise lethal antibiotics are compounds which kill bacteria, molds, etc.  Sulfur dye stuffs were found to be effective antibiotics.  The first evolved antibiotic discovered was penicillin.  Antibiotics are central to modern health care supporting the processes of: Surgery, Wound management, Infection control; which makes the development of antibiotic resistance worrying.  Antibiotics are:
  • Economically problematic to develop and sell. 
    
  • Congress enacted GAIN to encourage development of new antibiotics.  But it has not developed any market-entry award scheme, which seems necessary to encourage new antibiotic R&D. 
    
  • Medicare has required hospitals and SNFs to execute plans to ensure correct use of antibiotics & prevent the spread of drug-resistant infections.  
  • C.D.C. is acting to stop the spread of resistant infections and reduce unnecessary use of antibiotics.  
    
  • F.D.A. has simplified approval standards.  It is working with industry to limit use of antibiotics in livestock. 
    
  • BARDA is promoting public-private partnerships to support promising research.
    
  • Impacting the microbiome of the recipient.  Stool banking is a solution  (Sloan-Kettering stool banking).  
  • Associated with obesity, although evidence suggests childhood obesity relates to the infections not the antibiotic treatments (Nov 2016). 
    
  • Monitored globally by W.H.O.
    
  • Regulated in the US by the F.D.A. who promote voluntary labeling by industry to discourage livestock fattening (Dec 2013).  
  • Customer demands have more effect - Perdue shifts to no antibiotics in premier chickens (Aug 2015). 
    
  .  World leaders aims to develop plans and strategies which ensure effective coordination to improve the common good of the in-group.  John Adair developed a leadership methodology based on the three-circles model. 
  hope cooperation can preserve the power of last resort antibiotics: Carbapenems are a class of beta-lactam antibiotics with a broad spectrum of antibacterial activity.  Some bacteria (such as CRE) have developed resistance due to the development and r-factor distribution of carbapenemases.  This is a huge problem as carbapenems have been used as the last resort antibiotic.   , Colistin is an old antibiotic that is held in reserve in the US to treat especially dangerous infections (CREs) that are resistant to carbapenems.   (Oct 2016).  Worrying trends include: CRE is carbapenem-resistant Enterobacteriaceae.  When carbapenem fails to treat an infection the patient is in serious trouble.  The CDC estimated CRE accounts for around 9,300 infections and 610 deaths yearly in the US in 2010-15.  However the CDC also reports:
  
  • In July 2010 the state of Florida instigated procedures that reduced the number of patients with CRE from 60% to less than 10% at a problem LTCH.  The improvement was based on
  • Detecting and protecting - Screening, isolating, and grouping patients with CRE to prevent spread to other patients. 
    
  • Reviewing staff operations for 40 hours checking hand hygene, glove and gown use and other practices during care of patients. 
    
  • Iterative communications between the problem facility and local, state and federal public health workers.  
  (May 2016), C. diff. (May 2015), MDR is multidrug-resistant Tuberculosis (Vank's Disease).   It is difficult to treat.  Some of the medicines are intravenous, must be taken for two years (potentially just 9 months - Oct 2017) and can cause deafness, psychosis and kidney failure.  Patients must be hospitalized and their movements restricted to one or two corridors, for months until they stop coughing live bacteria. 
  & XDR is extensively drug-resistant tuberculosis.  It requires very toxic and costly drugs to treat.  Most patients die.   TB, consumption or otherwise TB, is mostly an airborn bacterial lung infection, but it can also infect the brain, kidneys and other parts of the body.  The only vaccine is still the BCG.  The deployment of antibiotics during the 1940s allowed effective treatment: Streptomycin.  Diagnostic tools for TB are insufficient.  And because TB grows slowly in walled off pockets in the lungs it takes many months of treatment for antibiotics to eradicate the infection.  TB benefits from compromised hosts and has benefited from HIV/AIDS.  TB is also leveraging the plasmids that now carry immunity to all current antibiotics.  In 2016 it is estimated to latently infect two billion people.  9.6 million worldwide became infected in 2014.  1.5 million people will die from TB in 2016.  Deaths from the disease have fallen drastically since 2000.  TB has been halted or reversed in 16 of the 22 countries: India (Sep 2016, Infection base estimate increased Oct 2016), Vietnam, Indonesia; that have the majority of cases.  But it is still the infectious disease causing the most deaths world-wide.  Nano scale drug delivery has the potential to push back on TB and is being actively researched (May 2016).   ; resulting in increased risk of sepsis is an infection triggered over-reaction by the immune system which causes general inflammation resulting in a cascade of problems: Blood clots, Leaky blood vessels; impeding blood flow to vital organs which can induce septic shock: Blood pressure drops, multiple organ failure, Heart damage and death.  For every hour without antibiotics the probability of death increases 8%.  Most cases start before people are hospitalized.  People over 65, infants under 1 year, people with chronic diseases such as diabetes, or weakened immune systems and healthy people with incorrectly treated infections are most likely to contract sepsis.  Most often the infections are of: lungs, urinary tract, skin, gut or intestines.  Typically such infections were the result of a previous visit to a clinic or hospital.  Symptoms of sepsis include: chills or fever, extreme pain or discomfort, clammy or sweaty skin, confusion or disorientation, shortness of breath and high heart rate.  Dr. Diane Craig noted that sepsis had become the leading cause of death among hospitalized patients.  Using patient matching on: age, symptoms, degree of illness; from the hospital system EHR, Craig identified the blood-lactate test as the key diagnostic that supported early, aggressive treatment of sepsis.  She argued that whenever a patient had two symptoms of significant infection a lactate test be used along with EGDT treatment for patients with lactate counts as low as 2.5 millimoles/liter.  This reduced sepsis mortality to 40% below the national average.  But only half the hospitals in the US followed Craig's recommendations.  Dr. Robert Pearl concludes this is because of the high risk of killing a patient with EGDT treatment, even though the protocol will reduce overall mortality by half.  Doctors don't want to be responsible for killing patients so they opt not to order the lactate test.  In 2017 sepsis is estimated to cost the US health care system more than $20 billion a year.  The C.D.C. is concerned (Sep 2016) with antibiotic resistance generating more sepsis. 
  and death.  The World Bank was setup as part of the Bretton Woods agreements, as the International Bank for Reconstruction and Development, to repair and reconstruct Europe after the Second World War and as the World Bank continues to provide reconstruction and development resources for projects in developing economies. It includes:
  • International Finance Corporation 
  estimates full resistance would reduce the global economy is the study of trade between humans.  Traditional Economics is based on an equilibrium model of the economic system.  Traditional Economics includes: microeconomics, and macroeconomics.  Marx developed an alternative static approach.  Limitations of the equilibrium model have resulted in the development of: Keynes's dynamic General Theory of Employment Interest & Money, and Complexity Economics.  Since trading depends on human behavior, economics has developed behavioral models including: behavioral economics.   in 2050 by between 1.1 and 3.8%. 
  
• Antibody is a y-shaped blood transported protein, a relatively long chain (polymer) of peptides.  Shorter chains of peptides are termed polypeptides.   generated by the adaptive immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  's plasma cells, B lymphocytes are a type of leukocyte.  They appear mainly in the lymphatic network.  Their are various types:
  • B cells which make antibodies that bind to pathogens, and activate the complement system.  When malignant these cells can produce multiple myeloma. 
    
  • Natural killer cells can kill body cells that do not display MHC class 1 molecules, or do display stress markers including MIC-A. 
    
  • T cells including CD4+ helper cells, Cytotoxic T cells, Gamma 5 T cells; 
    
  , to accurately identify and neutralize pathogens such as bacteria and viruses is a relatively small capsule containing genetic material which utilizes the cellular infrastructure of its target host to replicate its genetic material and operational proteins.  The relationship with the host is short term, relative to parasites, with the virus entering the host cell, leveraging the host infrastructure to replicate its self massively and then exiting the host cell by rupturing it. 
  that exhibit a matching antigen. 
  
• Anticipation compensates for the sluggishness of our consciousness.  Almost all sensory and motor areas contain temporal learning mechanisms that anticipate external events.  
• Antihypertensives are treatments for hypertension is high blood pressure.  It is directly associated with death rate due to pressure induced damage to the left ventricle and in general to cardiovascular diseases.  Treated with antihypertensives: Diuretics, Calcium channel blockers, Angiotensin receptor blockers or Beta blockers.   including: diuretics increase water excretion which results in reduced blood volume and pressure.  Many work by making the kidneys transport more sodium into the urine.  The sodium pulls water from the blood with it.  The reduced fluid level in the blood vessels reduces the pressure on the walls of the arteries.  , ACE inhibitors is angiotensin-converting-enzyme inhibitor.  They help relax blood vessels and are used to treat hypertension and CHF.  , calcium channel blockers make blood vessels expand.  They have four main effects:
  1. Reduce contraction of arteries by blocking calcium gates in vascular smooth muscle. 
     
  2. By blocking calcium gates in cardiac muscle they reduce the force of contraction of the heart. 
     
  3. By slowing the conduction of electrical flows within the heart they slow the heart beat. 
     
  4. By blocking the calcium signal on adrenal cortex cells, they directly reduce aldosterone production reducing blood pressure. 
     
  , beta blockers stop the action of beta-adrenergic signals and hence slow the heart.   and angiotensin antagonists block hormone signals (angiotensin II) from causing the contraction of muscles surrounding blood vessels and so stop the blood vessels contracting, lowering blood pressure. 
  . 
  
• Antisocial punishment is where someone is punished for being overly generous.  People from Greece and Oman, where there is low social capital is the collective quantity of resources such as trust, reciprocity & cooperation according to Sapolsky.  , were particularly likely to do this. 
  
• Anxiety is manifested in the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  mediating inhibition of dopamine is a synaptic signal supporting generalized goal-directed behavior & anticipation of reward.  Its significance is that the receptors that detect the signal are of the slow acting type and are used to alter (modulate) the response of fast acting dopaminergic neural circuits in which the receptors are deployed (LTP).  The signal detects significant changes including predictions of models and actual results which differ unexpectedly.  The dopamine network architecture is designed to signal the possibility of any type of reward: Norm violation punishment, Winning a lottery, & Misfortune of an envied competitor.  Dopamine signalling:
  
  • Rescales continuously to accommodate the range of intensity offered by different stimuli.  So dopamine's responses to any reward habituate.  GABA is released by some tegmental neurons to induce habituation. 
    
  • Reflects the anticipation of reward.  It supports establishment of a relationship between a signal, working for a reward and obtaining the reward, but subsequently dopamine is mainly released encouraging the work, right after the signal supporting anticipation of the reward.  Anticipation requires learning and is reflected in hippocampus activity.  That explains context dependent cravings.  And the learning architecture means reliable cues become rewarding.  The accumbens supports willpower.  And dopamine
    
  • Promotes goal-oriented behavior needed to obtain & likely to achieve the reward - through the dopamine projections to the prefrontal cortex.  That makes dopamine central to:
    
  • Motivation.  This binding fails in depression - due to stress and in anxiety - due to signals from the amygdala.  
  • The prefrontal cortex's mesocortically stimulated support for willpower to act to delay rewards.  To sustain work for delayed rewards additional dopamine is released based on the length of the delay and the rewards uncertainty (modelled in the dorsolateral prefrontal cortex - which promotes the long term and the ventromedial prefrontal cortex - which promotes the short term) and the anticipated size of the reward (modelled in the accumbens).  Impulsiveness in ADHD is reflected in abnormal dopamine processing.  Addictive drugs bias the dopamine network towards impulsiveness.  
  • Is lowered by certain gene variants which induce: less dopamine in the synapse, fewer receptors, lower responsiveness of receptors; associated with (as tiny effects in hugely varying social scenarios): sensation seeking, risk taking, attentional problems, extroversion; where:
    
  • The receptor D4's gene shows high variability.  The D47R form is relatively unresponsive to dopamine.  
  • Dopamine is degraded by COMT.  The COMT gene includes a variant which is highly efficient reducing dopamine signalling but with complicating gene/environment interactions.  
  • Dopamine is removed from the synapse by a reuptake transporter DAT. 
    
  rewards.  Major anxiety results in elevated glucocorticoids are corticosteroids which bind the glucocorticoid receptor.  They decrease excitability of prefrontal cortical neurons.  They have adverse effects in fetal/infant development having organizational effects on fetal brain construction and decreasing levels of: growth factors, neurons, synapses; resulting in an adult brain that is more sensitive to environmental triggers of depression and anxiety.  Glucocorticoids affect gene control structures and induce epi-genetic changes.  They have been found associated with high sodium chloride consumption (May 2017). 
  and reduces hippocampal is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
  dendrite & spine density.  Some estrogen is a generic term for a number of related steroid hormones each of which works differently.  Estrogen:
  • Contributes to maternal aggression but it can reduce aggression and enhance empathy, depending on brain state.  There are two different estrogen receptor types which mediate these conflicting effects.  The levels of each type of receptor is independently regulated.  Different receptor variants are associated with:
  • Higher rates of anxiety among women
  • Higher rates of antisocial behavior and conduct disorder in men
  receptor, in biological cells these proteins are able to span the cell membrane and present an active site which is tailored to interact with a specific signal.  When the receptor pairs with its signal, its overall shape changes resulting in changes in the part internal to the cell which can be relayed by the cells signalling infrastructure.  In neuron synapses one type of receptor (fast) is associated with an ion channel.  The other (slow) is associated with a signalling enzyme chain and modulates the neuron's response. 
  variants are associated with anxiety in women. 
  
• Aperture problem is the ambiguity introduced by sampling through a narrow peephole.  It is impossible to resolve direction of motion of a item sampled through the peephole for example. 
  
• Aplysia, a giant Californian marine snail has a limited neural network and large neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  .  Eric Kandel used it as an experimental system for studying neurons and was able to explain how long term memory is recorded by the Aplysia neurons. 
  
• APM is alternative payment model, Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  's risk based payments to organizations set up as ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness, improving the provision of primary care to a large group of Medicare patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV business.  The ACA regulates qualification to be a Medicare ACO.  Individual organizations within a Medicare shared savings ACO continue to submit their own claims and are paid by Medicare for FFS.  But the ACO is eligible for shared savings.  Within the shared savings program the CMS innovation center has setup advanced payment ACOs.  As an alternative to shared savings, in a Pioneer ACO, over time 50% of the FFS payments flow directly to the ACO as a bundled payment.  CMS has established quality measures for ACOs for Medicare.  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination. 
  
  • CMS initiated its Physician Group Practice Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
    
  • CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
  • CMS has developed APMs which include ACOs, and advanced APMs where the ACOs must be risk bearing. 
    
  • CMMI accepts providers' proposals to test various payment systems including shared savings and partial capitation.  
  • Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
  s.  It includes track 1 ACOs which are not risk bearing.  APMs have to report various measures to CMS is the centers for Medicare and Medicaid services.  .  
• APOE is Apolipoprotein are lipoproteins without the lipid bound.  They allow lipids to form into water-soluble complexes and can thus act as lipid transfer carriers, and are also found operating as enzyme cofactors and receptor ligands.   E which is essential for normal catabolism of triglyceride-rich lipoproteins.  It is used by the liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
  , macrophages, and central nervous system where astrocytes use it to transport cholesterol to neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  via APOE receptors. 
  
• ApoE4 is a gene variant which produces the E4 variant of APOE is Apolipoprotein E which is essential for normal catabolism of triglyceride-rich lipoproteins.  It is used by the liver, macrophages, and central nervous system where astrocytes use it to transport cholesterol to neurons via APOE receptors. 
  .  It is a risk-factor for late-onset sporadic Alzheimer's disease is a dementia which correlates with deposition of amyloid plaques in the neurons.  As of 2015 there are 5 million Alzheimer's patients in the USA.  It was originally defined as starting in middle age which is rare, so it was a rare dementia.  But in 1980s it was redefined as any dementia without another known cause. Early indications include mood and behavioral changes (MBI) and memory and thinking problems (MCI).  Variants include: late-onset sporadic; with risk factors - ApoE4, presenilin, androgen deprivation therapy (Dec 2015).  There are multiple theories of the mechanism of Alzheimer's during aging: Allen Roses argues that it is due to gene alleles that limit the capacity of mitochondria to support neuron operation; It is initiated by an increasingly leaky blood-brain barrier and the innate immune response to subsequent infections (May 2016).  The Alzheimer's pathway follows:
  • Plaques form and set off the formation of tangled thread-like tau protein.
  • Solanezumab aimed to inhibit plaque formation but clinical trials failed (Nov 2016).  
  • BACE inhibitors block an enzyme needed to form amyloid. 
    
  • The Tau tangles kill nerve cells.  LMTX is a drug treatment targeted at these tangles. 
    
  • The brain becomes inflamed resulting in the killing of many more nerve cells. 
    
  .  Being homozygote for E4 does not imply getting Alzheimer's but does increase the risk 20 fold.  ApoE2 may reduce the risk of Alzheimer's.  It appears that ApoE4 differentially affects women.  Apoe4 is known to be broken down into fragments which impare mitochondrial operation.  It also promotes amyloid plaque buildup.  Therapies are being developed based on small molecules which reshape ApoE4 to be more like ApoE3 reducing the breakdown.   
  
• Apolipoproteins are lipoproteins without the lipid bound.  They allow lipids to form into water-soluble complexes and can thus act as lipid transfer carriers, and are also found operating as enzyme cofactors and receptor ligands.  
• Apoptosis, programmed cell death is a signal, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  initiated DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  controlled process which results in eukaryotic, a relatively large multi-component cell type from which yeast and multi-celled plants and animals, including humans, is constructed.  It contains modules including a nucleus and production functions such as mitochondria. 
  cells self-destructing.  
• Appreciation of natural beauty is an emotion are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   which derives from the benefit to hunter gatherers of recognizing and seeking out the African savanna is the environment where hunter-gatherers primarily evolved.  Its grassland supported large herbivores that could be hunted.  Clumps of trees & rocks supported places to hide from large carnivores.  Streams and paths add to the signals enabling orientation. 
  setting in which humans evolved. 
  
• Arden Syntax is an HL7 standard.  It is a grammar for representing medical conditions and recommendations.  
• Area MT is the middle temporal motion area MT (V5 is visual cortex area 5 also called area MT.  ) located in the occipital lobe of the cerebral cortex includes the primary visual cortex area V1.  It performs early stages of visual analysis supporting recognition of shapes, colors and objects.  .  It contains many neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  detecting motion.  Each neuron suffers from aperture problems is the ambiguity introduced by sampling through a narrow peephole.  It is impossible to resolve direction of motion of a item sampled through the peephole for example. 
  but consciousness resolves the ambiguity with a most likely current Bayesian is an iterative form of statistics invented by Thomas Bayes.  It uses a 'prior' statistic to represent the prior situation and then performs a calculation that integrates the probability of new events occurring into a 'posterior' probability.  This posterior becomes the prior for the next iteration with the application of the Bayesian identity xpost = xprior*y/(xprior*y + z(1-xprior)).  The magic in Bayesian statistics is in accurately generating the prior xprior and the current event probabilities y and z.  R. A. Fischer was so skeptical of the legitimacy of the prior that he advocated an alternative statistical framework and experimental process.   sampling.  The resolution takes time.  Neuronal recordings show the inference may take a tenth of a second.  In the meantime MT neurons see only local motion.  Subsequently they encode the global direction.  Subjective consciousness sees only the end result.  The global resolution requires consciousness vanishing under anesthesia is the temporary removal of sensation.  It can be local, regional or general. 
  .  Consciousness enables the iterative exchange of modeling results resulting in eventual agreement.  
  
• Arms race, in a war where both sides use the strategy of development and use of advanced weapon systems to gain an advantage, each advance induces the other side to respond with its own
  This page introduces a series of asymmetries which encourage different strategic approaches.   
  The differences found in business, sexual selection, gamete structure, as well as in chess encourage escalations in the interactions. 
  And yet the systems including these asymmetries can be quite stable. 
  
  asymmetric advances.  Neither side will necessarily gain the upper hand in which case the weapon systems themselves advance rapidly with little direct benefit for the combatants. 
  
• Aromatase inhibitors limit the synthesis of estrogen by aromatase.  Breast is a variety of different cancerous conditions of the breast tissue.  World wide it is the leading type of cancer in women and is 100 times more common in women than men.  The varieties include: Hormone sensitive tumors that test negative for her2 (the most common type affecting three quarters of breast cancers in the US, BRCA1/2 positive, ductal carcinomas including DCIS, lobular carinomas including LCIS.  Receptor presence on the cancer cells is used as a classification: Her2+/-, estrogen (ER)+/-, progesterone (PR)+/-.  Metastasis classes the cancer as stage 4.  Genetic risk factors include: BRCA, p53, PTEN, STK11, CHEK2, ATM, GATA3, BRIP1 and PALB2.  Treatments include: Tamoxifen, Raloxifene; where worrying racial disparities have been found (Dec 2013). 
  
  and ovarian cancer is a relatively uncommon disease but is often fatal.  It has been associated with use of talcum powder (May 2016).  s grow more stimulated by estrogen. 
  
• ARRA is the American Recovery and Reinvestment Act of 2009.  It included health care provisions:
• COBRA payments
• Funds to help states with Medicaid is the state-federal program for the poor.  Originally part of Lyndon Johnson's 1965 Bill, eligibility and services vary by state.  Less than 10 percent of Medicaid recipients, those in long-term care including nursing homes where 64% are dependent on Medicaid, use one-third of all Medicaid spending which is a problem.  The ACA's Medicaid expansion program, made state optional by the SCOTUS decision, was initially taken up by fifty percent of states.  As of 2016 it covers 70 million Americans at a federal cost of $350 billion a year.  In 2017 it pays for 40% of new US births. 
  . 
  
• $20 billion to modernize health care IT systems.  
  
• $10 billion for health care research
• ART is an ARV is antiretroviral treatments for H.I.V. infection, such as abacavir. 
  therapy for H.I.V is human immunodeficiency virus, an RNA retrovirus which causes AIDS.  It infects T-lymphocytes destroying the host's immune system. 
  .  ART is a cocktail of drugs, such as the three in HAART is highly active ARV therapy using a combination of at least three drugs that supress HIV replication. 
  , which prevents the virus from replicating leaving it dormant so AIDS is acquired auto-immune deficiency syndrome, a pandemic disease caused by the HIV.  It also amplifies the threat of tuberculosis.   Initially deadly, infecting and destroying the T-lymphocytes of the immune system, it can now be treated with HAART to become a chronic disease.  And with an understanding of HIV's mode of entry into the T-cells, through its binding to CCR5 and CD4 encoded transmembrane proteins, AIDS may be susceptible to treatment with recombinant DNA to alter the CCR5 binding site, or with drugs that bind to the CCR5 cell surface protein preventing binding by the virus.  Future optimization of drug delivery may leverage nanoscale research (May 2016).   does not develop. 
  
• ARV is antiretroviral treatments for H.I.V. is human immunodeficiency virus, an RNA retrovirus which causes AIDS.  It infects T-lymphocytes destroying the host's immune system. 
  infection, such as abacavir is a nucleoside reverse transcriptase inhibitor, an ARV medication, branded as Ziagen, which is used in the prevention and constraint of AIDS.  It is a WHO essential medicine.  Its use is problematic in about 6% of the patient base.  Pharmacogenomics allows these patients to be identified and treated with an alternative ARV. 
  . 
  
• ASC is either:
  
• An ambulatory surgery center providing same day surgical care, or
  
• The accredited standards committee responsible for standard X.12. 
  
• ASC X12N is the insurance (N) subcommittee of the X12 EDI and XML ASC is either:
  
  • An ambulatory surgery center providing same day surgical care, or
    
  • The accredited standards committee responsible for standard X.12. 
    
  accredited by ANSI. 
  
