Socio cultural situation

Socio-cultural situation

Summary

In this page we review the proximate socio-cultural situation. 

Socio-cultural trends are discussed. 

Introduction

Heath care markets are key aspects of the US economy. 



Subtle socio-cultural effects influence the complex diseases of modern health care:




Socio-cultural complexity must be understood to be managed by the US health care network. 


Contents
  • Finding a good hospital leverages social networking (Aug 2016)
  • Microbeads are tiny plastic orbs.  They are used as abrasives in toothpastes and anti-acne lotions. 
    in the food chain (Aug 2015
  • PFAS are (poly|per)flouroalkyl substances.  They help with non-stick and water and stain resistance.  They have been implicated in testicular and kidney cancer, hypothyroidism, ulcerative colitis and other health problems.   contamination and 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).   (Jun 2015)
  • Complex 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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    issues in decisions about replacement water & sewer pipes.  Lobbyists: American Chemistry Council; have backed bills in states: Michigan, Ohio, South Carolina, Indiana, Arkansas; requiring local government to open up bids to all suitable materials: plastic; leveraging Koch Brothers' American Legislative Exchange Council & American City County Exchange (Nov 2017)
  • Calls for tougher regulation of toxic household chemicals (Jul 2016)
  • Paraquat is NN-dimethyl-44-bipyridinium dichloride, a systemic weed killer, used on oranges, coffee and suger cane, manufactured and sold by the Swiss pesticide company Syngenta.  It is banned in the EU, but still allowed to be sold and used in the US.  Drinking even a sip can be lethal.  Recent research by the NIH links paraquat to Parkinson's disease.  The 2011 research found Iowa and North Carolina farmers and family members that handled paraquat or rotenone were 2.5 times more likely to develop Parkinson's disease.  A 2012 study found paraquat increased the likelihood 11 fold for people with certain genetic variations.  The link is disputed by Syngenta. 
    linked to 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. 
    EPA is the Environmental Protection Agency of the Federal government. 
    considers restrictions in US is the United States of America.    (Dec 2016)
    • Syngenta's Eric Fyrwald responds (Jan 2017)
  • Syngenta linked to influence of scientists researching collony collapse disorder (Jan 2017)
  • P.M.F. is progressive massive fibrosis, a deadly form of the coal-mining disease 'black lung'.  It is caused by inhaling silica dust released during mining coal seams.   epidemic is the rapid spread of infectious disease: AIDS (Oct 2016), Cholera (2010), Clostridium difficile (May 2015), Ebola, Influenza, Polio, SARS, Tuberculosis, Typhoid (Apr 2018), Malaria, Yellow fever, Zika; to large numbers of people in a population within a short period of time -- two weeks or less.  Epidemics are studied and monitored by: NIAID, CDC, WHO; but are managed by states in the US.  Infection control escalation is supported by biocontainment units: Emory, Nebraska.  Once memes are included in the set of infectious schematic materials, human addictions can present as epidemics concludes Dr. Nora Volkow of the NIDA.  CEPI aims to ensure public health networks are effectively prepared for epidemics.  PHCPI aims to strengthen PCPs globally to improve responsiveness to epidemics.  GAVI helps catalyze the development and deployment of vaccines.  Sporadic investment in public health enables development of conditions for vector development: Mosquitos.  The increasing demands of the global population are altering the planet: Climate change is shifting mosquito bases, Forests are being invaded bringing wildlife and their diseases in contact with human networks.  Globalized travel acts as an infection amplifier: Ebola to Texas.  Health clinics have also acted as amplifiers: AIDS in Haiti, C. diff & MRSA infections enabled & amplified by hospitals.  Haiti earthquake support from the UN similarly introduced Cholera. 
    among miners in Appalachia (Dec 2016)
  • Health Care opens paths for Women (Feb 2015)
  • Dilemma of terminal treatments (late stage 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%). 
    questioned 24 Jul 2015, Rituxan 28 Jul 15, Difficulty in timing death from heart failure Aug 2015)
  • 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. 
    treatment based on Roche 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. 
    approved by F.D.A. Food and Drug Administration. 
    May 2016 
  • Problematic 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).   with 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: Caretaker proteins, detect and repair mutations of the DNA.  Genes coding for mismatch proteins include: MLH1, MSH2, MLH3.  Mutations in these genes are associated with high risk of colon and uterine cancer.  The gene BRCA1 is also involved in DNA repair.  
    ; inhibition, respond to 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. 
    blocker - Keytruda (Jun 2017)
  • Advanced Kidney Cancer - There are expected to be 61,560 new cases of kidney cancer in the US 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, high blood pressure, genetic mutations and heredity.   responds to MAB as a terminator in medication names indicates the drug is a monoclonal antibody biologic.  s and NIBs Sep 2015 
  • F.D.A. Food and Drug Administration. 
    commissioner Gottlieb champions easier drug approval.  But the approach exposes methodological issues: 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.  , reduced pressure to innovate is the economic realization of invention and combinatorial exaptation.  While highly innovative, monopolies: AT&T, IBM; usually have limited economic reach, constraining productivity and supporting the use of regulation, or even its threat, that can drive their creations across the economy. 
    , limited impact on value based drug pricing strategy, reduced feedback from smaller trials, targeted is a medical strategy where decisions, practices, and products are tailored to the individual patient.  Research is looking at the impact of providing potentially deleterious genomic testing information to people: The REVEAL study found no increased anxiety induced by hearing that one's genome implied increased risk of developing late onset Alzheimer's disease.  The take-up of personalized medicine benefits from the focus on genomics detailed by the NIH director Francis Collins and includes:
    • NCCN intensive cell therapies
    • Direct to consumer genomic testing
    • Direct to consumer diagnostics
    • Pharmacogenomics tailored drug treatments reducing the risk and cost of adverse drug reactions.   
    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).   therapies 2% success rate.  Faster approval does not affect the patient's price experience (Jun 2018)
  • Married people have lower rates of death from melanoma is a cancer of the melanocytes.  It is a less common form of skin cancer but is the most deadly once it has invaded deeply into layers of skin.  It is primarily caused by UV light.  It is tied to mutations in the signalling pathway (BRAF) and regulatory genes (P53) with a key dependency on crestin reactivation (Jan 2016).   (Apr 2018)
  • 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.   transplants get new tweak (Mar 2016)
  • Mysteries of the heart (Jun, Jul 15)
  • Stroke treatment improvements
  • 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.   while a young adult correlated with heart failure (Jul 15)
  • Blood pressure guidelines should be lowered (Sep 2015
  • Blood pressure associated with John Henryism (Jan 2017)
  • Breast feeding 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 - many of them targeted at support of Bifidobacterium infantis, Antibodies, Bacteriophages, & Peptidoglycans; which support the initial adaptations of the mammalian newborn, including its microbiome. 
    prevents later heart attacks is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    (Aug 2015)
  • Aspirin (acetylsalicylic acid) is a pain, fever and inflammation medicine.  It is a platelet aggregation inhibitor.  While its NNT is 2000 for cardiovascular disease prophylaxis, it is so cheap that this strategy is still important.  It has been found beneficial in limiting esophageal cancer. 
    recommendation as a colorectal 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;  and heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    preventative criticised (Sep 2015)
  • Exercise associated with reduced 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. 
    of 13 cancers (May 2016)
  • Collapsed environment limits welfare strategies 
  • 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
    drug Jardiance cut cardiovascular deaths 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). 
    by 38% (Sep 2015)
  • Diabetes cases start to decline (Dec 2015)
  • Potatoes increase 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. 
    of 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.   (May 2016
  • Idle children risk developing cardiovascular problems (Sep 2015)
  • A.D.H.D. is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    diagnosis rises (Nov 2015) and treatment options may expand (Nov 2015)
  • Talc is a naturally occuring clay mineral composed of magnesium and silicon.  It is soft and is used in cosmetic products (blush etc.), tablets, chewing gum and some rice.  It is often mined in the proximity of asbestos which requires manufacturers to avoid contamination.  The WHO's IARC has designated talc a possible human carcinogen if used in the female genital area.  Pediatricians discourage its use on babies and condom and surgical glove manufacturers have stopped dusting their products with talc. 
    associated with ovarian cancer is a relatively uncommon disease but is often fatal.  It has been associated with use of talcum powder (May 2016).   (May 2016)
  • Chilli peppers prevent heart and respiratory disease and cancer (Aug 2015)
  • Moderate alcohol consumption reduces the risk of 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). 
    (Nov 2016)
  • Coffee is associated with reduced risks of death from heart disease is cardiovascular disease which 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). 
    other causes (Nov 2015)
  • Tea associated with reduced risks of hepatocellular carcinoma is the sixth most frequent cancer globally, and the second leading cause of cancer based death.  It is mainly associated with cirrhosis from hepatitis B, C,  or alcohol, but there is also a correlation with obesity (Aug 2016).  The most common liver cancer is HCC.  Immature hepatocytes can produce hepatoblastomas.  Some types of the fungus Aspergillus produce aflatoxins, which can be dangerous to children when ingested or to adults in chronic exposure causing cirrhosis and carcinoma of the liver.  Aflatoxin metabolites intercalate into DNA and alkylate the bases.  This causes mutations in p53. 
    , 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 (Aug 2018) 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. 
    steatosis, liver cirrhosis is collapse of liver cell buffer function from long term damage due to: hepatitis, chronic alcoholism, fatty liver disease, hemochromatosis, obesity, and many other causes; with normal liver tissue being replaced by scar tissue. 
    , chronic liver disease, 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.  Michael Pollan concludes depression is fear of the past.  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 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). 
    (Oct 2015)
  • Supplements
  • CDC is the HHS's center for disease control and prevention based in Atlanta Georgia.  
    data analysed by Michigan's Dr. Tapper, shows cirrhosis is collapse of liver cell buffer function from long term damage due to: hepatitis, chronic alcoholism, fatty liver disease, hemochromatosis, obesity, and many other causes; with normal liver tissue being replaced by scar tissue. 
    deaths expanded 65% from 1999 to 2016, to 34,174.  Increases were most significant following 2008.  The most significant increases were in 25 to 34 year old adults.  Young adults are drinking heavily but there is no causal link yet.  The cirrhosis is leading to increased liver cancer is the sixth most frequent cancer globally, and the second leading cause of cancer based death.  It is mainly associated with cirrhosis from hepatitis B, C,  or alcohol, but there is also a correlation with obesity (Aug 2016).  The most common liver cancer is HCC.  Immature hepatocytes can produce hepatoblastomas.  Some types of the fungus Aspergillus produce aflatoxins, which can be dangerous to children when ingested or to adults in chronic exposure causing cirrhosis and carcinoma of the liver.  Aflatoxin metabolites intercalate into DNA and alkylate the bases.  This causes mutations in p53. 
    which increased 3% from 2008 to 2016 with 11,073 deaths (Jul 2018)
  • 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).   after prostate 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
    surgery found in NCI is the national cancer institute. 
    study to save lives after reccurence (Feb 2017)
  • Mediterranean diet reduces breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    (Sep 2015, Nov 2015)
  • Whole milk better than low-fat (Nov 2016)
  • Fruit and vegetables reduce risk of cataracts (Mar 2016)
  • Oral contraceptives lowers the risk of endometrial cancer (Aug 2015)
  • Major 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.  Most women diagnosed with early stage DCIS have surgical or chemotherapy treatment, which does not alter their life expectancy (Aug 2015).  No data is available detailing a correlation with breast cancer.  But it is now understood that metastatic cancers are different from localized cancers. 
    study questions use of aggressive treatment (Aug 2015, Cardiologist is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   comment Aug 2015)
  • Breast implant procedure change: leveraging ADM is accelular dermal matrix, generated by a soft tissue matrix graft where decellularization leaves the extracellular matrix intact. 
    ; removes the need to use chest muscle to retain the implants.  Issues include: cost of the material, infection control undermined, radiation treatment complicated; but it is less likely to induce 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.  , allows the implants to be added during the breast removal, does not impact the chest muscle (Sep 2018)
  • Early stage breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    aromatase inhibitor limit the synthesis of estrogen by aromatase.  Breast and ovarian cancers grow more stimulated by estrogen. 
    treatment study shows no change in mortality (Jun 2016). 
  • Lifestyle and cell situation affect cancer (Jul 2016)
  • Wellbeing is described by Angus Deaton as all the things that are good for a person:
    • Material wellbeing includes income and wealth and its measures: GDP, personal income and consumption.  It can be traded for goods and services which recapture time.  Material wellbeing depends on investments in:
      • Infrastructure
        • Physical
        • Property rights, contracts and dispute resolution
      • People and their education
      • Capturing of basic knowledge via science.  
      • Engineering to turn science into goods and services and then continuously improve them. 
    • Physical and psychological wellbeing are represented by health and happiness; and education and the ability to participate in civil society through democracy and the rule of law.  Life expectancy as a measure of population health, highly weights reductions in child mortality. 

  • Culture
  • Clinical announcement not followed for ten years (Aug 2015, Statins are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.   Aug 2015 heart scan Oct 2015)
  • Hernia's
  • Osteoporosis
    • Drugs rare side effects deter use (Jun 2016)
    • Radius bone building drug has successful trial (Aug 2016)
  • Osteoarthritis
    • Can be minimized before it develops (Sep 2016)
  • Social media signals and modelling
  • Social services net reduced (Oct 05 Florida 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. 
    , )
  • Loneliness
  • 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). 
    (Aug 2015 ACA drives market)
  • Wellness
  • Freedom
  • Sleep
  • Allergies
  • Autoimmune disease
  • Schizophrenia is a chronic, psychotic, brain disorder that affects 1.1 percent of the adult U.S. population.  It is characterized by hallucinations, delusions and disorganized and unusual thinking.  It seems to be caused by over pruning of prefrontal cortex neurons (Jan 2016).  There is evidence that some cases occur because of particular CNVs in the DNA of the sufferers: ZNF804A. 
    (Oct 15)
  • Policing



  • Aug 2015 NYT The Tiny Orb Threatening the Great Lakes

    The Great Lakes, the largest fresh water ecosystem on earth has been found to be highly polluted with microbeads.  Once the beads enter water they attract toxic substances, like PCBs.  They become part of the aquatic food chain.  And so they are eaten by fish and eventually humans. 

    When Great Lakes fish are dissected, "they are festooned with microbeads" said Henry Henderson, director of the National Resource Defense Council's Midwest office in Chicago. 
    Besides vectoring toxins the beads cause abrasions and can stunt the growth of fish. 

    Lake Ontario is the most microbead polluted of the lakes. 

    Microbeads are too small to be filtered by current water treatment plants.  The plants could be retrofitted but the cost would be high.  Instead states are considering restrictions on the use of the beads. 


    Jun 2015 NYT Chemicals In Your Popcorn?

    PFAS are (poly|per)flouroalkyl substances.  They help with non-stick and water and stain resistance.  They have been implicated in testicular and kidney cancer, hypothyroidism, ulcerative colitis and other health problems.  s make life convenient but they also increase the 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. 
    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).  .  They are found in almost all animals across the planet. 

    PFAS are used to make nonstick frying pans, waterproof clothes, stain-resistant fabrics, fast-food wrappers, microwave popcorn bags, and thousands of other products.  Many times the inclusion goes unlabeled. 

    The concerns about the health effects go back 50 years but are becoming more ominous.  In May 2015, 200 scientists released a Madrid statement in 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.  's Environmental Health Perspectives, warning of PFAS's severe health risks.  

    Industry has shifted from using long chain PFAS for which lots of issues have accumulated to short chain versions where there is less evidence available.  They are lobbying Congress hard spending $190 million from 2012 - 2014. 

    There is little US law regulating the 80,000 toxic chemicals used in consumer products.  Congress is drafting some initial regulations but it would only fund the assessment of only five chemicals a year.  Europe and Canada restrict hundreds of chemicals allowed by the US into consumer goods. 

    Some scientists advise replacing non-stick pans, carpets, microwave popcorn and stain resistant furniture. 

    Product evaluations are available free at the Good Guide and Skin Deep web sites. 



    Jul 2016 NYT Doctors and Scientists Call for Tougher Regulation of Toxic Household Chemicals

    Roni Caryn Rabin reports every day, children and adults are exposed to a variety of chemicals found in common household items.  Now a growing body of research suggests that many of these chemicals -- which are used to make plastic more flexible, fruits and vegetables more abundant and upholstery less flammable -- may also pose a threat to the developing brain. 

    A coalition of top doctors, scientists and health advocates is demanding legislation that will protect expectant mothers, infants and children from neurotoxic chemicals.  They argue this can be done by:
    The coalition endorsed Project Tendr is targeting environmental neurodevelopmental risks, a coalition of scientists, doctors and health advocates lobbying for improved legislation to protect homes from household toxins. 
    in a statement in the journal Environmental and Health Perspectives as their strategy to get legislative action one week after President Obama signed into law an overhaul of the TSC is the Toxic Substances Control Act of 1976 which governs the regulation of chemicals used in consumer products and manufacturing processes.  It was updated in 2016 and signed into law by President Obama.  But it still mainly reflects the needs of the chemical industry (Jul 2016).   act. 

    Critics of the TSCA is the Toxic Substances Control Act of 1976 which governs the regulation of chemicals used in consumer products and manufacturing processes.  It was updated in 2016 and signed into law by President Obama.  But it still mainly reflects the needs of the chemical industry (Jul 2016).   update (CSIA is the chemical safety improvement act of 2016 (formerly the Frank R. Lautenberg Chemical Safety for the 21st Century Act), which updates the TSCA with amendments:
    • EPA mandated to evaluate existing chemicals with clear and enforceable deadlines
    • Chemicals evaluated against a risk-based assessment
    • Unreasonable risks identified by the assessment must be mitigated
    • Increased authority to require development of chemical information
    ) argue:
    • The changes in the law do not go far enough.
    • The plan to test 64,000 chemicals will be far to slow with just twenty being tested at a time. 
    • The new law does not cover pesticides. 

    National health surveys show in 2008 15% of children had a developmental disability, up from 12.8% in 1996.  While increased awareness of developmental disorders: 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. 
    , A.D.H.D is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    , and learning disorders it does not account for the whole increase. 


    The American Chemistry Council said the new law already addresses the concerns of the Tendr coalition, by giving more authority to the EPA is the Environmental Protection Agency of the Federal government. 
    and requiring it to take acount of vulnerable populations like pregnant women, children and older people. 



    Jun 2018 NYT The Chemical Industry Scores a Big Win at the E.P.A. 

    Eric Lipton reports the Trump administration, after heavy lobbying by the chemical industry, is scaling back the way the federal government determines health and safety risks, 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. 
    associated with the most dangerous chemicals on the market, documents from the E.P.A. is the Environmental Protection Agency of the Federal government. 
    show. 

    The CSIA is the chemical safety improvement act of 2016 (formerly the Frank R. Lautenberg Chemical Safety for the 21st Century Act), which updates the TSCA with amendments:
    • EPA mandated to evaluate existing chemicals with clear and enforceable deadlines
    • Chemicals evaluated against a risk-based assessment
    • Unreasonable risks identified by the assessment must be mitigated
    • Increased authority to require development of chemical information
    required the E.P.A. to evaluate currently used chemicals to determine if their use should be restricted or removed from the market.  It was a bipartizan amendment to the TSCA is the Toxic Substances Control Act of 1976 which governs the regulation of chemicals used in consumer products and manufacturing processes.  It was updated in 2016 and signed into law by President Obama.  But it still mainly reflects the needs of the chemical industry (Jul 2016).   (Jul 2016). 

    The Trump E.P.A. has narrowly focused its assessment of risk, directing it towards the effects of direct contact.  However, the long term impacts of the chemicals, and any mitigation required of industry to remove the chemicals from ground, water, or air, are avoided since the E.P.A. has worked to exclude these situations from the assessment.  The strategy was lobbied for by the American Chemistry Council, and it is justified by reference to other laws that cover air is the clean air act of 1963.  It controlled air quality at the national level.  Air pollution laws followed.  The CAA amendments of 1970 expanded the mandate at the federal level and required federal and state regulations for stationary and mobile pollution sources. 
    and water is the clean water act of 1977 amended by the Water Quality Act of 1987.  The CWA amended the Federal Water Polution Act of 1948 rewrite of 1972.  The CWA is the primary law covering water pollution.  It aims to sustain the integrity of US waters by preventing pollution, assisting with treatment, and supporting wetlands.  It does not cover groundwater contamination, which is protected by: SDWA, RCRA, CERCLA (Superfund act). 
    .  It is inline with former lobbying position of Dr. Nancy Beck

    However, Lipton notes former E.P.A. officials: Cleland-Hamnett; assert that the analysis will be flawed.  Democratic legislators: Senator Tom Udall, Representative Frank Pallone; who participated in drafting the CSIA concluded the E.P.A. was ignoring the directive for a comprehensive analysis of risks. 


    Nov 2017 NYT $300 Billion War Beneath the Street: Fighting to Replace America's Water Pipes

    HIroko Tabuchi reports bursting pipes. Leaks.  Public health scares. 
    America is facing a crisis over its crumbling water infrastructure, and fixing it will be a monumental and expensive task. 
    Two powerful industries, plastic and iron, are locked in a lobbying war over the estimated $300 billion that local governments will spend on water and sewer pipes over the next decade. 

    Two thirds of the municipal water pipe infrastructure is currently iron or steel.  But the oil and gas industry and its chemical industry partners are keen to see more plastic pipes in the infrastructure:
    • The American Chemistry Council has backed bills in: Michigan, Ohio, South Carolina, Indiana, and Arkansas; to require local governments to open up the bidding process on municipal water projects to all suitable materials, to allow bids from plastic. 
    • The American Legislative Exchange Council (ALEC) is supporting state level legislation. 
    • The American City County Exchange (ACCE) was formed to help corporations influence public policy at the city and county level, leveraging support from ALEC and the Koch brothers' deep pockets and strategy organizations.  
      • Corporations pay membership fees to gain access to about 1,500 mayors and local council members who have joined ACCE. 