• ASCA is the Administrative Simplification Compliance Act of 2002.  Public Law 107-105 implemented as regulation 42 CFR 424.32.  It alters the SSA is the social securities act of 1935 was part of the second New Deal.  It attempted to limit risks of old age, poverty and unemployment.  It is funded through payroll taxes via FICA and SECA into the social security trust funds.  Title IV of the original SSA created what became the AFDC.  The Social Security Administration controls the OASI and DI trust funds.  The funds are administered by the trustees.  The SSA was amended in 1965 to include:
  • Title V is Maternal and child health services. 
    
  • Title XVIII is Medicare.  
  to make electronic claims submission a mandatory requirement for some classes of health care providers, health plans and health care clearing houses.  
• ASD is autism is a major hereditary mental disorder that starts before age three.  Autistics do not attribute minds to other people.  They almost never pretend.  They can't explain the difference between an instance of an object and a memory of it.  Autism occurs in every country and social class.  It lasts a lifetime.  It has genetic and neurological causes.  The genes: SHANK3, CDH10; are involved but account for a very small percentage of the risk.  Facial gaze studies indicate a high genetic influence and an opportunity to identify more genes associated with autism (Jul 2017).  ASD is associated with a reduced fusiform face area response.  Tests [in development] for autism include: SynapDx's blood test. 
  spectrum disorder.  People who suffer from ASD show a reduced fusiform is a region of the brain which supports advanced mechanisms of shape recognition and implements the early stages of reading.  Subliminal priming with words did not depend on the shape of the word.  The fusiform gyrus was able to process the abstract identity of a word without caring if it was upper or lower case.   While high up in the cortex it can operate below the level of conscious experience.  It contributes to social emotions with:
  
  • Its face area being more activated by faces with in-group skin color.  
  • It activating when shown pictures of cars in automobile aficionados. 
    
  • It activating when shown pictures of birds in birdwatchers; since it really recognizes examples of items from an individual's emotionally salient categories. 
    
  response to faces.  ASD is linked to gene variants affecting oxytocin is a peptide hormone which makes humans more prosocial to and socially competent in their in-group and more antisocial to everyone else.  The effects are contingent; changing during stress and in the presence of a threatening outgroup.  Oxytocin makes people look at eyes longer, encouraging improved accuracy at perceiving emotions.  It enhances activity in the TPJ supporting modeling of other people's thinking.  Dogs and their owners secrete oxytocin increasing the amount of eye contact between them.  It is associated with pair bonding.  It is central to female mammals wanting to nurse, nursing, and remembering their child.  Its effects are context dependent and so is the regulation of the genes that control oxytocin.  Variants of a gene CD38 which facilitates oxytocin secretion from neurons are associated with differing levels of activation of the fusiform face area when looking at faces.  Sapolsky describes an oxytocin receptor gene variant that is associated with children showing: Extreme aggression, A callous unemotional style; foreshadowing adult psychopathy.  And another receptor gene variant which is associated with childhood social disconnection and unstable adult relationships.  Gene/environment interactions complicate the interpretation of the presence of particular gene variants.  Hypothalamic neurons send projections to: ventral tegmentum which also becomes more receptive during child birth, nucleus accumbens, hippocampus, amygdala where it inhibits the central amygdala suppressing fear & anxiety consistently in men while still allowing women to respond to threats to their infants, frontal cortex, olfactory network where it helps new rat mums to learn the smell of their offspring; where oxytocin prepares the brain for in-group bonding, out-grouping, birth and maternal behavior.  Outside the brain hypothalamic neurons in females send oxytocin to the posterior pituitary where it enters the blood stream stimulating uterine contraction during labor & supporting milk production for weaning.  Disorders associated with oxytocin abnormalities include ASD. 
  and vasopressin developed by duplication and subsequent mutation of the vasotocin gene, along with oxytocin, during the initial formation of mammals.   It acts as a hormone regulating water retention in the kidneys.  It supports paternal behavior stimulated by a female giving birth.  Sex releases vasopressin in the nucleus accumbens of male prairie voles.  And prairie voles have more receptors in the accumbens than other voles supporting their pair bonding.  This situation is similar in bonobos relative to chimps where it encourages social bonding - but not monogamy.  Vasopressin is made in hypothalamic neurons which project to the posterior pituitary for release as a hormone.  It is also a neuropeptide transmitting from hypothalamic projections to the ventral tegmentum, nucleus accumbens, hippocampus, amygdala, and frontal cortex.  And it is made & secreted in other areas of the brain.  Vasopressin enhances aggression in paternal prairie vole males.  But the aggression is then maintained by social learning. 
  , to nongenetic mechanisms that silence the oxytocin receptor gene and to lower levels of the receptor, in biological cells these proteins are able to span the cell membrane and present an active site which is tailored to interact with a specific signal.  When the receptor pairs with its signal, its overall shape changes resulting in changes in the part internal to the cell which can be relayed by the cells signalling infrastructure.  In neuron synapses one type of receptor (fast) is associated with an ion channel.  The other (slow) is associated with a signalling enzyme chain and modulates the neuron's response. 
  itself. 
  
• Asexual reproduction, uses the current germ-line, a master copy of the schematic structures is maintained for reproduction of offspring.  There will also be somatic copies which are modified by the operational agents so that they can represent their current state.   DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  , without any sexual sharing and recombination process enforces the mixing of current germ-line DNA of a male and a female organism, with a recombination process, to ensure the generation of new schematic recipes and phenotypes in their shared offspring.  Matt Ridley argues that the cost of sexual reproduction is justified by the protection from parasites that long-lived organisms gain. 
  , to generate new clones of the original
  This page reviews the implications of reproduction initially generating a single child cell.  The mechanism and resulting strategic options are discussed. 
  
  organism.  
• ASHG is the American Society of Human Genetics. 
  
• Aspirin (acetylsalicylic acid) is a pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Pain is the main reason people visit the ED in the US.  , fever and inflammation medicine.  It is a platelet aggregation inhibitor block the formation of clots and inhibit thrombosis.  Clots are usually initiated by the aggregation of platelets.  Clots can be a risk factor in heart attack.  The inhibitors include: Low dose aspirin, Clopidogrel;
  .  While its NNT is number needed to treat.  Austin Frakt and Aaron Carroll explain in the NYT Upshot that it is a number that describes how many people must be treated for one to gain a benefit.  For aspirin protection from heart attack it is about 2000.  That means 2000 people taking aspirin for two years will result in 1 person not having a heart attack, while 3.6 will have a heart attack anyway, 1995.4 will never have heart attacks any way.  But we don't know who the one person is and aspirin are cheap and don't have many side effects.  The NNT for catching influenza is between 37 and 77.  Since millions can catch flu, and thousands of those die the payoff of flu vaccination is huge. 
  is 2000 for cardiovascular disease refers to:
  
  • Conditions where narrowed and blocked blood vessels result in angina, hypertension, CHD and heart attacks and hemorrhagic/ischemic strokes.  Mutations of the gene PCSK9 have been implicated in cardiovascular disease.  Rare families with dominant inheritence of the mutations have an overactive protein, very high levels of blood cholesterol and cardiac disease. Other rare PCSK9 mutations result in an 88% reduced risk from heart disease.  Inflammation is associated with cardiovascular disease (Aug 2017). 
    
  prophylaxis, it is so cheap that this strategy is still important.  It has been found beneficial in limiting esophageal cancer is a rare cancer (less than 200,000 cases per year in the US) that typically starts in the cells that line the esophagus: flat cell squamous cell carcinoma, and mucus secreting cell adenocarcinoma.  It is associated with: Failure of TAD borders,  Obesity (adenocarcinoma Aug 2016), Alcohol consumption and smoking (Jul 2016).  It appears to be inhibited by exercise (May 2016), helicobacter pylori and aspirin (ACS's Eric Jacobs argues Sep 2015). 
  . 
  
• Asprosin is a protein based hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  produced in white adipose tissue that signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  the brain and liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
  to release glucose into the blood stream.  It is encoded by the FBN1 is a gene which encodes fibrillin and in white adipose tissue the hormone asprosin. 
  gene.  cAMP, a nucleotide base is the side chain purine (A or G) or pyrimidine (T or C).  A is a natural pair for T.  G pairs naturally with C.  These bases have multiple uses in cells including energy transfer, second messenger signalling as well as genetic data storage, transcription and translation.  Deacon argues that the multiple uses are significant to the emergence of evolution. 
  is the second messenger in the signalling network. 
  
• Assertion is a hypothesis which can be tested and found to be true or false.  In the adaptive web framework's (AWF)
  This page describes the Adaptive Web framework (AWF) test system and the agent programming framework (Smiley) that supports its operation. 
  Example test system statements are included.  To begin a test a test statement is loaded into Smiley while Smiley executes on the Perl interpreter. 
  Part of Smiley's Perl code focused on setting up the infrastructure is included bellow. 
  The setup includes:
  

  • Loading the 'Meta file' specification,
    
  • Initializing the Slipnet, and Workspaces and loading them
    
  • So that the Coderack can be called. 

  The Coderack, which is the focus of a separate page of the Perl frame then schedules and runs the codelets that are invoked by the test statement structures. 
  
  Smiley assertion statements are used to define the test that will be applied by the application's codelets.  The statements must include
  Plans emerge in complex adaptive systems (CAS) to provide the instructions that agents use to perform actions.  The component architecture and structure of the plans is reviewed. 
  
  schematic strings which can
  This page describes the adaptive web framework (AWF) Smiley agent progamming infrastructure's codelet based Copycat grouping operation. 
  The requirements needed for a group to complete are described. 
  The association of group completion with a Slipnet defined operon is described.  Either actions or signals result from the association. 
  How a generated signal is transported to the nucleus of the cell and matched with an operon is described. 
  A match with an operon can result in deployment of a schematic string to the original Workspace.  But eventually the deployed string will be destroyed. 
  Smiley infrastructure amplification of the group completion operation is introduced.  This includes facilities to inhibit crowding out of offspring. 
  A test file awfart04 is included. 
  The group codelet and supporting functions are included. 
  
  group complete and become associated with codelets.  Smileys own codelets:
  This page describes the Copycat Coderack. 
  The details of the codelet architecture are described. 
  The specialized use of the Coderack by the adaptive web framework's (AWF) Smiley is discussed. 
  The codelet scheduling mechanism is discussed. 
  A variety of Smiley extensions to the Coderack are reviewed. 
  The Coderack infrastructure functions are included. 
  
  Coderack generated
  This page looks at how Smiley processes the statement, such as a test request, to ensure that each part of the statement is composed of groups. 
  Smiley does this through the operation of a part codelet which indirectly sponsors the modeling of the parts of the statement. 
  The modeling itself is performed by model codelets. 
  The part codelet synchronizes with the completion of the modeling. 
  The part evaluator's signal along with the associated operons and subgroup schematic sequences are included. 
  The group models' Slipnet associations are included. 
  The codelets and supporting functions are included. 
  
  part and
  This page looks at how Smiley processes the statement, such as a test request, to ensure that the statement contains all required parts. 
  Smiley does this through the operation of a statement codelet which indirectly sponsors the modeling of the whole statement. 
  The modeling itself is performed by model codelets. 
  The group models' Slipnet associations are included. 
  The codelets and supporting functions are included. 
  
  statement enforces the syntax of the assertion.  The specific form of the statements is defined in the application's Meta file is loaded by the adaptive web framework's (AWF) Smiley.  It defines the application system's basic rules, its keywords and their properties and the form of the assertion or implementation statement the application uses.  .  Statement codelets also support the operation of the application's
  Walter Shewhart's iterative development process is found in many complex adaptive systems (CAS).  The mechanism is reviewed and its value in coping with random events is explained. 
  
  Shewhart cycle. 
  
• Assisted living is an alternative to parents joining their children's nuclear family or entering a SNF is skilled nursing facility. 
  , or Greenhouse Nursinghome Greenhouse nursing homes offer personal service and private rooms.  This reduces the opportunities for cross infections reducing cost of errors. 
  
  • Most nursing homes are designed like hospitals.  They are designed around the nursing station.  They are institutions and aim to limit risk and serve the patient's childrens' interest in the safety of their parents.  But they actually undermine will to live. 
    
  • Greenhouses are smaller and designed around the kitchen.  They allow knives.  Patients keep their own shoes - even though they may increase the likelihood of falling.  Patients bring in their own furniture.  Greenhouse nursing home developers had to educate the regulators and health officials about the goal of improved purpose of life rather than patients being destroyed by 'safety' (really boredom, loneliness and helplessness).  
  .  Atul Gawande's
  Gawande uses his personal experience, analytic skills and lots of stories of innovators to demonstrate better ways of coping with aging and death.  He introduces the lack of focus on aging and death in traditional medicine.  And goes on to show how technology has amplified this stress point.  He illustrates the traditional possibility of the independent self, living fully while aging with the support of the extended family.  Central planning responded to the technological and societal changes with poorly designed infrastructure and funding.  But Gawande then contrasts the power of bottom up innovations created by experts responding to their own family situations and belief systems. 
  
  Gawande then explores in depth the challenges that unfold currently as we age and become infirm.  He notes that the world is following the US path.  As such it will have to understand the dilemma of integrating medical treatment and hospice strategies.  He notes that all parties involved need courage to cope. 
  
  He proposes medicine must aim to assure well being.  At that point all doctors will practice palliative care. 
  
  Complex adaptive system (CAS) models of agency, death, evolution, cooperation and adaptations to new technologies are discussed. 
  
  
  Being Mortal describes the situation.  Federal Medicaid is the state-federal program for the poor.  Originally part of Lyndon Johnson's 1965 Bill, eligibility and services vary by state.  Less than 10 percent of Medicaid recipients, those in long-term care including nursing homes where 64% are dependent on Medicaid, use one-third of all Medicaid spending which is a problem.  The ACA's Medicaid expansion program, made state optional by the SCOTUS decision, was initially taken up by fifty percent of states.  As of 2016 it covers 70 million Americans at a federal cost of $350 billion a year.  In 2017 it pays for 40% of new US births. 
  does not directly cover assisted living.  State Medicaid adds coverage through a federal waiver.  Congressional legislation covering assisted living is limited.  Assisted living providers are represented by the National Center for Assisted Living. 
  
• Asthma is inflammation of the airways resulting in their narrowing, swelling and generating additional mucus is used to cover tissues that are exposed.  It is made from mucins.  Mucous membranes may secrete mucus to generate a robust barrier. 
  which inhibits breathing.  Its prevalence doubled in the US between 1980 and 2000.  Diagnosis: Propeller Health; Treatments include: Xolair;
  
• This page introduces a series of asymmetries which encourage different strategic approaches.   
  The differences found in business, sexual selection, gamete structure, as well as in chess encourage escalations in the interactions. 
  And yet the systems including these asymmetries can be quite stable. 
  
  Asymmetry.
  
• Atezolizumab is a MAB as a terminator in medication names indicates the drug is a monoclonal antibody biologic. 
  of lgG1 targeting the apoptosis, programmed cell death is a signal initiated DNA controlled process which results in eukaryotic cells self-destructing.   ligand PD-L1.  It is marketed as Tecentriq.  It blocks PD-L1's interaction with PD-1 is programmed cell death protein 1 (CD279) is encoded by the PDCD1 gene.  It is a cell surface receptor that belongs to the immunoglobulin superfamily. It is expressed on T-cells and pro-B cells.  It acts as an immune checkpoint preventing the activation of T-cells to help self-tolerance and reduce autoimmunity.  When it fails people can suffer from: Lupus, Crohn's disease, Rheumatoid arthritis.  PD-1 inhibitor drugs activate the immune system to attack tumors.   PD-1 inhibitors are being approved for Melanoma and squamous-cell form of lung cancer. 
  and B7.1.  PD-L1 expression reduces the activation of cytotoxic T-cells (immune checkpoint inhibition release the immune system's checkpoints on attacking host cells: by 1) stopping T-cell division and 2) reducing their life spans.  They are used in immuno-oncology where, in 2016: They are approved for treatment of: Advanced melanoma, HL, lung, kidney, liver cancer; They have a general success rate of 20 - 40% and higher for melanoma.   Checkpoint inhibitors work best for tumors that have many mutations: melanomas, lung and bladder cancers.  They are enhanced by adjunct treatments that kill tumor cells generating debris to stimulate the immune system.  The drugs include: ipilimumab, nivolumab, pembrolizumab, atezolizumab;  They are costly and often have high copayments.  They cause auto-immune side effects including inflammation, rheumatoid arthritis and damage to glands: Adrenal, Thyroid, Pituitary.  Powerful steroids such as prednisone can help reduce the inflammation.  Damaged glands require sustained hormone treatment.  Checkpoint inhibitor research is funded by the CRI.  ). 
  
• Atherosclerosis is the thickening of an artery wall due to invasion and accumulation of leukocytes are produced by hematopoietic stem cells in the bone marrow and are a major part of the adaptive immune system.  Five types have been identified:
  1. Basophils,
     
  2. Eosinophils,
     
  3. Lymphocytes,
     
  4. Monocytes,
     
  5. Neutrophyls.  
  . 
  
• ATM is automated teller machine, supporting consumers by reducing the time for banking teller transactions and extending access to 24/7.  
  
• Atopic dermatitis, is also called eczema is atopic dermatitis. 
  is a long lasting inflammation of the skin.  It can be successfully treated with dupilumab is a monoclonal antibody which blocks two immune system pathways: interleukin 4 and interleukin 13; that are over produced in atopic dermatitis, by binding to the alpha subunit of the interleukin-4 receptor.  It was developed by Regeneron and marketed as Dupixent.  .  
• ATR is Americans for Tax Reform, Grover Norquist's powerful conservative-Republican advocacy group.  Norquist created the:
  
• Taxpayer Protection Pledge in 1986.  Republican Newt Gingrich and GOPAC is a GOP training 527 organization, founded by Pierre du Pont, Governor of Delaware in 1979.  It was leveraged by radical Republican Newt Gingrich to educate a new set of GOP activists.   ensured it became a mandatory step for Republicans seeking election.  
• Wednesday morning stategy meetings in 1993, to undermine the Clinton administration and weaken the Democrat's hold on power.  
• Atrial fibrillation is an irregular heart rate associated with poor blood flow.  It:
  
• Can lead to blood clots or coagulation is formation of a clot:
  • Platlets become activated, adhere and aggregate supported by
  • Fibrin polymerization, deposition and maturation.  
  , stroke is when brain cells are deprived of oxygen and begin to die.  750,000 patients a year suffer strokes in the US.  85% of those strokes are caused by clots.  There are two structural types: Ischemic and hemorrhagic.  Thrombectomy has been found to be a highly effective treatment for some stroke situations (Jan 2018). 
  , CHF is congestive heart failure which occurs when the heart is unable to generate enough blood flow to meet the body's demands.  There are two main types: failure due to left ventricular dysfunction and abnormal diastolic function increasing the stiffness of the left ventricle and decreasing its relaxation.  Treatments include: digoxin; , dementia is a classification of memory impairment, constrained feelings and enfeebled or extinct intellect.  The most common form for people under 60 is FTD.  Dementia has multiple causes including: vascular disease (inducing VCI) including strokes, head trauma, syphilis and mercury poisoning for treating syphilis, alcoholism, B12 deficiency (Sep 2016), privation, Androgen deprivation therapy (Oct 2016), stress, Parkinson's disease and prion infections such as Alzheimer's disease, CJD and kuru.  The condition is typically chronic and treatment long term (Laguna Honda ward) and is predicted by Stanley Prusiner to become a major burden on the health system.  It appears to develop faster in women than men.   and other complications.  
• Fibrillations allow blood to pool in the heart chambers and form small clots which can then lodge in small arteries and block blood flow. 
  
• Has become much more common being induced by endemic diseases: hypertension is high blood pressure.  It is directly associated with death rate due to pressure induced damage to the left ventricle and in general to cardiovascular diseases.  Treated with antihypertensives: Diuretics, Calcium channel blockers, Angiotensin receptor blockers or Beta blockers.  , obesity is a disorder where the brain is induced to require more eating, often because of limits to the number of fat cells available to report satiation (Jul 2016).  It is associated with: metabolic syndrome including inflammation, cancer (Aug 2016), high cholesterol, hypertension, type-2-diabetes and heart disease.  It is suspected that this is contributing to the increase in maternal deaths in the US (Sep 2016).  Obesity is a complex condition best viewed as representing many different diseases, which is affected by the: Amount of brown adipose tissue (Oct 2016), Asprosin signalling by white adipose tissue (Nov 2016), Genetic alleles including 25 which guarantee an obese outcome, side effects of some pharmaceuticals for: Psychiatric disorders, Diabetes, Seizure, Hypertension, Auto-immunity; Acute diseases: Hypothyroidism, Cushing's syndrome, Hypothalamus disorders; State of the gut microbiome.  Infections, but not antibiotics, appear associated with childhood obesity (Nov 2016). 
  and type-2-diabetes is the leading cause of blindness, limb amputations and kidney failure.  Insulin and glucose levels are regulated by the pancreas, liver, muscle, brain and fat.  Diabetes occurs when the insulin level is insufficient to regulate the glucose in the system.  Increased fat levels in obesity demand more insulin overloading the pancreas.  Persistent high glucose levels are also toxic to the pancreas beta cells.  High glucocorticoid levels have been associated with type 2 diabetes.  There are genetic risk factors since siblings of someone with the disease have three times the baseline risk (about 50% of the risk of getting type 2 diabetes is genetic).  The inheritance is polygenic.  More than 20 genes have been identified as risk factors, but that is too few to account for the 50% weighting so many more will be identified.  Of those identified so far many are associated with the beta cells.  The one with the strongest relative risk is TCF7L2.  The disease can be effectively controlled through a diligent application of treatments and regular checkups.  Doctors are monitored for how under control their patients' diabetes is (Sep 2015).  Treatments include:
  • Metformin - does not change the course of pre-diabetes - if you stop taking it, it is as if it hasn't been taken. 
    
  • Diet
  • Exercise
  . 
  
• Cocoa reduces risk of AF (May 2017)
• Treatments include: digoxin is a WHO essential medicine for treating heart conditions including: AF, atrial flutter and CHF.  It typically makes the heart beat more strongly, slowly and regularly.  But in one patient in ten a gut bacterium, Eggerthella lenta with two specific gene variants, inactivates the digoxin.  Digoxin was initially isolated from the foxglove, Digitalis lanata. 
  ;
  
• Attachment theory is John Bowlby's model of mother infant bonding.  He argued that infants need: love is an emotion, which generates a feeling of pleasure at a genetic relative's well-being and pain in their harm.  An inseminated human female is genetically a full relative of her partner since she carries his germ-line gametes.  From any of their pooled gene's perspective the offspring have a one-in-two chance of including the specific gene.  Hence love supports kin selection driven by the selfish actions of genes.  Emotions, including love and anger, help drive the interactions between people.  Compassionate love also supports the symbiotic partnership of true friends built on fairness and trust.  Sapolsky notes the opposite of love is indifference, not hate.  The amygdala's projection into the locus ceruleus drives autonomic intensity. 
  , warmth, affection, responsiveness, stimulation, consistency, reliability; or they become anxious is manifested in the amygdala mediating inhibition of dopamine rewards.  Major anxiety results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women. 
  , depressed is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult;, and/or poorly attached adults. 
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  Evolutionarily, sociopaths is a set of social behaviors displaying no empathy and unconstrained aggression.  A sociopath's aggressive behavior does not respond to negative feedback.  High pain thresholds make it hard for sociopaths to feel pain, so they struggle to relate to other's pain. 
  may be highly successful as managers and leaders aims to develop plans and strategies which ensure effective coordination to improve the common good of the in-group.  John Adair developed a leadership methodology based on the three-circles model. 
  but they are probably anxious.  Sapolsky notes the powerful association between murder rates and stopping pregnant girls from terminating unwanted pregnancies.  Typical mothers also provide training on social conventions and their children's position in the group hierarchy.  Children raised without a mother's support fail to understand social constraints and when to use social behaviors.  And in the presence of unsupportive mothers newborns attach to negative stimuli.  This response is explained by the SHRP is stress hypo-responsive period, an evolved strategy to protect the developing brain of a newborn from stress generated glucocorticoid based damage.  The many adverse effects on brain development of glucocorticoids induce an advantage from temporarily shrinking the adrenals.  SHRP makes sense since a newborn's mother will be better equipped to handle the stress.  During the SHRP any strong stimulus is assumed positive and the newborn attaches to it.  Without access to a mother the SHRP strategy is abandoned and the adrenals expand and secrete glucocorticoids. 
  .  Abused children subsequently seek out abusive relationships as adults.  And a percentage of infants abused by their mothers become abusive mothers. 
  