    The plastic pipe manufacturers are leveraging the problem history of lead leaching from metal pipes in Flint and other places. 

    Plastic pipes are: light, easy to install, corrosion-free, and relatively cheap.  But there have not been large numbers of 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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    studies to indicate if plastic pipes will be safe for carrying water supplies.  To date research shows leaching from plastic pipes of contaminants into the drinking water.  And there is little regulation developed for plastic pipes in the municipal infrastructure.  So the metal pipe industry is arguing for more studies. 

    Many cash strapped municipalities may find the low cost of plastic pipes very appealing. 


    Dec 2016 NYT A Weed Killer Made in Britain, for Export Only

    Danny Hakim reports the factory [in Huddersfield, England], set amid a brick campus in a green and hilly industrial town, recently celebrated its centennial. 

    It produces paraquat is NN-dimethyl-44-bipyridinium dichloride, a systemic weed killer, used on oranges, coffee and suger cane, manufactured and sold by the Swiss pesticide company Syngenta.  It is banned in the EU, but still allowed to be sold and used in the US.  Drinking even a sip can be lethal.  Recent research by the NIH links paraquat to Parkinson's disease.  The 2011 research found Iowa and North Carolina farmers and family members that handled paraquat or rotenone were 2.5 times more likely to develop Parkinson's disease.  A 2012 study found paraquat increased the likelihood 11 fold for people with certain genetic variations.  The link is disputed by Syngenta. 
    , but only for export outside the EU is European Union, the 1992 Maastricht Council of Ministers meeting agreed evolution of the ECSC & CAP cartels to include:
    • A single market across the members' countries supporting the transformation of the ECSC.  It maintained the CAP transfers assisting French farmers. 
    • A fixed currency 'snake' that allowed the ECSC to operate, binding the deutschmark to the other currencies of participating members: a mini Bretton Woods exchange rate mechanism; that became a single currency, the euro, managed by an independent ECB (based on the independent German Bundesbank). 
    .  The E.P.A. is the Environmental Protection Agency of the Federal government. 
    is worried by the epidemiological studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.   evidence linking the weed killer and 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. 
    . It is aiming to constrain its use on US crops by 2018.  The EU also banned Syngenta's atrazine.  Syngenta is funding Dr. Colin Berry to critique the research linking paraquat and Parkinson's. 

    Currently increasing amounts of paraquat are being used on US crops such as soybeans as weeds have become resistant to Monsanto's Roundup

    If paraquat is banned it is probable that another weed killer will replace it. 

    Chemical companies business models are now dependent on keeping markets outside of the EU open with the backing of the host governments.  Lobbyists for the companies are active.  So the Rotterdam Convention has had limited success in adding problem weed killers to its disclosure requirements list.  UK Green party activists are not monitoring the Syngenta paraquat factory. 


    Jan 2017 NYT Scientists Loved and Loathed By an Agrochemical Colossus

    Danny Hakim reports the bee findings were not what Syngenta expected to hear. 

    University of Exeter's Dr. James Cresswell had been commissioned to study why the world's bee colonies were dying by Syngenta.  Syngenta was arguing that the problem was associated with the varroa mite and not its pesticides.  Cresswell's 2012 research did not point to varroa as the culprite.  Syngenta argued that he should consider new data and alternative research approaches.  Subsequently Cresswell admitted "Syngenta clearly has got an agenda.  It's the varroa, stupid." 

    The EU is European Union, the 1992 Maastricht Council of Ministers meeting agreed evolution of the ECSC & CAP cartels to include:
    • A single market across the members' countries supporting the transformation of the ECSC.  It maintained the CAP transfers assisting French farmers. 
    • A fixed currency 'snake' that allowed the ECSC to operate, binding the deutschmark to the other currencies of participating members: a mini Bretton Woods exchange rate mechanism; that became a single currency, the euro, managed by an independent ECB (based on the independent German Bundesbank). 
    has now placed a moratorium on neonicotinoid pesticides. 


    A review of Syngenta's colony collapse strategic goals by NYT's Danny Hakim shows it alligned with other major agrochemical giants including: Bayer, Monsanto.  The companies fund and build relationships so that:
    • Scientists deliver outcomes favorable to the companies, while
    • University research departments court corporate support. 
    • Universities and regulators sacrifice full autonomy by signing confidentiality agreements. 
    • Academics sometimes double as paid consultants. 
    Syngenta has been effective:
    • In Britain it has a network of academics and regulators including the leading government scientist on the bee issue. 
    • In the US, Syngenta funds academics including Dr. James Simpkins of West Virginia University, to produce work that validates the safety of Syngenta's products.  
    • It has strategically hounded and undermined academics that are in conflict with its agenda.  Hakim explains:
      • The Swiss FIT's Dr. Angelika Hilbeck found that Cieba-Geigy's genetically pesticide integrated corn was killing lacewings.  Cieba argued that a confidentiality agreement signed by Agriscope, her employer, required that she stop publishing.  Dr. Hilbeck published her work anyway.  Ceiba then funded Dr. Jorg Romeis who consistantly worked on research focused on undermining Dr. Hilbeck's analyses.  Dr. Hilbeck commented "They were my little stalkers.  Whatever I did, they did."  The NYT review of Dr. Romeis emails concluded he and his collaborators seemed preoccupied with Dr. Hilbeck's work.  Dr. Hilbeck concluded "It's totally corrupted this field." 
      • UC Berkeley's Dr. Tyrone Hayes partnered with Syngenta but published research concluding atrazine changed the sex of frogs.  Syngenta started a campaign to discredit Dr. Hayes. 
    • Bayer, Monsanto, and Syngenta have succeeded in having research organizations and governments sign confidentiality ageements covering joint research and development, manufacturing processes and financial and marketing information about crop protection and seed technologies.  
    Still Syngenta's representative, Luke Gibbs, told the NYT "We are proud of the collaborations and partnerships that we have built.  All researchers we partner with are free to express their views publicly in regard to our products and approaches.  Syngenta does not pressure academics to draw conclusions and allows unfettered  and independent submission of any papers generated from commissioned research." 



    University of Exeter spokesperson Duncan Sandes argued 15% of university research in the UK is the United Kingdom of Great Britain and Northern Ireland.   is funded by industry.  He claimed "Industry sponsors are fundamentally aware that they will receive independent analysis that has been critically evaluated in an honest and dispassionate manner. 

    But Dr. Cresswell was more candid.  He explained:
    • Turning away research funding is difficult.  The British government ranks universities on how useful their work is to industry and society, tying government grants to their assessments.  He explained "I was pressured enormously by my university to take that money.  It's like being a traveling salesman and having the best possible sales market and telling your boss, 'I'm not going to sell there.'  You can't really do that"  
    • Syngenta had an effect on me.  They influenced what I did on the project. 
    • Criticism from other academics resulted in Dr. Cresswell having a breakdown. 


    West Virginia University's James Simpkins researches Syngenta's atrazine.  He joined the university in 2012.  His conclusions have been helpful to the company:
    Hakim explains that e-mails obtained by the NYT showed:
    • Syngenta provides research grants to Dr. Simpkins
    • Syngenta pays Dr. Simpkins $250 an hour as a consultant for work on expert panels, studies and manuscripts. 
    • Dr. Simpkins contributed to a Syngenta researcher Dr. Breckenridge's annual performance review.  He also partners with him in a venture Quality Scientific Solutions which consults on pesticides.  
    • Syngenta contributed $30,000 to the West Virginia University Foundation in 2014. 




    Jan 2017 NYT A Biotechnology Company Defends Its Science

    Erik Fyrwald wrote to the editor:


    "A Weed Killer Made in Britain, for Export Only" ("Uncertain Harvest" series, front page, Dec 21) highlighted differences in the way crop protection products are regulated in Europe and the United States.  But the reasons for those differences were not explored, leaving the readers without context. 

    Further, the article tries to link the herbicide paraquat is NN-dimethyl-44-bipyridinium dichloride, a systemic weed killer, used on oranges, coffee and suger cane, manufactured and sold by the Swiss pesticide company Syngenta.  It is banned in the EU, but still allowed to be sold and used in the US.  Drinking even a sip can be lethal.  Recent research by the NIH links paraquat to Parkinson's disease.  The 2011 research found Iowa and North Carolina farmers and family members that handled paraquat or rotenone were 2.5 times more likely to develop Parkinson's disease.  A 2012 study found paraquat increased the likelihood 11 fold for people with certain genetic variations.  The link is disputed by Syngenta. 
    used for half a century, with 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. 
    Syngenta's studies, based on the most widely used experimental mouse model, show unequivocally that paraquat is NN-dimethyl-44-bipyridinium dichloride, a systemic weed killer, used on oranges, coffee and suger cane, manufactured and sold by the Swiss pesticide company Syngenta.  It is banned in the EU, but still allowed to be sold and used in the US.  Drinking even a sip can be lethal.  Recent research by the NIH links paraquat to Parkinson's disease.  The 2011 research found Iowa and North Carolina farmers and family members that handled paraquat or rotenone were 2.5 times more likely to develop Parkinson's disease.  A 2012 study found paraquat increased the likelihood 11 fold for people with certain genetic variations.  The link is disputed by Syngenta. 
    does not cause Parkinson 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. 
    's like pathology.  These findings are published in science journals requiring peer review by scientists with no connection to Syngenta. 

    "Scientists Loved and Loathed by an Agrochemical Colossus" ("Uncertain Harvest" series, front page, Jan. 2) doesn't reflect the hard work and commitment of 28,000 Syngenta employees and our many partners in N.G.O. is non governmental organization.  s, academia, research institutes and governments who work together with one goal: to help farmers substantially feed the world. 

    Moreover, the article impugns the integrity of those partners, as well as the quality of their science.  Questioning the very concept of collaboration between industry and academia dismisses the considerable advantages of bringing together leading scientific challenges and bring benefits to society. 

    Given the article's focus on bee health, it is important to note Syngenta's Good Growth Plan, which includes a commitment to provide natural habitats for bees and other pollinating insects.  This biodiversity program has already positively affected nearly four million acres of farmland worldwide. 


    ERIK FYRWALD
    Chief Executive, Syngenta
    Basel, Switzerland



    Feb 2015 NYT As Market Evolves, Health Care Opens Paths, Often for Women


    Health care offers an attractive package to the US middle class.  Few middle income workers are doing physical work.  While millions more are in scrubs. 

    In 1980, 1.4 million jobs in health care paid a middle class wage of $40,000 to $80,000 adjusted to today.  Now the figure is 4.5 million. 

    The pay of RN is registered nurse. 
    s, which are now the third largest middle-income occupation and mostly female, has risen sharply with the demands of the job to a median $61,000.  

    In many working- and middle-class households, women earn the bigger paycheck, work longer hours and have greater career advancement opportunities.  That is creating tensions in the US family. 

    Most new jobs in the US 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.   are in highly paid occupations requiring advanced degrees or more often in lower-paid service positions.  But the NYT notes there are a set of occupations that supports the middle classes: Health care, Accounting, Financials, Professors and teachers, Sales supervisors, Adjusters, Legal assistants, Police, Office supervisors, Secretaries;

    Women, more than men, have responded to the opportunities getting the required training to become attractive candidates.  But that dependency becomes a problem when wives take time off to raise a family. 

    The NYT's Dionne Searcey, Edwardo Porter & Robert Gebeloff note that reducing health care costs may undermine the observed trends cutting health care job opportunities and salaries.  And many of the health care jobs require the workers to gain additional education at their own cost incurring sizable debts. 





    Jul 2015 NYT Study Questions Chemotherapy Use in Late Stages of Cancer


    Pam Belluck detailed a study in JAMA Oncology which questioned the current oncology guidelines for late stage 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).   treatment.  It followed 312 adult patients with a prognosis of six months or less to live.  The patients in six oncology clinics across the USA all had solid-tumor cancers that had metastasized including: lung 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. 
    , colon 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; , 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 
    , 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    ; with half opting for late stage 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%). 


    After each patient had died, researchers asked the relative or caregiver most knowledgeable about their wellbeing is described by Angus Deaton as all the things that are good for a person:
    • Material wellbeing includes income and wealth and its measures: GDP, personal income and consumption.  It can be traded for goods and services which recapture time.  Material wellbeing depends on investments in:
      • Infrastructure
        • Physical
        • Property rights, contracts and dispute resolution
      • People and their education
      • Capturing of basic knowledge via science.  
      • Engineering to turn science into goods and services and then continuously improve them. 
    • Physical and psychological wellbeing are represented by health and happiness; and education and the ability to participate in civil society through democracy and the rule of law.  Life expectancy as a measure of population health, highly weights reductions in child mortality. 
    to rate the patient's physical and psychological distress and overall quality of life in the last week of life.  The caregiver assessments matched the patient's own assessments. 

    For patients who were sicker at the start, caregiver ratings were similar whether or not they had the chemotherapy. 
    For the 122 patients with fewer initial symptoms those receiving chemotherapy 56% reported lower quality of life while those not getting chemotherapy only 31% reported lower quality of life. 

    Researchers also reported that there was no difference in survival between the two groups. 

    Oncologists responded that with newer treatments there are fewer side effects and better targeting.  They said advice to patients should be individualized. 
    Dr. Lowell Schnipper, chairman of the task force on value in cancer care for the ASCO and a clinical director at Beth Israel Deaconess cancer center in Boston said the current guidelines were based on chemotherapy diminishing end-stage tumors, "not the likelihood of improved quality of life".  He argued that the recommendations should stand for now. 


    Jul 2015 NYT Holding Out for a Cure

    Stuart Miller survived NHL is non-Hodgkin lymphoma, It is:
    • A group of blood cancers that include all (> 60) types of lymphoma except HL.  
    • Risk factors include: poor immune function, autoimmune disease, Helicobacter pylori infection, hepatitis C, obesity, Epstein-Barr virus infection, HIV infection, radiation therapy, chemotherapy, PCBs, dioxin, phenoxy herbicides. 
    .  He was treated with 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%). 
    with little likelihood of success when French scientists announced the results of their study of Rituxan in treating patients with NHL.  Rituxan put Stuart into remission. 

    He notes that the cure for a particular 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).   can come as a lightning bolt.  The longer one fights, the better one's chances became of being alive on the day the new therapy is discovered. 


    Sep 2015 NYT New Drugs Prove More Effective in Treatment of Kidney Cancer, Studies Find

    Denise Grady reports that new studies of two drugs nivolumab is a PD-1 inhibitor monoclonal antibody.  It is sold branded as Opdivo.  Its mode of action means it is likely to be toxic to a developing fetus.  It is used to treat:
    • Inoperable or metastatic melanoma (with no BRAF mutation) in combination with ipilimumab.  
      • As a second-line treatment when the cancer has a BRAF mutation - with an added BRAF inhibitor.  
    • Certain Hodgkin lymphomas. 
    • As a second-line treatment for squamous non-small cell lung cancer. 
    • As a second-line treatment for renal cell carcinoma. 
    (Bristol-Myer's Opdivo) and cabozamtinib (Exelixis's Cometriq) described in the New England Journal of Medicine, showed each worked better than the standard treatment for advanced kidney cancer - There are expected to be 61,560 new cases of kidney cancer in the US 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, high blood pressure, genetic mutations and heredity.  .   Both medications were studied only in people who had become resistant to one or more of the treatments generally used first.  Such patients are then typically given everolimus. 

    A study of Opdivo with 821 patients with advanced kidney 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).   funded by BMS, found 25 percent responded to Opdivo and only 5 percent to the standard treatment.  The study was stopped ahead of schedule when safety monitors found patients given the drug were living longer (mean of 25 months vs 19.6 for standard treatment) than controls receiving the standard treatment everolimus (Afinitor).  Optivo also had fewer side effects and more lasting responses. 

    A second study with 658 patients funded by Exelixis, looked at progression free survival testing Cometriq (21 percent responded -> 7.4 months) against Afinitor (5 percent responded -> 3.8 months) is also reporting more effectiveness in slowing the cancer's growth.  It is not yet possible to predict which people will respond to Cometriq.  This study has not progressed far enough to indicate any prolonged survival value. 

    Dr. Robert Motzer of Memorial Sloan Kettering Cancer Center was a 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. 
    of both studies.  He commented the findings for nivolumab were a major advance and affect most patients worldwide with advanced 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.   cancer. 

    The F.D.A. Food and Drug Administration. 
    has given both drugs "breakthrough designation is used to speed the development and review of drugs that may demonstrate substantial improvement compared to current therapies. 
    " for advanced kidney cancer, meaning that it will expedite their review. 

    Future studies will assess the use of these drugs earlier in the treatment regimen. 


    May 2016 NYT F.D.A. Approves Immunotherapy Drug for Treatment of Bladder Cancer

    Andrew Pollack reports the [F.D.A. Food and Drug Administration. 
    ] approved a new immunotherapy 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. 
    drug from Roche 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. 
    , a form 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).   for which there have been no significant new medicines in years. 

    Tecentriq is the first immune checkopoint inhibitor to be approved for bladder cancer.  Roche was given accelerated approval which requires Roche to perform additional studies.  In the study Tecentriq shrank tumours significantly in 14.8 percent of patients and cancer disappeared completely in 5.5%.  There was no control group.  It is not clear if treatment will allow patients to live longer yet. 

    Researchers reported that 40% of 655 patients' with advanced melanoma is a cancer of the melanocytes.  It is a less common form of skin cancer but is the most deadly once it has invaded deeply into layers of skin.  It is primarily caused by UV light.  It is tied to mutations in the signalling pathway (BRAF) and regulatory genes (P53) with a key dependency on crestin reactivation (Jan 2016).   who were treated with Keytruda in a clinical trial are alive three years later.  In Apr 2016, a 107 advanced melanoma patient trial of Opdivo reported one third were still alive after five years.  Prior to these treatments median survival for advanced melanoma was less than a year. 


    Jun 2018 NYT Easier Drug Approval Isn't Cutting Drug Prices

    Editorial board opinion argues Dr. Scott Gottlieb, the commissioner of the [F.D.A. Food and Drug Administration. 
    ] recently vowed to bring "new science" to market faster, in hopes that patients benefit from treatment advances sooner. 

    The board notes the effects of new drug regulation processes:
    Benefits of the reduced regulatory approach include:
    • Patients with fatal diseases gain access to drugs sooner 

    The editorial board raises concerns about the promise of relaxed regulations:
    They suggest
    • Require two successful clinical trials before a drug gains approval
    • Use independent cost-benefit analysis of drug pricing


    Aug 2018 NYT F.D.A. Approves Generic EpiPen That May Be Cheaper

    Sheila Kaplan reports the [F.D.A. Food and Drug Administration. 
    ] approved the first generic version of EpiPen, providing new competition that could help drive down the cost of a lifesaving product that had become a notorious symbol of high price drugs


    The F.D.A. Food and Drug Administration. 
    approved Teva's generic epinephrine auto-injector.  

    F.D.A. commissioner Gottlieb said he was pleased with the timing.  "It's a very important approval in advance of back-to-school season, when parents go out and buy these products.  This approval means patients living with severe allergies who require constant access to lifesaving epinephrine should have a lower-cost option, as well as another approved product to help protect against potential drug shortages." 


    Previously there were three approved epinephrine auto-injector products: EpiPen, Impax's Adrenaclick, Kaleo's Auvi-Q; with have all suffered from manufacturing, supply or insurance constraints. 


    Jun 2017 NYT Cancer Drug Proves to Be Effective Against Multiple Tumors

    Gina Kolata reports the 86 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).   patients were a disparate group, with tumors of the pancreas 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 
    , 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
    , uterus or bone.  One woman had a cancer: Ampullary; so rare there were no tested treatments.  She was told to get her affairs in order. 

    But Kolata notes there were some common aspects.  All the patients:

    The study lead by Dr. Luis Diaz Jr. then at Johns Hopkins and now MSK, used Keytruda to remove tumors' cloaking 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. 
    .  Once the 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. 
    inhibitor was present the mutant proteins on the cell's surface were targeted by the immune response. 

    The results reported in Science encouraged the F.D.A. Food and Drug Administration. 
    to approve the drug for patients whose cancers arise from this genetic mechanism.  That will allow:
    • 60,000 patients each year in the US to be:
      • Identified with a specific test for the mutational mechanism for $300 to $600.  
      • Treated with Keytruda



    Mar 2016 NYT Life-Saving Tweak for Many Kidney Transplants

    Gina Kolata reports in the anguishing wait for a new kidney is chronic kidney disease
    • Where there is permanent damage to the Kidneys.  Diabetes and high blood pressure are the leading causes of CKD.  This has driven up the percentage of American's suffering from CKD. 
    •  CKD is diagnosed via a GFR of less than 60, or another marker such as protein in the urine, for atleast three months. 
    • The disease, classed as having five stages, causes no symptoms until the later stages.  The fifth stage of CKD is ESRD.  CKD is associated with: Atherosclerosis, Cardiovascular disease, Iron deficiency anemia from reduced EPO synthesis, Fluid volume overload, Hyperphosphatemia, Hypertension, Metabolic acidosis, Mineral bone disorder, Potassium accumulation, & Urea accumulation. 
    , tens of thousands of patients on waiting lists may never find a match because their immune systems 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. 
    will reject almost any transplanted organ. 

    A revolutionary study reported in the New England Journal of Medicine, doctors altered patients' immune systems using desensitization is a two week long process that stops rejection of a transplanted incompatible organ.  The process is performed before an organ transplant.  So there must be a living donor.  Often these are relatives or friends who have incompatible organs.  Desensitization involves:
    • First filtering the antibodies out of a patient's blood. 
    • The patient is then given an infusion of other antibodies to provide some protection while the immune system regenerates its own antibodies.  The person's regenerated antibodies are less likely to attack the new organ. 
    • If the person's regenerated natural antibodies are still a concern, the patient is treated with drugs that destroy any white blood cells that might make antibodies that would attack the new organ.  
    to allow them to accept 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.   from incompatible donors.  Significantly more of the altered patients were still alive after eight years than patients who remained on waiting lists or received a kidney transplanted from a deceased donor. 

    In the study 1,025 patients at 22 medical centers who had an incompatible donor were compared to an equal number of patients who remained on waiting lists for organs or had one from a compatible dead donor.  After eight years 76.5 % of those receiving an incompatible kidney were still alive compared to 62.9% who waited and got a compatible kidney and 43.9 % who remained on a waiting list but never got a transplant. 

    The desensitization process is expensive, costing $30,000 and it uses drugs that are not approved for the purpose.  The transplant costs about $100,000.  But since kidney dialysis costs $70,000 per year for the rest of the patient's life the desensitization is probably cost effective. 

    Kidneys will be the major use, but 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 (Aug 2018) 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. 
    and lung transplants may be treated with the procedure.  Livers are less sensitive to rejection so there is less value in the process. 


    Aug 2015 NYT Failing Patients With Heart Failure


    Haider Javed Warraich writes that death from heart failure 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.  Heart expansion in CHF distorts the mitral valve which exacerbates the problems.  MitraClip surgery trials found effective in correcting the mitral valve damage (Sep 2018).  Treatments include: digoxin; is handled particularly poorly by modern medicine.  He notes they suffer excessively relative to other conditions and are more likely to die in an institution. 

    Heart disease is cardiovascular disease which 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). 
    always results in failure of the heart.  Symptoms include: difficult breathing, fatigue and swelling of the legs and abdomen.  Heart failure is the leading cause of hospital admissions for those over 65. 

    Warraich notes it is hard to predict how individual cases of heart failure will progress (Jul 2015).  And they can last days or years.  Warraich argues that a lack of research and training results in poor care.  And patients do not see heart disease as serious as malignant 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).   even though Warraich notes the prognosis is often worse.  Both doctors and patients over estimate the chance of survival. 

    Paliative treatment of difficult breathing induced by heart disease has not been a priority.  And because of the problems with accurately estimating how much longer a heart failure victim will live hospices often refuse acceptance. 

    Aug 2016 NYT Why its Crucial to Choose the Right Hospital

    Austin Frakt reports there's an exceedingly simple way to get better health care: Choose a better hospital.  A recent study shows that many patients have already done so, driving up the market share of higher-quality hospitals. 

    It is not easy to evaluate hospitals directly:
    Most patients don't choose hospitals this way.  Some people rely on their doctor for a recommendation.  But most use their social networks to find out how satisfied a friend was with a particular hospital.  Rather than trying to find out clinical quality people guage the satisfaction of their friends with the care package.  
    And it appears that satisfaction correlates with clinical quality: based on readmission rates 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. 
    , heart attacks and their outcomes; and surgical quality.  . 


    Nov 2015 NYT Are Good Doctors Bad for Your Health

    Ezekial Emanuel wrote an opinion about JAMA Internal Medicine reports detailing that a review of ten years of hospital admission data involving tens of thousands of people, found patients with acute, life-threatening cardiac conditions did better when the senior cardiologists is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   at top teaching hospitals were out of town.  There was a 1/3 lower 30 day mortality. 

    However the teaching hospitals had better mortality results than other hospitals.  It is not clear why the presence of senior cardiologists had the adverse effect on mortality.  Possibly:
    Emanuel noted that overtreatment often produces worse outcomes.  A study from Israel of elderly patients still living in their communities but with multiple health problems and taking more than seven medications, on average, tried discontinuing medicines to see if patients got better.  Researchers discontinued five drugs per patient for more than 90% of patients.  Only in 2 % of cases did the drugs need to be restarted.  Almost all of the patients reported improvements in health, and costs fell.  (See similar Nov 2015 report)

    Emanuel recommends patients ask four questions which ensure they consent to fewer interventions and feel more informed about their decisions:
    1. What difference will the intervention make? Will the test results change our approach to treatment?
    2. How much improvement in terms of prolongation of life, reduction in the 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. 
      of heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
      • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
      • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
      or other problem is the treatment actually going to make?
    3. How likely and severe are the side effects?
    4. Is the hospital a teaching hospital?


    Aug 2015 NYT Ovarian Cancer Treatment Is Found Underused

    Experts in 2006 Urged Therapy That could Extend Lives

    A 2015 report found that the benefits of Intraperitoneal (IP) 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%). 
    were long lasting.  It is possible that surgeons without sufficient experience do not remove all the 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).   tissue and so the IP helps destroy the remaining cells.  The study of regular clinical practice also looked at the toxicology of the treatment which did not have severe side effects. 

    In 2006 the National Cancer Institute issued a clinical announcement is an NIH special alert for advances so important that they should change medical practice.   on intraperitoneal (IP) ovarian cancer treatment.  Ten years later fewer than half of ovarian cancer is a relatively uncommon disease but is often fatal.  It has been associated with use of talcum powder (May 2016).   patients at US providers are receiving the recommended IP treatment.  Dr. Deborah K. Armstrong of Johns Hopkins Kimmel Cancer Center, who lead the original 2006 trial attributed the failure to switch to a reluctance on the part of oncologists. 

    A 2015 report of a study in the Journal of Clinical Oncology looked at the use of IP in six National Comprehensive Cancer Network hospitals.  While IP was used in 50% of cases by 2008 it then plateaued and use varied by hospital. 

    Experts suggest this is because:
    • It is harder to administer abdominal chemotherapy.  It requires a port to be surgically implanted in the abdominal wall.  Patients are rolled back and forth to bath the abdomen in the chemotherapy fluids. 
    • Some doctors doubt the effectiveness. 
    • Some doctors view the treatment as too toxic. 
    • Some doctors see it as a drain on income being time consuming to do and because it can be performed with generic low profit drugs. Similarly
    • No device or drug company is interested in alerting and training doctors to do the procedure. 
    So patients have to be aware of the option and search for a doctor that will provide it.  Dr Armstrong suggests that patients moving their money will catalyze a change in practice. 


    Dec 2016 NYT Simple Life Changes to Help Prevent Heart Disease


    Indiana University SOM Aaron Carroll reports billions of dollars are spent each year on medications that reduce the 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. 
    of heart disease is cardiovascular disease which 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). 
    -- the No. 1 killer in the United States.  But he notes new research analyzing four large prospective cohort studies indicates simple lifestyle changes can have more impact than the expensive medicines the US invests in. 

    The study reported in the New England Journal of Medicine looked at SNP is single nucleotide polymorphism where single base pairs have changed in two chromosomes of the same type.  There are 10 million common SNPs in the human genome.  There are a limited number of chromosomal types (Haplotypes).  This results in SNPs clustering into packs.  On average 30 to 40 SNPs travel together.  Knowing one or two SNPs in a local neighborhood predicts the others that are likely to be present. 
    s associated with the earlier studies to build a genetic risk score for diseases have been found for type 1 and 2 diabetes, heart disease, common cancers, asthma, stroke, obesity, hypertension, atrial fibrillation and gallstones.  Mostly the individual risk changes are small (10 to 40%) except for AMD.  In some instances, however, they interact synergistically making the total relative risk much higher.  The genetic variants often affect whether a response is [de]activated at the right time and in the right amount.  Variations in a single gene were implicated in type 1 diabetes, rheumatoid arthritis, and Crohn's disease.  And variations in one small region of chromosome 9 independently affects risk in type 2 diabetes and coronary heart disease.  Rare variants of the PCSK9 gene significantly alter the risk of cardivascular disease.  It is important to include family medical history in the assessment of risk.  .  They also looked at how lifestyle factors such as: Not smoking, Not being obese 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). 
    , Being physically active, A healthy diet of fruit, nuts, vegetables, whole grains, fish and avoiding processed food, sugar, trans-fats and sodium; were associated with the outcomes.  The researchers concluded:


    Jul 2015 NYT Mysteries of the Heart

    Patients and doctors are uncertain about the best way to fight coronary heart disease is cardiovascular disease which 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). 

    From 2003 to 2013 the death rate from coronary heart disease dropped 38 percent due to: cholesterol and 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.   control, reduced smoking, improved treatments (Jul 2015) and faster care for people after a heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    .  This is true in hospitals treating the poorest as well as the richest people in the US. 

    Yale researchers found that some hospitals reduced the time between when a patient suffers a heart attack and had a clogged artery opened by changing ED 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). 
    procedures. 

    They realized that their old procedures were not acceptable and took control of improving them.  Dr Krumholz a Yale Cardiologist is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   had realized a decade earlier that 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.  
    had built a national database showing how long it took hospitals across the country to get heart patients' arteries opened.  It was a bell curve much the same year after year.  But there were some hospitals that were always fastest.  Krumholz visited the eleven fastest.  Some were community hospitals; others were far from major population centers.  The investigators recorded every detail of the fastest hospitals' processes looking for commonality.  The list they developed was the set of items that Lourdes later adopted.  The more items a hospital in the database was using the faster they worked and the better the results.  The American College of Cardiology announced a national campaign to get hospitals to change their ways.  1200 hospitals signed up for the campaign.  Intermountain Health have used the process improvements to save $639,000 a year

    The analysis was not straight forward.  As the operation became more popular older, more risky types of patients got involved. That reduced the correlation between timeliness and reduced death rate.  And measuring has changed behaviors.  Cardiologists are still convinced - but then they have every reason to be! 

    They altered protocols to reduce the time before treatment from over two hours to less than an hour:
    • Having paramedics transmit an electrocardiogram to the ED. 
    • Having ED doctors decide whether a patient was having a heart attack rather than a cardiologist.  That is a big shift of power!
    • Summoning all members of a heart attack team with a single phone call. 

    Improved surgical techniques are saving lives.  Threading a catheter is a thin tube that can be inserted into the body.   through a blood vessel and using it to insert a new valve, made of cow or pig tissue without removing the old valve has allowed treatment of the frail with aortic valve stenosis.  It may well become the standard treatment for this condition. 

    But it is hard to say:

    And with the shifting landscape of health care provision it is getting harder to sustain the minimal time to treat.  Patients having heart attacks may go to urgent care clinics is an efficient and less costly 'alternative' to the ER.  There is no accepted standard.  Urgent care clinics also compete with Primary care based on extended hours and accessible locations including Medical Malls.  Most have a physician on staff and treat ailments like feavers, sprains and sinus and urinary tract infection, but they also can perform X-rays, stitch up cuts and set broken bones.  Unlike an ER they can not admit patients to a hospital.  Some also offer services like pre-employment drug screening and summer camp physicals. 
    that are not integrated into the rapid surgery protocol.  Lourdes has experienced this handoff issue


    Jun 2015 NYT Racing the Clock, Saving the Heart

    The improvements in treatment seen in heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    care (Jul 2015) spilled over into the care of 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). 
    victims.  Having seen cardiologists is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   improve their processes neurologists decided they must do the same.  The results have been similarly remarkable.  Stroke has fallen to fifth as a major killer and this timeliness process improvement is the reason. 


    Jan 2018 NYT New Findings Could Save Lives of More Stroke Patients

    Denise Grady reports many more 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). 
    victims than previously thought can be saved from disability and death if doctors remove blood clots or coagulation is formation of a clot:
    • Platlets become activated, adhere and aggregate supported by
    • Fibrin polymerization, deposition and maturation.  
    that are choking off circulation to the brain, a new study has shown. 

    An 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.   funded study, led by Stanford researchers, published in The New England Journal of Medicine, reported that there is often more time when brain cells can be rescued by thrombectomy uses a mechanical device to pull clots out of a blood vessel. 
    than the six hour window in the American Heart Association's current guidelines.  It was found the window can be 16 hours allowing people who were asleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    when the stroke occured to be treated.  Special brain imaging is used to see if the thrombosis is the formation of a blood clot inside a blood vessel.   impacted cells are still alive. 

    182 patients at 38 hospitals were included in the study.  It was stopped early because people who had the clots removed did so much better than those that did not.  Ninety days after treatment:
    • 45 % of the thrombectomy patients were well enough to be functionally independent.  14% of the thrombectomy patients died. 
    • 17% of the control patients were well enough to be functionally independent.  26% of the control group died. 





    Jun 2015 NYT Rethinking Cardiac Care

    Gina Kolata reports doctors prefer 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)
    s to treat chest 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.  , but drug therapy may work better. 

    The National Heart, Lung and Blood Institute is trying to find out definitively whether 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)
    prevent heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    s or if statins are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.   might be a better answer (Aug 2015).  The answer could alter the standard of care for more than half a million Americans annually who get a diagnosis of heart disease is cardiovascular disease which 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). 
    (Jul 2015) when they see a doctor about Angina. 

    The typical diagnostic for Angina is to perform an angiogram is a diagnostic test where a doctor threads a narrow catheter up from a blood vessel in the groin to the heart and squirts in a dye that allows a cardiologist to see blockages in the arteries on X-ray displays/films. 
    and if treatment is needed, because an artery is blocked to perform an angioplasty involves inserting a catheter, inflating a balloon to expand a narrowed artery, and inserting a stent to keep the area propped open.  Christensen argues angioplasty should be part of a radically lower cost business which should disrupt the solution business of the general hospital. 

    Half the people over 65 have blockages.  If you have some degree of atherosclerosis is the thickening of an artery wall due to invasion and accumulation of leukocytes. 
    you have blockages. 



    Sep 2015 NYT Aspirin as Cancer Drug

    Roni Caryn Rabin reports a panel's recommendation to prevent colorectal 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;  and heart attacks is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    draws criticism.  Baby aspirin (acetylsalicylic acid) is a pain, fever and inflammation medicine.  It is a platelet aggregation inhibitor.  While its NNT is 2000 for cardiovascular disease prophylaxis, it is so cheap that this strategy is still important.  It has been found beneficial in limiting esophageal cancer. 
    has been recommended for lowering cardiovascular 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). 
    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. 
    in certain men and women for years.  Now the HHS is the U.S. Department of Health and Human Services.   sponsored USPSTF is United States preventative services task force.  It is an independent expert panel focused on prevention and evidence-based medicine appointed by HHS.  , an expert panel, is recommending aspirin to prevent heart attacks and colorectal 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).   for adults ages 50 to 69 who are at high risk for heart disease is cardiovascular disease which 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). 
    .  The recommendations suggest consulting your 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 assessing the risks and benefits.  The recommendation responds to a growing body of evidence that suggests aspirin may be a powerful colorectal cancer preventative.  Aspirin use cut colorectal cancer deaths by 33 percent and reduced 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;  incidence by 40 percent.  People needed to take aspirin at least five to 10 years to have the protection.  The benefits are best for 50 year olds as the risks of the treatment increase with age. 

    Some expert critics worry that people who take aspirin expose themselves to serious side effects: stomach bleeds, hemorrhagic strokes is the hemorrhage of a weakened blood vessel causing blood to leak into and around the brain creating swelling and pressure, damaging cells and tissue in the brain.  There are two main types:
    1. Intracerebral - where the hemorrhage is in small arteries or arterioles within the brain. 
    2. Subarachnoid - where the hemorrhage is in a blood vessel just outside the brain leading to the skull filling with blood. 
    and brain bleeds.  Others view cholesterol lowering drugs and 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.   lowering drugs as better preventatives for heart attacks is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    (Jul 2015), and colonoscopy screening as better for colorectal cancer prevention.  The vice-chair of the task force Dr. Kirsten Bibbins-Domingo said the challenge is weighting the risks and benefits of daily aspirin for healthy adults "who have no other signs and symptoms but have multiple risk factors that put them at risk" 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). 


    It is still not known how aspirin interacts with statins are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.   and proton pump inhibitors. 

    The AHA and ACS praised the recommendation. 


    Spring 2017 Georgetown Magazine Dividing Line

    Jeffrey Donahoe notes the gulf between the health of Washington, D.C.'s African American and white citizens is profound.  In a significant new report, Georgetown calls for action -- moving beyond health care's traditional walls and going directly to where people live. 

    Donahoe asks why the high rate of health insurance coverage across D.C. does not translate into even: life expectancy, health outcomes; Black African results are much worse than white.  Georgetown's School of Nursing & Health Studies report 'The health of the African American Community in the District of Columbia: Disparities and Recommendations' aims to highlight remedies. 

    They conclude the African American neighborhoods have collapsed inducing food & recreation deserts, subsistence wage jobs, and few options to escape.  The result is poor health and low longevity.  New infrastructure must be invested in to turn the situation around. 


    Aug 2017 NYT Making Affirmative Action White Again

    Columbia University political science & history professor Ira Katznelson's opinion piece notes Jeff Sessions told the Senate Judiciary Committee 20 years ago that affirmative action irritated people (he meant white people) because it could cause them to lose opportunities "simply because of their race."  This sense of grievance lies behind the Justice Department's recent memo seeking lawyers to investigate "race-based discrimination" in college admissions. 

    Professor Katznelson goes on to detail the strategic processes that have limited progress for Blacks and Mexican Americans ever since the 1930s:
    He laments that the Trump Administration is now considering weakening the DOJ - U.S. Department of Justice. 
    's Civil Rights Division which since 1957 has worked to fight Jim Crow restrictions on black voting.  And Katznelson argues that this strategy is likely to increase white resentment in the Trump voting base. 


    Sep 2015 NYT Diabetes Drug Cut Cardiovascular Deaths by 38%, Study Says

    Andrew Pollack reports that Jardiance, a modern diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections.   drug has been shown in a trial reported in the New England Journal of Medicine, to reduce deaths from 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). 
    by 38% and deaths from heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    and 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). 
    by 14%. 

    The study funded by Lilly and Boehringer, and carried out by Dr. Bernard Zinman of Mount Sinai Hospital in Toronto who consults to Lilly and Boehringer, involved 7,000 people with 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
    who already had cardiovascular disease.  They were randomly assigned to get either Jardiance or a placebo.  The patients were allowed to take other diabetes drugs as well. 

    After a three year follow-up about 10.5 percent of those getting Jardiance had suffered a heart attack or a stroke, or had died of cardiovascular causes.  With the placebo it was 12.1 percent. 
    About 3.7% of those taking Jardiance died of cardiovascular causes compared to 5.9 percent taking the placebo. 

    There was also a 32% reduction of 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. 
    of death from all causes
    There is a 35% reduction for hospitalization for heart failure 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.  Heart expansion in CHF distorts the mitral valve which exacerbates the problems.  MitraClip surgery trials found effective in correcting the mitral valve damage (Sep 2018).  Treatments include: digoxin;

    The authors suggested the reduction was based on Jardiances ability to reduce 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.  , weight and arterial stiffness. 

    Dr. Steven Nissan of Cleveland Clinic says this is a landmark result

    There were some concerns about the trial results: 
    • The drug did not reduce the risk of heart attack over all by a statistically significant amount.
    • The drug seemed to raise the risk of stroke by a statistically insignificant amount. 
    Instead the drug reduced the deaths from heart failure where the heart can't pump enough blood. 

    The result is likely to cause increased sales of SGL2 inhibitors including Jardiance, Invokana and Farxiga

    It is possible that the results do not apply to the majority of people with type 2 diabetes who have a far lower risk of cardiovascular problems than the people in the trial.  

    The F.D.A. Food and Drug Administration. 
    has a policy of requiring large cardiovascular studies to aim to rule out risks for new diabetes drugs.  The American Diabetes Association is critical of the cost and lack of necessity for the policy. 



    Dec 2015 NYT In Major Shift, Diabetes Cases Start to Decline

    Sabrina Tavernise reports after many decades of relentless rise, the number of new cases of diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections.   in the United States has finally started to decline. 

    The CDC is the HHS's center for disease control and prevention based in Atlanta Georgia.  
    reported the new case rate fell by a fifth from 2008 to 2014.  This is the first sustained decline in 25 years when 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
    cases exploded.  The 2014 data, 1.4 million new cases as opposed to 1.7 million in 2008, firms up the trend. 

    CDC diabetes researcher Edward Gregg commented "It seems pretty clear that incidence rates have now actually started to drop.  Initially it was a little surprising because I had become so used to seeing increases everywhere we looked." 

    Massachusetts General's director of the Diabetes Center, Dr. David Nathan commented "It's not yet time to have a parade.  It has finally entered into the consciousness of our population that the sedentary lifestyle is a real problem, that increased body weight is a real problem." 

    It is not possible yet to tell if treatment and behavior change are having an effect or if the disease has peaked in the population (complex trending issue).  Progress is mainly in educated whites. 


    The percentage of Americans with diabetes is twice what it was in the early 1990s. 

    There is growing evidence that:
    In Alabama, which has the highest prevalence of diabetes in the U.S., the rate of new cases has started to taper.  The local population has been devastated by diabetes with friends and family loosing limbs or dying.  But they are responding with increased awareness, exercise and better diet.  People are switching away from soda.  They are attending prevention programs.  Still poverty is a problem.  The Black Belt of Alabama is locked in to poverty from slavery onwards through share cropping and Jim Crow until today.  Health education was very limited until recently.  Now they are aware of the need for activity and better diet. 


    Dec 2015 NYT editorial Fighting Obesity Is Not Just for Kids

    Former New York commissioner of health Thomas Farley argues the fight to stop 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). 
    is too focused on children. 

    Farley notes that childhood obesity is dropping while adult obesity rates are still increasing (Dec 2015).  He argues this is a serious problem.  He sees the situation as akin to smoking 25 years ago.  Based on that model Farley warns that our obesity strategy is wrong. 

    Farley reminds us that the smoking campaign illustrated the power of marketing and how it had to be curbed to fix the smoking trends. 
    Children were banned from smoking.  The obvious result was that it became a forbidden fruit and associated with 'being adult'.  The manufacturers leveraged this fact in their marketing strategies.  Eventually the anti-smoking strategy was broadened to position cigarettes as indiscriminate killers, matched with taxes, smoke-free zones and media campaigns ensuring that everyone smoked less. 