• Attention is the focusing of our mental resources onto a specific piece of information.  Attention uses valuations assigned to each potential object of thought by the basal ganglia are a set of nuclei near the base of the brain that operate an evolved neural network that unconsciously models the attentional value of each potential object of thought.  It includes the: dorsal striatum which is involved in habit and the ventral striatum which is associated with rewards for winning and losing money. 
  . 
  
• Attentional blink is an experimental technique to create a minimal contrast between conscious and unconscious processing.  A brief period of invisibility of an image is created by saturating the conscious mind with attention is the focusing of our mental resources onto a specific piece of information.  Attention uses valuations assigned to each potential object of thought by the basal ganglia. 
  on letters within a stream of symbols which are mostly digits.  A first letter is perceived.  A second letter presented in close succession (100 milliseconds) is completely missed by conscious perception.  The delay can be adjusted until 50% of the time the second letter is perceived allowing
  Agents use sensors to detect events in their environment.  This page reviews how these events become signals associated with beneficial responses in a complex adaptive system (CAS).  CAS signals emerge from the Darwinian information model.  Signals can indicate decision summaries and level of uncertainty. 
  
  sensors to look at the differences in brain activity between the two minimally different situations. 
  
• Auditory cortex is part of the temporal lobe of the cerebral cortex is involved in associating sensory input with comprehending language (TEO), storing new memories, visual memory, emotion and deriving meaning.  The temporal lobe is located bellow the parietal lobe, and between the frontal lobe and occipital lobe. 
  that processes auditory information.  It is present in both brain hemispheres.  Auditory sensations only reach consciousness is, argues Stanislas Dehaene, when some attended information eventually enters our awareness and becomes reportable to others.   once signalled, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  by the auditory cortex.  Final sound processing is performed by the parietal of the cerebral cortex is at the back of the brain divided into two.  It associates sensory signals of various modalities with:
  
  • Details about the location of the body and
    
  • Models interpreting touch, visual signals, language and mathematics. 
    
  and frontal lobes of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  in humans. 
  
• Authentication identifies a user to a service.  Internet standards include: OpenID; 
• Authoritarian parenting is a parenting style is a psychological classification including: authoritative, authoritarian, permissive, neglectful; ways of parenting that provide children with their first experience of proximate culture.  Each style typically produces adults that use that same approach.  Different cultures value different styles. 
  focused on arbitrary, rigid rules and demands with behavior shaped by punishment.  
• Authoritative parenting is a parenting style is a psychological classification including: authoritative, authoritarian, permissive, neglectful; ways of parenting that provide children with their first experience of proximate culture.  Each style typically produces adults that use that same approach.  Different cultures value different styles. 
  focused on clear, consistent explicable rules. 
  To benefit from shifts in the environment agents must be flexible.  Being sensitive to environmental signals agents who adjust strategic priorities can constrain their competitors. 
  
  Flexibility and praise are offered to develop a child's potential and autonomy. 
  
• Authorization is a facility that acts as a gate-keeper to protected resources.  Internet standards for authorization: OAuth; can be used to support sign-in via third-party authentication identifies a user to a service.  Internet standards include: OpenID;  services including social networks: Facebook, Google+, Twitter;
  
• Autism is a major hereditary mental disorder that starts before age three.  Autistics do not attribute
  Computational theory of the mind and evolutionary psychology provide Steven Pinker with a framework on which to develop his psychological arguments about the mind and its relationship to the brain.  Humans captured a cognitive niche by natural selection 'building out' specialized aspects of their bodies and brains resulting in a system of mental organs we call the mind. 
  
  He garnishes and defends the framework with findings from psychology regarding: The visual system - an example of natural selections solutions to the sensory challenges of inverse modeling of our environment; Intensions - where he highlights the challenges of hunter gatherers - making sense of the objects they perceive and predicting what they imply and natural selections powerful solutions; Emotions - which Pinker argues are essential to human prioritizing and decision making; Relationships - natural selection's strategies for coping with the most dangerous competitors, other people.  He helps us understand marriage, friendships and war. 
  
  These conclusions allow him to understand the development and maintenance of higher callings: Art, Music, Literature, Humor, Religion, & Philosophy; and develop a position on the meaning of life. 
  
  Complex adaptive system (CAS) modeling allows RSS to frame Pinker's arguments within humanity's current situation, induced by powerful evolved amplifiers: Globalization, Cliodynamics, The green revolution and resource bottlenecks; melding his powerful predictions of the drivers of human behavior with system wide constraints.  The implications are discussed. 
  
  
  minds to other people.  They almost never pretend.  They can't explain the difference between an instance of an object and a memory of it.  Autism occurs in every country and social class.  It lasts a lifetime.  It has genetic and neurological causes.  The genes: SHANK3 is a gene on chromosome 22 encoding cell membrane scaffold protein ProSAP2.  It is necessary for effective postsynaptic signalling.  SHANK3 mutations have been associated with about 1% of autism cases. 
  , CDH10 is a gene encoding the cadherin-10 cell adhesion protein.  ; are involved but account for a very small percentage of the risk.  Facial gaze studies indicate a high genetic influence and an opportunity to identify more genes associated with autism (Jul 2017).  ASD is autism spectrum disorder.  People who suffer from ASD show a reduced fusiform response to faces.  ASD is linked to gene variants affecting oxytocin and vasopressin, to nongenetic mechanisms that silence the oxytocin receptor gene and to lower levels of the receptor itself. 
  is associated with a reduced fusiform is a region of the brain which supports advanced mechanisms of shape recognition and implements the early stages of reading.  Subliminal priming with words did not depend on the shape of the word.  The fusiform gyrus was able to process the abstract identity of a word without caring if it was upper or lower case.   While high up in the cortex it can operate below the level of conscious experience.  It contributes to social emotions with:
  
  • Its face area being more activated by faces with in-group skin color.  
  • It activating when shown pictures of cars in automobile aficionados. 
    
  • It activating when shown pictures of birds in birdwatchers; since it really recognizes examples of items from an individual's emotionally salient categories. 
    
  face area response.  Tests [in development] for autism include: SynapDx's blood test. 
  
• Autoimmune diseases include: celiac disease, eczema is atopic dermatitis. 
  , IBD is inflammatory bowel disease, which is a chronic inflammation of part of the digestive tract.  It includes Crohn's disease and Ulcerative colitis.  Symptoms include: Severe diarrhea, Pain, Fatigue & weight loss.  It typically begins in the teens or twenties.  Incidence has increased exponentially since 1945 in developed countries.  160 genes have been associated with IBD.  These genes all relate to: Producing mucus, solidifying the lining of the gut, or regulating the immune system.  The rapid increase in the incidence of IBD can be explained by societal impacts on the gut microbiome which interacts with these genes and their products.  No particular culprit has been found.  It is probably an ecological shift away from symbiosis.  There is a shift from fibre-fermenters: Faecalibaterium prausnitzii, Bacteroides fragilis; to: Fusobacterium nucleatum, Escherichia coli; which are more inflammatory.  The trigger for disease appears complex: Less early infections with tapeworms, bacteria & viruses, Smaller families - which are typically cleaner, More urban environments - resulting in less contact with animals, Less pets, Antibiotics, Endocrine disrupters, Caeserean births, Formula fed babies - rather than breast milk; all potentially contributing to the altered setup and operation of the immune system and microbiome.  , lupus, multiple sclerosis is caused by collapse of the protective covering of certain neurons.  It is the most common disabling neurologic disease of young adults.  It may be due to problems with the Schwann cells that generate the myelin sheath or an autoimmune response where the myelin sheath covering of certain neurons are attacked.  Somatic DNA editing provides one direction for treatment adding surface signals which will tell the immune system cells to ignore the neurons.  Multipe sclerosis has been linked to Epstein-Barr virus which establishes a lifelong, mostly asymptomatic, infection in the majority of adults.  Harvard's Alberto Ascherio argues analogous to the late Polio infection induced paralysis model, that early infection with Epstein-Barr virus protects against M.S. while if infected in adolescence or adulthood the risk of M.S. doubles.   M.S. has been treated with Glatiramer acetate. 
  , type-1-diabetes is also called juvenile diabetes.  It is an autoimmune disease that destroys the insulin producing beta cells of the islets of Langerhans.  It normally presents with high levels of glucose in the blood.  More than a dozen genetic risk factors have been identified: Some associated with the immune system, others with other aspects.  There are a growing number of children with type 1 diabetes throughout the world.  Finland has the highest prevalence -- nearly one in 200 under the age of 15 of type 1 diabetes.  In the United States one in 300 under 15 have the disease and an estimated 167,000 children developed the condition in 2009.  A societal shift in the microbiome appears to be one facet driving the trend (Jun 2016). 
  ; are often debilitating and life long conditions.  Autoimmune diseases are increasing in prevelence rapidly over two or three generations in advanced societies.  One in thirteen Americans has an autoimmune condition.  Some are associated with gene alleles encoding the immune system.  
• Autonoetic memory is the ability to recall and analyse one's own thoughts.  
• Autonomy is decision making based on careful weighting of the pros and cons before committing to a course of action according to Dehaene.  
• Autostereograms are flat pictures that generate a three dimensional illusion within the human visual system supports processing of visual data into what and how.  To do this it has two distinct paths: The ventral path and the dorsal path. 
  .  They operate directly through our eyes are major sensors in primates, based on opsins deployed in the retina & especially fovea, signalling the visual system: Superior colliculi, Thalamus (LGN), Primary visual cortex; and indirectly the amygdala.  They also signal [social] emotional state to other people.  And they have implicit censorious power with pictures of eyes encouraging people within their view to act more honorably.  Eyes are poor scanners and use a saccade to present detail slowly to the fovea.  The eye's optical structures and retina are supported by RPE.  Eyes do not connect to the brain through the brain stem and so still operate in locked-in syndrome.  Evo-devo shows eyes have deep homology.  High pressure within the eye can result in glaucoma.  Genetic inheritance can result in retinoblastoma.  Age is associated with AMD. 
  without support from apparatus.  Autostereograms:
  
• Include: Wallpaper, Random-dot, Magic eye; stereograms,
  
• Depend on four tricks used by
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  natural selection to rapidly resolve a retinal sensor report into a competitively useful representation.  The tricks include:
1. Leverage the resolution of three dimensional objects projections onto the retina, by building a picture which overlays onto the equivalent 3 dimensional projections.  Natural selection leveraged properties of: Surfaces being evenly colored and textured so a gradual change in the markings of the surface is caused by lighting and perspective, Parallel symmetrical right-angled figures appearing to similarly taper are allocated to effects of perspective, Objects have regular compact silhouettes that can be used to predict which ones are nearer. 
   
2. Use of the field of overlap from two separate forward facing eyes to rapidly perform the trigonometry operation to obtain stereo depth information about objects in view.  This operation of vision is assisted by each eye's lens focusing to maximize fine detail.  And each eye is pointed at the same logical spot in the visual world using a control circuit that attempts to minimize double images.  These two mechanisms are integrated causing difficulties for stereogram designers.  
3. A pattern of repeating shapes can lure the eyes into fixating on separate components.  When this results in the patterns falling at the same points in both retinas the brain recognizes that it is not seeing double and accepts the alignment driving the objects into three dimensional representations. 
   
4. The brain solves the correspondence problem in human vision asks how the marks on the retina of one eye are matched up rapidly with the marks in the other eye's retina.  The stereo disparity of a pair of marks is difficult to calculate until you pick the marks to compare.  But there are sometimes thousands of candidates, and the brain does not know how far away the marks are.  With many candidates for pairing a combinatorial explosion is probable.   by filtering, assuming that the viewed configuration is typical of those
   This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
   
   natural selection has experienced on Earth.  The resulting cyclopean eye is the ability to see shapes in stereo that neither eye's visual data can represent in mono. 
   allows the detection of camouflaged prey, unless they have evolved in response by flattening their bodies.  The matcher only considers valid matches:
• A valid match must pair up identical points in the two eyes. 
  
• A point in one eye should be matched with no more than one point in the other eye. 
  
• Matter is assumed to be cohesive and smooth.  Boundaries take up a small percentage of the view.  
• Unconscious constraint matching can apply at the depth the eyes have settled upon using a large array of neural processors.  The processors:
  
• Activate when they get the same input from both eyes.  
• Signal nearby processors of their state.  Nearby processors registering similar depths excite each other. 
  
• Inhibit other processors for different matches lying along the same line of sight.  
• Images may contain parts that are only visible from one eye.  There are neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  that report such occlusions as being from an edge in the visual space.  
• Availability Bias is our perception that objects we can recall easily are present more often.  Items we have been made aware of recently will be judged more available than otherwise.  Differences in how our brains recall different objects similarly introduces this bias as described by Kahneman & Tversky in Judgement Under Uncertainty: Heuristics and Biases. 
• AVRC is AIDS vaccine research committee of the NIH is the National Institute of Health, Bethesda Maryland.  It is the primary federal agency for the support and conduct of biomedical and behavioral research.  It is also one of the four US special containment units of the CDC.  . 
  
• AWF is the adaptive web supports the agents writing and using the dark webs by:
  
  • Leveraging unstructured HTML documents to allow clusters of related information to be juxtaposed.  
  • Allowing source data to be private to a particular agent or shared and jointly edited within a team. 
    
  • Allowing the writers to define streams of information (signals) within the source HTML. 
    
  • Supporting the linkage of the signals to other streams of information deployed into specific dark webs. 
    
  • Genetic operations can be applied to the source data.  Key items are labelled.  They are prioritized.  But they should never be deleted from the source documents. 
    
  • Transforming the streams of information as they are gathered for deployment into target dark webs.  Aspects like checklist and glossary references can be augmented with details.  Changes in one area of the dark web can be signalled in other pages. 
    
  • Constraining which dark webs the information streams will deploy too.  
    
  framework.  
• Axon, a long extension of a neuron, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  which has a membrane, formed from a lipid (fat) bilayer which creates a barrier between aqueous (water soluble) media.  In AWF a key property of membranes - their providing a catalytic environment and supporting the suspension of enzymatically active proteins within the membrane; is simulated with a Workspace list where 'active' structures can be inserted and codelets can detect and act on the structure's active promise configured as an association in the Slipnet.   constructed to support the uni-directional flow of action potential are the actively generated waves of voltage change across the neuron's membrane that flow down a neuron's axon.  Helmholtz noted that while they propagate far more slowly than electrical transmissions action potentials do not attenuate.  Lord Adrian showed the action potential to be an all-or-nothing signal.  Consequently Adrian extended the neuron doctrine from anatomy to function demonstrating:
  • Sensitivity is indicated by the frequency of transmission of action potentials. 
    
  • Anatomy indicates the meaning of the signal.  Hodgkin and Huxley's ionic hypothesis completed the characterization of the action potential. 
    
  from the dendritic tree and cell body to the synaptic terminals, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
  .  
• Axonal plasticity is where axons generate projections that head off in novel directions.  A notable example involves blind people reading Braille where typical tactile cortex activation is accompanied by activation of the visual cortex.  Injuries to the nervous system can produce similar remapping as axons, a long extension of a neuron which has a membrane constructed to support the uni-directional flow of action potential from the dendritic tree and cell body to the synaptic terminals.   that have lost contact with targets because the targets were previously destroyed, search for other active neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  to synapse, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
  with in neighboring parts of the cortex.  The remapping of the axon's path results in waves of plasticity as the newly targeted neurons perform remapping too.  Such remapping is seen when practicing a skill, such as learning to play a new song by repeated physical or mental activity. 
  
• BA is a HIPAA is the Health Insurance Portability and Accountability Act of 1996.  It added part C (administrative simplifications) to the SSA. 
  
  • CFR 45CFR 160.103 is the general provisions section of the regulations.  HIPAA Transactions and Code Sets Standards regulations 45CFR 162.923(a) Covered entities must use adopted transaction standards for inter and intra covered entity transactions.  
  • HIPAA only applies to health care providers, health insurers, clearinghouses of health care data, and their BAs. 
    
  • Initially HIPAA was designed to specify a secure standardized MPI.  Late in the development of the legislation the MPI was viewed as too risky and was removed from the legislation.  
  • The law does not prohibit health care providers from sharing information with family, friends or caregivers unless the patient specifically objects.  Providers can use 'professional judgement' to disclose information to a relative or friend if it is in the best interest of an incapacitated patient. 
    
  • It is also allowed to share general information about a patient's condition and location in a facility. 
    
  • Family members can provide information.  
  • Caregivers who are a patient's personal representative, such as: a health care proxy or guardian or with power of attorney; or who have had the patient authorize the release of information must be provided with it.  
  • HHS office of Civil Rights enforces HIPAA but typically they try to fix problems rather than applying penalties.  
  business associate. 
  
• Baars global workspace is an architecture for consciousness based on a network of neural assemblies performing on a theater stage for an unconscious audience.  It is a type of blackboard architecture. 
  
• Backpropagation is the backward propagation of errors which is used together with an optimization method such as gradient descent is an optimization search algorithm for finding global minima by following the direction with the steepest descent locally, that can be used to identify the minimum error in a non-linear artificial neural network.  How often the algorithm samples the local gradients is controlled by the learning rate which trades off accuracy in finding the global minimum with processing time.  There are three types of gradient descent:
  1. Batch
     
  2. Online
     
  3. Stochastic
     
  to train artificial neural networks.  With GPU performance helped by Moore's law, Gordon Moore characterized the two yearly doubling of the number of transistors in each new generation of integrated circuit. 
  it has become an important strategy.  It uses the chain rule in calculus computes the derivative of the composition of two or more functions F'(x), which is usually very difficult, into the calculation of several easy derivatives.  F'(x) = f' (g(x)) g'(x); where F(x) = f(g(x)) for all x.   to iteratively compute gradients for each layer of the network.  Backpropagation assumes there is a known correct output (y) for each training input (x) making it a supervised learning method.  Backpropagation typically repeats two phases until performance is satisfactory:
  
1. Propagation includes:
   
1. Forward propagation of the training pattern's inputs through the network to generate the output activations: hypothesis (Weight,bias). 
• The total weighted sum of inputs to unit i in layer l including bias: z i(l) = sum from j=1 to n of Weight ij (l) xj + bias i(l) -> activation a i(l) = f (z i(l)); Final layer activation vector (a) is the output hypothesis vector. 
  
2. Backward propagation of the propagation's output activations of each neuron like element (a) through the network using the training pattern target (y) to determine the deltas of all output and hidden nodes.  One determination of the error between y and hidden layer element output activation is error = 1/2*(hypothesis (Weight,bias) - y)**2 + weight decay in backpropagation is a regularization term appended to the error function.  Weight decay is used to decrease the magnitude of the weights and prevent over-fitting.   (Weight). 
   
2. Input weights are updated by gradient descent:
   
1. Multiplying the weight's output delta and input activation to generate a gradient from the weight.  
2. Subtracting a percentage (learning rate is the sample step size in machine learning.  Its size depends on the algorithm it is being used in.  SGD requires a smaller step size be used than BGD because there is more variance in the update.  It is difficult to choose an effective initial learning rate and schedule.  Methods include:
   • Select a small enough constant learning rate to get stable convergence after one or two full passes through the training set.  Then halve the value of the learning rate as convergence slows down. 
     
   • Evaluate a held out set after each full run through and anneal the learning rate when the change in objective between each full pass is bellow a small threshold. 
     
   • Anneal the learning rate at each iteration t as a/(b+t) where
     
   • a dictates the initial learning rate and
     
   • b when annealing begins.  
   • Using a backtracking line search to find the optimal update. 
     
   ) of the gradient from the weight. 
   
• Baldwin effect suggests learning can guide evolution.  While some aspects of the organism are setup directly by genes others are left to be set through learning.  Trial and error is used to tune the learned settings.  Learning can allow a configuration that natural selection is highly unlikely to generate and that is tuned to the proximate environment, to be found by iterative testing.  Natural selection can retain the schematic structures that specify the learning infrastructure and the most successful aspects set directly evolving towards a desired outcome.  The result looks Lamarckian. 
  
• Banking Act of 1933 was New Deal was FDR's political platform to help the poor, support the economy and reform the banking system.  The architects included Henry Morgenthau, Harry Hopkins, and Frances Perkins.  It:
  
  • Included liberal legislation: Emergency Banking Relief Act, Banking Act, SSA, Securities Act, Securities Exchange Act, National Housing Act, NIRA, National Labor Relations Act, FLSA, RTAA, Wealth Tax Act;
    
  • Presidential executive orders,
    
  • Enhanced the role of federal government in promoting economic growth with programs supporting:
    
  • Reformed trade policy with the RTAA. 
    
  • Blocked deflation by limiting economic competition with the NRA. 
    
  • Rural standard of living through electrification with the REA and TVA.  
  • Reduced unemployment with the WPA and CCC.  
  • Made taxation progressive through the Wealth Tax Act, capturing private wealth and allowing income to flow to the emergent middle class. 
    
  legislation that reformed the banking system: limiting commercial bank securities operations, constraining integration of commercial banks and securities firms; and created the FDIC is the Federal Deposit Insurance Corporation which was created by the Banking Act and designed as part of the New Deal to mitigate risk for Americans by practically eliminating bank failures and loss of depositors' savings. 
  
  .  It was sponsored by Senator Carter Glass and Representative Henry Steagall (Glass-Steagall Banking Act of 1933 prohibits commercial banks from engaging in the investment business. 
  ) and was initially resisted by the FDR is President Franklin Delano Roosevelt.  He is notable for his contributions to the US CAS:
  • New Deal strategies including:
  • SSA
    
  • FFDCA 
  • IRC
    
  • Lend-lease which pushed the US and Japan into World War 2 and helped the US to become the world's predominant military power.  
  • Bretton Woods's agreement which economically constrained any politically driven collapse of the world economy after the war and helped the US to become the world's predominant economic power.  
  administration. 
  
• Bankruptcy is a legal status for an entity that cannot repay its creditor's loans.  It holds creditor lawsuits in abeyance while the restructuring process proceeds to allow the entity to continue operations.  It also has legal tools for forcing holdout creditors to accept repayments that are lower than the bond sale initially promised. 
  
• Banyan Brain Trauma Indicator is a blood test for mTBI is mild traumatic brain injury (TBI)
  that measures the levels of UCH-L1 and GFAP that are released into the blood stream when brain tissue is damaged.  It is approved for marketing by the F.D.A. Food and Drug Administration. 
  and should reduce the need for CT is computerized tomography in which a series of X-ray views taken from many angles are combined by computer processing to create 3-D images.  It is very useful for examining people who have been subject to trauma such as car accidents.  The high dose of radiation is a cause for concern with over use of CT scanning (Jan 2014).  The Banyan Brain Trauma Indicator blood test should help here. 
  scans of those with suspected brain injuries by a third.  (Feb 2018)
  
• BAPCPA is the Bankruptcy is a legal status for an entity that cannot repay its creditor's loans.  It holds creditor lawsuits in abeyance while the restructuring process proceeds to allow the entity to continue operations.  It also has legal tools for forcing holdout creditors to accept repayments that are lower than the bond sale initially promised. 
  Abuse Prevention and Consumer Protection Act of 2005.  It:
• Made it more difficult for consumer debtors to file for chapter 7 bankruptcy which writes off the debt.  Instead they must use chapter 13 where the discharge is dependent on paying off some part of the debt.  
• Added waiting period between bankruptcy filings. 
  