    Farley argues that we must do the same with processed foods. 
    He sees the nation overwhelmed by food marketing ($14 billion in advertising).  No one can resist it because it bypasses our rational minds. 
    And to avoid taking on the powerful groups who gain from the marketing directly health advocates are using 'protect the innocent' as a focus.  But Farley says this is failed strategy. 

    He writes that to reach the people on the verge of diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections.   we should:
    • Fight the marketing of junk foods everywhere -- not just in schools. 
    • Tax sugary drinks (Mar, Apr 2016)
    • Counter with advertising of the bad effects of junk food.
    • Limitation on where the junk food can be deployed
    The improvement in the environment of adults will then trickle through to their children. 


    Jan 2018 NYT Why 2017 Was the Best Year in HUman History

    Nicholas Kristof writes we all know that the world is going to hell.  Given the rising 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. 
    of nuclear war with North Korea, the paralysis in Congress, warefare in Yemen and Syria, atrocities in Myanmar and a president who may be going cuckoo, you might think 2017 was the worst year ever. 

    Kristof argues this conclusion is wrong because:


    Jan 2018 NYT The U.S. Can No Longer Hide From Its Deep Poverty Problem

    Angus Deaton's opinion piece argues: You might think that the kind of extreme poverty that would concern a global organization like the [UN is the United Nations.  ] has long vanished in this country.  Yet the special rapporteur on extreme poverty and human rights, Philip Alston, recently made and reported on an investigative tour of the [US is the United States of America.  ]. 

    Deaton explains that recently making comparisons of poverty between countries has become easier:
    Deaton notes that the data indicates the US has an urgent problem, and should rethink how the poor are assisted.  769 million people live on less than $1.90 a day in 2013.  Of these: 3.2 million of them lived in the US, 3.3 million lived in Japan, Italy, Spain and other high-income countries.  Additionally Deaton stresses that existence in rich, cold, urban, individualistic countries requires more resources: Housing, Heat, Child care, Transportation; that adds to the 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.  
      • Increases the risk of autoimmune disease (Jan 2017) 
    • During depression, stress inhibits dopamine signalling.  
    • Strategies for stress reduction include: Mindfulness. 
    of the poverty stricken. 

    Using Allen's framework for the US poverty line implies 5.3 million Americans are absolutely poor.  And Deaton notes that the US use of $2 a day leaves some of its absolutely poor in a nightmare situation. 

    Deaton notes the contrarian argument that in the US people are living longer and have the support of a strong 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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    infrastructure (Jan 2018).  He notes that
    Deaton suggests it is time to question where US aid should be directed.  Currently it is mostly targeted at: Afghanistan, Iraq, and Israel. 


    Aug 2018 NYT Surprise Gift: Free Tuition for All N.Y.U. Medical Students

    David W. Chen reports the New York University School of Medicine announced [] that it would cover the tuition of all its students, regardless of merit or need, citing concerns about the "overwhelming financial debt" facing graduates. 

    Chen notes affordability has become an increasing concern in higher education. 

    A variety of schemes have been developed to reduce the debt burden on graduating students.  Medical schools are worried that students' debts are driving them towards high remuneration specialties (Jan 2014, Jun 2017), and way from careers in: family medicine, pediatrics and research.  Already Columbia has leveraged a gift from Merck's former chairman Dr. P. Roy Vagelos, to help students in the greatest need.  UCLA SOM has a $100 million merit based scheme.  Case Western's SOM at Cleveland Clinic covers tuition and fees for its 5 year research program. 

    The N.Y.U. proposal will provide free tuition to all medical students.  It will cost $600 million to finance.  NYU say they have already raised $400 million including $100 million from Ken Kangone, of Home Depot.  The plan does not cover room and board or fees that add $27,000 to the yearly cost. 

    Average N.Y.U. SOM graduate final debt is $184,000.  In 2017 the median debt for US graduating medical students was $192,000. 


    Jan 2018 NYT Why It's Still Worth Getting a Flue Shot

    Aaron Carroll reports this years flu is a virus, normally hosted in birds, which jumps to humans causing pandemics of infection and deaths.  There are various types including: H1N1, H3N2 which mutates more causing vaccination strategies problems, B/Victoria, B/Yamagata; strains.  The "Spanish flu" epidemic of 1918-1919 killed between 50 and 100 million people.  The 2017 winter flu killed 80,000 people in the US.  Infection in people appears to depend on host genetics but no mechanism has been identified.  Flu is spread by droplets in the air.  Being within 3 to 6 feet of someone who is affected means likely breathing in their exhaled virus.  In the initial one to four day phase of infection the virus latches onto the mucous membranes that line the back of the nose, throat, and bronchial tubes.  The viruses then leverage the metabolic and replication systems of the epithelial cells that make up the mucous membranes.  People typically don't know they are infected in this first phase.  In the next phase the immune system mounts an attack on the virus which is concentrated in the respiratory tract: releasing interferon and cytokines generating the classic symptoms: aches, fever, dehydration; of flu.  Drinking lots of fluids compensates for the dehydration and helps the immune system agents to circulate.  The respiratory tract epithelial cells are typically inflamed and damaged and release their contents which are experienced as a runny nose and cough.  Stay upright and get fresh air to support the coughing.  Medications that suppress this are not helping with recovery.  If enough cells in the bronchial tubes are destroyed to create holes then secondary bacterial infections can occur including pneumonia.   season is shaping up to be a bad one.  Much of the country endured a bitterly cold stretch, causing more people to be crowded together inside.  The strain that has been most pervasive, H3N2, is nastier than most.  And, we're being told, the vaccine are a core strategy of public health and have significantly extended global wellbeing over 200 years.  Recent successes include: HPV vaccine: Gardasil.  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, Jul 2018).  
      • 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), Cervical Cancer (Gardasil HPV Jun 2018, Oct 2018), 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). 
    this year is particularly ineffective. 

    Vaccine ineffectiveness reports create an 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. 
    against getting the flu vaccination.  But getting vaccinated will save lives and Carroll warns get vaccinated soon.  It takes two weeks after the vaccine is administered to gain immunity and the peak infection rates stretch from December 2017 to February and possibly through till May 2018. 

    The guess scientists made about which strains to build a vaccine against included H3N2 so the vaccine is targeted correctly.  But H3N2 mutates rapidly and it hard to make vaccine for. 

    Carroll notes that getting vaccinated aims to build herd immunity.  And the result of everyone getting vaccinated is that less people get infected, not no infections.  The 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. 
    for this flu is likely between 70 and 100.  Carroll's argument is that:



    Aug 2015 Studies Back Guidelines for Wider Use of Statins


    A pair of small JAMA studies supports vastly increasing the number of Americans taking statins are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.  .  One found that it will be cost effective to treat vastly more people (56 million Americans) and prevent costly treatment of 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). 
    .  The other showed that new guidelines are much better at identifying who is truly at 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. 
    of a heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    and should be treated with statins. 

    But the guidelines are contested by people who argue the increased use of statins will cause additional cases of muscle 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.   and damage. 

    The cholesterol guidelines issued in 2013 do not appear to have altered medical practice as of 2015. 


    Oct 2015 NYT Heart Scan Can Fine-Tune the Risk for Patients Considering Statins

    Gina Kolata reports a large study of 4,000 men and women aged 45 - 84 of various ethnicities followed for 10 years, in the journal of the American College of Cardiology by Yale cardiologist Dr. Harlan Krumholtz, of people who had an inexpensive ($75 - $100) heart 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. 
    scan found that half of those who were statin are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.   candidates had no signs of plaque in their heart and very little chance of having a heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    in the next decade.  This could modify the use of statins in the new treatment guidelines (Aug 2015).  The actual incidence of heart attacks or disabling chest 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.   in those with zero calcium was half or less than what the 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. 
    calculator predicted. 

    Dr Krumholtz argued that for those with no objection to statins there was no need to take the test.  But it can let those who do not want to take statins know whether their chance of a heart attack is actually extremely low. 

    Critics note the study was observational.  No study has been done which randomly assigns people to a change in treatment based on a scan and demonstrated that the change improves outcomes.  The short period of study (10 years) is seen by some as insufficient for heart attacks to develop. 
    Others say the test can lead to an array of other medical problems.  A scan can lead to incidental findings which were reported in 5% of the study sample.  These can lead to more tests, diagnostics and even exploratory surgery.  And some people with no symptoms of heart disease is cardiovascular disease which 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). 
    may get a high calcium score.  Some times that results in the recommendation of an angiogram is a diagnostic test where a doctor threads a narrow catheter up from a blood vessel in the groin to the heart and squirts in a dye that allows a cardiologist to see blockages in the arteries on X-ray displays/films. 
    .  That may be followed by angioplasty involves inserting a catheter, inflating a balloon to expand a narrowed artery, and inserting a stent to keep the area propped open.  Christensen argues angioplasty should be part of a radically lower cost business which should disrupt the solution business of the general hospital.  even though it is unlikely to prevent a heart attack (Aug 2015).  CT scans can potentially induce 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).   (Jan 2014). 

    CT scans detect calcium in the blood vessels.  Plaques are initially bumps which eventually get waxy and fill with calcium and harden.  It is the soft plaques, without calcium, which may rupture. 



    Jul 2015 NYT Early Blood Pressure Effects

    Researchers following 3,500 men and women for 25 years with periodic physical examinations starting in 1985 when all the subjects were healthy and between 18 and 30 years old.  They calculated the cumulative exposure to 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.  .  They tracked left ventricular dysfunction - the main cause of heart failure 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.  Heart expansion in CHF distorts the mitral valve which exacerbates the problems.  MitraClip surgery trials found effective in correcting the mitral valve damage (Sep 2018).  Treatments include: digoxin;
    The lead author was Dr. Joao A.C. Lima of Johns Hopkins. 
    Reporting in the Journal of the American College of Cardiology their paper highlighted that higher blood pressure in the first half of adult life corresponds to greater damage to the left ventricle.  They recommended 130/70 should be the goal for people under 50 rather than the current guidelines of 140/90. 


    Sep 2015 NYT Study Testing Blood Pressure Says Go Lower

    Gina Kolata reports the NHLBI 'Sprint' federal study of 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.   was terminated a year early due to 'potentially lifesaving information'.  The study conclusively indicated current blood pressure guidelines should be lowered.  

    Doctors were previously concerned about:
    • Side effects of blood pressure treatments
    • The blood pressure required to keep older patient's brains supplied. 
    Sprint found patients assigned to reach a systolic pressure lower than 120 (current guidelines are 140 and 150 for over 60s) had 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. 
    of heart attacks is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    , heart failure 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.  Heart expansion in CHF distorts the mitral valve which exacerbates the problems.  MitraClip surgery trials found effective in correcting the mitral valve damage (Sep 2018).  Treatments include: digoxin; and 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). 
    s reduced by a third and their risk of death reduced by nearly a quarter.  To reach 120 many had to take three generic blood pressure medications on average. 

    Previously there were concerns that reaching a target of 120 via medications could increase side-effect issues.  Old people could end up falling.  Sprint answered these concerns by including 28% of study group were over 75. 

    The analysis of data for kidney disease is chronic kidney disease
    • Where there is permanent damage to the Kidneys.  Diabetes and high blood pressure are the leading causes of CKD.  This has driven up the percentage of American's suffering from CKD. 
    •  CKD is diagnosed via a GFR of less than 60, or another marker such as protein in the urine, for atleast three months. 
    • The disease, classed as having five stages, causes no symptoms until the later stages.  The fifth stage of CKD is ESRD.  CKD is associated with: Atherosclerosis, Cardiovascular disease, Iron deficiency anemia from reduced EPO synthesis, Fluid volume overload, Hyperphosphatemia, Hypertension, Metabolic acidosis, Mineral bone disorder, Potassium accumulation, & Urea accumulation. 
    and 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.   is still being performed. 


    Jan 2017 NYT Why Succeeding Against the Odds Can Make You Sick

    James Hamblin's opinion notes in 1997, a few hundred people who responded to a job posting in the Pittsburgh newspaper agreed to let researchers spray their nostrils with a rhinovirus known to cause the common cold.  The people would then be quarantined in hotel rooms for five days and monitored for symptoms.  In return they'd get $800. 

    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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    researcher Gene Brody notes that the study, when associated with socio-economic and personality differs in at least five key ways:
    • Extroversion-introversion - whether the person gains energy from socializing or retiring
    • Neuroticism-stability - does a person worry or are they calm and self-satisfied
    • Agreeableness-antagonism - is a person courteous & trusting or rude and suspicious
    • Conscientiousness-un-directedness - is a person careful or careless
    • Openness-non-openness - are they daring or conforming
    data confirmed that people with John Henryism is the effect of using high-effort coping in a system which undermines the strategy.  John Henry Martin was from a family of North Carolina sharecroppers who worked tirelessly to escape from the situation.  He did so but developed hypertension, arthritis and a peptic ulcer.  The effect is true of poor blacks in the US and poor white Fins who had heart attacks.  High-effort coping correlated with increased disease in both cases. 
    are likely to get more colds than other people.  He implies that something in 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. 
    suffers when people persevere in the face of adversity. 

    Brody has found:
    It is argued that prolonged 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.  
      • Increases the risk of autoimmune disease (Jan 2017) 
    • During depression, stress inhibits dopamine signalling.  
    • Strategies for stress reduction include: Mindfulness. 
    results in elevated 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
    and adrenaline levels which increase autoimmune disorders include: celiac disease, eczema, IBD, lupus, multiple sclerosis, type-1-diabetes; are often debilitating and life long conditions.  Autoimmune diseases are increasing in prevalence 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.  Stress is associated with increased autoimmune problems (Jan 2017)
    .  Social context and lifestyle are key to 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.   levels globally.  In the US is the United States of America.   as the wealth gap expands more people will suffer chronic illness. 


    Aug 2015 NYT Breast-Feeding's Heart Benefits

    From 1985 846 pregnant women were studied longitudinally.  Twenty years on ultrasound was used to measure the thickness of their carotid arteries -- as an indicator of atherosclerosis is the thickening of an artery wall due to invasion and accumulation of leukocytes. 
    .  The results were reported in August 2015 Obstetrics and Gynecology. 

    The less time a woman breast-fed 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 - many of them targeted at support of Bifidobacterium infantis, Antibodies, Bacteriophages, & Peptidoglycans; which support the initial adaptations of the mammalian newborn, including its microbiome. 
    , the thicker were her carotid arteries.  17 percent of women who lactated for a month or less also had sclerotic plaques compared with less than 11 percent for those who breast-fed for 10 months or longer.  While pregnancy makes the cardiovascular system work harder lactation helps restore maternal physiology to the pre-pregnancy state. 


    May 2016 NYT A Cloud of 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.  Michael Pollan concludes anxiety is fear of the future. 

    Roni Caryn Rabin reports Dean Berg thought she was going to die, and she wanted to know why.  She was 49, way too young, she thought, to have advanced 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).   in her overies. 

    Berg had been using J&J Baby Powder on her thighs for 30 years.  But on the Internet there were assertions linking the powder to ovarian cancer is a relatively uncommon disease but is often fatal.  It has been associated with use of talcum powder (May 2016).  .  She was the first of thousands of women with ovarian cancer to file a law suite against J&J claiming that Baby Powder caused their disease and pointing to a long trail of scientific studies starting in 1971 linking talc to the cancer. 

    In 1982 Harvard's professor Dr. Daniel Cramer compared 215 women with ovarian cancer with 215 healthy women controls.  Women who used talc were at nearly twice the 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. 
    of having ovarian cancer, and those that used it regularly on genitalia and sanitary pads were three times higher. 
    Ten or more subsequent studies reported similar findings. 
    Researchers who pooled the results of similar studies involving 20,000 women found talc use associated with a 24% increased risk of ovarian cancer. 
    The issue with such studies is that they rely on questionaires which have bias problems.  A government-funded study, the Women's Health Initiative asked 61,576 women if they had used perineal powder at the start of the study and tracked their health over time.  After 12 years no correlation was found.  The issue with this paper is its sample size is relatively small and the time scale is short for a cancer assessment study.  It does not invalidate the other research so far. 

    Earlier in May 2016 a report noted that in African-American women genital use of powder is linked with a 44% increased risk of invasive epithelial ovarian cancer.  J&J has grown the Baby Powder franchise by targeting African-American & Hispanic customers. 

    The IARC in 2006 classified talcum powder is a naturally occuring clay mineral composed of magnesium and silicon.  It is soft and is used in cosmetic products (blush etc.), tablets, chewing gum and some rice.  It is often mined in the proximity of asbestos which requires manufacturers to avoid contamination.  The WHO's IARC has designated talc a possible human carcinogen if used in the female genital area.  Pediatricians discourage its use on babies and condom and surgical glove manufacturers have stopped dusting their products with talc. 
    as a possible human carcinogen if used in the female genital area.  One theory suggests the particles cause inflammation which is believed to be important in the development of ovarian cancer. 

    J&J say its trademark Baby Powder is safe.  It argues the research is flawed.  But its talc supplier added warning labels in 2006, while J&J did not.  An internal J&J memo notes "Negative publicity from the health community on talc (inhalation, dust, negative doctor endorsement, cancer linkage) continues," from 1992. 


    Aug 2016 NYT A Fertility Study's Warning for Dogs

    Jan Hoffman reports for decades, generations of dogs have been bred, raised and trained as service animals for disabled people at a center in England: Labrador retrievers, golden retrievers, curly coat retrievers, Border collies and German shepherds.  Scientists at the University of Nottingham realized that they had an ideal opportunity to study dog fertility -- five types of purebreds, uniform conditions, one location, systematic record-keeping.  So in 1988, they started annually testing the sires' sperm.  

    University of Nottingham researchers: Associate professor of reproductive biology Richard Lea; reported in Scientific Reports that environmental causes were producing:
    From 1988 to 2014, 42 to 97 stud dogs were analyzed.  Records of breeding allowed the researchers to rule out inbreeding as a cause of the decline which occurred for five breeds. 

    For 70 years, studies have reported a decline in human sperm quality and gradual increase in rates of testicular cancer and genital tract abnormalities, such as undescended testicles.  But the implications and causes of the trends have been hotly disputed.  The Nottingham study is important because it:
    • Detected the chemicals in the dogs' tissue and also in their food. 
      • Researchers noted the presence over decades
      • Tracked a concurrent decline in reproductive markers. 
    • Study was very rigorous. 
    • Study agrees with the human data where the data could not be gathered with similar rigor. 


    Dec 2016 NYT Black Lung Stalks Coal Miners Anew

    Appalachian health officials report a shocking rise in cases of black lung -- the deadly coal-mining disease thought to have been reined in by a landmark federal law passed in 1969.  Young miners are proving particularly vulnerable because the thinner coal seams now being worked in Appalachia leave them vulnerable to a more volatile black lung strain rooted in silica dust is progressive massive fibrosis, a deadly form of the coal-mining disease 'black lung'.  It is caused by inhaling silica dust released during mining coal seams.  , according to an investigative report by National Public Radio. 

    P.M.F. is progressive massive fibrosis, a deadly form of the coal-mining disease 'black lung'.  It is caused by inhaling silica dust released during mining coal seams.  's resurgence in Appalachia appears due to:



    Aug 2015 NYT The Spice of (a Longer) Life

     A study in the BMJ of 485,000 people found that eating spicy food is associated with a reduced disk of death. 

    A large Chinese study enrolled participants from 2004 to 2008 and followed them for an average of seven years.  20,224 deaths were recorded. 
    Having controlled for other variables researchers found that eating hot food in differing quantities correlated with reduced 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. 
    of death - mainly chilli peppers:
    • less than once a week,
    • once or twice a week reduced the risk 10 percent. 
    • six to seven times a week reduced the risk 14 percent. 
    Rates of ischemic is a restriction in blood supply to an organ such as the heart.   heart 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). 
    , respiratory diseases: COPD is chronic obstructive pulmonary disease.  It is one of the most common lung diseases.  Chronic bronchitis and emphysema are the major forms.  ; and 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).   were lower for hot-food eaters. 


    Oct 2015 NYT Health Benefits of Tea? What the Evidence Says

    Indiana University SOM's Aaron Carroll reports large numbers of studies have looked at associations between tea and health.  But most are not randomized control trials.  Aaron looked at the associations indicated by the meta analysis of the studies. 

    Several studies with more than 23,000 participants showed those who drank tea were less likely to have:
    Carroll concedes that his associations may have other causes than direct effects of tea.  The US population does not drink large amounts of tea relative to many countries included in the analysis.  So some other factors associated with those countries may have been significant. 


    Jul 2018 NYT More Americans Are Dying of Cirrhosis and Liver Cancer

    Nicholas Bakalar reports death rates from cirrhosis is collapse of liver cell buffer function from long term damage due to: hepatitis, chronic alcoholism, fatty liver disease, hemochromatosis, obesity, and many other causes; with normal liver tissue being replaced by scar tissue. 
    and liver cancer is the sixth most frequent cancer globally, and the second leading cause of cancer based death.  It is mainly associated with cirrhosis from hepatitis B, C,  or alcohol, but there is also a correlation with obesity (Aug 2016).  The most common liver cancer is HCC.  Immature hepatocytes can produce hepatoblastomas.  Some types of the fungus Aspergillus produce aflatoxins, which can be dangerous to children when ingested or to adults in chronic exposure causing cirrhosis and carcinoma of the liver.  Aflatoxin metabolites intercalate into DNA and alkylate the bases.  This causes mutations in p53. 
    are rising dramatically in the [US is the United States of America.  ]. 