• Added a constraint that to use chapter 7 an individual debtor must have had credit counseling and accredited education.  
• Required the automatic stay of collection proceedings be reduced for subsequent bankruptcy filings. 
  
• Added stricter notice requirements make the debtor give notice at an address filed by the creditor with the court. 
  
• Reduced opportunities for discharge
  
• Reduced ability to avoid liens
  
• Restricted exemptions
  
• Added additional requirements for filing
  
• BARDA is the biomedical advanced research and development authority, an HHS is the U.S. Department of Health and Human Services.   ASPR office responsible for procurement and development of vaccines are a core strategy of public health and have significantly extended global wellbeing over 200 years.  Recent successes include: HPV vaccine.  They induce active acquired immunity to a particular disease.  But the development and deployment of vaccines is complex:
  • The business model for vaccine development has been failing (Aug 2015): 
    
  • No Zika vaccine was available as the epidemic grew (Mar 2016).  No vaccine for: CMV;
    
  • Major foundations: Michael J. Fox, Gates, Wellcome; are working to improve the situation including sponsorship of the GAVI alliance.  A geographic cluster is forming in Seattle including PATH (Apr 2016). 
    
  • Commercial developers include: Affiris, Cell Genesis, Chiron, CSL, Sanofi, Valeant;
    
  • Vaccine deployment traditionally benefited from centrally managed vertical health programs.  But political issues are now constraining success with less than 95-99% coverage required for herd immunity (Aug 2015, Sep 2015, Nov 2015, Nov 2016).  
  • Where clinics have been driven into local neighborhoods health improves (Apr 2016).  
  • Retail clinics (Mar 2016): CVS Minute Clinics focus on vaccination. 
    
  • NNT is a useful metric for vaccine benefit.  Influenza vaccine has an NNT of between 37 and 77, is cheap and causes little harm, so it is very beneficial. 
    
  • Key vaccines include: BCG, C. difficile (May 2015), Cholera (El Tor), Dengvaxia (Mexico Dec 2015), Gvax, Malaria vaccine, Provenge, Typbar-TCV (XDR typhoid Pakistan Apr 2018);
  • Regulation involves: FDA (CBER), with CMS monitoring (star ratings, PACE (Aug 2016), Report cards (Sep 2015)) & CDC promoting vaccines: as a sepsis measure, To control C. difficile (May 2015);  
  • Coding : CVX, MVX;
    
  • Research on vaccines includes: 
  • NIH: AIDS vaccines (AVRC), Focus on using genetic analysis to improve vaccine response.  
  • NCI:
  • Roswell Park clinical trial of immuno-oncology vaccine cimavax. 
    
  • Geisinger: effective process leverage in treatment. 
    
  • Stanford Edge immuno-oncology for cancer vaccines.  
  • P53-driven-cancer focused, gene therapy (Jun 2015). 
    
  , drugs, therapies and diagnostic tools for public health is the proactive planning, coordination and execution of strategies to improve and safeguard the wellbeing of the public.  Its global situation is discussed in The Great Escape by Deaton.  Public health in the US is coordinated by the PHS federally but is mainly executed at the state and local levels.  Public health includes:
  • Awareness campaigns about health threatening activities including: Smoking, Over-eating, Alcohol consumption, Contamination with poisons, Joint damage from over-exercise;
    
  • Research, monitoring and control of disease agents, processes and vectors by agencies including the CDC. 
    
  • Monitoring of the public's health by institutes including the NIH.  
  • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
  • Development, deployment and maintenance of vaccination strategies. 
    
  • Regulation and constraint of foods, drugs and devices by agencies including the FDA. 
    
  emergencies. 
  
• Barriers are particular types of constraints on flows.  They can enforce separation of a network of agents allowing evolution to build diversity.  Examples of different types of barriers and their effects are described. 
  
  Barriers.  
• Basal ganglia are a set of nuclei near the base of the brain that operate an
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  evolved neural network that unconsciously models the attentional value of each potential object of thought.  It includes the: dorsal striatum is a region within the basal ganglia.   It has been associated with habitual behavior.  which is involved in habit and the ventral striatum is a region within the basal ganglia.   It is a target of the tegmentostriatal dopamine pathway.  It has been captured by brain imaging assigning values to subliminal symbols experimentally associated with winning (highly valued) and losing (low valuation) money.  During adolescence, prior to the deployment of the prefrontal cortex, the ventral striatum helps balance/control emotional decision making. 
  which is associated with rewards for winning and losing money. 
  
• Base, a nucleotide base is the side chain purine (A or G) or pyrimidine (T or C).  A is a natural pair for T.  G pairs naturally with C.  These bases have multiple uses in cells including energy transfer are the energy molecule generating production functions of eukaryotic cells.  They are vestigial blue-green bacteria with their own DNA and infrastructure.  Unlike stand-alone bacteria they also use the eukaryotic host DNA and infrastructure for some functions.  The high energy molecules are nucleotides with a high energy phosphate bond.  The most used high energy molecule is Adenosine-tri-phosphate.  , second messenger, provide an amplified form of signals within a cell.  Since cells need to stabilize their overall state with many operations happening in parallel second messengers are useful in clarifying the signals effect.  The second messenger strategy is seen repeatedly in CAS including: neuro-transmitter guidance signals such as dopamine distribution in the brain, corporate positioning email messages in response to new situations, newspaper articles aligning the population;  signalling, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  as well as genetic data storage, transcription is the process where DNA is converted into messenger m-RNA.  A complex of enzymes cooperates to bind to the DNA and generate the m-RNA copy.  There are a number of such transcription complexes which are based on RNA polymerase I, II or III. 
  and translation is the process where messenger m-RNA is cross coded by Ribosomal agents and t-RNA into an amino-acid polymer.  .  Deacon argues that the multiple uses are significant to the
  This page discusses the mechanisms and effects of emergence underpinning any complex adaptive system (CAS).  Key research is reviewed. 
  
  emergence of
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  evolution. 
  
• Basic-level categories is psychologist Eleanor Rosch's term for evolved mental categories.  These categories reflect the way the world works.  They are the first words a child learns: Rabbit, Car; categories that in consequence are useful, since they have high predictive value.  This value results from the actions of: Physical forces,
  Plans emerge in complex adaptive systems (CAS) to provide the instructions that agents use to perform actions.  The component architecture and structure of the plans is reviewed. 
  
  Genetics and
  This page reviews the implications of selection, variation and heredity in a complex adaptive system (CAS).  The mechanism and its emergence are discussed. 
  
  natural selection; constraining the characteristics of occupants of particular classes of niche.  
  
• Basophils are a type of leukocyte are produced by hematopoietic stem cells in the bone marrow and are a major part of the adaptive immune system.  Five types have been identified:
  1. Basophils,
     
  2. Eosinophils,
     
  3. Lymphocytes,
     
  4. Monocytes,
     
  5. Neutrophyls.  
  .  They respond to antigens by releasing histamine causing vasodilation and heparin inhibiting blood clotting or coagulation is formation of a clot:
  • Platlets become activated, adhere and aggregate supported by
  • Fibrin polymerization, deposition and maturation.  
  and supporting the invasion of other leukocytes into the infected area.  
• Batch gradient descent is used to identify the parameter settings which result in a minimal cost function comparing a predicted outcome to the real outcome.  The basic operation is:
• Choose an initial vector of parameters assumes that data comes from a probability distribution and so makes inferences about the parameters of the distribution.  For example when a distribution is assumed to be normal then it is described by two parameters: its mean and standard distribution from the mean.   and a learning rate is the sample step size in machine learning.  Its size depends on the algorithm it is being used in.  SGD requires a smaller step size be used than BGD because there is more variance in the update.  It is difficult to choose an effective initial learning rate and schedule.  Methods include:
  • Select a small enough constant learning rate to get stable convergence after one or two full passes through the training set.  Then halve the value of the learning rate as convergence slows down. 
    
  • Evaluate a held out set after each full run through and anneal the learning rate when the change in objective between each full pass is bellow a small threshold. 
    
  • Anneal the learning rate at each iteration t as a/(b+t) where
    
  • a dictates the initial learning rate and
    
  • b when annealing begins.  
  • Using a backtracking line search to find the optimal update. 
    
  ;  and then
  
• Repeat until an appropriate minimum is obtained -- This can be computationally expensive pushing machine learning towards SGD (SGD) follows the negative gradient of the objective J (parameter) after seeing only a single or few training examples.  That is an advantage with big real data sets over the more robust batch gradient descent.  In machine learning the goal is to estimate the parameter that minimizes the loss.  It is of the form
  
  • parameter := parameter - (learning rate * Del * Objective J (parameter; x**(i), y ** (i) ) i.e. using the pair x**(i), y**(i) from the training set.  
  • The learning rate is set smaller than for batch gradient descent because there is more variance in the update.  Choosing a good learning rate and schedule for changing it is difficult.  
  .  Also by replacing these iterative operations with equivalent vector computations the speed can be massively increased. 
  
• Randomly shuffle examples in the training set - The data should be presented randomly to avoid biasing the gradient which may undermine convergence. 
  
• For i = 1 to n do
  
• Parameter = parameter - learning rate * del is the differential operator (gradient) acting on functions f: R**n  -> R.  
  (objective function maps an event onto a real number representing the cost associated with the event.  It can be used to estimate the parameter that minimizes the difference between an estimated and true value.  If the cost function has the form of a long shallow ravine heading to the optimum and steep walls on the sides the negative gradient of standard SGD will point down one of the steep sides rather than along the ravine to the optimum creating time consuming oscillations.  Machine learning's DNN architectures have this shape of objective (cost function).  Strategies such as momentum are used to push the objective more quickly along the ravine. 
  on i (parameter) )
• Stanford notes that the objective function on i is really replaced by an expectation maximization E is an algorithm for maximum likelihood parameter estimating in machine learning that alternates between estimating the unobserved variables given  the current model and refitting the model given the estimated, complete data.  It takes discrete steps in parameter space similar to a first order method operating on the gradient of a locally reshaped likelyhood function. 
  algorithm
• Bayes, Thomas was an 18th century clergyman who wrote "An Essay toward Solving a Problem in the Doctrine of Chances" in which he argued that the way we learn about the world is through approximation, getting closer and closer to the truth as we gather more evidence.  Laplace developed this idea into the Bayesian is an iterative form of statistics invented by Thomas Bayes.  It uses a 'prior' statistic to represent the prior situation and then performs a calculation that integrates the probability of new events occurring into a 'posterior' probability.  This posterior becomes the prior for the next iteration with the application of the Bayesian identity xpost = xprior*y/(xprior*y + z(1-xprior)).  The magic in Bayesian statistics is in accurately generating the prior xprior and the current event probabilities y and z.  R. A. Fischer was so skeptical of the legitimacy of the prior that he advocated an alternative statistical framework and experimental process.   statistical method.  The method is iterative and adaptive. 
  
• Bayes Rule specifies a conditional probability P(A|B) the posterior belief = (P(B|A) the likelyhood * P(A) our prior belief) /P(B).  This says our belief in hypothesis A is updated in light of new evidence B.  The power of Bayes rule is that often P(A|B) may be difficult to compute directly but can be calculated from P(B|A).  For example:
• A is the event a person has cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).  . 
  
• B is the event a person smokes. 
  
• If 10% of people who enter a clinic have cancer then P(A) = 0.1;  Assumed accurate Baysian is an iterative form of statistics invented by Thomas Bayes.  It uses a 'prior' statistic to represent the prior situation and then performs a calculation that integrates the probability of new events occurring into a 'posterior' probability.  This posterior becomes the prior for the next iteration with the application of the Bayesian identity xpost = xprior*y/(xprior*y + z(1-xprior)).  The magic in Bayesian statistics is in accurately generating the prior xprior and the current event probabilities y and z.  R. A. Fischer was so skeptical of the legitimacy of the prior that he advocated an alternative statistical framework and experimental process.   prior. 
  
• P(B) is the percentage of people who smoke = 0.5; Assumed accurate prior. 
  
• P(B|A) = 0.8 is the proportion of smokers among those diagnosed with cancer at the clinic from the clinics records.  
• P(A|B) = (0.8 * 0.1)/0.5 = 0.16.  With evidence that a person is a smoker we revise our estimate of P(A) from 0.1 to a posterior probability of 0.16.  
• Bayesian is an iterative form of statistics invented by Thomas Bayes, Thomas was an 18th century clergyman who wrote "An Essay toward Solving a Problem in the Doctrine of Chances" in which he argued that the way we learn about the world is through approximation, getting closer and closer to the truth as we gather more evidence.  Laplace developed this idea into the Bayesian statistical method.  The method is iterative and adaptive. 
  .  It uses a 'prior' statistic to represent the prior situation and then performs a calculation that integrates the probability of new events occurring into a 'posterior' probability.  This posterior becomes the prior for the next iteration with the application of the Bayesian identity xpost = xprior*y/(xprior*y + z(1-xprior)).  The magic in Bayesian statistics is in accurately generating the prior xprior and the current event probabilities y and z.  R. A. Fischer, R. A. is an eminent geneticist who developed a statistical method, Fisherian or frequentist statistics, based on population samples and distributions. 
  was so skeptical of the legitimacy of the prior that he advocated an alternative statistical framework and experimental process.  
• BBA is the Balanced Budget Act of 1997.  This act aimed to balance the federal budget by 2002.  It was enacted using the budget reconciliation is a fast-track Senate procedure defined in title III of the CBIC act.  In response to a stagnant economy and President Nixon's spending controls it was hoped this process would help with acting rapidly on the rising budget deficit and increasing entitlement spending.  The process is constrained by Senate rules that limit its use to provisions that deal with government tax and spending activities, but not policy:
  • Senators can object to a reconciliation bill if they see the rules being broken & ask for the parliamentarian to judge if a provision of a bill fails the rules. 
    
  • If the parliamentarian judges the proposal does fail the rules, the bill must be passed by 60 votes to overcome the objections, rather than a simple majority of the Senate or the provision must be stripped from the bill. 
    
  process.  In part it reduced Medicare is a social insurance program that guarantees access to health insurance for Americans aged 65 and over, and younger people with disabilities and end stage renal disease or ALS.  Medicare includes:
  
  • Benefits
  • Part A: Hospital inpatient insurance.  As of Dec 2013 Medicare pays for home care in only limited circumstances, such as when a person needs temporary nursing care after a hospitalization.  Part A covers 20 days of inpatient rehabilitation at a SNF after discharge from inpatient care at a hosptial. 
    
  • Part B: Medical insurance
    
  • Part C: Medicare Advantage 
  • Part D: Prescription drug coverage The MMA prohibits Medicare from directly negotiating drug prices. 
    
  • Eligibility
    
  • All persons 65 years of age or older who are legal residents for at least 5 years.  If they or a spouse have paid Medicare taxes for 10 years the Medicare part A payments are waived. 
    
  • Persons under 65 with disabilities who receive SSDI. 
    
  • Persons with specific medical conditions:
  • Have end stage renal disease or need a kidney transplant. 
    
  • They have ALS. 
    
  • Some beneficiaries are dual eligible. 
    
  • Part A requires the person has been admitted as an inpatient at a hospital.  This is constrained by a rule that they stay for three days after admission.  
    
  • Premiums
  • Part A premium
  • Part B insurance premium
    
  • Part C & D premiums are set by the commercial insurer. 
    
  (replacing MVPS is Medicare Volume Performance Standard a mechanism CMS used to control spending.   It was replaced through the BBA of 1997 with SGR. 
  with the SGR is medical Sustainable Growth Rate.  It is a CMS method to control Medicare spending on physician services.  It aims to ensure the yearly increase in expense per Medicare beneficiary does not exceed the growth in GDP.  To do this CMS reports to the MedPAC which advises the U.S. Congress on the previous year's total expenditures and the target expenditures.  The report includes a conversion factor that constrains the payments for physician services to match the target SGR.  On March 1st of each year the physician fee schedule is updated accordingly.  Congress can and does adjust the target SGR outside of these bounds.  SGR replaced MVPS.  It was introduced via the BBA.   and commissioning the MedPAC is the Medicare Payment Advisory Commission.  It was established by the BBA.  The mandate is to advise the U.S. Congress on payments to private health plans participating in Medicare and health providers with Medicare beneficiaries.  It produces two major reports each year for Congress.  ) and Hospital inpatient and outpatient payment cuts to do this.  It also enacted Medicare Advantage (MA) is a private provider administered health insurance plan providing access to Medicare benefits.  It was originally enacted as part of BBA Medicare + Choice or Part C plans.  The government funded the plan with an annual fee, based on age and severity of the subscriber's medical conditions, rather than FFS.  When a Medicare eligible person enrolls in a MA plan the government pays the private provider a set amount each month.  The participant pays the Medicare part B premium and if required a part C premium each month.  When they obtain treatment they will have to pay a copayment which may be quite high for some specialists.  It is the health plan's responsibility to contract the physician network that will provide the care, leaving the risk with the insurer.  About 25% of Medicare beneficiaries are enrolled with Medicare Advantage.  The ACA introduced quality outcome and patient satisfaction based differential payments into MA.  To measure the performance it added a five-star quality rating scheme.  MA plans report their quality and patient satisfaction data to CMS annually and based on the results are awarded one to five stars.  The highest rated plans are provided with large additional payments.  It was assumed that subscribers would shift to the highest rated plans and the other plans would improve or drop out of MA.  And the ACA eliminated subsidies which the federal government used to establish Medicare Advantage.  However, the Obama administration has used a $8.5 Billion demonstration project to maintain this funding.  It is intended that it will eventually taper off so that the cost of Medicare Advantage coverage will be equivalent to standard Medicare. 
  and SCHIP is the State Children's Health Insurance Program provides health insurance to children in families at or below 200 percent of the federal poverty line.  It was created by the BBA of 1997 & was later designated CHIP. 
  .  BBA mandated risk adjustment and the HCC is:
  
  • Hepatocellular carcinoma, a cancer of the hepatocytes or 
  • Hierarchical condition category - a BBA mandated and CMS implemented payment model, required for Medicare Advantage reimbursement.  It utilizes diagnoses from all hospital and physician encounters to produce a health-based measure of future medical need or
    
  • Hospital condition category - an AHA guideline for describing a patient's condition to the media in just one word. 
    
  coding payment model, through CMS is the centers for Medicare and Medicaid services.   rules. 
  
• BC is Before Christ also reffered to as before common era (BCE). 
  
• BCA is the budget control act of 2011.  It was agreed between House leader aims to develop plans and strategies which ensure effective coordination to improve the common good of the in-group.  John Adair developed a leadership methodology based on the three-circles model. 
  Boehner and President Obama to:
  
• $1.2 trillion deficit reduction by joint agreement or sequestration
  
• $900 billion in cuts over 10 years. 
• BCG is the Bacille Calmette-Guerin vaccine are a core strategy of public health and have significantly extended global wellbeing over 200 years.  Recent successes include: HPV vaccine.  They induce active acquired immunity to a particular disease.  But the development and deployment of vaccines is complex:
  • The business model for vaccine development has been failing (Aug 2015): 
    
  • No Zika vaccine was available as the epidemic grew (Mar 2016).  No vaccine for: CMV;
    
  • Major foundations: Michael J. Fox, Gates, Wellcome; are working to improve the situation including sponsorship of the GAVI alliance.  A geographic cluster is forming in Seattle including PATH (Apr 2016). 
    
  • Commercial developers include: Affiris, Cell Genesis, Chiron, CSL, Sanofi, Valeant;
    
  • Vaccine deployment traditionally benefited from centrally managed vertical health programs.  But political issues are now constraining success with less than 95-99% coverage required for herd immunity (Aug 2015, Sep 2015, Nov 2015, Nov 2016).  
  • Where clinics have been driven into local neighborhoods health improves (Apr 2016).  
  • Retail clinics (Mar 2016): CVS Minute Clinics focus on vaccination. 
    
  • NNT is a useful metric for vaccine benefit.  Influenza vaccine has an NNT of between 37 and 77, is cheap and causes little harm, so it is very beneficial. 
    
  • Key vaccines include: BCG, C. difficile (May 2015), Cholera (El Tor), Dengvaxia (Mexico Dec 2015), Gvax, Malaria vaccine, Provenge, Typbar-TCV (XDR typhoid Pakistan Apr 2018);
  • Regulation involves: FDA (CBER), with CMS monitoring (star ratings, PACE (Aug 2016), Report cards (Sep 2015)) & CDC promoting vaccines: as a sepsis measure, To control C. difficile (May 2015);  
  • Coding : CVX, MVX;
    
  • Research on vaccines includes: 
  • NIH: AIDS vaccines (AVRC), Focus on using genetic analysis to improve vaccine response.  
  • NCI:
  • Roswell Park clinical trial of immuno-oncology vaccine cimavax. 
    
  • Geisinger: effective process leverage in treatment. 
    
  • Stanford Edge immuno-oncology for cancer vaccines.  
  • P53-driven-cancer focused, gene therapy (Jun 2015). 
    
  for tuberculosis, consumption or otherwise TB, is mostly an airborn bacterial lung infection, but it can also infect the brain, kidneys and other parts of the body.  The only vaccine is still the BCG.  The deployment of antibiotics during the 1940s allowed effective treatment: Streptomycin.  Diagnostic tools for TB are insufficient.  And because TB grows slowly in walled off pockets in the lungs it takes many months of treatment for antibiotics to eradicate the infection.  TB benefits from compromised hosts and has benefited from HIV/AIDS.  TB is also leveraging the plasmids that now carry immunity to all current antibiotics.  In 2016 it is estimated to latently infect two billion people.  9.6 million worldwide became infected in 2014.  1.5 million people will die from TB in 2016.  Deaths from the disease have fallen drastically since 2000.  TB has been halted or reversed in 16 of the 22 countries: India (Sep 2016, Infection base estimate increased Oct 2016), Vietnam, Indonesia; that have the majority of cases.  But it is still the infectious disease causing the most deaths world-wide.  Nano scale drug delivery has the potential to push back on TB and is being actively researched (May 2016).   .  It has unpredictable results and is not fully protective for severe forms of the disease.  It is also being used to treat bladder cancer affects 77,000 new people each year in the US.  And there are 16,000 deaths.  It is typically fast growing, and is often associated with mutated Ras, which may indicate it can be treated by reducing the methylation of the DNA (Dec 2015).   A rare form is plasmacytoid.  Bladder cancer is traditionally treated with surgery, chemotherapy and radiation but these have not been effective with the advanced disease.  New treatments are being deployed:
  • Immuno-oncology immune checkpoint inhibitor Tecentriq (May 2016) is approved for locally advanced or metastatic urothelial carcenoma which accounts for 90% of bladder cancers, where the disease is not controlled by platinum chemotherapy.  Bladder cancer tends to result in many mutations which typically present to the immune system making it a good candidate for immuno-oncology. 
    
  . 
  
• BCR is a gene on chromosome 22 which normally codes the breakpoint cluster region protein which is a GTPase-activating protein for RAC1 is the gene for Rac1, a G protein from the Rac superfamily of regulators of many cell pathways.   and CDC42 is the gene encoding Cdc42, cell division control protein 42 involved in regulation of the cell cycle. 
  .  In many cases of CML is chronic myelogenous leukemia.  It is a leukemia characterized by the unregulated growth of myeloid cells in the bone marrow.  The growth is encouraged by the cellular signalling system (gene change that generates a faulty tyrosine kinase) being locked on.  Visual methods allowed Dr. Janet Rowley's team to recognize that most CML includes the Philadelphia chromosome.  It encodes the chimeric always on tyrosine kinase protein seen only in CML.  Targeted treatments such as Gleevec block the pathway for the tyrosine kinase. 
  part of the BCR gene gets translated onto an additional Philadelphia chromosome is a chromosome fragment generated by a mutation copying bits of chromosome 9 including part of gene BCR and part of gene ABL from chromosome 22.  In the majority of cases of CML Philadelphia chromosome is present and generates an aways on tyrosine kinase signalling protein which causes vast proliferation of white blood cells.  Since the protein is aberrant blocking its production pathway with drugs such as Gleevec stop the excessive white blood cell production. 
  along with part of gene ABL is a gene on human chromosole 22.  In the majority of cases of CML part of ABL is coppied into a merged chromosome with part of BCR from chromosome 9, in a transformation initially noted by Dr. Janet Rowley and colleagues and called the Philadelphia chromosome.   from chromosome 9. 
  
• BDNF is brain-derived neurotropic factor which stimulates the formation of new dendrites and synapses, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
  . 
  
• Beacon Community is supported by the ONC is the Office of the National Coordinator for Health Information Technology of the US Department of Health and Human Services.  It was required to support the President's 10 year goal of interoperable EHR, and lead the nation in the strategic planning for nationwide interoperable HIT.  It develops the US HIT strategic plan.  It specifies the standards, implementation specifications and certification criteria used to certify meaningful use.  It develops key programs: RECs, HITRC, State HIE Cooperative Agreements, Beacon Communities, Health IT Workforce Development, SHARP, National Health Information Network, FHA, CONNECT.  It must encourage the development of RHIOs to facilitate community and regional clinical data exchange.   because of its cutting edge use of EHR refers to electronic health records which are a synonym of EMR.  EHRs have strengths and weaknesses:
  • The EHR provides an integrated record of the health systems notes on a patient including: Diagnosis and Treatment plans and protocols followed, Prescribed drugs with doses, Adverse drug reactions;
  • The EHR does not necessarily reflect the patient's situation accurately. 
    
  • The EHR often acts as a catch-all.  There is often little time for a doctor, newly attending the patient, to review and validate the historic details. 
    
  • The meaningful use requirements of HITECH and Medicare/Medicaid specify compliance of an EHR system or EHR module for specific environments such as an ambulatory or hospital in-patent setting. 
    
  • As of 2016 interfacing with the EHR is cumbersome and undermines face-to-face time between doctor and patient.  Doctors are allocated 12 minutes to interact with a patient of which less than five minutes was used for recording hand written notes.  With the EHR 12 minutes may be required to update the record!
    
  adoption and HIE a Health Information Exchange is responsible for the transmission of healthcare-related data among facilities, health information organizations and government agencies according to national standards.  They are designed to address legal, organizational and technical challenges that would otherwise impede the sustainability of health information interchange.  An HIE is a component of the HIT.  It must enable reliable and secure transfer of data among diverse systems and facilitate access and retrieval.  The two main types are private and public exchanges.  Private exchanges may be able to leverage homogeneous IT infrastructure to facilitate data sharing.  Public exchanges are likely to be heterogeneous.  RHIO provide the regional organizations to support such HIE.  They are there to ensure that infrastructure amplification initiates.  The government will ensure that low healthcare density areas are served by public HIE infrastructure.  Both centralized and federated technical solutions were initially considered for implementation by the RHIOs for deploying HIE as specified in the Markle Foundation's NHIN common framework.  Common framework clients such as appropriately architected HIE use SOAP messaging to interact with their local SNO's ISB and RLS.  The HIE SOAP query transactions follow the HL7 Query Model.  Alternatively some HIE's are now using direct messaging to support interoperation.  HIE deployment goals have been phased (1 - supporting care transitions, 2 - Quality and care management, 3 - Population health).  Some HIEs will support "EHR-lite" as part of their functionality.  HIE does not yet solve some difficult challenges:
  • Safeguarding the security of health information.  Currently HIEs conforming to the common framework only provide locations of clinical data held remotely.  
  • Providing effective life cycle management.  The HIE is dependent on the local set of entities to provide updates that match the current state of the entity data. 
    
  .  Their grantees are acting as test sites for Health IT to analyze disparities due to race, gender, language or disability.  
• BECs are biliary epithelial cells which are part of the adult liver is an emergent cellular system providing metabolic: Dietary compound metabolism and signalling: After gorging on sugar-rich foods the liver releases FGF21 hormone to dampen further eating activity; Detoxification, Regulation of glucose through glycogen storage (asprosin signalling from white adipose tissue); clotting, immune, exocrine and endocrine functions.  It is supplied with oxygen-rich blood via the hepatic artery and blood rich in semi-processed foodstuffs from the intestines & spleen via the hepatic portal vein.  It is constructed from: Hepatocytes which swim in the blood to process it, BECs, Stromal cells, Hepatic stellate cells, Kupffer cells, and blood vessels.  The embryonic endoderm cells invade the mesoderm to form the liver bud.  Subsequently the liver bud vascularizes and is colonized by hematopoietic cells.  The liver operates on a daily cycle allowing it time to recover from the stress of processing toxic substances.  There are over 100 disorders of the liver.  Obesity and diabetes are associated with increased prevalence of these liver disorders worldwide. 
  .  They are derived from embryonic endoderm is the inner most layer of the developing embryonic tube in humans. 
  .  
• Beta bend, provides a structural building block (a turn) that can be conserved and used by
  Richard Dawkin's explores how nature has created implementations of designs, without any need for planning or design, through the accumulation of small advantageous changes. 
  
  natural selection. 
  
• Beta blockers stop the action of beta-adrenergic signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  and hence slow the heart.  
• Beta sheet provides a structural building block (a sheet with consistent electrical and physical properties) that can be conserved and used by
  Richard Dawkin's explores how nature has created implementations of designs, without any need for planning or design, through the accumulation of small advantageous changes. 
  
  natural selection. 
• BI is business intelligence.  Compliance is demanding providers measure, understand and respond to the data about their patients and care.  Hospital groups know they must take steps to allow their data silos to integrate, even as they must take care to follow HIPAA is the Health Insurance Portability and Accountability Act of 1996.  It added part C (administrative simplifications) to the SSA. 
  
  • CFR 45CFR 160.103 is the general provisions section of the regulations.  HIPAA Transactions and Code Sets Standards regulations 45CFR 162.923(a) Covered entities must use adopted transaction standards for inter and intra covered entity transactions.  
  • HIPAA only applies to health care providers, health insurers, clearinghouses of health care data, and their BAs. 
    
  • Initially HIPAA was designed to specify a secure standardized MPI.  Late in the development of the legislation the MPI was viewed as too risky and was removed from the legislation.  
  • The law does not prohibit health care providers from sharing information with family, friends or caregivers unless the patient specifically objects.  Providers can use 'professional judgement' to disclose information to a relative or friend if it is in the best interest of an incapacitated patient. 
    
  • It is also allowed to share general information about a patient's condition and location in a facility. 
    
  • Family members can provide information.  
  • Caregivers who are a patient's personal representative, such as: a health care proxy or guardian or with power of attorney; or who have had the patient authorize the release of information must be provided with it.  
  • HHS office of Civil Rights enforces HIPAA but typically they try to fix problems rather than applying penalties.  
  requirements.  And global networking and CMS is the centers for Medicare and Medicaid services.   policies on providing access to their population data creates new business intelligence opportunities and threats.  CMS incentives to adopt ACO is an Accountable Care Organization. These are accredited bundles of companies which together try to offer Dartmouth-Hitchcock like business models (Dec 2015, Sep 2016) focused on wellness, improving the provision of primary care to a large group of Medicare patients, and rewarding doctors for preventing problems.  Advocate health illustrates the idea.  Robert Pearl notes that the transition is difficult: hospitals that find their efficiency improving should reduce the number of doctors they utilize.  But any doctors that are pushed out of the ACO will likely take their patients with them, undermining the revenues that support the FFV business.  The ACA regulates qualification to be a Medicare ACO.  Individual organizations within a Medicare shared savings ACO continue to submit their own claims and are paid by Medicare for FFS.  But the ACO is eligible for shared savings.  Within the shared savings program the CMS innovation center has setup advanced payment ACOs.  As an alternative to shared savings, in a Pioneer ACO, over time 50% of the FFS payments flow directly to the ACO as a bundled payment.  CMS has established quality measures for ACOs for Medicare.  The CMS program's purpose is to reward providers for reducing total cost of care for patients through prevention, disease management, and coordination. 
  
  • CMS initiated its Physician Group Practice Demonstration in 2005.  By 2008 the congressional budget office reported on Bonus-eligible organizations. 
    
  • CMS defines ACOs as organizations that "create incentives for health care providers to work together to treat an individual patient across care settings - including doctors' offices, hospitals and long-term care facilities."
  • CMS has developed APMs which include ACOs, and advanced APMs where the ACOs must be risk bearing. 
    
  • CMMI accepts providers' proposals to test various payment systems including shared savings and partial capitation.  
  • Private market ACOs have formed including: Providence Health & Services, Blue Shield California, Anthem Blue Cross, United Health Care, BCBS Minnesota, BCBS Illinois, Humana, CIGNA, Main Health Management Coalition, BCBS Massachusetts, Aetna.  
  structures similarly will require inter-business data visualization to be able to spread costs and revenues among the partners.  Patients are using social networking to review their symptoms, diagnosis and treatments forcing providers to respond.  But providers may also obtain behavioral signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  from social media allowing them to better understand chronic diseases.  Providers must also avoid drowning in the rapidly expanding volume of data.  And it will be essential to adopt predictive statistical models to avoid the increasing likelihood of invalid sampling resulting in false positives are correlations between a random variable and markers of some event of interest.  Over a statistically significant period the correlation of a false positive will fail but in small sample sizes it may hold.  Identifying a statistically significant period is non-trivial.  As more data becomes available via the web and it is applied in BI the problem of false positives will become more significant.   and regression-to-the-mean is an artifact of limited sampling in a statistical study.  In a short time period exceptional scores are possible.  But as more samples are taken the results will shift back to the mean.  Two illustrative examples are Kahneman's explanation of Israeli fighter pilot trail scores and Deming's paddle wheel.  .  So providers must decide on effective governance structures, priorities and effective coherent strategies.  They have lacked the analytics infrastructure to support rapid effective decision making.  This likely requires tools that can do 'what if' analysis and other forms of sophisticated modeling and visualization aims to communicate information clearly and effectively via signals presented as information graphics. 
  .  But integration and analytics tools and methods have improved recently.  And the development of OpenStack and equivalent infrastructure presents opportunities for associative searches to integrate disparate data sources from across the medical neighborhood.  Genome data may allow precision medicine to disrupt previous intuitive medicine businesses. 
  
• Bifidobacterium infantis is a key symbiont is a long term situation between two, or more, different agents where the resources of both are shared for mutual benefit.  Some of the relationships have built remarkable dependencies: Tremblaya's partnership with citrus mealybugs and bacterial DNA residing in the mealybug's genome, Aphids with species of secondary symbiont bacteria deployed sexually from a male aphid sperm reservoir and propagated asexually by female aphids only while their local diet induces a dependency.  If the power relations and opportunities change for the participants then they will adapt and the situation may transform into separation, predation or parasitism. 
  in the human infant microbiome, the trillions of bacteria and viruses that live inside higher animals' guts, on their skin etc.  These bacteria and viruses seem to play a role in: immune responses, digesting food, making nutrients, controlling mental health and maintaining a healthy weight.  The signals from the gut microbiota are relayed by major nerve fibers: vagus; to the central nervous system.  The symbiotic relationship must be actively managed.  In the human gut: Barriers are setup: Mucus secretions form a physical constraint and provide sites for bacteriophages to anchor and attack pathogenic bacteria; Symbiont tailored nourishment: Plant-heavy food creates opportunities for fibre specialists like Bacteroides thetaiotaomicron; is provided, Selective binding sites are provided, Poisons are deployed against the unwelcome, and Temperature, acidity and oxygenation are managed.    High throughput sequencing allows the characterization of bacterial populations inside guts.  Beginning at birth, as they pass down the birth canal infants are supplied with a microbiome from their mothers.  If they are borne via cesarean they never receive some of the key bacteria from their mothers.  A variety of diseases may be caused by changes in the microbiome:
  • Eczema can be related to changes in the skin microbiome. 
    
  • Obesity can be induced by changes to the gut microbiome. 
    
  .  It is selected for by breast milk is a mammalian adaptation.  It provides highly effective nutrition, signalling, protection & controls for newborns, constructed by mothers during 200 million years of evolution.  It includes: Lactose, Fats, Over 200 oligosaccharides, Antibodies, Bacteriophages, & Peptidoglycans; which support the initial adaptations of the mammalian newborn, including its microbiome. 
  's array of oligosaccharides.  This structures the microbiome and helps bootstrap the immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  .  But its transmission to further generations may depend on large families where the children typically cross infect.  It appears to be collapsing in western societies with small nuclear families and a focus on cleanliness. 
  
• Big Data encompasses the IT systems and processes necessary to do population based data collection, management and analysis.  For the analysis to be useful it requires a hierarchy of supporting BI is business intelligence.  Compliance is demanding providers measure, understand and respond to the data about their patients and care.  Hospital groups know they must take steps to allow their data silos to integrate, even as they must take care to follow HIPAA requirements.  And global networking and CMS policies on providing access to their population data creates new business intelligence opportunities and threats.  CMS incentives to adopt ACO structures similarly will require inter-business data visualization to be able to spread costs and revenues among the partners.  Patients are using social networking to review their symptoms, diagnosis and treatments forcing providers to respond.  But providers may also obtain behavioral signals from social media allowing them to better understand chronic diseases.  Providers must also avoid drowning in the rapidly expanding volume of data.  And it will be essential to adopt predictive statistical models to avoid the increasing likelihood of invalid sampling resulting in false positives and regression-to-the-mean.  So providers must decide on effective governance structures, priorities and effective coherent strategies.  They have lacked the analytics infrastructure to support rapid effective decision making.  This likely requires tools that can do 'what if' analysis and other forms of sophisticated modeling and visualization.  But integration and analytics tools and methods have improved recently.  And the development of OpenStack and equivalent infrastructure presents opportunities for associative searches to integrate disparate data sources from across the medical neighborhood.  Genome data may allow precision medicine to disrupt previous intuitive medicine businesses. 
  infrastructure:
• Analytics utilization and integration delivered via SaaS is software as a service. 
  and the Cloud to cope with the silos and data intensive nature. 
  
• Analytics tools (BI) for PHM is population health management.  It aims to use big data to extend the EHR infrastructure to provide cost effective personal treatment.  This implies reengineering the health care payment and delivery process.  
  • IT tools must be developed. 
    
  • Administrative structures must be updated. 
    
  • Clinical processes must be redesigned and accepted.  Successful workflow process reengineering will depend on integration with existing workflows and presence of added value! 
    
  • Payment mechanisms must be overhauled ensuring that the physicians get incented to move on from FFS.  
  • It must be financed.  It is not obvious where this will come from!  Providers like fixed costs.  ROI seems limited atleast initially.  Subscriptions may work for both vendors and providers. 
    
  will be hard to develop.  
• Complex data models must include clinical aspects of the patient specific data, including disease state population wide.  
• A key aspect is providing clear signals about the nature of the data using data visualization aims to communicate information clearly and effectively via signals presented as information graphics. 
  . 
  
• Data communication with the ability to exchange and transact.  HIE a Health Information Exchange is responsible for the transmission of healthcare-related data among facilities, health information organizations and government agencies according to national standards.  They are designed to address legal, organizational and technical challenges that would otherwise impede the sustainability of health information interchange.  An HIE is a component of the HIT.  It must enable reliable and secure transfer of data among diverse systems and facilitate access and retrieval.  The two main types are private and public exchanges.  Private exchanges may be able to leverage homogeneous IT infrastructure to facilitate data sharing.  Public exchanges are likely to be heterogeneous.  RHIO provide the regional organizations to support such HIE.  They are there to ensure that infrastructure amplification initiates.  The government will ensure that low healthcare density areas are served by public HIE infrastructure.  Both centralized and federated technical solutions were initially considered for implementation by the RHIOs for deploying HIE as specified in the Markle Foundation's NHIN common framework.  Common framework clients such as appropriately architected HIE use SOAP messaging to interact with their local SNO's ISB and RLS.  The HIE SOAP query transactions follow the HL7 Query Model.  Alternatively some HIE's are now using direct messaging to support interoperation.  HIE deployment goals have been phased (1 - supporting care transitions, 2 - Quality and care management, 3 - Population health).  Some HIEs will support "EHR-lite" as part of their functionality.  HIE does not yet solve some difficult challenges:
  • Safeguarding the security of health information.  Currently HIEs conforming to the common framework only provide locations of clinical data held remotely.  
  • Providing effective life cycle management.  The HIE is dependent on the local set of entities to provide updates that match the current state of the entity data. 
    
  s and EMPI is enterprise MPI.  These are being developed as part of the frameworks of the CommonWell and Healtheway alliances. 
  alliance approaches are all struggling to provide effective exchange. 
  
• Data labeling and secure access and retreival.  While HIPAA is the Health Insurance Portability and Accountability Act of 1996.  It added part C (administrative simplifications) to the SSA. 
  
  • CFR 45CFR 160.103 is the general provisions section of the regulations.  HIPAA Transactions and Code Sets Standards regulations 45CFR 162.923(a) Covered entities must use adopted transaction standards for inter and intra covered entity transactions.  
  • HIPAA only applies to health care providers, health insurers, clearinghouses of health care data, and their BAs. 
    
  • Initially HIPAA was designed to specify a secure standardized MPI.  Late in the development of the legislation the MPI was viewed as too risky and was removed from the legislation.  
  • The law does not prohibit health care providers from sharing information with family, friends or caregivers unless the patient specifically objects.  Providers can use 'professional judgement' to disclose information to a relative or friend if it is in the best interest of an incapacitated patient. 
    
  • It is also allowed to share general information about a patient's condition and location in a facility. 
    
  • Family members can provide information.  
  • Caregivers who are a patient's personal representative, such as: a health care proxy or guardian or with power of attorney; or who have had the patient authorize the release of information must be provided with it.  
  • HHS office of Civil Rights enforces HIPAA but typically they try to fix problems rather than applying penalties.  
  was initially drafted as a secure MPI is master patient index used by a health care organization to correlate all activity across departments with one patient demographic and medical data for a patient.  The US still lacks a standardized MPI resulting in difficulties with matching patient identities from different systems.  the index was removed from the legislation leaving the US is the United States of America.   without such a tool.  Silos imply that the security architecture will need to be robust. 
  
• Raw data scrubbing, restructuring and standardization.  Even financial data is having to be restandarized shifting from ICD-9 to -10 is the 2009 iteration of the ICD.  ICD is mainly focused on billing.  ICD-10 allows for greater specificity which is assumed to translate into lower rejection rates, easier audit compliance, and better data mining.  ICD is seen as less rich as a representation for clinical record keeping than SNOMED-CT which becomes a concern if the EHR standards force ICD-9 codes to be the required but insufficient representation of a medical procedure.  .  The intent is to transform the unstructured data via OCR is HHS Office of Civil Rights.  It enforces four key privacy and security laws:
  1. HIPAA Privacy Rule.  
  2. HIPAA Security Rule. 
     
  3. HIPAA Breach Notification Rule. 
     
  4. Confidentiality provisions of the Patient Safety Rule. 
     
  and NLP is natural language processing.   to structured records to support the analytics process. 
  
• Raw data warehousing is distributed across silos including PCP is a Primary Care Physician.  PCPs are viewed by legislators and regulators as central to the effective management of care.  When coordinated care had worked the PCP is a key participant.  In most successful cases they are central.  In certain Medicare ACO models (Pioneer) PCPs are committed to achieve meaningful use requirements.  Working against this is the: replacement of diagnostic skills by technological solutions, low FFS leverage of the PCP compared to specialists, demotivation of battling prior authorization for expensive treatments. 
  , Hospital system is the owner of a set of hospitals and other owned infrastructure and employer of direct staff.   and network, cloud and SaaS for process, clinical and financial data. 
  
• Data collection from the patient's proximate environment as well as provider CPOE is computerized provider order entry.  Certified EHR technologies are required to support CPOE ordering of medications, laboratory and radiology/imaging.  CPOE can provide physician support reducing medication errors significantly, as illustrated at Beth Israel.  ISVs such as Surescripts can then route the order to the pharmacy.  , EHR refers to electronic health records which are a synonym of EMR.  EHRs have strengths and weaknesses:
  • The EHR provides an integrated record of the health systems notes on a patient including: Diagnosis and Treatment plans and protocols followed, Prescribed drugs with doses, Adverse drug reactions;
  • The EHR does not necessarily reflect the patient's situation accurately. 
    
  • The EHR often acts as a catch-all.  There is often little time for a doctor, newly attending the patient, to review and validate the historic details. 
    
  • The meaningful use requirements of HITECH and Medicare/Medicaid specify compliance of an EHR system or EHR module for specific environments such as an ambulatory or hospital in-patent setting. 
    
  • As of 2016 interfacing with the EHR is cumbersome and undermines face-to-face time between doctor and patient.  Doctors are allocated 12 minutes to interact with a patient of which less than five minutes was used for recording hand written notes.  With the EHR 12 minutes may be required to update the record!
    
  s, workflow and process infrastructure.  The integration of the EHR into a big data collection tool is key.  
• Bigram is an ordered pair of letters.  The human visual system supports processing of visual data into what and how.  To do this it has two distinct paths: The ventral path and the dorsal path. 
  potentially includes bigram neurons, specialized eukaryotic cells include channels which control flows of sodium and potassium ions across the massively extended cell membrane supporting an electro-chemical wave which is then converted into an outgoing chemical signal transmission from synapses which target nearby neuron or muscle cell receptors.  Neurons are supported by glial cells.  Neurons include a:
  • Receptive element - dendrites
    
  • Transmitting element - axon and synaptic terminals
    
  • Highly variable DNA schema using transposons. 
    
  which respond to specific letter conjunctions.   Dehaene illustrates with the example of a neuron that signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  the presence of a letter 'n' one or two letters to the left of a letter 'a'.  That allows us to discriminate between 'AND' and 'DNA'.  Bigram neurons have not been isolated experimentally.  Dehaene explains how they might work:
• A bigram neuron would collect signals from several partially overlapping detectors with the prior letter fields appearing mostly on the left. 
  
• The bigram detector would end up with greater location invariance than any of the underlying detectors.  
• The architecture would be tolerant to the presence of one or more intermediate letters. 
  
• The underlying letter detectors receptive fields would be spread over part of the retina. 
  
• Billing mediation is a technology which connects a usage report from a piece of network equipment to a billing, configuration or auditing system.  2.5G, 3G and 4G are generation ids of types of architecture of wireless network equipment.  
• Binocular rivalry is a visual illusion caused by presenting each eye are major sensors in primates, based on opsins deployed in the retina & especially fovea, signalling the visual system: Superior colliculi, Thalamus (LGN), Primary visual cortex; and indirectly the amygdala.  They also signal [social] emotional state to other people.  And they have implicit censorious power with pictures of eyes encouraging people within their view to act more honorably.  Eyes are poor scanners and use a saccade to present detail slowly to the fovea.  The eye's optical structures and retina are supported by RPE.  Eyes do not connect to the brain through the brain stem and so still operate in locked-in syndrome.  Evo-devo shows eyes have deep homology.  High pressure within the eye can result in glaucoma.  Genetic inheritance can result in retinoblastoma.  Age is associated with AMD. 
  with a different image.  Consciously we perceive alternately one of the images and then the other.  It was first discovered by Sir Charles Wheatstone in 1838.  
• Bioinformatics develops techniques for storing, retrieving, organizing and analyzing biological data. 
  
• Biological profile of childhood adversity:
• The adversities are stressful and alter stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  
  • The short term response to the stressor
    
  • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
    
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    
  • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    
  • Activates the integration between the thalamus and amygdala. 
    
  • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
    
  • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    
  • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    
  • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    
  • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention. 
    