    A study by Michigan's Dr. Tapper analysing CDC is the HHS's center for disease control and prevention based in Atlanta Georgia.  
    data showed:
    • 1999 to 2016 annual cirrhosis deaths increased to 34,174 (65%).  The largest increase were associated with alcoholic cirrhosis in people 25 to 34 years old. 
      • 2009 to 2016 10.5% annual increase in cirrhosis deaths of people aged 25 to 34, after prior declines amongst some groups.  
    • 1999 to 2016 Liver cancer deaths doubled to 11,073 annually. 
      • 2009 to 2016 3.0% average annual increase.  Native Americans, whites and African-Americans all saw increases of more than 2% a year, while Asians and Pacific Islanders saw rates decline 2.7%
    The underlying cause of the rise in deaths is not known. 


    Nov 2015 NYT Another Plus for Coffee

    Nicholas Bakalar reports a large study by the Harvard School of 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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    's Dr. Ming Ding, that followed 200,000 doctors and nurses for up to 30 years, described in Circulation, has found drinking coffee is associated with a reduced 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. 
    of dying from: heart 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). 
    , 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). 
    , 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
    , neurological diseases and suicide; but not 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).  .  The association was overwhelmed by smoking. 


    Nov 2016 NYT Whole Milk May Beat Low-Fat

    Nicholas Bakalar reports many experts recommend low-fat milk to fight 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). 
    for children over 2, but it may not be the best option. 

    University of Toronto pediatrics associate professor Jonathon Maguire reports in the American Journal of Clinical Nutrition that higher fat content milk correlated with a lower B.M.I. is body mass index.   and higher vitamin D levels. 

    The researchers collected height and weight data on 2,745 healthy children aged 1 to 6 years.  They took blood samples.  They asked the children's parents to report how much skim, 1%, 2% or whole milk the children drank. 

    Controlling for age, sex, outdoor play and other factors affecting vitamin D level they found:
    • Children who drank one cup of whole milk per day had a vitamin D level comparable with Children who drank 2.9 cups of 1% milk and their B.M.I. was lower by 0.79 points. 
    • The higher the fat content of the milk, the lower the children's B.M.I. and the higher their vitamin D level. 

    Maguire postulated that vitamin D is better absorbed with fat, so drinking low-fat milk may leave children hungrier for more calorie-dense food. 

    (AWF This finding seems in conflict with inflammation issues of saturated fats (Sep 2016)). 


    May 2016 NYT Potatoes Tied to Hypertension

    Nicholas Bakalar reports eating potatoes four or more times a week may increase the 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. 
    of high blood pressure, a large new study has found. 

    Pooled results from three observational studies involving 187,453 people followed for more than 25 years, controlled for BMI is body mass index.  , physical activity, smoking and other factors, found that compared with eating potatoes once a month, having one potato -- baked, boiled or mashed -- four to six times a week increased the 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. 
    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.   by 11%. 
    Eating four or more ounce servings of chipped potatoes a week increases the risk by 17%. 

    The researchers speculate that potato causes a rapid rise in blood glucose which is associated with blood vessel problems and inflammation which increases the risk of hypertension. 



    Nov 2016 NYT Drinking and Stroke Risk

    Nicholas Bakalar reports having one or two alcoholic drinks a day is associated with a lower 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. 
    of stroke, a review of studies has found.  But drinking more alcohol than two increased the risk. 

    An analysis by Sweden's Karolinska Institute epidemiologist studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.   Susanna Larsson in BMC Medicine, of data from 27 studies, compared nondrinkers/occasional drinkers with people who had one or two drinks a day.  Two drinks resulted in 8% reduced risk of ischemic stroke is a clot that occurs as a result of an Ischemia within a blood vessel supplying blood to the brain.  They account for 87% of all strokes.  There are two main types:
    1. Thrombotic - where cerebral arteries become diseased or damaged and then blocked by a blood clot within the brain. 
    2. Embolic - where a blood clot or plaque fragment forms outside the brain (usually the heart) and travels to the brain where it blocks a blood vessel. 


    The analysis concluded that more than two drinks increased stroke risk:


    May 2016 NYT Reducing Risks of 13 Cancers

    Gretchen Reynolds reports anyone who still needs motivation to move more may find it in a new study showing that, in addition to its other health benefits, exercise appears to substantially reduce the 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. 
    of developing 13 types 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).   -- far more than scientists had thought might be affected by exercise.  The comprehensive study also suggests that the potential cancer-fighting benefits of exercise seem to hold true even if someone is overweight. 

    The study reported in JAMA Internal Medicine by NCI is the national cancer institute. 
    , and Harvard Medical School epidemiology studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.   and genetics scientists leveraged a large set of epidemiological health studies (1.44 million sample) from the US and Europe where BMI is body mass index.   and other health markers were correlated with diet and exercise habits.  The researchers looked at any cancer diagnoses.  They statistically looked at the effect of exercise.  They found that exercise is associated with significantly reduced 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. 
    of developing 13 different types of cancer: 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    , Lung 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. 
    , Colon 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; , liver is the sixth most frequent cancer globally, and the second leading cause of cancer based death.  It is mainly associated with cirrhosis from hepatitis B, C,  or alcohol, but there is also a correlation with obesity (Aug 2016).  The most common liver cancer is HCC.  Immature hepatocytes can produce hepatoblastomas.  Some types of the fungus Aspergillus produce aflatoxins, which can be dangerous to children when ingested or to adults in chronic exposure causing cirrhosis and carcinoma of the liver.  Aflatoxin metabolites intercalate into DNA and alkylate the bases.  This causes mutations in p53. 
    , esophagus 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). 
    , kidney, stomach, endometrium, blood, bone marrow, head and neck, rectum is also called colon cancer. 
    and bladder 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. 
    .  They also found an associated increased risk of melanoma is a cancer of the melanocytes.  It is a less common form of skin cancer but is the most deadly once it has invaded deeply into layers of skin.  It is primarily caused by UV light.  It is tied to mutations in the signalling pathway (BRAF) and regulatory genes (P53) with a key dependency on crestin reactivation (Jan 2016).   and slow growth prostate 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




    Apr 2018 NYT Married People Less Likely to Die From Melanoma

    Nicholas Bakalar reports married people are more likely than the unmarried to get timely diagnosis and treatment for malignant skin 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).  

    Early detection of melanoma is a cancer of the melanocytes.  It is a less common form of skin cancer but is the most deadly once it has invaded deeply into layers of skin.  It is primarily caused by UV light.  It is tied to mutations in the signalling pathway (BRAF) and regulatory genes (P53) with a key dependency on crestin reactivation (Jan 2016).   is seen as essential to effective treatment.  A study in JAMA dermatology of 52,063 patients looked at marital status in a large cancer registry.  Stage 1 five year survival rate is 98% while stage 3 is only 62%.  46% of married people went to a doctor about the earliest stage of the disease.  39% of divorcees and 32% of widowed did. 

    People should: get regular skin exams, bring someone on the visit.  Having someone with you can help in making good decisions. 




    Feb 2017 NYT Hormone Blockers Can Prolong Life if Prostate Cancer Recurs

    Denise Grady reports men whose prostate 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
    comes back after surgery are more likely to survive if, along with usual radiation, they also take drugs to block male 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. 


    A report in the New England Journal of Medicine details conclussions from a long-running NCI is the national cancer institute. 
    funded study that will clarify treatment options for patients. 

    After surgery to remove the prostate 30% of men have a reccurence.  The study found:


    Jul 2016 NYT Small Lifestyle Changes Can Sharply Cut Cancer Risk

    Aaron Carrol's opinion notes Americans seem very afraid 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).  , with good reason.  Unlike other things that kill us, it often seems to come from nowhere. 

    Carrol argues that there is evidence that cancer is preventable.  He notes some of the research seems contradictory:
    These studies were not randomized control trials.  No causation was proved in the studies. 



    Sep 2015 NYT Never Too Young to Get Moving

    Gretchen Reynolds reports a study says idle children can develop cardiovascular woes 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). 


    A new study, in Experimental Physiology, on healthy young girls found that after a single session of prolonged inactivity, the children developed changes in their blood flow and arteries that, in grown-ups, would signal the start of serious cardiovascular problems. 

    The nine children, aged 9 to 12, were asked to sit still and as with adults, arteries in the legs were found to contract, constricting blood flow, raising blood pressure and, over time contributing to the development of 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). 
    .  The control group was allowed to get up every hour and move about or exercise.  Their arteries functioned well.  The test group, constrained to sit still for hours, arteries deteriorated. 

    Children now seem to become inactive after age 8 -- especially girls.  iPads and movies make it very easy to remain sitting for long periods. 


    Nov 2015 NYT A.D.H.D. Rises, but Support Lags

    Katherine Ellison reports Controversy over A.D.H.D. is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    has erupted all over the world. 
    In Turkey children with A.D.H.D. are seen as weird, stupid, and lazy by their peers and teachers.  Children in such situations see themselves as hopeless and give up trying to succeed. 

    Some children show symptoms at age four.  They may be unruly, hitting other children and not be able to share.  They have trouble sitting still for more than ten minutes.  They may suffer the consequences of poorly developed judgement. 

    The global diagnosis of A.D.H.D. is on the rise.  But the nature of the condition is not well understood.  The diagnosis and treatments are questioned in many countries. 
    Diagnosis rates:
    • Germany 381% increase from 1989 to 2001. 
    • UK prescriptions increased 50% between 2007 and 2012 to 657,000.  
    • Isreal consumption of medicines doubled between 2005 and 2012. 
    The surge in the use of medications to treat A.D.H.D. has induced criticism of the pharmaceutical industry.  Ritalin has surged outside the U.S. from 17% to 34% of treatments. 

    Families are in a dilemma and prescription medications are a relatively easy option in comparison to altered parenting, job and social relationships.  But they do include side effects.  Either way their children aren't getting effective diagnosis, medical, social or educational support. 



    Nov 2015 NYT Treating A.D.H.D. Electronically

    Katherine Ellison reports in a pilot study, a video game Akili Interactive's Project: EVO, was shown to help children with A.D.H.D. is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    concentrate. 
    Still a 2013 analysis of 25 studies on brain training programs for A.D.H.D. indicated the training had a "nonsignificant or negligible" effect on academic functioning.  And the F.T.C. - is either:
    • Federal Trade Commission.  Setup during the Wilson administration.  Its powers include blocking mergers due to antitrust concerns using the powers of the Clayton act. 
    • Follicular thyroid cancer. 
    has been punishing false claims made by the $1.3 billion brain training industry. 


    2018 Measure What Matters The Remind Story

    John Doerr & Brett Kopf describe an approach to coping with A.D.H.D. is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    and dyslexia is expressed as severe reading problems.  However, these problems fall on a normal distribution of reading skills.  The majority of the problems affect the letterbox region.  But many issues are indirect.  In particular disorganization of the left lateral temporal region disrupts phonological generation of the alphabet mapping required for neuronal recycling in the letterbox.  Because of the long chain of dependencies in neuronal recycling required for the letterbox to support reading there are many potential developmental aspects that can fail.  A variety of gene mutations have been found to induce dyslexia. 
    , that inspired an education technology company, Remind

    A.D.H.D. and dyslexia initially undermined Brett Kopf's ability to study, and his confidence.  But teacher Denise Whitefield taught him to focus on one goal at a time, and partnered with his mother to help him succeed.  And Brett and his brother David subsequently transformed this support model into a simple technology solution that sent reminders to Brett and other students of upcomming deadlines. 

    Brett noted that:
    • When a child lags in school it can take weeks or months for a parent to find out. 
    • Teachers were spending to much time reminding students of goals and deadlines - without any technology support to assist them. 

    Brett and David responded by building the education technology company Remind. 
    Remind:


    Mar 2016 NYT Eating to Save Your Sight

    Roni Caryn Rabin reports here's another reason to eat your fruits and vegitables: You may reduce your 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. 
    of vision loss from cataracts.  Cataracts develop naturally with age, but a study authored by King's College London's Dr Christopher Hammond in 'Opthalmology' reports diet may play a greater role (65%) than genetics (35%) in their progression.  Key to the effect was large amounts of vitamin C in the diet.  Significant sources were: Oranges, Cantaloupes, Kiwi, Broccoli, Dark leafy greens; Supplements did not have an effect. 



    May 2017 NYT He Was on Blood Thinners and Supplements.  Could He Still Have Had a Stroke?

    Lisa Sanders reports the woman was surprised to find her 69-year-old partner still in bed after she got home from church.  He was usually an early riser -- up and dressed by 7.30 every morning, even after he retired, even after two strokes 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). 
    , even after a heart attack is an AMI. It can induce cardiac arrest.  Blocking the formation of clots with platelet aggregation inhibitors, can help with treating and avoiding AMI.  Risk factors include: taking NSAID pain killers (May 2017).  There is uncertainty about why AMI occur.  Alternative hypotheses include:
    • Plaques started to gather in the coronary arteries and grew until no blood flow was possible.  If this is true it makes sense to preventatively treat the buildup with angioplasty. 
    • Plaques form anywhere in the body due to atherosclerosis and then break up and get lodged in the coronary artery and start to clot.  If this is true it makes sense to preventatively limit the buildup of plaques with drugs like statins or PCSK9 inhibitors. 
    .  He just needed a little more sleep, he mumbled when she tried to rouse him.  But she was worried.  He was slurring his words and his face didn't look right -- it seemed strangely lopsided. 

    During a trip to UConn Health's John Dempsey hospital ED 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). 
    , the patient, already suffering from a complex condition explained:
    • Feeling woozy & tired
    • Had a headache
    • Felt off balance when walked
    The examination found his:
    • Blood pressure was high 164/114.  
    • Heart was racing
    • Speech slurred.  ER physician, Neurologist; suspected another stroke

    He had:
    He was taking supplements:
    • Cinnamon
    • Coenzyme Q10. 

    ED Diagnosis was assisted by taking a 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. 
    scan.  It revealed unexpected bleeding in the brain.  The patient was admitted to a hospital ICU is intensive care unit.  It is now being realized that the procedures and environment of the ICU is highly stressful for the patients.  In particular sedation with benzodiazepines is suspected to enhance the risk of inducing PTSD.  Intubation and catheterization are also traumatic.  Sometimes seperated into MICU and SICU.  eICU skill centralization may bring down costs. 
    for observation, under the care of internist Dr. Ursula Bailey.  A second CT indicated the bleeding had stopped.  By the morning the patient's blood pressure and heart rate were normal.  Dr. Bailey wanted to explain the cause of the bleeding.  There was no detected infection or weak blood vessels.  But checking the patient's medications and supplements revealed a new item, turmeric which contains curcumin.  Bailey's supporting pharmacist Stephen Rappaport checked with the University of Illinois's Drug Information Group who warned that curcumin was a blood thinner.  Rappaport warned Bailey the turmeric could be enhancing the prescription anticoagulant's effects.  Bailey recommended avoiding turmeric while on the anticoagulant. 

    Anticoagulants are difficult to prescribe, since they will alter the balance of clotting and bleeding in the patient.  Supplement based curcumin is far stronger than the powder used in cooking. 


    Sep 2015 NYT A Diet May Fight Breast Cancer

    Nicholas Bakalar reports that a randomized trial described in JAMA international medicine suggested the Mediterranean diet is associated with reduced 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. 
    for breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)


    4,152 women with an average age of 68 were assigned to one of three eating plans:
    1. the Mediterranean diet supplemented with extra-virgin olive oil - had a 68% lower risk of breast 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).   vs controls,
    2. the diet supplemented with mixed nuts, or
    3. A control group given only advice to reduce dietary fat. 
    The women were tracked for 4.8 years and the trial controlled for variables like age, smoking, BMI, family history of cancer and physical activity. 


    Nov 2015 NYT A Foray Into the Mediterranean

    Jane Brody reports a healthy diet and regular exercise maximize the benefits of cholesterol-lowering drugs. 

    Cardiologists is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   recommend shifting to a Mediterranean diet even when on statins are serum cholesterol lowering drugs established as safe and effective at reducing the risk of heart-attacks, hemorrhagic & Ischemic strokes and deaths from atherosclerotic heart disease.  They also reduce inflammation that can induce blood clots.  They appear to stabilize plaque.  About 5% of people, most with a specific allele of SLCO1B1, have muscle aches, and in some blood sugar increases.  Statins inhibit HMG-CoA reductase which produces cholesterol in the liver.  .  Studies suggest the Greek and southern Italian life style and diet reduces the 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. 
    of 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 may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the 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. 
    , 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).  , 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. 
    , 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
    , arthritis, and metabolic syndrome.  But the cardiologists know changing eating habits is hard. 


    Aug 2015 NYT A long-Term Cancer Fighter

    A new study published in Lancet Oncology reports that the protection afforded by oral contraception against endometrial cancer lasts for many years after women stop taking the contraceptives. 

    Lead author was Valerie Beral of the University of Oxford. 

    The study pooled data from 36 prospective and retrospective epidemiological studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.   studies that included 27,276 women with endometrial 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).   and 115,743 healthy controls.  The longer women used oral contraceptives the greater the protection.  Each five years of use was correlated with 24% lower 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. 
    as compared with those who never used them.  For women who took the pills for 10 to 15 years the protection lasted for more than 30 years after the women stopped using the pills. 


    Jun 2016 NYT Longer Use of Drug May Aid Breast Cancer Patients

    Andrew Pollack reports women with early-stage breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    could benefit from taking an estrogen-suppressing drug for 10 years rather than the standard five, researchers reported here on Sunday, citing the results of a new study. 

    A study funded by the NCI is the national cancer institute. 
    , Novartis and the Canadian Cancer Society Research Institute and authored by Dana-Faber's Dr. Eric Winer, in the New England Journal of Medicine reports, 1,900 postmenopausal women from Canada and the US, who took an aromatase inhibitor limit the synthesis of estrogen by aromatase.  Breast and ovarian cancers grow more stimulated by estrogen. 
    (letrozole in the study) for an additional five years lowered the 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. 
    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).   occurring in the other breast or returning.  However, the women did not live longer than those in the control group.  And It appears unclear if the benefits of 10 years of aromatase inhibitor out-weighs the side-effects: bone loss and joint and muscle 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.  

    Most breast cancers are 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. 
    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. 
    -positive, so they will grow faster with estrogen or progesterone.  Because there is some risk for such women many take tamoxifen is a cancer treatment (initially breast cancer) that was discovered in 1967 and is now a WHO essential medicine.   or an aromatase inhibitor.  But it is difficult to judge how long to take the drugs for.  Guidelines from the oncology society recommend women take tamoxifen for 10 years or take it for five years and then an aromatase inhibitor.  But in 2016 most postmenopausal women start out on aromatase inhibitors and are seeking a guideline. 

    The study subjects had often already taken tamoxifen for five years and aromatase inhibitors for five years at the start of the study.  They were randomly assigned to two groups: one was given letrozole each day for five years.  The other group was given a placebo.  After six years 67 (7%) women in the letrozole group had experienced a recurrence or developed a new cancer in the opposite breast.  98 (10.2%) women in the control group had a recurrence or new cancer.  The hazard ratio indicted the risk was reduced by 34%.  The strongest effect was prevention of new cancer occurrence.  Recurrence, often in bones, livers or other places outside of the breast showed a smaller difference between the groups. 
    The drug increased the onset of osteoporosis is a set of diseases where the bones are being broken down faster than they are being renewed.  The effect is for bones to lose strength and become brittle.  The more bone mass developed the less likely osteoporosis becomes.  The risk increases with age and more often impacts women.  Certain hormone levels have an impact: Increased glucocorticoids and reduced sex hormone levels increase bone loss, over active: Thyroid, Parathyroid and Adrenal glands.  Some medical treatments can accelerate bone loss (prostate cancer treatments).  Osteoporosis treatments include:
    • Eli-Lilly's Forteo (teriparatide) a parathyroid hormone analog which encourages bone growth but is very expensive.  And it is only allowed to be taken for two years since it was associated with bone cancer in rats. 
    • Biphosphonates reduce the rate of bone loss but have frightening side effects in a small number of patients (Jun 2016). 



    Dr. Winer commented "It's an option but not the standard.  I think this is one of the situations where you have a new approach that probably makes sense for some women and probably doesn't make sense for a lot of women.  You have to be careful not to over-treat everyone."  He explained it is most important to prevent recurrence outside of the 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    because that is what kills people.  He suspected that may be why there was no difference in mortality. 




    Aug 2015 NYT Doubt is raised on quick surgery on breast lesion

    A report in JAMA Oncology describing 100,000 in a 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).   study questions the value of aggressive moves in the earliest stages of 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.  Most women diagnosed with early stage DCIS have surgical or chemotherapy treatment, which does not alter their life expectancy (Aug 2015).  No data is available detailing a correlation with breast cancer.  But it is now understood that metastatic cancers are different from localized cancers. 
    .  The diagnosis has soared in recent decades, from hundreds before 1983 to 60,000 a year in 2015, accounting for as much as a quarter of cancer diagnoses made with mammography is an X-ray record of the breast used for screening and diagnosis of breast cancer.  Mammograms have become progressively more sensitive allowing detection of smaller tumors.  This has allowed aggressive treatment practices which may be counterproductive (Aug 2015).  Mammography policies are defined by: ACOG, ACS, NCCN, USPSTF; 
    , as radiologists are able to identify smaller and smaller lesions. 

    Almost every women diagnosed with stage 0 DCIS has a lumpectomy, and or 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%). 
    or a double mastectomy.  It now appears that treatment may make no difference in their outcomes.  But if DCIS was a cancer predictor then women who had their breasts removed should have been less prone to cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    which was not the case.  Patients with DCIS have about the same likelihood of dying from breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    as the general population.  The few that did have DCIS and died did so despite the treatment. 
    The new data on outcomes begs the question - Is DCIS cancer, a precursor, or just a 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. 
    factor in some women? 
    Women tend to overestimate their risk of dying from cancer and underestimate the harms of overtreatment is the application of unnecessary health care.  It is a complex problem:
    • Overtreatment needs to be adaptive.  As people age their medicine levels typically need to be changed.  Often, as in the case of blood pressure, and blood sugar reduction, they should be reduced to avoid inducing falls (Nov 2015).  
    • Patients with chronic diseases, such as type 2 diabetes, often require different treatment settings.  And again these vary with age. 
    • Patients who have learned a regime, and been told it was successful, may resist instructions to change it.  Some worry that they will impact their health care provider's treatment performance measures. 
    .  Treatment often results in: job losses, reduced income, 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.   issues, relationship issues, and risks of lymphedema is a permanent pooling of lymphatic fluid.  This is a serious condition that can result in massive swelling.  It can be induced surgically when lymph nodes are removed for biopsy.   Prophylactic switching to nano-sensors to detect cancer metastasis in the nodes and sensing of high risk situations is developing.  Until 2016 there were no recognized treatments.  Collagen structures deployed by surgeons may encourage cells to rebuild the lymphatic network. 