  • During depression, stress inhibits dopamine signalling. 
    
  • Strategies for stress reduction include: Mindfulness. 
    
  physiology producing children and adults with elevated: Glucocorticoids are corticosteroids which bind the glucocorticoid receptor.  They decrease excitability of prefrontal cortical neurons.  They have adverse effects in fetal/infant development having organizational effects on fetal brain construction and decreasing levels of: growth factors, neurons, synapses; resulting in an adult brain that is more sensitive to environmental triggers of depression and anxiety.  Glucocorticoids affect gene control structures and induce epi-genetic changes.  They have been found associated with high sodium chloride consumption (May 2017). 
  , CRH is corticotropin-releasing hormone which triggers the pituitary to relase ACTH. 
  and ACTH is adrenocorticotropic hormone which stimulates the adrenal glands to release glucocorticoids. 
  , Sympathetic nervous system activity.  Early stress permanently impacts the brains ability to control glucocorticoid secretion.  The more stressors experienced and the less protective factors, the less likely it is that the child will cope and become a resilient adult.  The stressors expand the size and activity of the amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  helping it ignore prefrontal cortex (PFC) is
  
  • The front part of the frontal lobe of the cerebral cortex.  It evolved most recently.  During adolescence when the PFC is still deploying, older brain agents provide equivalent strategies: ventral striatum.  The PFC has been implicated in planning, working memory: dorsolateral; decision making: Orbitofrontal cortex; and social behavior.  Different PFC circuits track internal reward driven strategies and externally signalled advice.  The PFC chooses between conflicting options, letting go or restraint, especially between cognition and emotions.  It imposes an overarching strategy for managing working memory.  It is essential for thinking about multiple items with different labels.  It includes neurons that are interested in particular sub-categories: Dog, Cat.  Once it has made a decision it signals the rest of the frontal lobe just behind it.  Glucocorticoids decrease excitability of the PFC.  
  constraints.  And they degrade the dopamine network are categorized anatomically into three key types:
  • Ultra-short systems,
    
  • Intermediate length systems,
    
  • Long systems. 
    
  through impacts to the development of the mesolimbic system includes projections between the tegmentum and the accumbens, amygdala, hippocampus;
  and elevated adult glucocorticoids depleting dopamine. 
  
• The problems include attachment is John Bowlby's model of mother infant bonding.  He argued that infants need: love, warmth, affection, responsiveness, stimulation, consistency, reliability; or they become anxious, depressed, and/or poorly attached adults.  Evolutionarily, sociopaths may be highly successful as managers and leaders but they are probably anxious.  Sapolsky notes the powerful association between murder rates and stopping pregnant girls from terminating unwanted pregnancies.  Typical mothers also provide training on social conventions and their children's position in the group hierarchy.  Children raised without a mother's support fail to understand social constraints and when to use social behaviors.  And in the presence of unsupportive mothers newborns attach to negative stimuli.  This response is explained by the SHRP.  Abused children subsequently seek out abusive relationships as adults.  And a percentage of infants abused by their mothers become abusive mothers. 
  issues and adults with: depression is a debilitating state which is facilitated by genetic predisposition - for example genes coding for relatively low serotonin levels; and an accumulation of traumatic events.  There is evidence of shifts in the sleep/wake cycle in affected individuals (Dec 2015).  The affected person will experience a pathological sense of loss of control, prolonged sadness, irritability, sleep disturbances, loss of appetite, and inability to experience pleasure.  It affects 12% of men and 20% of women.  It appears to be associated with androgen deprivation therapy treatment for prostate cancer (Apr 2016).  Chronic stress depletes the nucleus accumbens of dopamine, biasing humans towards depression.  Depression easily leads to following unhealthy pathways: drinking, overeating; which increase the risk of heart disease.   It has been associated with an aging related B12 deficiency (Sep 2016).  During depression, stress mediates inhibition of dopamine signalling.  There is an association between depression and particular brain regions: Hippocampal dendrite and spine number reductions, Dorsal raphe nucleus linked to loneliness, Abnormalities of the ACC.  Childhood adversity can increase depression risk by linking recollections of uncontrollable situations to overgeneralizations that life will always be terrible and uncontrollable.  Treatments include: CBT, UMHS depression management.  As of 2010 drug treatments take weeks to facilitate a response & many patients do not respond to the first drug applied, often prolonging the agony.   Genomic predictions of which treatment will be effective have not been possible because: Not all clinical depressions are the same, a standard definition of drug response is difficult; (dopamine depletion and lowered thresholds making adult stressors more influential), anxiety is manifested in the amygdala mediating inhibition of dopamine rewards.  Major anxiety results in elevated glucocorticoids and reduces hippocampal dendrite & spine density.  Some estrogen receptor variants are associated with anxiety in women. 
  , substance abuse (dopamine depletion, excessive adult exposure to glucocorticoids increasing drug craving & poorly developed frontal cortex of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  ), impaired cognitive abilities especially frontocortical with impaired hippocampal is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
  -dependent learning, impaired impulse control (amygdala), impaired emotional are low level agents distributed across the brain and body which associate, via the amygdala and rich club hubs, important environmental signals with encoded high speed sensors, and distributed programs of action to model: predict, prioritize guidance signals, select and respond effectively, coherently and rapidly to the initial signal.  The majority of emotion centered brain regions interface to the midbrain through the hypothalamus.  The most accessible signs of emotions are the hard to control and universal facial expressions.  Emotions provide prioritization for conscious access given that an animal has only one body, but possibly many cells, with which to achieve its highest level goals.  Because of this emotions clash with group goals and are disparaged by the powerful.  Evolutionary psychology argues evolution shaped human emotions during the long period of hunter-gatherer existence in the African savanna.  Human emotions are universal and include: Anger, Appreciation of natural beauty, Disgust, Fear, Gratitude, Grief, Guilt, Happiness, Honor, Jealousy, Liking, Love, Rage, Romantic love, Lust for revenge, Passion, Sadness, Self-control, Shame, Sympathy, Surprise; and the sham emotions and distrust induced by reciprocal altruism.   control, antisocial behavior and violence, relationships that replicate the childhood adversities.  Abused children who develop PTSD is post-traumatic stress disorder, an induced level of stress that is so troubling to the brain that it avoids processing it, change that is necessary if the stress is to be dissipated by the normal brain processes.  The hippocampus loses volume.  The amygdala increases in volume and is hyperactive.  As a result it remains in a heightened state, resulting in fear of recall and further stress.  It is now being realized that PTSD can be introduced into patients by traumatic treatment regimens such as ICU procedures.  Traumatic head injuries, seen in athletes and soldiers can be reflected in PTSD and can subsequently become associated with prion based dementia.   show decreased hippocampal is a part of the brain involved in the temporary storage or coding of long-term episodic memory.  Memory formation in the cells of the hippocampus uses the MAP kinase signalling network which is impacted by sleep deprivation.  The hippocampus dependent memory system is directly affected by cholinergic changes throughout the wake-sleep cycle.  Increased acetylcholine during REM sleep promotes information attained during wakefulness to be stored in the hippocampus by suppressing previous excitatory connections while facilitating encoding without interference from previously stored information.  During slow-wave sleep low levels of acetylcholine cause the release of the suppression and allow for spontaneous recovery of hippocampal neurons resulting in memory consolidation.  It was initially associated with memory formation by McGill University's Dr. Brenda Milner, via studies of 'HM' Henry Molaison, whose medial temporal lobes had been surgically destroyed leaving him unable to create new memories.  The size of neurons' dendritic trees expands and contracts over a female rat's ovulatory cycle, with the peak in size and cognitive skills at the estrogen high point.  Adult neurogenesis occurs in the hippocampus (3% of neurons are replaced each month) where the new neurons integrate into preexisting circuits.  It is enhanced by learning, exercise, estrogen, antidepressants, environmental enrichment, and brain injury and inhibited by various stressors explains Sapolsky.  Prolonged stress makes the hippocampus atrophy.  He notes the new neurons are essential for integrating new information into preexisting schemas -- learning that two things you thought were the same are actually different. 
  volume.  Glucocorticoids decrease hippocampal production of BDNF is brain-derived neurotropic factor which stimulates the formation of new dendrites and synapses. 
  .  Childhood poverty impacts development of the corpus callosum is a large tract of nerve cells that connect the cerebral cortex on one side of the head to that on the other side. 
  & ensures by kindergarten, poor marshmallow test is Stanford psychologist Walter Mischel's experiment studying gratification postponement.  A child is presented with a marshmallow and told that the experimenter is leaving the room and if the child doesn't eat the marshmallow before the experimenter returns he will be given another.  The child is then observed through a two way mirror.  Only a third of the children lasted the fifteen minutes.  To achieve the task the children had to: Trust in the system, avoid hot ideation of the marshmallow, or displace it with cold ideation of the marshmallow or hot ideation of some other object.   It was performed on three to six year olds, but subsequently predicted their SAT scores at high school, social success and lack of aggression, and forty years on more PFC activation during a frontal task and a lower BMI!  performance.  Childhood poverty increases impacts from environmental stressors: Toxins, Liquor stores instead of fresh food markets, No transport infrastructure, Limited jobs in the immediate vicinity, Little access to low cost capital is the sum total nonhuman assets that can be owned and exchanged on some market according to Piketty.  Capital includes: real property, financial capital and professional capital.  It is not immutable instead depending on the state of the society within which it exists.  It can be owned by governments (public capital) and private individuals (private capital). 
  , Low positions in all social hierarchies.  
• Biologics are drugs made in living cells.  Typically they are proteins, a relatively long chain (polymer) of peptides.  Shorter chains of peptides are termed polypeptides.   developed using genetic engineering to develop the cellular host, and to customize animal source, DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  to produce human target proteins.  Biologics solve the problem of previous protein sources, extracted from animals or human sources, of contamination and immune responses has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  .  The strategy is very effective for blood transported proteins such as antibodies is a y-shaped blood transported protein generated by the adaptive immune system's plasma cells, B lymphocytes, to accurately identify and neutralize pathogens such as bacteria and viruses that exhibit a matching antigen. 
  , hormones are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  and blood factors.  But intra-cellular proteins still demand delivery and accurate cell targeting.  This creates analogous problems to those of gene therapy is the deployment of genes into patient's cells to treat or prevent diseases.  It can be performed outside the body (ex vivo) or in place (in vivo).  It requires a vector such as a: Virus, Ligandal style nanoparticle; to perform the deployment.  But viruses are: Difficult to sanitize (bringing in oncogenes etc.) and hard to target as needed,  Unable to target where the DNA is deployed into the target cell chromosomes, Key targets of the immune system.  The process is disease specific:
  • Blood cancers: NHL; can be treated with ex vivo CAR-T (Jul 2017, Oct 2017)
  • Cystic fibrosis requires a virus that infects the airways and then deploys a non-cystic fibrosis allele into the nucleus of the patient's cells.  The obstacles to this process have been challenging: 
    
  • The virus must not have any problematic effects.  In the case of cystic fibrosis one virus activated a cancer gene leaving several trial subjects with leukemia. 
    
  • Efficiency of delivery has to be very high and this has not proved possible as of 2015. 
    
  • The newly delivered DNA must remain intact and be replicated and transcribed.  This has not proved to be the case. 
    
  • The process has not been able to avoid an immune response.  Gene therapy has consequently been of limited value for cystic fibrosis. 
    
  • ADA based SCID was the first human treatment with gene therapy.  A normal ADA gene was inserted ex vivo into immune system cells.  Initially the updated cells did not live as long as needed. 
    
  • Sickle-cell anemia requires a non-sickle-cell trait allele of the hemoglobin gene to be vectored into the bone marrow of the affected person. 
    
  . 
  
• Biology-culture distinction asserts that babies are collections of instincts which parents socialize into competent members of society. 
  
• Bio-MEMS is biomedical/biological microelectromechanical systems.  It is related to LOC is lab-on-a-chip a device that integrates one or several laboratory functions on a single chip.  LOCs allow the use of extreemly small fluid volumes.  It uses microfluidics via a microarray. 
  and MTAS is micro total analysis system meaning a flow chemistry chip integrating the total sequence the lab processes (LOCs) to perform a chemical analysis.   but focuses more on the mechanical parts and microfabrication instead of the flows and lab processes. 
  
• Biopsychosocial model of Dr. George Engel places the patient's social and psychological well being at the core of any medical treatment.  
• Biosimilars are generic drugs made to copy biologics are drugs made in living cells.  Typically they are proteins developed using genetic engineering to develop the cellular host, and to customize animal source, DNA to produce human target proteins.  Biologics solve the problem of previous protein sources, extracted from animals or human sources, of contamination and immune responses.  The strategy is very effective for blood transported proteins such as antibodies, hormones and blood factors.  But intra-cellular proteins still demand delivery and accurate cell targeting.  This creates analogous problems to those of gene therapy. 
  .  They could undermine the pharmaceutical industry's biologic profit model and so are subject to trade constraints: TRIPS are trade-related aspects of intellectual property rights.  These are internationally negotiated rules that constrain members of the WTO to honor patents, copyrights and trademarks.  , TPP is the Trans Pacific Partnership, a twelve country, Pacific regional, trade deal between: Australia, Brunei, Canada, Chile, Japan, Malaysia, Mexico, New Zealand, Peru, Singapore, United States, Vietnam;  The U.S. aims to use the agreement to constrain competition from China.  The initial 12 countries account for more than a quarter of global seafood trade and a quarter of the World's timber and pulp production.  Five of the nations are among the World's most biologically diverse.  The TPP includes:
  • Patents and copyrights chapters. 
    
  • State-owned businesses chapter. 
    
  • Investor-state dispute settlement chapter which enforces extrajudicial tribunals for arbitrating disputes.  The tribunals give investors legal recourse if a government changes policies in ways that hurt the value of their investments. 
    
  • An environmental chapter that covers illegal wildlife trafficking, forestry management, overfishing and marine protection.  Environmentally destructive subsidies, such as cheap fuel for illegal fishing boats and subsidies for boat building in overfished waters are banned.  The chapter enforces Cites with economic sanctions and disallows trade in wildlife taken illegally from a country. 
    
  • Requirements that member countries strengthen port inspections and document checks. 
    
  • Requirements that a country in the agreement take action if they discover contraband that has been harvested illegally, even if the product is not illegal in that country. 
    
  . 
  
• BIS is the Bank for International Settlements based in Basel, Switzerland.  It was initially setup to manage Germany's war reparations payments. 
  
• Bitcoin is a set of open-source software, used to provide infrastructure that supports a distributed cryptocurrency and payment system, based on the blockchain is a bitcoin distributed database technology that allows several bitcoin operators to keep a shared, cryptographically verified, ledger and consensus mechanism to allow agreement on what transactions have happened and in what order.  It implements a Merkle tree.  Six times an hour on average, a new group of validated transactions, a block, is created, added to the local block chain and published to all nodes.  Paraphrasing breadwallet's Aaron Voisine, publishing is robust because: Each operator has connected via references from its initial peers to a random subset of all the other operators; and the new block is offered to the connected peers who can both ask for it if they have not seen it previously from some other source and pass it on to their other peers in a cascade (a gossip network).  To build new blocks an operator must have all the prior blocks in the chain.  All unspent bitcoins are represented [only] in the blockchain.  Miners keep the blockchain consistent by verifying that a new block has a proof-of-work.  This requires that miners find a nonce that multiplied by the block hash is smaller than the network's difficulty target.  .   All transaction inputs are unspent outputs from previous transactions.  All transaction inputs are signed.  Change is provided in an additional output to the transaction. 
  
• BLA is the basolateral amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  , a relatively recently evolved part of the amygdala which learns stimuli to fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
  and then signals, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  the central amygdala is a relatively ancient evolved part of the amygdala which processes 'innate' fears.  It projects to the BNST to raise the heart rate and blood pressure in preparation for fight and flight. 
  .  It recieves inputs from all sensory networks.  Some are fast pathways that allow the BLA to detect and respond when the sensory cortex is unaware.  But it is far less accurate than the cortex.  The BLA's learning involves increased excitability of synapses, a neuron structure which provides a junction with other neurons.  It generates signal molecules, either excitatory or inhibitory, which are kept in vesicles until the synapse is stimulated when the signal molecules are released across the synaptic cleft from the neuron.  The provisioning of synapses is under genetic control and is part of long term memory formation as identified by Eric Kandel.  Modulation signals (from slow receptors) initiate the synaptic strengthening which occurs in memory. 
  coupling the BLA and central amygdala.  This is due to gene driven: Increased levels of growth factors are chemical signals which stimulate cellular growth.  In the brain they induce plasticity. 
  promoting new connections, more receptors for excitatory neurotransmitters in dendritic spines.  The BLA also responds to signals from the frontal cortex that a stimulus no longer appears frightening.  This subset of BLA cells respond inhibiting the associating subset.  Stress and glucocorticoids increase levels of CRH is corticotropin-releasing hormone which triggers the pituitary to relase ACTH. 
  and BDNF is brain-derived neurotropic factor which stimulates the formation of new dendrites and synapses. 
  encouraging the building of new dendrites and synapses. 
  
• Black-Scholes algorithm can solve the contingent investment discount rate dilemma for pricing options.  It establishes a tracking portfolio with the same payoffs as the option and dynamically tracks the portfolio as the stock price evolves, adjusting the value of the option.  It is argued that the adjustment ensures the rate of return to a hedge position remains constant over time. 
  
• Bladder cancer affects 77,000 new people each year in the US.  And there are 16,000 deaths.  It is typically fast growing, and is often associated with mutated Ras is the master controller of the MAP kinase-phosphorylation cascade.  Ras is a GTPase.  It is a prototypical monomeric G protein.  In the GTP-bound state its activity is switched on.  In the GDP-bound state it is switched off.  It is anchored to the cell membrane where it interacts with linkers.  The linkers connect Ras with membrane-bound RTKs, which provide it with signals from growth-promoting factors: EGF.  Ras then activates Raf kinase.  Mutated Ras is found in a high proportion of colon and bladder cancers.  , which may indicate it can be treated by reducing the methylation of the DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  (Dec 2015).   A rare form is plasmacytoid is a rare and aggressive bladder cancer. 
  .  Bladder cancer is traditionally treated with surgery, chemotherapy is the treatment of cancers by highly cytotoxic chemicals: Paclitaxel, Platinum, 6-mercaptopurine; assuming that cancer cells are unusually active and will be differentially poisoned.  It has been successful in offering treatments when no other course was available, but non-specificity means that healthy cells also get poisoned resulting in side effects which increase with age: Permanent nerve damage, heart failure (4-5%) and leukemia (0.5-1%). 
  and radiation but these have not been effective with the advanced disease.  New treatments are being deployed:
• Immuno-oncology uses the immune system to treat cancer.  Cancer cells often have different molecules on their cell surface.  Studies have shown that genetic signatures of tumors can help predict which patients will benefit from treatment with PD-1 checkpoint inhibitors.  Checkpoint inhibitor based treatments aim to make the immune system target these antigens.  Clinical trial results indicate they are prolonging lives - even if only by a few months.  They have reduced side effects relative to generic chemo therapy.  There are three main strategies: cellular, antibody and cytokine.  
  • Antibody therapies target receptors including CD20, CD274, CD279 and CTLA-4.  These therapies include MABs: Alemtuzumab, Ofatumumab, Rituximab; and may induce checkpoint inhibition.
    
  • Cellular therapies have typically involved removing the immune cells from the blood or a tumor, activating, culturing and then returning them to the patient.  Trials of these CAR and TCR therapies are proceeding, with some significant problems (Jul 2016). 
    
  • Cytokine therapies enhance anti-tumor activity through the cytokine's regulation and coordination of the immune system. 
    
  • Vaccines, including Sipuleucel-T for prostate cancer and BCG, classically a vaccine for tuberculosis, which is used for treating bladder cancer. 
    
  immune checkpoint inhibitor release the immune system's checkpoints on attacking host cells: by 1) stopping T-cell division and 2) reducing their life spans.  They are used in immuno-oncology where, in 2016: They are approved for treatment of: Advanced melanoma, HL, lung, kidney, liver cancer; They have a general success rate of 20 - 40% and higher for melanoma.   Checkpoint inhibitors work best for tumors that have many mutations: melanomas, lung and bladder cancers.  They are enhanced by adjunct treatments that kill tumor cells generating debris to stimulate the immune system.  The drugs include: ipilimumab, nivolumab, pembrolizumab, atezolizumab;  They are costly and often have high copayments.  They cause auto-immune side effects including inflammation, rheumatoid arthritis and damage to glands: Adrenal, Thyroid, Pituitary.  Powerful steroids such as prednisone can help reduce the inflammation.  Damaged glands require sustained hormone treatment.  Checkpoint inhibitor research is funded by the CRI.  Tecentriq (May 2016) is approved for locally advanced or metastatic urothelial carcenoma which accounts for 90% of bladder cancers is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).  , where the disease is not controlled by platinum chemotherapy.  Bladder cancer tends to result in many mutations which typically present to the immune system has to support and protect an inventory of host cell types, detect and respond to invaders and maintain the symbiont equilibrium within the microbiome.  It detects microbes which have breached the secreted mucus barrier, driving them back and fortifying the barrier.  It culls species within the microbiome that are expanding beyond requirements.  It destroys invaders who make it into the internal transport networks.  As part of its initialization it has immune cells which suppress the main system to allow the microbiome to bootstrap.  The initial microbiome is tailored by the antibodies supplied from the mother's milk while breastfeeding.  The immune system consists of two main parts the older non-adaptive part and the newer adaptive part.  The adaptive part achieves this property by being schematically specified by DNA which is highly variable.  By rapid reproduction the system recombines the DNA variable regions in vast numbers of offspring cells which once they have been shown not to attack the host cell lines are used as templates for interacting with any foreign body (antigen).  When the immune cell's DNA hyper-variable regions are expressed as y-shaped antibody proteins they typically include some receptor like structures which match the surfaces of the typical antigen.  Once the antibody becomes bound to the antigen the immune system cells can destroy the invader. 
  making it a good candidate for immuno-oncology. 
  
• Blindsight is a condition induced by lesions in the primary visual cortex is the visual gateway into the cortex.  .  It deprives sufferers of their concious vision and they behave as though blind.  But they respond unconsciously to the objects that are no longer processed by consciousness. 
  
• Blockbuster, a business model which requires substantial resources to produce the product, but also generates outsize returns if it converts a majority of its potential market into customers.  
• Blockchain is a bitcoin is a set of open-source software, used to provide infrastructure that supports a distributed cryptocurrency and payment system, based on the blockchain.   All transaction inputs are unspent outputs from previous transactions.  All transaction inputs are signed.  Change is provided in an additional output to the transaction. 
  distributed database technology that allows several bitcoin operators to keep a shared, cryptographically verified, ledger and consensus mechanism to allow agreement on what transactions have happened and in what order.  It implements a Merkle tree is a form of tree structure where every non-leaf node is labelled with a hash of the labels (values for leaf children) of its child nodes.  This tree is used by: Git, BitTorrent and bitcoin. 
  .  Six times an hour on average, a new group of validated transactions, a block, is created, added to the local block chain and published to all nodes.  Paraphrasing breadwallet's Aaron Voisine, publishing is robust because: Each operator has connected via references from its initial peers to a random subset of all the other operators; and the new block is offered to the connected peers who can both ask for it if they have not seen it previously from some other source and pass it on to their other peers in a cascade (a gossip network).  To build new blocks an operator must have all the prior blocks in the chain.  All unspent bitcoins are represented [only] in the blockchain.  Miners search the bitcoin blockchain for nonces.  Any new nonces they identify they can trade for the current market value of a bitcoin.  In performing the search they will also verify the integrity of the current blockchain.  To perform the computationally costly search miners build optimized computing networks. 
  keep the blockchain consistent by verifying that a new block has a proof-of-work.  This requires that miners find a nonce is a bitcoin proof-of-work that when included in the new block's header and hashed, results in a block hash that is smaller than the networks difficulty target.  The nonce is computationally easy to verify but very costly to generate.  The difficulty target is varied according to a pre-defined algorithm to maintain the six-per-hour block average no matter how many miners are attempting to generate block nonces. 
  that multiplied by the block hash is smaller than the network's difficulty target.  
• Blue Button is a web-based patient portal provides web and or application based access to a patient's EHR based health care information and services.  Specific portal services are mandated by meaningful use.  They include at a minimum lab test results, problem list, medication list, and medication allergy list. 
  .  A tool that patients can use to download, view, print and transmit personal health information.  It was specified and developed by the VA - Department of Veterans Affairs.  Includes the Veterans Health Administration.  , HHS is the U.S. Department of Health and Human Services.   and DOD - U.S. Department of Defense. 
  .  There are multiple versions:
• First version is download only, with an unstructured format and best for reading and printing on download. 
  