    There are some cases of DCIS where the women are at higher risk: Black women, Women younger than 40, Those with DCIS cells with molecular markers of aggressive invasive cancers. 
    Deciding what to do - the problem of low probability events
    The majority of women in the study had lumpectomies with or without radiation.  Most others had mastectomies.  The death rates from breast cancer 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.  260,000 new cases of breast cancer will occur in the US in 2018 causing 41,000 deaths.  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 carcinomas 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).  International studies indicate early stage breast cancer typed by a genomic test: Oncotype DX, MammaPrint; can be treated without chemotherapy (Aug 2016, Jun 2018)
    of these patients over the next 20 years regardless of their treatment was about the same as the lifetime 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. 
    in the general population, 3.3 percent. 
    The arguments are:
    It is unlikely that a large clinical trial will ever occur.  The risk of dying of breast cancer is so low for women treated for DCIS the study would take 10 to 20 years and involve tens of thousands of women, assuming it would be possible to recruit so many who would agree to have their treatment randomly assigned.  The cost would be prohibitive and at the end doctors would argue that the treatment regimes studied were out of date. 


    Aug 2015 NYT Fear, a Useful Ally in Deciding Cancer Care



    Lisa Rosenbaum, a cardiologist is the diagnosis and treatment of: Congenital heart defects, CAD, Heart failure, Valvular heart disease; by cardiologists.   at Brigham and Women's Hospital, in an opinion responding to the NYT report on doubts about surgery for DCIS explained:
    Rosenbaum concluded "The medical community has a role not only in alleviating unwarranted fears, but also in identifying rational ones.  Both are essential to making good decisions in the face of uncertain trade-offs. 



    Sep 2018 NYT New Approach to Breast Reconstruction May Reduce Pain and Weakness for Some

    Roni Caryn Rabin reports before Deborah Cohan had a double mastectomy and breast reconstruction five years ago, her plastic surgeon explained that he would "create a little pocket" behind her chest muscle and "slip the implant in." 

    Rabin notes the details are often more problematic:
    • The large pectoralis major muscles are detached from some underlying ribs, stretched for months to prepare them to support insertion of the implants
    • The process may weaken the muscle and leave nerve damage - tingling and numbness
    • The procedure was introduced because women developed infections, scaring and other problems when implants were placed directly under the skin. 
    An alternative approach, prepectoral breast reconstruction, leverages ADM is accelular dermal matrix, generated by a soft tissue matrix graft where decellularization leaves the extracellular matrix intact. 
    , which substitutes for the muscle, covering, protecting and supporting the breast implants.  It can be performed at the same time as the mastectomy.  However, the new material is expensive, may not be covered by insurance, and may increase complications of radiation therapy including more infections. 



    Oct 05 US gives Florida a sweeping right to curb medicaid

    The Bush administration approved a sweeping 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. 
    plan for Florida that limits spending for many of the 2.2 million beneficieries there and gives private health plans new freedom to limit benefits. 

    The Florida program is expected to be a model for other states.  It shifts away from defined benefits to a defined contribution, where the state sets a ceiling on spending for each recipient.  Children under 21 and pregnent women are exempt from the limits. 

    The amount set aside by the state varies per person, depending on that person's medical condition and historic use of health care. 

    The federal government and the states will now decide which benefits people get.  Under the Florida plan many of those decisions will be made by private health plans out of public view. 



    Mar 2018 NYT How Trump Consultants Exploited the Facebook Data of Millions

    Matthew Rosenberg, Nicholas Confessore & Carole Cadwalladr report as the upstart voter-profiling company Cambridge Analytica prepared to wade into the 2014 American midterm elections, it had a problem.  Its $15 million project for Robert Mercer was based on the provision of tools that could model American voters, type them and influence them.  The tools, which had been developed by Christopher Wylie's team at SCL Group/Cambridge Analytica, needed data about the voters, which was difficult to obtain. 

    Cambridge Analytica solved the problem by using data provided by Facebook to Cambridge University psychologist Dr. Aleksandr Kogan, who had told Facebook he would use the data in his research.  Cambridge Analytica provided the $800,000 finance for Kogan to develop the tools that allowed him to analyse the Facebook data.  Kogan provided Cambridge Analytica with 50 million profiles for use in Wylie's tools.  30 million included enough information to be able to match real people to the models.  270,000 people had been surveyed and had consented to share their data. 

    The UK parliament and UK regulators are investigating allegations that Cambridge Analytica performed illegal work on the "Brexit" campaign. 

    However, Cambridge Analytica's CEO Alexander Nix told a UK parliamentary committee that Kogan's data was of no use.  And he has denied using Facebook data. 

    Facebook deputy general counsel Paul Grewal noted "this was a scam -- and a fraud."  They have suspended Cambridge Analytica, Christopher Wylie & Aleksandr Kogan's access to Facebook data. 

    Congressional investigators also questioned Alexander Nix.  Foreign nationals must not get involved in US elections. 

    Robert Mueller's investigation requires access to Cambridge Analytica 'Trump team' employee's emails



    Alexander Nix initially met with Robert Mercer and Steve Bannon who were interested in his claims for psychological profiling in election campaigns. 
    Mercer agreed to fund a US based development using SCL Group's technology based modelling to develop targeted 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. 
    that can influence voters.  Bannon and Rebekah Mercer would be directors. 
    Nix agreed to setup a US based shell company Cambridge Analytica

    A pilot project funded by Robert Mercer with $1.5 million targeted the 2013 Virginia Gubernatorial race. 

    Mercer then funded work to support Ted Cruz's presidential campaign.  But this was project was national in scale and SCL (Wyle's team)'s tools did not have information on the voters.  Nix's organization completed the profiling with Facebook data obtained from Kogan. 





    Hernias



    Mar 2016 NYT How to Spot and Treat a Child's Hernia

    Jane Brody reports when my twin sons were 21/2, their pediatrician is a doctor who specializes in the treatment of infants, children and adolescents.  They are represented by the American Academy of Pediatrics. 
    detected a hernia is a bulging of tissue or an organ through an abnormal hole in the musculature.  Hernias include: inguinal, umbilical.  It the protruding tissue or organ becomes trapped (incarceration) the situation can deteriorate and may become life threatening.  Treatment of babies over three months of age with hernias requires a checkup (blood tests, urine analysis, medicine checks, and possibly an ultrasound) and straight forward outpatient surgery with general anesthesia.   in the right [side of the] groin of one of the boys.  The doctor minced no words: The hernia would not repair itelf and surgery was necessary to avoid a serious, potentially life-threatening complication.  But he added reassuringly that the operation was routine and the patient nearly always went home the same day. 

    Inguinal hernia is a protrusion of tissue through the abdominal muscle.  Inguinal hernias affect 3 to 5% of children born full term and up to 30% of children born premature.  Most of those affected are boys.  During fetal development the testes have to pass from the abdominal cavity through the inguinal canal to reach the scrotum.  Before birth, the opening to the canal is supposed to close.  When it doesn't, a hernia may result. 
    correction is the most common elective surgery that pediatric surgeons perform. 


    Osteoporosis  is a set of diseases where the bones are being broken down faster than they are being renewed.  The effect is for bones to lose strength and become brittle.  The more bone mass developed the less likely osteoporosis becomes.  The risk increases with age and more often impacts women.  Certain hormone levels have an impact: Increased glucocorticoids and reduced sex hormone levels increase bone loss, over active: Thyroid, Parathyroid and Adrenal glands.  Some medical treatments can accelerate bone loss (prostate cancer treatments).  Osteoporosis treatments include:
    • Eli-Lilly's Forteo (teriparatide) a parathyroid hormone analog which encourages bone growth but is very expensive.  And it is only allowed to be taken for two years since it was associated with bone cancer in rats. 
    • Biphosphonates reduce the rate of bone loss but have frightening side effects in a small number of patients (Jun 2016). 



    Jun 2016 Osteoporosis Drugs Shunned For Fear of Rare Side Effects

    Gina Kolata reported millions of Americans are missing out on a chance to avoid debilitating fractures from weakened bones, researchers say, because they are terrified of exceedingly rare side effects from drugs that can help them. 

    Fractures caused by fragile bones is a set of diseases where the bones are being broken down faster than they are being renewed.  The effect is for bones to lose strength and become brittle.  The more bone mass developed the less likely osteoporosis becomes.  The risk increases with age and more often impacts women.  Certain hormone levels have an impact: Increased glucocorticoids and reduced sex hormone levels increase bone loss, over active: Thyroid, Parathyroid and Adrenal glands.  Some medical treatments can accelerate bone loss (prostate cancer treatments).  Osteoporosis treatments include:
    • Eli-Lilly's Forteo (teriparatide) a parathyroid hormone analog which encourages bone growth but is very expensive.  And it is only allowed to be taken for two years since it was associated with bone cancer in rats. 
    • Biphosphonates reduce the rate of bone loss but have frightening side effects in a small number of patients (Jun 2016). 
    are a problem, particularly for women.  A 50 year old women has a 50% chance of an osteoporotic fracture in her subsequent years.  And these injuries are often the start of other problems for older adults who never walk properly again.  Many are forced into nursing homes. 

    The side effects of taking bisphosphonates: Alendronate, Ibandronate, Risedonate, Zoledronate; include:
    • Jawbones rotting in 1 of 100,000 patients. 
    • Thighbones snapping in 10 to 40 of 100,000 patients
    Doctors hoped a new class of medications might avoid the side effects but romosozumab was found to have the same problem in an Amgen clinical trial

    The ASBMA, NBHA and NOF called for doctors to promote the benefits of the treatments.  But the low but notable 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. 
    is significant to our decision processes. 


    Aug 2016 NYT Osteoporosis, a Disease With Few Treatment Choices, May Soon Have Another

    Gina Kolata reports a large clinical trial of an new osteoporosis is a set of diseases where the bones are being broken down faster than they are being renewed.  The effect is for bones to lose strength and become brittle.  The more bone mass developed the less likely osteoporosis becomes.  The risk increases with age and more often impacts women.  Certain hormone levels have an impact: Increased glucocorticoids and reduced sex hormone levels increase bone loss, over active: Thyroid, Parathyroid and Adrenal glands.  Some medical treatments can accelerate bone loss (prostate cancer treatments).  Osteoporosis treatments include:
    • Eli-Lilly's Forteo (teriparatide) a parathyroid hormone analog which encourages bone growth but is very expensive.  And it is only allowed to be taken for two years since it was associated with bone cancer in rats. 
    • Biphosphonates reduce the rate of bone loss but have frightening side effects in a small number of patients (Jun 2016). 
    drug found that it stimulates bone growth and prevents fractures at least as well as the only other drug on the market.  The new drug, expected to win approval from federal regulators, would offer another much needed treatment for some of the 10 million Americans, 80 percent of them women, who have a disease that weakens bones and often leads to years 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.  , disability and early death. 

    The results of the clinical trial by Colorado Center for Bone Research's Dr. Paul Miller of Radius Health's drug published in JAMA showed the new drug to be as effective as Forteo and far more effective than a placebo. 

    Forteo has been made progressively more expensive.  Insurers are either refusing to pay for the drug or making the deductible large.  But alternative drugs, such as Amgen's Prolia, have alarming side-effects which limit their popularity (Jun 2016). 
    Radius has not described its pricing strategy. 


    Osteoarthritis is a common inflammatory disease of the joints.  Prophylaxis can mitigate the eventual development (Sep 2016).  Factors that increase likelihood of developing osteoarthritis includes: Obesity, Joint injuries, Joint surgery to repair a torn meniscus; with athletes who develop a tear getting osteoarthritis at a rate five to ten times greater than people who do not have this surgery.  Osteoarthritis accounted for 95% of the 757,000 total knee replacements and 80% of the 512,000 total hip replacements in the US in 2011. 


    Sep 2016 NYT Don't Take Osteoarthritis Lying Down

    Jane Brody reports one of the biggest mistakes sufferers make is to limit movement of affected joints. 

    Brody suffers from osteoarthritis is a common inflammatory disease of the joints.  Prophylaxis can mitigate the eventual development (Sep 2016).  Factors that increase likelihood of developing osteoarthritis includes: Obesity, Joint injuries, Joint surgery to repair a torn meniscus; with athletes who develop a tear getting osteoarthritis at a rate five to ten times greater than people who do not have this surgery.  Osteoarthritis accounted for 95% of the 757,000 total knee replacements and 80% of the 512,000 total hip replacements in the US in 2011. 
    and says almost everyone who lives long enough will develop the condition.  But she notes its onset can be mitigated prophylactically.  And sufferers can mimimize symptoms to overcome the disability that otherwise results.  Diet is of significance. 

    Brody notes recent evidence suggests osteoarthritis may be caused and promoted by chronic low-grade inflammation that is also associated with 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 may be initiated by: stress induced HHV-6a, HHV7 herpes activation (Jun 2018) and or an increasingly leaky blood-brain barrier; and a subsequent innate immune response to the 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. 
    and heart disease is cardiovascular disease which 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). 
    .  Diet may protect against this inflammatory response. 

    Limiting movement in affected joints is a significant mistake.  It results in: Stiffness, Weakness, Decline in neuromuscular function; which can undermine balance and lead to falls. 
    A 2012 CDC is the HHS's center for disease control and prevention based in Atlanta Georgia.  
    survey found people with osteoarthritis are 137% more likely to have had two or more falls in the previous year.  And they are 147% more likely to suffer from fall injuries than people of equivalent age without the condition. 


    Stanford University researchers: Dr. William Robinson & Dr. Mark Genovese concluded that injuries and age-related wear and tear cause low-grade inflammation that further damages the joints.  The link to inflammation may explain the influence of diet: Sugar, Saturated and trans fats, refined carbohydrates and alcohol all stimulate inflammation while vegetables, fruit, whole grains, nuts, legumes, omega-3 and polyunsaturated fats were associated with less problems. 


    Exercise can be beneficial but in excess exacerbates the issues of joint wear and 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. 
    of damage.  Walking, swimming and cycling are typically beneficial.  Walking for 30 - 50 minutes three times a week relieved arthritic knee 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.  .  Daily tai chi improves balance and relieves arthiritic pain and stiffness.  Strength training is also necessary. 



    Loneliness is an aversive signal like thirst, hunger or pain.  It has been associated with the dorsal raphe nucleus (Sep 2016).  Loneliness affects several important bodily functions through overstimulation of the stress response.  Chronic loneliness is associated with increased cortisol levels, hypertension and impaired production of white blood cells undermining the immune system.  


    Sep 2016 NYT Healing the Lonely

    Katie Hafner reports the woman on the other end of the phone spoke lightheartedly of spring and her 81st birthday the previous week.  "Who did you celebrate with, Beryl?" asked Alison, whose job was to offer a kind ear.  "No one, I..." And with that, Beryl's cheer turned to despair.  Her voice began to quaver as she acknowledged that she had been alone at home not just on her birthday, but for days and days.  The telephone conversation was the first time she had spoken in more than a week. 

    In the UK the approach to countering loneliness is an aversive signal like thirst, hunger or pain.  It has been associated with the dorsal raphe nucleus (Sep 2016).  Loneliness affects several important bodily functions through overstimulation of the stress response.  Chronic loneliness is associated with increased cortisol levels, hypertension and impaired production of white blood cells undermining the immune system.   is:
    • Increased public awareness
    • Media attention
    • Local authority interest
    • Department of Health activity 
    • Private organizations: Age UK; similar to US AARP. 
    • Volunteer services: Silver Line, Open Age, Men's Shed; San Francisco has: The Friendship Line;
    Research studying loneliness has found:
    One in three people over 65 live alone in Britain and the US.  In the US half of those over 85 live alone.  In the UK and US between 10 and 46% of people over 60 are lonely. 


    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). 
     



    Aug 2015 Obesity treatments funded by ACA

    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 patient-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. 
    mandates insurance 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.  
    for 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). 
    treatment.  It has resulted in the emergence of for-profit diet-clinics run by doctors. 

    But sustained weight loss is hard to achieve.  Dr Peter Cohen of Cambridge Health Alliance and Harvard Medical School argues that nine out of ten patients who use a weight loss clinic return for hospital treatment having added weight.  Michael Jenson of Mayo Clinic agrees treatment is difficult


    Dec 2015 NYT Fitness Versus Fatness

    Nicholas Bakalar reports that researchers studied the records of 1,317,713 Swedish men conscripted for mandatory military service from 1969 to 1996.  They found that fit, fat men are at higher 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. 
    of premature death. 
    The study, headed by Umea University geriatrician Dr. Peter Nordstrom, in the International Journal of Epidemiology studies patterns, causes and effects of health and disease in populations.  It identifies risk factors for disease and focuses on preventative health care.  Being observational it suffers from a core limitation.  It can only show association, not causation.  It can suggest hypothesis but it can not disprove them.  , is interesting because:
    • The subjects were 18 years of age at the start and were representative of Swedish men in general. 
    • All the men had their fitness tested objectively by cycling to exhaustion. 
    • Over 29 years the highest one-fifth for fitness in adolescence had a 51% reduced risk of dying prematurely compared with those in the lowest fifth. 
    • Normal-weight men, no matter what their level of fitness were at 30 to 48% lower risk of premature death than obese men in the highest one-quarter for fitness. 

    Aug 2015 NYT More Rooms for All Sizes

    Maxine Levy reports many hospitals, and architects (HDR) and consultants (Hammes), are focusing on obese patients' needs with new designs and equipment. 

    Most hospitals being built are providing an increasingly large percentage of rooms that can accommodate the larger person.  Parkland Hospital is an exemplar. 



    Sep 2016 NYT When Doctors Can't See Past Patients' Weight

    Gina Kolata reports the system is unprepared to treat the obese 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). 


    Many people have grown to sizes that limit use of standard infrastructure: Scales, MRI is functional magnetic resonance imaging.  Seiji Ogawa leveraged the coupling of neuronal circuit activity and blood flow through the associated glial cells to build a 3 dimensional picture of brain cell activity.  As haemoglobin gives up its oxygen to support the neural activity it becomes magnetic and acts as a signal detected by the fMRI.  fMRI easily visualizes the state of activity in the living human brain at millimeter resolution, up to several times a second but it cannot track the time course of neural firing so it is augmented with EEG. 
    and 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. 
    machine cubic volume, OR is operating room.   tables; in their treatment. 

    Additionally their weight is seen as a 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. 
    indicator for complications during surgery which could impact both specialist and affiliated hospitals quality numbers with likely reductions 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.  
    reimbursements 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.  
    .  Hence many surgeons place arbitrary restrictions on the body mass index of patients: 40 or higher.  And 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 assume problems are driven by the effects of obesity. 
    But that is not always the case:
    Kolata notes that many fat people just avoid going to the doctor at all. 


    Nov 2016 NYT Many Wrong On Causes Of Obesity, Study Finds

    Gina Kolata reports Americans believe that 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). 
    is the biggest health threat in the nation today -- bigger even than 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).  .  But though scientific research show that diet and exercise are insufficient solutions, a large majority say fat people should be able to summon the willpower to lose weight on their own. 

    The ASMBS funded a study at NORC to survey 1,509 people's opinions about obesity.  Researchers argued: Obesity is caused by interactions between the environment and genetics and has little to do with sloth or gluttony; there are hundreds of genes that can predispose to obesity in an environment where food is cheap and portions abundant; which they contrast with the findings:
    • Concerns about obesity had risen.  
    • Obesity resulted from a lack of willpower
    • The best treatment is to take responsibility for oneself, go on a diet and exercise.  60% of respondents believed diet and exercise were more effective treatments than surgery.  68% felt it was safer to remain obese than have surgery. 
    • 94% of obese respondents had used diet and exercise with poor results.  15% of these had tried more than 20 times.  
    • 12% of severely obese respondents said a doctor had suggested surgery. 
    Obesity specialists note that there are reasons that people may have to seek medical help:
    • They are struggling with weight gain side-effects of certain medications
    • They wish to use prescription drugs to treat their obesity. 
    • For the bariatric there is surgery. 
    Obesity specialists worry that doctors are not taught about obesity in medical school compounding the misunderstandings of their patients. 


    Oct 2015 NYT Schools Report Varying Results in Their Efforts to Comply With Nutrition Guidelines

    Ron Nixon reports Schools try to offer a mix of foods -- pizza and fresh fruits and vegetables.  School systems are trying to comply with school meal standards promoted by Michelle Obama's "Let's Move!" campaign.  In a few schools, fewer children are participating in the school meals program and food waste is increasing because students are not eating the healthier alternatives. 

    The schools have asked Congress to delay some of the rules.  That will set back efforts to fight childhood 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). 
    (Jul 2015) according to some 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: lead; 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.  This includes screening for cancer & heart disease. 
    • Development, deployment and maintenance of infrastructure including: sewers, water plants and pipes.  
    • Development, deployment and maintenance of vaccination strategies.  
    • Development, deployment and maintenance of fluoridation. 
    • Development, deployment and maintenance of family planning services. 
    • Regulation and constraint of foods, drugs and devices by agencies including the FDA.  
    advocates, school officials and former military officials. 
    The CDC is the HHS's center for disease control and prevention based in Atlanta Georgia.  
    reports 12.7 million children and adolescents, 17% of American children, are overweight. 

    Tom Vilsack, the agriculture secretary, acknowledges that some schools are struggling to meet the new standards.  But their statistics say 95% of schools have met the rules.  The D.O.A. - U.S. Department of Agriculture. 
    is partnering failing schools with ones that are doing well.  It has also provided $98 million, with $28 million still unspent, to help schools buy equipment and pay for training.  Some failing schools still argue that the funds are too small and that they have to shift education funds to cover school meal program losses.  

    Food companies are providing the majority of funding for the School Nutrition Association, which is critical of the government rules.

    Elbert County, Ga has five schools which are meeting the new regulations with no funding issues and no drop in participation.  The key said school nutrition director, Bridgette Matthews is that food workers have learned to balance healthy foods with those that children are used to eating and still stay within the guidelines.  "The sodium levels, for example, are weekly averages so you can serve something with somewhat high sodium one day and come back and balance that out with something with less sodium.  It's a matter of playing with the menu." 

    De Soto, Kansas Unified School District 232 director of student nutrition Amy Droegemeier, said her district of 7,000 students had not had a decline in the students using the program and found success by working with food manufacturers.  "We worked with one of our manufacturers to come up with a different breadstick that meets the new health guidelines while also meeting the high expectations of our kids.  No one is saying that it's easy.  There is short-term pain, but it can be done without delaying the rules." 


    Oct 2015 NYT How Salad Can Make Us Fat

    Alex Hutchinson's opinion explains it only takes a health choice on the menu to let us pick something wicked. 



    Shoppers in Pennsylvania who put kale into their carts were more likely to head next to the ice-cream or beer section.  This is the licensing effect describes the brain's unconscious operation of a balance of virtuous and less honorable actions.  The key insight first described by Uzma Khan and Ravi Dhar is that our choices are contingent.  We use a self-concept to adjust as we judge our actions to be swinging away from our reference image of how: good/bad, healthy/unhealthy, selfish/altruistic; we are.   where a more "virtuous" product encourages the shopper to succumb to purchase of a vice. 

    Research indicates the effect is deeply wired into us.  And advertisers know it.  Having a healthy option on a menu increases the chances of ordering the least healthy choice.  It's those with the greatest self-control is an emotion, the ability to trade current for future use of resources.  Hunter-gatherers are likely to benefit from immediate use of resources, since they have little opportunity to store them.  Otherwise the resources, including men & women to reproduce with, may be lost, stolen or degrade.  Since the intense drive for men to breed with any available woman can lead to costly disputes and lack of focus on strategic activities, self-control is promoted by parents and other powerful group leaders.  But the frontal cortex can promote willpower to increase self-control.  Genes also allocate more resources early in the life-cycle to avoid compounding failure to leverage resources to reproduce, with agent accidents and deaths.   who are most influenced. 

    A Taiwanese study gave two groups a placebo pill to take.  But the experimental group was told it was a vitamin.  That group consistently chose less healthy options:
    • They selected the shorter route to walk. 
    • They picked the all-you-can-eat buffet rather than organic option. 
    • They expressed desire for hedonic activities like casual sex, sun bathing and excessive drinking. 
    • They smoked twice as many cigarettes. 
    To offset the licensing effect:
    • Focus on the process of living healthfully rather than the goal of being healthy. 
    • Narrow the focus of the decision so that the pros and cons are judged in isolation.  This stops the decision being part of a broader assessment of the current offset from the base line self-image.  
    • Tune out the advertising signals and ignore silver bullets. 




    Freedom




    Nov 2017 NYT America Is Now an Outlier on Driving Deaths


    David Leonhardt reports this week, millions of Americans will climb into their cars to visit family.  Unfortunately, they will have to travel on the most dangerous roads in the industrialized world. 

    Other countries have spent recent decade limiting the dangers of driving:
    • Speed is the most significant problem.  Other countries have reduced maximum speed limits and enforce them with speed cameras. 
    • Seat belts are used more in other countries.  In the US one in seven people still don't use them.  
    • In most countries sixteen year olds aren't licensed to drive. 
    • Alcohol limits are lower in other countries. 
    The US didn't follow, leaving 10,000 extra deaths on its roads per year, many of them young males 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. 


    Leonhardt hopes that driverless cars will help reduce the additional 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. 
    in the US. 


    Wellness



    Oct 2015 NYT The Sticks and Carrots of Wellness Programs

    Tara Siegel Bernard reports Honeywell has implemented a sticks and carrots 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.   program. 

    Federal regulations require wellness programs to be voluntary.  But 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 patient-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. 
    (IV is ACA preventing of chronic disease and improving public health. 
    • Subtitle A: Modernizing disease prevention and public health systems. 
    • Subtitle B: Increasing access to clinical preventative services. 
    • Subtitle C: Creating healthier communities. 
    • Subtitle D: Support for prevention and public health innovation. 
    • Subtitle E: Miscellaneous provisions. 
    ) expanded existing rules for certain types of wellness programs with incentives contingent on specific health outcomes or activities.  The law said employers could levy more surcharges than previously:
    • Maximum rewards and penalties increased from 20 to 30 percent of the total cost of the worker's insurance.  Kaiser family foundation says average total cost is $17,545 in 2015. 
    • If a tobacco cessation program is included the max. can reach 50 percent.   

    The EEOC is the equal employment opportunity commission.  It is the federal agency with oversight of employer actions and develops the rules that implement employment legislation, including: wellness. 
    tried to stop Honeywell from penalizing employees who did not take medical tests. But the motion was denied.  The EEOC then developed its own rules that now allow employers to gather genetic testing uses genomic analysis to diagnose genetic disorders - for example Genomic Health's Oncotype DX & Agendia's MammaPrint.  The desire to see the genetic risk factors identified by such tests should depend on the risk * burden * Possibility of intervention.  Early tests look at only single gene mutations, but big data research tools are showing promise with large gene algorithms (Aug 2018).  Genomic testing can be performed direct-to-consumer.  Data is being collated on the genetic components of most diseases to enable more sophisticated diagnosis in the future such as the OPHG (EGAPP initiative), USPSTF recommendations and NCBI (Genetic test registry).  While there is only limited identification of the significant mutations and limited patient bases misdiagnosis is a problem (Aug 2016). 
    data on employees and spouses.  Siegel Bernard says employees beware employer plans.  Group health plans are constrained by 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.  
    which provides more privacy protection, except when the wellness program is offered via a website tied to the wellness vendors contractual conditions which can set its own arbitrated privacy policies. 
    Similarly data from a Fitbit, or similar device, purchased by the employer for the employee is not constrained by HIPAA. 

    Critics of the programs say they are just a way to push more of the cost of health care onto the employees.  Worse they suggest that unhealthy employees can be discriminated against by the programs.  If the program fails to build wellness it can still make the employees pay rather than the employer. 
    They also worry about privacy.  Sensitive medical information could become stolen or leaked. 

    Sixty percent of large employers ask for a biometric blood analysis.  Many of the wellness vendors require yearly tests, ignoring USPSTF is United States preventative services task force.  It is an independent expert panel focused on prevention and evidence-based medicine appointed by HHS.   guidelines, just to obtain the 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.  .  The market is now worth $7.2 billion. 

    56 percent of large employers offered incentives, such as a premium reduction, to complete surveys and tests.  If you can't make yourself well, you have to pay more!


    Oct 2016 NYT AARP Sues U.S. Over Rules for Wellness Programs

    Reed Abelson reports employers have raced to offer workers a hefty financial incentive to sign up for programs meant to improve their health, submitting personal medical details in the process.  But as these programs have spread, so has resistance from employees dubious about sharing that information with employers. 

    The AARP questions if these 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.   programs are voluntary since refusing to take part can be costly for the employee.  In a lawsuit against the EEOC is the equal employment opportunity commission.  It is the federal agency with oversight of employer actions and develops the rules that implement employment legislation, including: wellness. 
    the AARP is seeking a preliminary injunction.  It argues:
    • The programs violate anti-discrimination laws that aim to protect workers' medical information. 
    • The programs aren't voluntary since the price of not participating can be high. 
    In may 2016 the EEOC issued final rules, which will go into effect in 2017, which stipulated employers could set the incentive for conforming to the company wellness program as high as 30% of the annual cost of a worker's health insurance cover, which Kaiser estimates at $6,435, or an incentive of nearly $2,000. 

    The ERISA is the Employee Retirement Income Security Act of 1974 signed by President Ford.  It regulated both pension and health benefit plans once an employer had established one.  It setup the PBGC to support voluntary private defined benefit pension plans.  Where self-funded health plans under ERISA are exempt from a state's insurance regulation there will be no solvency or consumer protection in place to support providers that do business with ERISA plans.  States may consequently require provider networks that do business with employer self-insured ERISA plans be licensed as an insurance company (an HMO, medical insurance plan, preferred provider arrangement or general casualty insurer).  ERISA section 404(a)(1)(B) defines the prudent person rule associating prudence with portfolio theory allowing pension funds to invest in stocks.  The labor department's interpretation of an ERISA employer has been modified to support President Trump's executive order to enable more use of AHPs (Jan 2018). 
    Industry Committee (ERIC) is critical of the AARP lawsuit. 


    James Gelfand noted employers are not told which employees have certain conditions, and are not using any information to discriminate.  He also argued that no one was forcing employees to participate, even if the decision meant they would forgo a potential reward of thousands of dollars.  "If you don't have to do it, it's voluntary."  He noted this was the opinion of a federal judge who sided with Orion Energy Systems against an EEOC lawsuit.  The judge argued "Even a strong incentive is still no more than an incentive; it is not compulsion." 


    Orion required a worker to complete a health 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. 
    assessment or pay the full cost of that person's health insurance premium each month.  The EEOC argued this violated the ADA is either the Americans with Disabilities Act of 1990 or a label for the gene that encodes the enzyme adenosine deaminase. 
    because it was onerous.  The AARP has typically been in agreement with such actions by the EEOC.  However, the AARP felt the EEOC was changing its position. 

    The EEOC has had limited success with stoping Employers tough policies and it is facing pressure from the Obama administration wishing to leverage employer efforts to bend the cost curve on health care. 


    Nov 2015 NYT Tracking Activity When Years Add Up

    Jane Brody reports older adults can benefit from an extra nudge to get moving, but incentives are a key, too. 

    The main motivator for those who love the fitness tracker is the pat on the back when the goals are achieved. 

    A study by University of Pennsylvania's Dr. Mitesh Patel reported in JAMA in Feb 2015, found:
    • Most smart phone apps were just as accurate as wearable devices for tracking activity. 
    • For most people to persist with use of fitness tracking it must be supported by social or employer support.  Often the person needs some kind of reward at the end of each month. 
    Half the people that purchase fitness trackers abandon them. 

    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 patient-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. 
    allows employers to use part of the employees' health insurance dollars to underwrite provision of a wearable device (Oct 2015). 

    A British study found that Fitbit's had a profound effect on the decision making about diet, exercise and how the wearers chose to travel about.  Three-fourths of users had shifted to eating healthier food, smaller portions and less takeout.  But there were also issues:
    People need to manage their relations to the devices and applications. 


    Sep 2016 NYT The False Hope of Activity Trackers

    Gretchen Reynolds reports people who used them for 18 months lost fewer pounds than those who did not. 

    A University of Pittsburgh Weight Management Research Center study published in JAMA reported finding:
    • 250, overweight young (18 - 35) dieting adults who wore activity monitors for 18 months lost significantly fewer pounds than 250 people who did not wear the devices. 
    For an initial period of six months all 500 followed a straightforward, low-calorie diet, and were asked to move more (at least 100 minutes of moderate exercise a week).  At the end of the six months all had lost weight. 
    Half the group then started logging their daily exercise session onto a study website.  The other half were given a monitor designed to be worn on the upper arm. 


    After 18 months all the subjects returned to the lab and were re-measured.  Those who had not worn activity monitors were 13 pounds lighter on average than two years previously.  Those who had worn the monitors were only eight pounds lighter on average. 

    The data from the monitors showed that that group had exercised less than the 'controls.'  Lead author of the study, Professor John Jakicic noted "What these results say to me is that we still have a great deal to learn."  People's responses to a monitor strapped to their arm may not always be rational and could result in behaviors that are the opposite of those that the monitor would be expected to encourage. 





    Nov 2015 NYT Information Can Become Information Overload

    Dr. Perri Klass reports tracking the physical activities of children could lead to problems with self-image. 

    University of Washington's associate pediatrics professor Megan Moreno studied middle school and high school children fitted with fitness tracker devices.  They responded in different ways:
    • Loved the device and strove to take 10,000 steps
    • Stopped using the device that made activity a burden.  They felt stressed if they couldn't get the time to do the stepping.  They felt bad about themselves when they failed. 
    • There were children who used the device for a while and got bored with it and stopped using it. 
    People, who study the quantified self, worry about the way this data can influence a child or adolescent's self-image. 

    There are concerns that the continual updates about performance may be interpreted as constraints undermining their beliefs in being able to change their own stories. 

    The Data and Society Research Institute's Amanda Lenhart says "Some people are motivate, 'I see how I'm not doing so well, so I need to walk more,' Other people see, 'I'm going to catch up to my sister, so I'm just going to sit here."


    Also who owns the data collected by the probes and how secure is it?  It is not protected by 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.  
    (Oct 2015).  It can be sold to marketers.  Adult equipment used by children are not constrained by restrictions setup for restricting products targeted at children. 


    Nov 2015 NYT Taking the (Opten Imprecise) Measure of Stress

    Karen Weintraub reports there are many devices for measuring symptoms, but they can lack context or rigor. 

    Devices are now attempting to monitor 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.  
      • Increases the risk of autoimmune disease (Jan 2017) 
    • During depression, stress inhibits dopamine signalling.  
    • Strategies for stress reduction include: Mindfulness. 
    and warn the wearer to change their situation.  But the monitored indicators of stress: breathing patterns, skin sweat etc. can indicate other states, like excitement, rather than stress leading to false positives. 

    MIT is Massachusetts Institute of Technology.  's Media Lab Professor Rosalind Picard studies stress monitors and she concludes most of the devices lack scientific rigor.  It is hard Picard argues with so much variation:
    • Individual,
    • Diet,
    • Lifestyle
    • Medication,
    • Environmental factors
    Dr. Picard does aim to build a stress monitor.  She is chief scientist at Empatica.  They are developing the Embrace Watch. 


    Dec 2015 NYT A Surgery Center That Doubles as an Idea Lab

    Natasha Singer reports from the moment patients register at Memorial Sloan Kettering Cancer Center's new $300 million, state of the art outpatient surgery center on the Upper East Side of Manhattan, they will be taking part in a test bed for emerging ideas in patient experience design, health care technology and data tracking. 

    Singer explains that across the country, leading medical centers are:
    • Trying new approaches to technology and information management with the aim of increasing efficiency, reducing costs and assuring health care quality.
    • Engaged in a marketing arms race: Most advanced, pioneering, or cutting-edge; to out-tech one another to attract patients. 
    Singer argues there is a problem with this approach to health care (Berman institute).  Hospitals are not required to advise patients that they are part of these 'experiments' to test: a new health application, nursing staff reduction processes or data analysis technique.  Dr. Simon argues that MSK wants to communicate the details to patients.  "I'm not sure we have 100 percent figured out how to do that." 



    Sleep

    Jul 2015 Sleep debt

    Chronic lack of sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    has been associated with a host of physical ailments, including heart disease is cardiovascular disease which 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). 
    , diabetes includes type 1 and type 2.  Common side effects include: increased heart disease, hypertension, kidney disease, vision loss, nerve damage, and infections.   and memory loss. 
    A better sleep pattern can improve 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.   in just a few weeks. 

    Less than six hours of sleep is too little (But see Oct 2015).  However, a day time nap of less than 20 minutes can equate to an extra hour of nighttime sleep. 

    You can't pay off your sleep debt, you just carry it with you. 


    Oct 2015 NYT A fresH look at Sleep needs

    Anahad O'Connor reports the results of a new study in Current Biology by Dr. Jerome Siegel a professor of psychiatry UCLA, call into question the notion that modern people sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    less. 

    The study reports that the Hazda, San and Tsimane tribes all live without modern infrastructure including lighting.  They all have similar sleep patterns even though the Tsimane live in South America while the Hazda and San live in Africa.  

    All the groups studied slept outside or in crude huts.  They usually stayed awake for three or four hours past sunset.  Most days they would wake about an hour before sun rise.  In a typical night they slept just six and a half hours, and were in bed for seven to eight and a half hours.  They slept continuously through.  They did not nap during the day. 

    Siegel's report indicates they may sleep based on ambient temperature falling asleep at night as the temperature began to fall and waking up right as the temperature would rise again.  Light did not seem to be important.  Their sleep did not seem to be problematic.  Chronic insomnia, which affects 20 - 30 % of Americans, occurred in just 2% of the hunter-gatherers. 



    Jul 2015 NYT Sleep Apnea Can Hurt Children Too

    Sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    experts argue that between 1% and 3% of children have sleep apneas that, if not treated, can inhibit their normal development 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. 


    They are excessively sleepy during the day and memory, cognitive development, ability to learn and I.Q. can suffer.  With effective treatment behavior can improve dramatically. 
    Dr. David Gozal of the University of Chicago Medical Center warned "the presence of snoring should not be viewed as a normal feature of sleeping children, since it indicates the presence of increased upper airway resistance." 

    Adenoids and tonsils typically enlarge from infancy through childhood and then shrink during adolescence and adulthood.  If they grow faster than the nose and throat bones they can reduce the capacity of the upper airway. 

    The problem is more common among blacks than whites. 

    Mild cases can be treated with steroidal nasal spray.  More severe cases can be treated with surgery to remove the tonsils and adenoids.  Obese children may also need additional air supply from a positive airway pressure machine. 


    Dec 2015 NYT Seeking Gears of Our Inner Clock

    Carl Zimmer reports a study of donated brains suggests that the mind has a rhythm of its own. 

    The brain operates to a cyclic pattern associated with the sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    /wake cycle.  And neuroscientists have concluded that it contributes to psychiatric illness. 

    University of Michigan's Dr. Huda Akil looked at donated brains from people who died at different times of the day in 2013.  They looked for biochemical differences in the brains mainly looking at the RNA that was being generated at the time of death.  They looked at cells from regions important for learning, memory and 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.  

    The researchers found that more than a 1000 genes become active and then inactive dependent on the time of day.  The patterns were highly consistent in healthy individuals killed in car crashes etc. 
    However, people suffering from 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.  Michael Pollan concludes depression is fear of the past.  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; before death had RNA profiles that were shifted significantly (8 hours) from the healthy profile. 

    The University of Pittsburgh, School of Medicine, repeated the experiments with high agreement in the results. 

    Further, Pittsburgh compared the brains of young and old people.  Old peoples' circadian cycle is a CAS process that has a 24 hour oscillation driven by a circadian clock.  In humans there are many such processes: sleep cycle (Dec 2015), liver, metabolism, immune system, oxidative stress;
    is different.  They found that as people age (60 plus) their profile deteriorated and shifted forward.  It seems likely that some people stop producing the proteins that maintain the cycle as they age.  And others seem to startup a secondary clock to help recover from deterioration of the primary mechanism.  Dr. Akil speculated that this secondary mechanism may help prevent neuro-degenerative diseases.  The neurons do housekeeping during sleep cycles. 



    Sep 2015 NYT Mood Lighting, From a Lab


    Diane Cardwell reports that doctors are giving out 'Sleepy Baby' bulbs to help babies sleep facilitates salient memory formation and removal of non-salient memories.  The five different stages of the nightly sleep cycles support different aspects of memory formation.  The sleep stages follow Pre-sleep and include: Stage one characterized by light sleep and lasting 10 minutes, Stage two where theta waves and sleep spindles occur, Stage three and Stage four together represent deep slow-wave sleep (SWS) with delta waves, Stage five is REM sleep; sleep cycles last between 90-110 minutes each and as the night progresses SWS times reduce and REM times increase.   Sleep includes the operation of synapse synthesis and maintenance through DNA based activity including membrane trafficking, synaptic vesicle recycling, myelin structural protein formation and cholesterol and protein synthesis. 
    soundly.  Mothers commented that the bulb is a 'life saver'.  Scientists identified that different levels and colors of light influence human biology.  Costly bulbs have been used to mimic the 24-hour cycle for astronauts and treating jaundice in newborns.  Now LEDs have allowed 'biological lighting describes lighting systems and LED bulbs which can regulate the body's natural 24 hour cycles by stimulating receptors in the eyes which signal the brain about when it is time to sleep and get up.  Standard LEDs by stimulating the receptors with short-wavelength light suppress melatonin release.  Biological lighting products aim to undo the damage that traditional lighting has done to the body's natural rhythms.  By releasing longer range yellow light after sunset these bulbs assist the body in maintaining its natural sleep cycle. 
    ' cost to drop. 

    'Just in the last 50 years we have had a tenfold increase in the amount of artificial light being used per capita, so everything is much brighter between when the sun sets and when we go to bed at night.  That had the effect of pushing back the body's internal clock by three to five hours but they are still trying to get up with the chickens,' explained Dr. Charles Czeisler of Brigham and Women's Hospital Division of Sleep and Circadian Disorders

    Researchers are looking at ways to:

    Allergies


    Jan 2017 NYT Feed Children Peanuts Early, Doctors Advise

    Roni Caryn Rabin reports in a significant reversal from past advice, new national health guidelines call for parents to give their children foods containing peanuts early and often, starting when they are infants, as a way to help avoid life-threatening peanut allergies. 

    The new guidelines were written by the American College of Allergy, Asthma and Immunology's food allergy committee chairman Dr. Matthew Greenhawt published in the Annals of Allergy, Asthma and Immunology and other journals.  They replace the American Academy of Pediatrics previous guidelines, telling parents to withhold peanuts from children at high 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. 
    for allergies until they were at least 3 years old, which were at odds with the new recommendations. 