• '+' version supports effective download and transmission bringing Blue Button in line with MU is the set of standards defined by CMS Incentive Programs that governs the use of electronic health records and allows eligible providers and hospitals to earn incentive payments by meeting specific criteria.  It aims to ensure that ARRA subsidies for HIS are used to generate health improvements.  It is staged:
  1. 2011-2012 Data capture and sharing - Criteria focus on electronically capturing health information in a standardized format.  Using that information to track key clinical conditions.  Communicating that information for care coordination processes.  Initiating the reporting of clinical quality measures and public health information.  Using information to engage patients and their families in their care.  Achieving meaningful use stage 1 requires meeting all core and selected menu objectives. 
     
  2. 2014 Advance clinical processes - More rigorous health information exchange requirements.  Increased requirements for e-prescribing and incorporating lab results.  Electronic transmission of patient care summaries across multiple settings.  More patient-controlled data.  A patient portal is required.  CMS hospital core measures, CMS hospital menu set measures, NPRMs of stage 2 meaningful use and certification criteria have been announced (2013).  
  • MU2 requires EHR systems to support direct messaging to send PHI to registered users. 
    
  3. 2016 Improved outcomes - Improving quality, safety, and efficiency, leading to improved health outcomes.  Decision support for national high-priority conditions.  Patient access to self-managed tools.  Access to comprehensive patient data through patient-centered HIE.  Improving population health.  
  2.  It uses a structured format (C-CDA refers to Consolidated-CDA a HL7 standard used to meet 2014 EHR Certification Criteria for MU stage 2.  Consolidation pulled together disparate HL7 IGs to stop them diverging and drive a single source for CDA templates. 
  + electronic EOB is explanation of benefits - sent by a health insurance company to covered individuals explaining what was covered. 
  ).  It transmits via Direct messaging is a secure messaging technology used by HIEs (& Blue Button+) to directly interoperate.  It uses SMIME body in a SMTP protocol and X.509 certification. 
  .  It supports automation via triggers.  The automation/changes to data require multipe transmissions.  Third party applications holding data that is sent as a trust bundle will 
• Blue Cross initially developed in the early 1930s to provide health insurance for hospital treatments.  Blue Cross introduced the mechanism of individuals paying premiums into a collective pool that a third party can then use to pay for medical expenditures.  The subscriber base was limited until World War 2 when wages were frozen and employers offered a benefit of health insurance tied to employment.  Being associated with employment made the facility regressive since those working part-time or in small businesses had to pay for services out of pocket and could induce bankruptcy is a legal status for an entity that cannot repay its creditor's loans.  It holds creditor lawsuits in abeyance while the restructuring process proceeds to allow the entity to continue operations.  It also has legal tools for forcing holdout creditors to accept repayments that are lower than the bond sale initially promised. 
  . 
  
• Blue Shield initially developed in the early 1930s to provide health insurance for physician visits.  
• BMI is body mass index.  
• BNST is the bed nucleus of the stria terminalis.  It receives 'innate fear is an emotion which prepares the body for time sensitive action: Blood is sent to the muscles from the gut and skin, Adrenalin is released stimulating: Fuel to be released from the liver, Blood is encouraged to clot, and Face is wide-eyed and fearful.  The short-term high priority goal, experienced as a sense of urgency, is to flee, fight or deflect the danger.  There are both 'innate' - really high priority learning - which are mediated by the central amydala and learned fears which are mediated by the BLA which learns to fear a stimulus and then signals the central amygdala. 
  ' signals from the central amygdala is a relatively ancient evolved part of the amygdala which processes 'innate' fears.  It projects to the BNST to raise the heart rate and blood pressure in preparation for fight and flight. 
  .  It projects to: Parts of the hypothalamus is essential to many operations of the body.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, and similar body operations.  Its (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).   that initiate the hormonal are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  stress is a multi-faceted condition reflecting high cortisol levels.  Dr. Robert Sapolsky's studies of baboons indicate that stress helps build readiness for fight or flight.  As these actions occur the levels of cortisol return to the baseline rate.  A stressor is anything that disrupts the regular homeostatic balance.  The stress response is the array of neural and endocrine changes that occur to respond effectively to the crisis and reestablish homeostasis. 
  
  • The short term response to the stressor
    
  • activates the amygdala which: Stimulates the brain stem resulting in inhibition of the parasympathetic nervous system and activation of the sympathetic nervous system with the hormones epinephrine and norepinephrine deployed around the body, Activates the PVN which generates a cascade resulting in glucocorticoid secretion to: get energy to the muscles with increased blood pressure for a powerful response.  The brain's acuity and cognition are stimulated.  The immune system is stimulated with beta-endorphin and repair activities curtail.  But when the stressor is
    
  • long term: loneliness, debt; and no action is necessary, or possible, long term damage ensues.  Damage from such stress may only occur in specific situations: Nuclear families coping with parents moving in.  Sustained stress provides an evolved amplifier of a position of dominance and status.  It is a strategy in female aggression used to limit reproductive competition.  Sustained stress:
    
  • Stops the frontal cortex from ensuring we do the harder thing, instead substituting amplification of the individual's propensity for risk-taking and impairing risk assessment! 
    
  • Activates the integration between the thalamus and amygdala. 
    
  • Acts differently on the amygdala in comparison to the frontal cortex and hippocampus: Stress strengthens the integration between the Amygdala and the hippocampus, making the hippocampus fearful. 
    
  • BLA & BNST respond with increased BDNF levels and expanded dendrites persistently increasing anxiety and fear conditioning. 
    
  • Makes it easier to learn a fear association and to consolidate it into long-term memory.  Sustained stress makes it harder to unlearn fear by making the prefrontal cortex inhibit the BLA from learning to break the fear association and weakening the prefrontal cortex's hold over the amygdala.  And glucocorticoids decrease activation of the medial prefrontal cortex during processing of emotional faces.  Accuracy of assessing emotions from faces suffers.  A terrified rat generating lots of glucocorticoids will cause dendrites in the hippocampus to atrophy but when it generates the same amount from excitement of running on a wheel the dendrites expand.  The activation of the amygdala seems to determine how the hippocampus responds. 
    
  • Depletes the nucleus accumbens of dopamine biasing rats toward social subordination and biasing humans toward depression. 
    
  • Disrupts working memory by amplifying norepinephrine signalling in the prefrontal cortex and amygdala to prefrontal cortex signalling until they become destructive.  It also desynchronizes activation in different frontal lobe regions impacting shifting of attention. 
    
  • During depression, stress inhibits dopamine signalling. 
    
  • Strategies for stress reduction include: Mindfulness. 
    
  response, Midbrain and brain-stem includes: medulla, raphe, pons, substantia nigra, ventral tegmental area, pituitary, superior colliculi, cerebellum, thalamus (LGN), basal ganglia including caudate nucleus and striatum; amygdala, hypothalamus, nucleus accumbens; networks that activate the sympathetic nervous system and inhibit the parasympathetic.  Winning in competition induces the addition of testosterone is a hormone secreted by the testes in response to stimulation from the hypothalamic/pituitary/testicular cascade, that makes humans more willing to do what it takes to attain and maintain status, according to Sapolsky.  That means players of the Ultimatum Game, if previously given testosterone can become more generous.  Testosterones effect is highly socially contextual so it may encourage acts of kindness or aggression (when challenged).  The level of testosterone does not predict which individuals will be aggressive in: Birds, Fish, Mammals including primates.  Genes impact the potency of testosterone by altering the enzymes that: Construct it, Convert it to estrogen, code the androgen receptor.   This androgen receptor includes a variable polyglutamine repeat which alters the sensitivity to the testosterone signal.  The more potent form is associated with boys showing more dramatic 'masculinization' of the cortex.  But the detected genetic influences are small.  Testosterone decreases activity in the prefrontal cortex and its functional coupling to the amygdala while increasing the coupling between the amygdala & the thalamus.  Testosterone shortens the refactory period of amygdaloid & amygdaloid target neurons.  This results in impulsive risk taking and more focus on unfamiliar faces and distrust of them.  Testosterone increases activity in the ventral tegmentum projecting dopamine to enhance place preference.  Winners of fights become more willing to fight in part due to testosterone increasing confidence and optimism and reducing fear and anxiety.  And winning at: Chess, Athletics, Stock trades; induces the BNST to add testosterone receptors increasing its sensitivity to the hormone.  People become overconfident and overly optimistic. 
  receptors increasing the sensitivity of the BNST to the hormone.  That will lead to reduced fear and increased confidence. 
  
• Body scan is a mindfulness is an active meditative state of non-doing, attentively seeking each 'present moment' with ones body and mind 'being' at rest and so cultivating awareness.  The thinking mind usually spends a lot of time relating to the future and past which Kabat-Zinn argues limits its ability to become fully aware of the present.  In times of stress those thoughts are so overpowering that they crowd out awareness and appreciation of the present.  Mindfulness shifts attention to calming internal feelings.  It allows review and prioritization of thoughts as they are recognized.  Major attitude based pillars of successful mindfullness are: impartial to judging, patience, a beginner's mind, trust, non-striving, acceptance of seeing things the way they are, and letting go.  An awareness of the body's state can be built from attention to:
  • Breathing - which is a proxy for the environmental situation and through its rhythms is a model of our emotional state.  Attention to breathing reminds people to feel their bodies too.  Belly breathing is particularly relaxing.  
  • Sitting - erect with head, neck and back aligned vertically.  Then attend to breathing moving back to it each time you observe the mind has wandered.  When the body becomes uncomfortable direct attention to the discomfort and observe and welcome it.  
  • Experience our body - rather than model, judge or hate it relative to an ideal - with a body scan. 
    
  • Hatha yoga - very slow stretching and strengthening exercises with moment-to-moment awareness supports being in your body.  
  • Walking meditation - Intentionally attend to the immediate experience of walking.  
  meditation exercise where the attention is moved around the body noticing the sensations of the visited part.  At the same time the brain models the visited part participating in flows in and out of the body with tensions and pain amplifies the aggression response of people by interoceptive signalling of brain regions providing social emotions including the PAG projecting to the amygdala; making aggressive people more so and less aggressive people less so.  Pain is the main reason people visit the ED in the US.   signals flowing out.  Move the mind to each part and feel it.  Breath in to and out from each region.  Imagine breathing in vitality and relaxation on each in breath.  Imagine the tensions are exhailed with the out breath.  As you let go of the sensations the muscles also let go of tensions.  First from the toes of the left foot to the pelvis and then the right foot to the pelvis.  From there move up through the torso, lower back and abdomen, upper back and chest, sholders.  Then from the fingers of both hands move simultaneously up both arms returning to the shoulders.  Then move through the neck and throat, all regions of the face, back of the head and top of the head to an imaginary hole at the top of the head where we release our breath. 
  
• Bonding, there are different types of chemical bonds.  Ionic bonds stabilize two oppositely charged ionized atoms when the negative atom gives up an electron to the positively charged atom.  Covalent bonds stabilize the two reactants when they adopt a more stable structure with electrons shared between them.  Hydrogen bonds stabilize charged groups when they are surrounded by water molecules, multiple atoms bonded together.  The physical and chemical phenomena associated with the molecule such as charge, size, shape, and potential energy reflect the constituent atoms, the types of bonds between them and the topology of the bonding.  Charged molecules dissolve in aqueous solutions (water).  Uncharged molecules dissolve in lipid bilayers.  .  In
  This page discusses the interdependence of perception and representation in a complex adaptive system (CAS).  Hofstadter and Mitchell's research with Copycat is reviewed. 
  
  Copycat codelets can bond two
  This page describes the Copycat Workspace. 
  The specialized use of the Workspace by the adaptive web framework's (AWF) Smiley is discussed. 
  How text and XML are imported into the Smiley Workspace is described. 
  Telomeric aging of schematic structures is introduced. 
  The internal data structure used to represent the state of each workspace object is included. 
  The Workspace infrastructure functions are included. 
  
  Workspace objects together.  In the
  This page describes the Adaptive Web framework (AWF) test system and the agent programming framework (Smiley) that supports its operation. 
  Example test system statements are included.  To begin a test a test statement is loaded into Smiley while Smiley executes on the Perl interpreter. 
  Part of Smiley's Perl code focused on setting up the infrastructure is included bellow. 
  The setup includes:
  

  • Loading the 'Meta file' specification,
    
  • Initializing the Slipnet, and Workspaces and loading them
    
  • So that the Coderack can be called. 

  The Coderack, which is the focus of a separate page of the Perl frame then schedules and runs the codelets that are invoked by the test statement structures. 
  
  Smiley implementation a bondbuilder adds a bonding descriptor to one of the objects bonding it to the other. 
  
• Bowling alley, in Geoffrey Moore's marketing strategies is a metaphor for focusing on a limited market segment, so as to capture and own it with a discrete product repeatedly. 
• BPCI bundled payments for care improvements is a CMS is the centers for Medicare and Medicaid services.   initiative to explore bundled payments is where the purchaser disburses a single predefined payment to cover certain combinations of hospital, physician, post-acute, or other services performed during an episode of care relating to a particular condition (unlike capitation).  This bundling is assumed to allow the value delivery system to optimize around low cost high quality long term health care.  With one bundled payment physicians & hospitals must coordinate care and reduce the unit costs to remain profitable.  And to avoid taking on risk of expensive complications physicians & hospitals are incented to standardize and focus on quality.  This optimization is dependent on quantifying the value of the outcome of the episode of care.  Previously FFS payments induced excessive treatment activity.  Bundled payment is included in CMS ACE demonstrations and BPCI initiatives.  There are significant impacts on IT. 
  
  1. It is argued that effective pricing of the bundle requires marketing data which must be extracted from the historic transaction base.  
  2. Billing and payment systems must be updated to handle the receipt and distribution of the bundled payments. 
     
  3. Care delivery must be re-architected to reduce costs and improve quality. 
     
  4. Monitoring sensors can be used to feed reports to ensure re-architected operations conform.  
  .  Its purpose is to incent multiple types of provider to coordinate care reducing expenses associated with care episodes - An episode of care is the treatment of a specific medical condition during a set period of time.  After MedPac recommended episode based payment bundling for inpatient hospital care it has become a key focus of Medicare incentive strategies. 
  .  CMMI is the center for Medicare and Medicaid Innovation.  It is a test bed for new ways of financing and delivering care.  It allowed Congress to institutionalize innovation sending a signal to providers that they would be participating in CMS driven programs that could become mainstream.  It funds evaluations of innovative health care models.  Under the ACA if the HHS secretary finds any of its projects would reduce Medicare spending without harming the quality of care the projects may be expanded nationwide.  The CBO estimates the CMMI will save $34 billion between 2016 and 2026.  CMMI projects include:
  • Medicare will make a bundled payment for hip and knee replacement surgery (CJR) and 90 days of follow-up care forcing hospitals to work closely with doctors, nursing homes and home health agencies.  
  • New ways to pay for prescription drugs, medical devices, cancer care (OCM).  
  • HHS secretary has invoked his 3021 authority to institute DPP. 
    
  accepts providers' proposals to test the four different bundled payment models.  The program consists of:
• Seeking voluntary participation in four bundled payments models. 
  
• Model 1: 3 days pre-acute + hospital inpatient stay.  
• Model 2: 3 days pre-acute + hospital inpatient stay + inpatient MD services + post-acute facility services + post-acute MD services + related readmissions have become a source of increased revenue for hospitals.  But with government interested in reducing the US health care cost curve ACA's HRRP (pay-for-performance), BPCI and CTI and Interact discharge initiative have all increased the focus on unnecessary readmissions.  Now the end-to-end process is under scrutiny with hospitals reengineering discharge (RED) and PAC providers using RAI and TCN. 
  . 
  
• Model 3: Post-acute facility services + post-acute MD services + related readmissions. 
• Models 1 - 3 provide retrospective reimbursement is the payment process for much of US health care.  Reimbursement is the centralizing mechanism in the US Health care network.  It associates reward flows with central planning requirements such as HITECH.  Different payment methods apportion risk differently between the payer and the provider.  The payment methods include:
  • Fee-for-service,
    
  • Per Diem,
    
  • Episode of Care Payment, 
  • Multi-provider bundled EPC,
    
  • Condition-specific capitation,
    
  • Full capitation.  
  . 
  
• Models 2 - 3 include post episode reconciliation.  
• Model 4: 3 days pre-acute + hospital inpatient stay + inpatient MD services + related readmissions. 
  
• Model 4 offers a single prospective payment. 
  
• Acute care hospitals, physicians groups, health systems eligible for all models; post-acute facilities may participate without hospitals in Model 3. 
  
• Physicians eligible for gain sharing bonuses up to 50% of traditional fee schedule. 
  
• For all models, applicants must propose quality measures, which CMS will use to develop a set of standardized metrics. 
  
• BPIP is best practices intervention package for transitional care is a set of discharge - have costly handoff problems reviewed by project BOOST.  When discharge takes too long it ties up acute bed space which can result in adding up to 30% more (unnecessary) capacity when improved discharge would translate into additional revenue.  Various interventions aim to improve the execution of the process including: CTI, TCN and RED for discharge to outpatient; InterAct for discharge to SNFs and BPIP to HHAs.  Discharge information can include:
  • Patient info
    
  • Behavioral summary
  • Treatment history
  • Medical history
  • Treatment objectives
  • Insurance policy
  • Discharge plans
  improvement strategies for hospital to HHA is home health agency. 
  s. 
  
• Bracciolini, Pogio invented a highly effective writing script and discovered and replicated a copy of Lucretius's poem On The Nature Of Things as
  An epistatic meme suppressed for a thousand years reemerges during the enlightenment. 
  It was a poem encapsulating the ideas of Epicurus rediscovered by a humanist book hunter. 
  Greenblatt describes the process of suppression and reemergence.  He argues that the rediscovery was the foundation of the modern world. 
  Complex adaptive system (CAS) models of the memetic mechanisms are discussed. 
  
  
  described by Steven Greenblatt. 
  
• BRAF is a human gene that codes for the protein B-Raf is a serine/threonine protein kinase homologous with PKC.  It is a key signalling protein.  Growth factor signalling flows through Raf to the MAP Kinase cascade.  . 
  
• Brain-computer interfaces use custom silicon chips with thousands of electrodes can be implanted in the cortex includes the paleocortex a thin sheet of cells that mostly process smell, archicortex and the neocortex.  The cerebral cortex is a pair of large folded sheets of brain tissue, one on either side of the top of the head connected by the corpus callosum.  It includes the occipital, parietal, temporal and frontal lobes.   of experimental animals to increase the bandwidth of connections between the brains and researchers' computers.  
• Brain stem includes: medulla includes nuclei that control vital functions such as regulation of the cardiovascular system, respiration, and skeletal muscle tone.  It also contains nuclei that relay somatosensory information from the spinal cord to the thalamus. 
  , raphe consists of a group of nuclei running through the core of the brain stem from the medulla to the back of the midbrain.  It projects to the tegmentum, accumbens, prefrontal cortex, & amygdala where serotonin enhances dopamine's effects on goal-directed behavior.  The raphe is associated with:
  
  • Neural mechanisms of sleep and waking.  Jouvet and Renault produced large lesions that destroyed 80 - 90 % of the raphe in cats inducing complete insomnia for 3-4 days.  Slow-wave, but not REM sleep, gradually returned, but never exceeded 2.5 hours a day.  Sleep amount correlates to the 5-HT concentration.  The neurons of the raphe nuclei are rich in serotonin (5-HT).  It is suspected that the dorsal raphe nuclei inhibit the phasic components of REM sleep and thus prevent them from occurring at inappropriate times.  The activity of serotonergic neurons is low during REM sleep and higher at other times.  The dorsal raphe nucleus has been associated with 
  • Depression.  
  • Impulsive aggression which is associated with relatively low serotonin levels.   
  , pons is part of the brain stem.  It includes nuclei that support sleep and arousal.  , substantia nigra is part of the mid-brain's motor system.  It contains dopamine secreting neurons with high levels of D(2) that project to the caudate nucleus.  In a rare hereditary subset of early onset Parkinson's disease a mutation in the alpha-synuclein gene causes degeneration of the substantia nigra. 
  , ventral tegmental area is part of the tegmentum which contains dopamine long system cell bodies (high levels of D(2)).  Their axons branch extensively and reach many areas including: Mesolimbic to the limbic system: amygdala, hippocampus; Tegmentostriatal to the nucleus accumbens, Mesocortical to the forebrain including the prefrontal cortex.  The terminals are fairly evenly distributed through out layers 1 - 6.  So dopamine can modulate input and output excitatory and inhibitory transmissions.  If a rodent wins a fight on his home territory, there are long-lasting increases in levels of testosterone receptors enhancing pleasurable effects.  The lateral ventral tegmental area is now known to be one of two large adrenergic pathways, along with the locus ceruleus.  During child birth the ventral tegmentum deploys more oxytocin receptors increasing its sensitivity to the neuropeptide.  
  , pituitary is a protrusion off the bottom of the hypothalamus.  The anterior lobe regulates stress, growth, reproduction and lactation.  The intermediate lobe synthesizes and secretes melanocyte stimulating hormone.  The posterior lobe is functionally connected to the hypothalamus by the pituitary stalk. 
  , superior colliculi are a pair of structures at the top of the brain stem that contribute to the visual system.  They are called the optic tecta in lower vertebrates.  In mammals and especially primates much of this visual processing operates in the neocortex.   The superior colliculi in mammals still support eye movement, including involuntary eye movements.  Neurons in the superior colluculus code the location of auditory stimuli in eye-centered reference frame.  , cerebellum is involved with the efficiency of fine movement. It modulates the force and range of motion and is involved in motor coordination and the learning of motor skills.  Damage to the cerebellum impairs standing, walking, or performance of coordinated movements. A virtuoso pianist or other performing musician depends on their cerebellum.  The cerebellum receives visual, auditory, vestibular, and somatosensory information.  It also receives information about individual muscular movements being directed by the brain.  The cerebellum integrates this information and modifies the motor outflow, exerting a coordinating and smoothing effect on the movements.  However, patients born without a cerebellum have survived reasonably well.  The cerebellum is part of the implicit learning mechanism.  It is required for the rabbit eye-blink to be classically conditioned to respond to a sound, and puff of air (threat to eye).  It integrates the sound and puff and outputs the response to the motor area (blink).
  , thalamus has all the main inputs to the cortex passing through it.  It is massively supplied with return innervations from the cortical regions it routes too.  It does not stand on the route of the main exits from the cortex.  The parafascicular nucleus of the rat thalamus contains relatively high levels of D5 dopamine receptors.  For human vision the primary system connects to the neocortex via a small part of the thalamus the LGN.   (LGN is lateral geniculate nucleus.  It is a contradiction:
  
  • It looks like a relay and nothing more.  Both anatomically and physiologically it seems to be a relay.  The principal cells receive inputs from the retina and send outputs, seen radiating out to the visual cortex, to the first visual area (V1) of the neocortex (in primates - in cats they go to a number of visual areas).  These axons have very few collateral branches to other principal cells or to other parts of the LGN.  There is a direct map from retinal area to primary visual cortex area.  But Francis Crick argued in contradiction to this
    
  • It is probably doing something a lot more complicated which we do not yet fully understand!  The macaque LGN has six layers.  The inputs from two eyes and M & P cells within them are all kept separate within the LGN.  
  • Two of these layers have large cells (magnocellular).  One of them gets its inputs from the right eye, the other from the left eye.  There is little interaction between the layers.  Their input is mainly from the M cells of the retina.  These two layers specialize in detecting movement and flicker. 
    
  • Four of the layers are smaller (parvocellular).  They receive input from the P cells of the retina.  They seem to carry signals relating to color, texture, shape & steropsis. 
    
  • The LGN neurons also get input coming back from the first visual area of the cortex.  There are many more axons coming back than go to the neocortex from the LGN.  However, they tend to synapse onto those parts of the dendrites rather distant from the cell bodies so their effects are probably subdued. 
  • There are also inputs from the brain stem that modulate the behavior of the thalamus and especially its reticular nucleus.  This means that the LGN freely transmits visual information in the awake animal but blocks this transmission somewhat when the animal is in slow wave sleep.  
  • Dehaene identifies the LGN as at the base of a hierarchy of reading neurons signalling local contrasts and oriented bars.  The signals reach
    
  • V1 which associates them with oriented bars,
    
  • V2 - letter fragments,
    
  • V4 Letter shapes,
    
  • V8 abstract letters,
    
  • Left occipital temporal sulcus - bigrams,
    
  • Left occipital temporal sulcus - small words, frequent substrings and morphemes. 
    
  ), basal ganglia are a set of nuclei near the base of the brain that operate an evolved neural network that unconsciously models the attentional value of each potential object of thought.  It includes the: dorsal striatum which is involved in habit and the ventral striatum which is associated with rewards for winning and losing money. 
  including caudate nucleus is a motor area which is involved in the inhibitory control of movement and includes high levels of D(1), D(2) and some D(3) dopamine receptors.  It is part of the basal ganglia - striatum.  It also includes the putamen and globus pallidus. 
  and striatum (basal ganglia) is a brain region which is important in learning motor habits.  To do this the ventral striatum assigns values to winning. 
  ; amygdala contains > 12 distinct areas: Central, Lateral.  It receives simple signals from the lower parts of the brain: pain from the PAG; and abstract complex information from the highest areas: Disgust from the insula cortex.  It sends signals to almost every other part of the brain, including to the decision-making circuitry of the frontal lobes.  It has high levels of D(1) dopamine receptors.  During extreme fear the amygdala drives the hippocampus into fear learning.  It outputs directly to subcortical reflexive motor pathways when speed is required.  Its central nucleus projects to the BNST.  It signals the locus ceruleus.  The amygdala:
  
  • Promotes aggression.  Stimulating the amygdala promotes rage.  It converts anger into aggression and when impaired it impacts the ability to detect angry facial expressions.  
  • Participates in disgust
  • Perceives fear promoting stimuli.  In PTSD sufferers the Amygdala overreacts to mildly fearful stimuli and is slow to calm down and the amygdala expands in size over a period of months.  Fear is processed by the lateral nucleus which serves as the input from various senses, and the central nucleus which outputs to the brain stem (central grey - freezing, lateral hypothalamus - blood pressure, activates paraventricular hypothalamus => crf -> hormone adjustments). 
    
  • Has lots of receptors for and is highly sensitive to glucocorticoids.  Stress inhibits the GABA interneurons in the basolateral amygdala (BLA) allowing the excitatory glutamate releasing neurons to excite more. 
    
  • Is sensitive to unsettling/uncertain social situations where it promotes anxiety.  It is also interested in uncertain but potentially painful situations.  The amygdala contributes to social and emotional decision making where the BLA supports rejecting an unacceptable offer, as allowed in the Ultimatum Game, by injecting implicit mistrust and vigilance, generating an anger driven rejection that is used as punishment.  The amygdala is very rapidly excited by subliminal signals from the thalamus of outgroup skin color.  The amygdala subsequently tips social emotions against outgroups unless restrained by the frontal lobe or influenced by subliminal priming to prioritize inclusion.  The fast path from the thalamus rapidly but inaccurately signals its identified a weapon. 
    
  • Promotes male, but not female, sexual motivation when it is an uncertain potential pleasure. 
    
  • Responds to the longing for uncertain potential pleasures and fear that the reward will not be worth it if it happens.  The amygdala turns off during orgasm. 
    
  • Uses but is not directly involved in vision. 
    
  , hypothalamus is essential to many operations of the body.  It has many small sub-regions whose main functions are to regulate hunger, thirst, temperature, sexual behavior, and similar body operations.  Its (paraventricular nucleus) is closely connected to the pituitary which secrets hormones into the bloodstream ( => acth -> adrenal cortex => cortisol (+)->  amygdala & (-)-> hippocampus).  , nucleus accumbens is a region of the basal forebrain rostral to the preoptic area and immediately adjacent to the septum.  The nucleus accumbens was closely associated with the limbic system and plays an important role in reinforcement.  If a rodent wins a fight on his home territory, there are long-lasting increases in levels of testosterone receptors enhancing pleasurable effects.  When prairie voles first mate, epi-genetic state changes are induced in the accumbens to support pair-bonding.  The accumbens projects to brain regions associated with movement.  The major pathways of dopaminergic neurons begin in the substantia nigra and the ventral tegmental area.  The amygdala projects back to the accumbens.  The tegmentostriatal system begins in the ventral tegmental area and projects to the nucleus accumbens.  The nucleus accumbens includes high levels of D1, D2 and D3 dopamine receptors located on the spine & shafts of dendrites of excitatory cells reduce the transfer of excitation from the dendrites to the cell bodies, so only especially strong excitatory inputs get through to the cell body to elicit excitation.  It also has D4 dopamine receptors which are highly variable.  The accumbens responds differently to rewards depending on maturity: In juveniles all reward levels result in the same response activity level, During adolescence the accumbens responds to small rewards negatively, and large rewards hugely, In adults the rewards result in measured scaled positive responses.  Chronic stress depletes dopamine from the nucleus accumbens biasing humans towards depression.  ;
• BRCA is breast cancer type 1 or 2 susceptibility gene.  The two types provide related cellular functions maintaining the validity of the cell.  If either gene product fails there is an increased likelihood of cancer is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).  .  Still individuals with mutations in BRCA1/2 genes account for only 5 to 10 percent of breast cancers.  The:  
• Type 1 gene codes for a protein that supports DNA (DNA), a polymer composed of a chain of deoxy ribose sugars with purine or pyrimidine side chains.  DNA naturally forms into helical pairs with the side chains stacked in the center of the helix.  It is a natural form of schematic string.  The purines and pyrimidines couple so that AT and GC pairs make up the stackable items.  A code of triplets of base pairs (enabling 64 separate items to be named) has evolved which now redundantly represents each of the 20 amino-acids that are deployed into proteins, along with triplets representing the termination sequence.  Chemical modifications and histone binding (chromatin) allow cells to represent state directly on the DNA schema.  To cope with inconsistencies in the cell wide state second messenger and evolved amplification strategies are used. 
  repair and where this is not possible can stimulate cell death, programmed cell death is a signal initiated DNA controlled process which results in eukaryotic cells self-destructing.  .  Hence if the protein becomes defective one or both of these key caretaker functions may stop and increase the susceptibility to cancer.  The BRCA1 protein has multiple actions.  It:
  
• Combines with other tumor suppressors, DNA damage sensors and cellular signal, is an emergent capability which is used by cooperating agents to support coordination & rival agents to support control and dominance.  In eukaryotic cells signalling is used extensively.  A signal interacts with the exposed region of a receptor molecule inducing it to change shape to an activated form.  Chains of enzymes interact with the activated receptor relaying, amplifying and responding to the signal to change the state of the cell.  Many of the signalling pathways pass through the nuclear membrane and interact with the DNA to change its state.  Enzymes sensitive to the changes induced in the DNA then start to operate generating actions including sending further signals.  Cell signalling is reviewed by Helmreich.  Signalling is a fundamental aspect of CAS theory and is discussed from the abstract CAS perspective in signals and sensors.  In AWF the eukaryotic signalling architecture has been abstracted in a codelet based implementation.  To be credible signals must be hard to fake.  To be effective they must be easily detected by the target recipient.  To be efficient they are low cost to produce and destroy. 
  transducers to form the BASC surveillance complex monitoring the health of the cells DNA. 
  
• Associates with RNA (RNA), a polymer composed of a chain of ribose sugars.  It does not naturally form into a paired double helix and so is far less stable than DNA.  Chains of DNA are converted by transcription into equivalently sequenced messenger m-RNA.  RNA also provides the associations that encode the genetic code.  Transfer t-RNAs have a site that maps to the codon and match the associated amino-acid.  Stuart Kauffman argues that RNA polymers may be the precursor to our current DNA based genome and protein based enzymes.  In the adaptive web framework's (AWF) Smiley we use a similar paradigm with no proteins. 
  pol is an enzyme which generates a multi-component nucleic acid polymer chain by bonding the monomer molecules together using an existing DNA or RNA molecule as a template.   II to support transcription is the process where DNA is converted into messenger m-RNA.  A complex of enzymes cooperates to bind to the DNA and generate the m-RNA copy.  There are a number of such transcription complexes which are based on RNA polymerase I, II or III. 
  . 
  
• Interacts with histone, in the eukaryotic cell are enzymes which bind to the DNA polymers supporting them and controlling their interactions with other enzymes.  In particular sets of DNA operons can be enabled or disabled by histone induced changes in the DNA polymers shape.  In AWF the histone control of DNA has been abstracted in a codelet based implementation of operon controlled programmed case control. 
  deacetylase to regulate transcription.  
• It is a marker of high risk of breast and uterine cancer. 
  
• It was collaboratively researched by Dr. Mary-Claire King and Francis Collins's labs studying chromosome 17 using genomics combines recombinant DNA, DNA sequencing and bioinformatics  to sequence, assemble and analyse genomes.  .  
• In 1990 Dr. King had reported to ASHG is the American Society of Human Genetics. 
  evidence of 'this' single gene linked to a highly heritable form of breast cancer.  
• Over the next two years the labs gathered details of BRCA1, allowing families with the mutation to understand their individual risk and plan for their futures.  
• In 1993 BRCA1 was identified by Mark Skolnick of Myriad Genetics. 
  
• Type 2 gene codes for a protein that binds both single stranded DNA and the recombinase RAD51 to facilitate homologous recombination.  
• Advice from Dr. Collins, for families who have a history of breast or ovarian cancer includes:
• Counselling women with the high risk BRCA mutations, about the risk of breast and ovarian cancer and the treatments available
• Telling women who choose watchful waiting to have periodic MRI is magnetic resonance imaging where the nucleus of any atom with a net spin will produce a response to the signal.  The variety of molecules that can be detected has generated a variety of specialized medical applications. 
  s.  And warn that watchful waiting is unreliable for ovarian cancer allowing metastasis before detection.  
• Prophylactically removing the ovaries and Fallopian tubes on completion of childbearing.  
• Teaching about breast reconstruction and recommending prophylactic mastectomy.  
• Males with BRCA mutations should have careful surveillance for: Prostate is cancer of the prostate gland.  Genomics detected several common DNA variants associated with increased risk of prostate cancer.  Dr. Francis Collins explains that a cluster of these risk variants lies in a stretch of 1 million DNA base pairs on chromosome 8.  The cluster contains seven or more risk variants, each of which can raise the risk of prostate cancer by 10 to 30%.  The high risk variants occur more frequently in African-American men than European or Asians.  African-Americans die from prostate cancer at more than twice the rate of Europeans.  Research in mice may explain a link between obesity and prostate cancer (Jan 2018).  The average diagnosis is at age 66.  Worldwide in 2012 there were 1.1 million cases from which 307,000 died.  A common life-saving (Feb 2017) treatment is androgen deprivation therapy, but it has worrying side effects.  Various classically defined types of cancer can occur.  The most common is adenocarcinoma associated with the epithelial gland cells that generate seminal fluid.  Epithelial cell differentiation potency makes these significant cancer agents.  Other very rare types of cancer that can start in the prostate are:
  • Sarcomas
  • Small cell carcinomas
  • Neuroendocrine tumors
  • Transitional cell carcinomas
    
  , Pancreatic is most often an exocrine tumor.  Islet cell tumors are less common.  These are rare cancers: less than 200,000 US cases per year, but the five year survival rates are extremely low 3%.  They all have KRAS mutations.  Diagnostics are starting to leverage genomics and big databases (23 and me).  Treatments include:
  • Avastin
    
  • Tarceva 
  and breast cancer.  
• No one being given the test without being fully counselled beforehand about the implications of the result.  Negative results may bring survivor guilt while positive results will need careful management.  
• Breast cancer is a variety of different cancerous is the out-of-control growth of cells, which have stopped obeying their cooperative schematic planning and signalling infrastructure.  It results from compounded: oncogene, tumor suppressor, DNA caretaker; mutations in the DNA.  In 2010 one third of Americans are likely to die of cancer.  Cell division rates did not predict likelihood of cancer.  Viral infections are associated.  Radiation and carcinogen exposure are associated.  Lifestyle impacts the likelihood of cancer occurring: Drinking alcohol to excess, lack of exercise, Obesity, Smoking, More sun than your evolved melanin protection level; all significantly increase the risk of cancer occurring (Jul 2016).   conditions of the breast tissue.  World wide it is the leading type of cancer in women and is 100 times more common in women than men.  The varieties include: Hormone are signalling molecules: ACTH, TRH, Melanocyte stimulating hormone, Testosterone, Oxytocin, Vasopressin, Insulin, Growth hormone, Estrogen, Progesterone, Angiotensin II, Asprosin, EPO, Irisin, Leptin, FGF21 hormone, Prostaglandins, TSH, Thyroxine, Glococorticoids; that are transported by the circulatory system to interact with target organs having appropriate receptors.  The levels of hormones can fluctuate massively, as in pregnancy. 
  sensitive tumors that test negative for her2 (the most common type affecting three quarters of breast cancers in the US is the United States of America.  , BRCA is breast cancer type 1 or 2 susceptibility gene.  The two types provide related cellular functions maintaining the validity of the cell.  If either gene product fails there is an increased likelihood of cancer.  Still individuals with mutations in BRCA1/2 genes account for only 5 to 10 percent of breast cancers.  The:  
  • Type 1 gene codes for a protein that supports DNA repair and where this is not possible can stimulate cell death.  Hence if the protein becomes defective one or both of these key caretaker functions may stop and increase the susceptibility to cancer.  The BRCA1 protein has multiple actions.  It:
    
  • Combines with other tumor suppressors, DNA damage sensors and cellular signal transducers to form the BASC surveillance complex monitoring the health of the cells DNA. 
    
  • Associates with RNA pol II to support transcription. 
    
  • Interacts with histone deacetylase to regulate transcription.  
  • It is a marker of high risk of breast and uterine cancer. 
    
  • It was collaboratively researched by Dr. Mary-Claire King and Francis Collins's labs studying chromosome 17 using genomics.  
  • In 1990 Dr. King had reported to ASHG evidence of 'this' single gene linked to a highly heritable form of breast cancer.  
  • Over the next two years the labs gathered details of BRCA1, allowing families with the mutation to understand their individual risk and plan for their futures.  
  • In 1993 BRCA1 was identified by Mark Skolnick of Myriad Genetics. 
    
  • Type 2 gene codes for a protein that binds both single stranded DNA and the recombinase RAD51 to facilitate homologous recombination.  
  • Advice from Dr. Collins, for families who have a history of breast or ovarian cancer includes:
  • Counselling women with the high risk BRCA mutations, about the risk of breast and ovarian cancer and the treatments available
  • Telling women who choose watchful waiting to have periodic MRIs.  And warn that watchful waiting is unreliable for ovarian cancer allowing metastasis before detection.  
  • Prophylactically removing the ovaries and Fallopian tubes on completion of childbearing.  
  • Teaching about breast reconstruction and recommending prophylactic mastectomy.  
  • Males with BRCA mutations should have careful surveillance for: Prostate, Pancreatic and breast cancer.  
  • No one being given the test without being fully counselled beforehand about the implications of the result.  Negative results may bring survivor guilt while positive results will need careful management.  
  1/2 positive, ductal carcinomas including DCIS is ductal carcinoma in situ where abnormal cells have been found piled up confined to the lining of the milk ducts of the breast.  They are detectable in a mammogram and can look like cancer cells to a pathologist.  The cells could be spread along the whole of the milk duct suggesting a need for mastectomy rather than lumpectomy analogous to cervical cancer treatments after a Pap test.  It is now known that the DCIS may disappear over time, or stop growing and remain stable.  No data is available detailing a correlation with breast cancer.  But it is now understood that metastatic cancers are different from localized cancers. 
  , lobular carinomas including LCIS.  Receptor presence on the cancer cells is used as a classification: Her2 is a gene encoding the protein 'human epidermal growth factor receptor 2', which is similar in structure to the native receptor HER1. 
  +/-, estrogen (ER)+/-, progesterone (PR)+/-.  Metastasis classes the cancer as stage 4.  Genetic risk factors include: BRCA, p53 is a tumor suppressor which improves the specificity of transcription's DNA binding and promotes the transcriptional activity of E2F.  P53's activity is controlled by phosphorylation by cyclin Cdk complexes allowing indirect control of the cell cycle.  Among the many genes controlled by p53 are cyclin genes, genes for an inhibitor of cyclin-dependent kinases (Cdk), and the bax gene, which promotes apoptosis.  p53 can thus promote cell proliferation.  It can drive cells into apoptosis.  But it can also stop cell proliferation by arresting the cell cycle.  Normally there is a dynamic balance between proliferation of cells and their death.  In cancer proliferation may become unregulated due to oncogenic mutations or over expression of key regulatory signalling G proteins such as Ras.  Mutations of the p53 suppressor gene are the most frequent suppressor gene mutations in human cancers.  Elephants like humans, have a relatively low buildup of cancer with age.  Elephant's cells have twenty copies of p53 gene pairs which ensure cells with damaged DNA go into apoptosis blocking cancer onset. 
  , PTEN is a gene encoding the protein phosphatidylinositol-3,4,5-triphospate 3- phosphatase, which controls apoptosis through the PI3K/Akt pathway.  Mutations which inhibit the action of the protein allow cells to remain alive when they have been signalled to die.  A potentially cancerous situation. 
  , STK11, CHEK2, ATM, GATA3 is a gene for a transcription factor regulating luminal epithelial cell differentiation into mammary gland.  In mutations which up-regulate the differentiation, cancer can be induced.  , BRIP1 and PALB2.  Treatments include: Tamoxifen is a cancer treatment (initially breast cancer) that was discovered in 1967 and is now a WHO essential medicine.  , Raloxifene; where worrying racial disparities have been found (Dec 2013). 
  
• BRICS is Brazil, Russia, India, China and South Africa; the set of country's with economies which grew rapidly in 2008 - 2013. 
  
• Bringing criminal charges against corporations is the title of Clinton Administration Deputy Attorney General Eric Holder's 1999 memo setting rules for deciding if to prosecute corporate cases.  It included:
• A series of factors to be considered when deciding whether to charge a company:
• Completeness of its disclosure including a waiver of attorney-client and work product protections
• If the corporation seems to be protecting its culpable employees and agents. For example by advancing attorney fees.  This turned out to be very problematic implyimg to judges that DOJ - U.S. Department of Justice. 
  was trying to limit the ability of defendents to get a good defense. 
  
• A later section titled 'Charging the Corporation: Collateral Consequences' which introduced factors that might influence the decision to file charges.
  
• Broca's area is the inferior frontal cortex of the cerebral cortex is at the front of the brain.  It includes the: prefrontal cortex, motor cortex.  Sapolsky asserts it makes you do the harder thing when it's the right thing to do.  The frontal cortex supports working memory to sustain focus on a task.  It also coordinates the strategic actions necessary to achieve success.  It provides impulse control, regulation of emotion, and willpower.  The prefrontal cortex maintains focus by deprioritizing currently irrelevant streams of information.  The frontal cortex tracks rules.  Over a lifetime that builds into a costly activity.  Once it tires responses become less prosocial.  But practice shifts operation of tasks to the cerebellum.  The frontal cortex signals the tegmentum and accumbens with the conclusions of its expectancy/discrepancy calculations.  The frontal lobe provides executive function, considering bits of information, assessing patterns and then prioritizing the strategies.  The frontal lobe is the most recent part of the brain to evolve and involves a disproportionate percentage of primate-unique genes in its development and operation.  It does not complete development until the mid-20s.  It includes spindle neurons.  It is easily damaged.  Sapolsky (Nauta) notes that its ventromedial prefrontal cortex is a quasi-member of the limbic system. 
  .  It is involved with spoken language.  Lesions have resulted in an inability to speak or write even though language is understood.  
• Broken link analyzer is a Perl is Larry Wall's programming language.  It is designed to make easy tasks easy and hard tasks possible.  It has powerful text processing features and can interpret a string of text as code. 
  script, typically launched as a child process within the configuration editor is the graphical user interface that allows its users to generate dark web pages, check the links of dark webs, and change the filters and frame configuration files that control the generation process. 
  , by clicking 'find broken links', which checks each relative file based HTML link in a dark web is a web site that is not open to the Internet.  It is a set of deployed HTML files in a directory which refer to each other via file based references relative to the directory.   reachable from an initial target file in the dark web directory.  It repeats the analysis for all the pages that it is requested to open.  With the highly connected topology of a planning web it is expected to reach all the files in the web from any start point.  It reports any links which did not resolve to target HTML IDs within the web's pages and any links where the file specified could not be opened. 
  
• Broken windows is a 1982 crime theory of James Wilson and George Kelling, that was inspired by the results of vandalism experiments by Philip Zimbardo, which assumes urban disorder and vandalism undermine social constraints and encourage additional criminal and anti-social behavior.  By detecting and responding to petty vandalism rapidly it is assumed that more serious crime will be discouraged.  In New York Broken Windows was used to justify 'stop, question and frisk'.  However, Donohue & Levitt's analysis suggests an observed precipitous drop in crime rates depended on legal access to abortion. 
  
• Bronchitis is an inflammation of the medium size airways in the lung.  It is defined clinically as a persistent cough with mucus is used to cover tissues that are exposed.  It is made from mucins.  Mucous membranes may secrete mucus to generate a robust barrier. 
  .  
• BSD is Berkeley Software Distribution, an operating system based on UNIX is a computer operating system.  It is a registered trademark of AT&T. 
  's architecture. 
  
• Bullies often come from families with single mothers or younger parents with low
  Salman Khan argues that the evolved global education system is inefficient and organized around constraining and corralling students into accepting dubious ratings that lead to mundane roles.  He highlights a radical and already proven alternative which offers effective self-paced deep learning processes supported by technology and freed up attention of teams of teachers.  Building on his personal experience of helping overcome the unjustified failing grade of a relative Khan:
  

  • Iteratively learns how to teach: Starting with Nadia, Leveraging short videos focused on content, Converging on mastery, With the help of neuroscience, and filling in dependent gaps; resulting in a different approach to the mainstream method. 
    
  • Assesses the broken US education system: Set in its ways, Designed for the 1800s, Inducing holes that are hidden by tests, Tests which ignore creativity.  The resulting teaching process is so inefficient it needs to be supplemented with homework.  Instead teachers were encouraging their pupils to use his tools at home so they could mentor them while they attended school, an inversion that significantly improves the economics. 
    
  • Enters the real world: Builds a scalable service, Working with a real classroom, Trying stealth learning, At Khan Academy full time,  In the curriculum at Los Altos, Supporting life-long learning. 
    
  • Develops The One World Schoolhouse: Back to the future with a one room school, a robust teaching team, and creativity enabled; so with some catalysis even the poorest can