    The new guidelines were developed after several studies from 2008 which anecdotally found low incidence of allergy in Israel in comparison to Jewish children in the UK is the United Kingdom of Great Britain and Northern Ireland.  .  Israeli children ate foods containing peanuts from early in infancy.  King's College London's Dr. Gideon Lack and colleagues then tested the hypothesis in a large clinical trial in England.  Hundreds of high 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. 
    infants (they had eczema or egg allergy) from 4 to 11 months, excluding those that had already developed a peanut allergy were randomly fed peanut products while controls were not.  By the time they turned 5 only 1.9% of the 530 allergy-prone children fed peanuts had developed a peanut allergy, compared to 13.7% who were denied peanuts. 
    Other tests generated similar findings.  The results were published in the New England Journal of Medicine. 

    Dr. Greenhawt commented "You have the potential to stop something in its tracks before it develops."  "There is a window of time in which the body is more likely to tolerate a food than react to it, and if you can educate the body during that window, you're at much lower likelihood of developing an allergy to that food." 

    With the previous recommendations the prevalence of peanut allergies kept rising until 2% of children had the allergy in 2010 up from 0.5% in 1999. 

    The new guidelines divide children by risk: 
    • Low-risk infants (no eczema or egg allergy) who have started solid food are introduced to peanut-containing foods around 6 months at home by their parents. 
    • Moderate-risk infants, who have mild eczema are also given peanuts at 6 months. 
    • High-risk infants with severe eczema or an egg allergy are introduced 4 to 6 months after they start solid food, but with medical evaluation, by an allergy specialist for safety. 
    Peanut containing foods should be administered three times a week through childhood. 




    Jul 2018 NYT What the Mystery of the Tick-Borne Meat Allergy Could Reveal

    Moises Velasquez-Manoff reports one spring evening in 2016, Lee Niegelsky's underarm began to itch.  An investment manager, he was doing housework around his condo, and he thought he'd been bitten by a chigger.  But within 15 minutes, hives had erupted all over his body.  He responded with what he calls a "typical man reaction" -- if the hives didn't clear up by the next day, he would have them checked.  Fifteen minutes later, the itch had become unbearable.  He needed help right away. 

    Niegelsky was suffering from MMA is:
    • The Medicare Modernization Act of 2003.  It includes Medicare part D, the Medicare prescription drug benefit, which constrains Medicare from negotiation of its drug prices and created MAC and RAC.  It was sponsored by Senator Bill Tauzin and implemented by Tom Scully.  
    • Mammalian meat allergy which is induced by a month prior tick bite that introduced the allergen alpha-gal.  About 1% of bitten humans develop the allergy & prevalence is increasing.  Humans & old world primates & monkeys don't make alpha-gal (Jul 2018).  Symptoms can include: hives, anaphylactic shock, low blood pressure. 
    .  Velasquez Manoff argues that:
    An 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.   study has linked allergic sensitization to alpha-gal with increased 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. 
    of arterial plaques. 


    Autoimmune disease



    A variety of 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. 
    drug platforms will be trained on autoimmune diseases include: celiac disease, eczema, IBD, lupus, multiple sclerosis, type-1-diabetes; are often debilitating and life long conditions.  Autoimmune diseases are increasing in prevalence 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.  Stress is associated with increased autoimmune problems (Jan 2017)
    : Celgene, Immunocore, Juno Therapeutics


    Jul 2015 NYT Opinion The Myth of Big, Bad Gluten

    Moises Velasquez-Manoff, the author of "An epidemic of Absence" suggests the Western life style rather than agonists like Gluten is responsible for the increased prevalence of auto-immune disease such as Celiac disease in the West. 

    Proponents of bad Gluten argue:
    • We haven't eaten wheat for long enough to adapt to it as a species. 
    • Agriculture began just 12,000 years ago, not enough time for evolution to act. 

    Velasquez-Manoff sees issues with the argument.  He notes:
    • Wheat was first domesticated in Anatolia 11,000 years ago.  
      • And it seems unlikely there was less gluten in more historic wheat. 
      • Americans ate more wheat in the late 19th century than they do now. 
    • But using Lactase persistence Velasquez-Manoff notes that we have adapted to adult lactose consumption which began about 11,000 years ago too. 
      • As dairying spread so did lactase persistence.  And this has continued.  Few Scandinavian hunter gatherers living 5,400 years ago had lactase persistence genes.  Today most Scandinavians do.  
    • Active Celiac disease causes serious health problems.  It typically affects about 1% of the population. 
    • The genes for Celiac disease are abundant and have spread recently.  It is a pattern seen with auto-immune genes.  It is suggested by Dr. Barreiro of Montreal that:

    Velasquez-Manoff discusses Karelia which spans the Russian Finnish border.  It is a powerful example of reduced expression of auto-immunity.  The details are:
    Velasquez-Manoff asks what is different.  The Russian side is:
    Finns say Russian Karelia resembles Finland 50 years ago.  Americans in the late 19th century likely had a similar low expression of auto-immunity. 

    Now in the West many disorders of auto-immunity have increased.  We are more sensitive to pollens (hay fever), our own microbiomes, 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: Bifidobaterium infantis which is also dependent on oligosaccharides in breast milk; 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.  
    • Chronic inflammation
    • Allergies
    • Type 1 diabetes
    (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.  ) and our own tissues (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. 
    ). 

    Velasquez-Manoff admits he does not know why this is occurring.  He speculates:


    Jun 2016 NYT Educate Your Immune System

    Moises Velasquez-Manoff opinion piece notes in the last half-century, the prevalence of autoimmune disease include: celiac disease, eczema, IBD, lupus, multiple sclerosis, type-1-diabetes; are often debilitating and life long conditions.  Autoimmune diseases are increasing in prevalence 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.  Stress is associated with increased autoimmune problems (Jan 2017)
    - disorders in which 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. 
    attacks healthy tissue in the body - has increased sharply in the developed world. 

    One in thirteen Americans has a debilitating autoimmune disease. 

    Researchers, including Dr. Ramnik Xavier at the Broad Institute, are investigating if 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: Bifidobaterium infantis which is also dependent on oligosaccharides in breast milk; 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.  
    • Chronic inflammation
    • Allergies
    • Type 1 diabetes
    has contributed to the rapid increase in 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). 
    .  They followed 33 mostly Finnish newborns whose genes put them at 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. 
    for the disease.  They periodically sampled the population's microbiome.  After three years, four of the children developed the condition.   In these children the microbiome changed about a year before disease onset.  The microbiome diversity declines and inflammatory microbes bloomed.  The hygiene hypothesis argues that to avoid hyper-reactive tendencies in the immune response that underlie autoimmune and allergic diseases need stimulation early in life.  Lifestyle is assumed to be a major aspect:
    • How the way you live guarantees exposure to a rich variety of microbes that favorably impact the immune system.  
    predicts such effects.  And Xavier argues that it may be possible to intervene and correct the decline. 

    To test this hypothesis University of Helsinki professor Mikael Knip and Dr. Xavier began a study, reported in May 2016's Cell, of 222 newborns with diabetes genetic risks from Finland, Russia (Karelia) and Estonia. Estonia's prevalence is rising but less than Finland's.  After three years, 16 Finnish children, 14 Estonian and 4 Russian children developed 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. 
    associated with autoimmune diabetes.  A microbiome comparison showed:
    • Bacteroides dominated the Finnish and Estonian children's microbiomes.  Finnish microbiome endotoxins were ineffective at stimulating white blood cell activity.  The endotoxin did not protect diabetes-prone mice from developing diabetes. 
    • Karelia children's microbiomes were mainly bifidobacteria and Escherichia coli.  These generated endotoxins that strongly stimulated white blood cell activity.  The endotoxin protected diabetes-prone mice from developing diabetes.  
    It seems likely that Karelia children encounter microbes that are not present in Finland and are infected much earlier.  Dr. Knip assumes a polio based immune response model that implies the immune system anticipates microbiome trends still seen in Karelia. 


    2018 Measure What Matters track: the Gates Foundation

    John Doerr, Bill Gates & former Gates Foundation CEO Patty Stonesifer, discuss tracking high investment objectives when time is limited. 


    The Bill and Melinda Gates Foundation was formed in 2000 as a $20 billion startup with a blank sheet to change the world.  It rapidly hired lots of talented people, while Bill was still deeply involved with Microsoft.  He had little spare time but still needed a way to ensure achievement of the foundations mission, adapt to shifting conditions, and for him to make the best choices.  The Foundation's articles require that it spend at least $1billion each year. 

    It is driven by the mission that everyone deserves a healthy and productive life. 

    This vast ambition makes it hard to identify if your making progress which presented then CEO Stonesifer with a challenge.  How to: move fast and make the best choice, be adaptable; when investing huge sums in uncertain is when a factor is hard to measure because it is dependent on many interconnected agents and may be affected by infrastructure and evolved amplifiers.  This is different from Risk.   activities.  Bill & Melinda wanted to see a disciplined system in place to direct the hard choices about what the foundation could be the best at in the world.  Once that was figured out an OKR is objectives and key results, Intel CEO Andy Grove's methodology for leveraging goals and strategies.  Key results are: specific, time-bound, measurable & verifiable.  They are expected to change as the actions proceed.  The OKR framework is a main subject of John Doerr's book Measure What Matters. 
    framework was laid on top of it. 

    Stonesifer recalls the Gates Foundation adopted a global health metric DALY is disability adjusted life years. 
    that provided a data-driven framework for the key results.  They could compare the impact of one type of investment with another.  DALY drove the Foundation to focus on vaccines are a core strategy of public health and have significantly extended global wellbeing over 200 years.  Recent successes include: HPV vaccine: Gardasil.  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, Jul 2018).  
      • 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), Cervical Cancer (Gardasil HPV Jun 2018, Oct 2018), 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). 
    , these make an enormous difference in productive life years. 


    Bill Gates believes in vision and goals.  Moore's Law, Gordon Moore characterized the two yearly doubling of the number of transistors in each new generation of integrated circuit. 
    , implied to Gates and Paul Allen, that exponential growth of computing platforms would support 'information at your fingertips.'  There would be 'a computer on every desktop and in every home.'  Big goals were justified by this vision of the future, which pushed Gates & Allen to aim higher, creating a big advantage for Microsoft over its competitors. 


    CEO Stonesifer, was introduced to John Doerr's OKR is objectives and key results, Intel CEO Andy Grove's methodology for leveraging goals and strategies.  Key results are: specific, time-bound, measurable & verifiable.  They are expected to change as the actions proceed.  The OKR framework is a main subject of John Doerr's book Measure What Matters. 
    framework when he described it to Amazon's board.  At the Gates Foundation it allowed her to optimize the limited time Bill Gates was available to meet, while placing more structure on the activities of the expanding organization.  

    Gates management experience highlighted the difference between a mission which indicates direction and goals which must include concrete steps that are being intentionally executed, and be scalable and measurable.  Objectives must be concrete and must be associated with a strategy that will get you there. 

    OKRs include ambitious and disciplined objectives and key results highlight any that aren't making required progress or are unachievable.  Until the really big goal is set it is not possible to determine which strategies will be important. 
    • The foundation's malaria team adopted an objective of eradicating the disease by 2015.  But Gates notes this wasn't realistic and undermined credibility. 
    The annual strategy reviews would begin by qualifying the objective.  Then they would get practical with the key results. 
    Setting big goals was not as difficult as breaking them down:
    • The fight against the mosquito - In 2016 the Gates Foundation and the British Government invested in a 5 year $4.3 billion campaign to eradicate malaria.  Tracking data indicated that they must adapt the focus away from attacking with a transmission blocking vaccine to a comprehensive eradication strategy. 
    • Bill Gates accepts its not easy, but by tracking what matters they have a chance




    2018 Measure What Matters Culture Change: The Lumeris Story

    John Doerr explains Lumeris was at a crossroads.  They were using OKR is objectives and key results, Intel CEO Andy Grove's methodology for leveraging goals and strategies.  Key results are: specific, time-bound, measurable & verifiable.  They are expected to change as the actions proceed.  The OKR framework is a main subject of John Doerr's book Measure What Matters. 
    s but without much buyin from the organization.  They concluded they must change the culture 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. 
    to gain from OKRs and CFR is the Code of Federal Regulations or in OKR terminology it is Conversations: about optimizing performance, Feedback: in all directions to evaluate progress and guide improvement, Recognition of individuals for their contributions.  s. 

    The initial approach to using OKRs was superficial.  Participation was only driven by an HR representative calling for updates prior to each board meeting. 
    The business rationale for using OKRs was not widely understood.  The executive leadership were not fully committed.  Objectives weren't connected to the work being performed. 

    The chief human resources (HR)/Organization Development Officer, Andrew Cole concluded the root cause of the problem was the organization's passive-aggressive culture.  There was little trust.  There were two clashing cultures: Essence healthcare reflected its deep partnership with St. Louis doctors' group, and was risk averse, Lumeris was keen to push the envelope to use big data encompasses the IT systems and processes necessary to do population based data collection, management and analysis.  The very low cost, robust, data storage organized by infrastructure: HADOOP; allows digital data to be stored en mass.  Data scientists then apply assumptions about the world to the data, analogous to evolved mechanisms in vision, in the form of algorithms.  Rather than depending on averages, analysis at Verisk drills down to specifics and then highlights modeling problems by identifying the underlying CAS.  For the analysis to be useful it requires a hierarchy of supporting BI infrastructure:
    • Analytics utilization and integration delivered via SaaS and the Cloud to cope with the silos and data intensive nature. 
    • Analytics tools (BI) for PHM 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. 
    • Data communication with the ability to exchange and transact.  HIEs and EMPI alliance approaches are all struggling to provide effective exchange. 
    • Data labeling and secure access and retreival.  While HIPAA was initially drafted as a secure MPI the index was removed from the legislation leaving the US 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.  The intent is to transform the unstructured data via OCR and NLP to structured records to support the analytics process. 
    • Raw data warehousing is distributed across silos including PCP, Hospital system and network, cloud and SaaS for process, clinical and financial data. 
    • Data collection from the patient's proximate environment as well as provider CPOE, EHRs, workflow and process infrastructure.  The integration of the EHR into a big data collection tool is key. 
    to innovate is the economic realization of invention and combinatorial exaptation.  While highly innovative, monopolies: AT&T, IBM; usually have limited economic reach, constraining productivity and supporting the use of regulation, or even its threat, that can drive their creations across the economy. 
    ; as Lumeris shared Essence Group's discoveries with the world the gap in cultures became an inhibitor to moving cast.  Essence Group aimed to fix the problems with a transformation to one organization under the Lumeris name. 

    Chief executive officer (CEO) Mike Long and Cole worked to build one culture that they desired:
    • Removed autocratic leaders who resisted the Lumeris core values of: ownership, accountability, passion for the job, and loyalty to the team.  
    • Replaced 85% of the HR professionals to ensure middle management was strong and aligned with the new leadership. 
    • Held culture meetings with employees, stressing "You have the right--no, the obligation--to hold your executive team accountable for what we're saying our culture should be.  If we're not following through, make an appointment or send an email.  Or just walk up to us in the hallway and tell us we are not getting it done." 
    • CEO pushed the organization "Why would anybody want to work in an environment with a fear of holding east other accountable?" 
    • Slowly worked to convince each employee that collaboration, shared accountability, and transparency will be rewarded & they had nothing to fear from the new Lumeris. 
    Cole then reintroduced OKRs and CFRs:
    • The President and COO agreed that the implementation must be to all 800 employees. 
    • Training on how it worked.  HR used classroom instruction to align every manager. 
    • Sixty day pilot program covering 100 employees from operations.  
    • OKRs were seen to allow employees to fail smart and fail fast.  
    • Executive monthly reviews of OKRs, run by the COO.  
    Cole notes the transformed Lumeris values interdependence and intentional coordination.  It has moved from a hero culture to a team culture. 


    Sep 2016 NYT The Trouble With Tylenol

    Moises Velasquez-Manoff opinion piece notes if you're a pregnant woman and have a backache or headache, or a fever, your options for over-the-counter treatment basically boils down to one medication: the 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.   reliever acetaminophen is a generic analgesic (pain killer) marketed by many companies including J&J's Tylenol, Paracetamol; discovered in 1877.  At high doses there is risk of liver failure.  Acetaminophen is the most common cause of acute liver failure in the US in 2017. 
    , better known as Tylenol.  Doctors advise against using nonsteroidal anti-inflammatories, like ibuprophen and asparin, during late pregnancy because they can compromise fetal circulation and have other adverse consequences. 

    There are new, well designed and controlled studies that associate high dose Tylenol taken in pregnancy with asthma is inflammation of the airways resulting in their narrowing, swelling and generating additional mucus which inhibits breathing.  Its prevalence doubled in the US between 1980 and 2000.  Diagnosis: Propeller Health; Treatments include: Xolair;
    and A.D.H.D. is attention-deficit/hyperactivity disorder, a chronic condition including hyperactivity, impulsiveness and low attention.  Dopamine 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 problems.   
    :
    The kind of study that would unequivically resolve the doubts about the associations is unlikely to occur because it would be considered unethical.  During pregnancy, not taking acetaminophen could result in untreated infection, feaver, pain etc. which could place the fetus at risk. 

    It is recommended to take, but minimize the amount of, acetaminophen consumed. 


    Schizophrenia

    Oct 2015 NYT New Approach May Alleviate Schizophrenia

    Benadict Carey reports Schizophrenia is a chronic, psychotic, brain disorder that affects 1.1 percent of the adult U.S. population.  It is characterized by hallucinations, delusions and disorganized and unusual thinking.  It seems to be caused by over pruning of prefrontal cortex neurons (Jan 2016).  There is evidence that some cases occur because of particular CNVs in the DNA of the sufferers: ZNF804A. 
    Study Advises Therapy and Reduced Drugs
    The NIMH funded study begun in 2009 and described in the American Journal of Psychiatry, and overseen by Dr. Robert Heinssen and led by Dr. John Kane of Hofstra North Shore-LIJ School of Medicine, recommended combined therapy.  CMS is the centers for Medicare and Medicaid services.   responded by a strong endorsement of the recommendations in its guidelines.   Congress awarded $25 million in block grants to states to be set aside for early-intervention mental health programs.  32 states have begun using these grants to fund combined therapy. 

    The study concluded that schizophrenia patients who received smaller doses of antipsychotic are diseases of the brain which impact the patient's models of reality and their ability to differentiate illusion from reality.  Anti-psychotic medications are prescribed: Risperdal; medication and a bigger emphasis on one-on-one talk therapy and family supports recovered more over the first two years of treatment than patients who got the usual drug-focused care.  The sooner after the first break with reality that the patient started the combined therapy the better they did.  The doctors used medications as part of a package of treatments and worked to keep the doses as low as possible. 

    The study was based on the good results of programs in Australia and Scandinavia running for decades.  It was the first U.S. study delivered through the existing community mental health centers. 

    The study randomly assigned 34 community care clinics in 21 states to provide either treatment as usual, or the combined therapy. 

    The combined therapy included:
    • Antipsychotic medication - constrained as noted above. 
    • Help with work or school
    • Education for family members to increase their understanding of the disorder. 
    • One-on-one talk therapy where tools to build social relationships, reduce substance abuse and to manage symptoms are discussed. 

    Antipsychotics are effective at eliminating psychosis are diseases of the brain which impact the patient's models of reality and their ability to differentiate illusion from reality.  Anti-psychotic medications are prescribed: Risperdal; but they have some unfortunate side effects: weight gain, drowsiness and 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.   numbing.  So three quarters of the people stop adherence is focused on improving how effectively patients take their medicines.  In the US in 2017 the problem is huge and costly (Apr 2017).  Chronic diseases such as Malaria illustrate the complexity of the task.  A coherent medical network with shared access to EHR should help.  So do blister packs with the days of the week marked.  M-health glow caps with a wireless transmitter that lights up if medication has not been taken as expected.  An improved prescription label is less open to confusion.  Codes on drugs can be scanned by smartphones to initiate download of an informational video.  Smart pillboxes control when pills are dispensed.  Measuring the contents of a medication bottle can alert for intervention if too much or too little is in the bottle.  Drug manufacturers see ways to get closer to the patient: Sanofi Toujeo deployment; Pharmacies are implementing VDS to support medication adherence: Connected Care;
    within a year and a half. 


    Jan 2016 NYT Scientists Home In on Cause of Schizophrenia

    Benedict Carey reports on a combined Harvard Medical School, Boston Children's Hospital, Broad Institute research study led by Harvard associate professor Steven McCarroll  and Aswin Sekar detailed in Nature finds 'pruning' of brain synapes may go awry causing schizophrenia is a chronic, psychotic, brain disorder that affects 1.1 percent of the adult U.S. population.  It is characterized by hallucinations, delusions and disorganized and unusual thinking.  It seems to be caused by over pruning of prefrontal cortex neurons (Jan 2016).  There is evidence that some cases occur because of particular CNVs in the DNA of the sufferers: ZNF804A. 


    They used statistical methods to study the MHC is the major histocompatibility complex, the variable cell surface proteins that bind to foreign molecules as part of the acquired immune system.  It is encoded by the gene complex HLA which includes complement component gene C4. 
    locus gene C4 is the complement component C4 gene.  It generates complement proteins C4-A and C4-B. 
    variants producing proteins C4-A is an anaphylatoxin. 
    and C4-B is forms part of C3-convertase.   of 64,000 people's genomes.  C4-A seemed to be associated with the increased 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. 
    of schizophrenia.  Partnering with Boston Children's neurologist Beth Stevens they concluded too much C4-A leads to inappropriate pruning of the planning areas during late teens. 







    Psychology

    28 Oct 04 Psychology of Evil and Politics of Fear

    Philip Zimbardo presented a three part lecture (as part of the ethics series of Professor Deborah Rhode) on the psychology of Evil and how it is being used to coerce the ideas of the US public. 

    Following Stanley Milgram's experiments on what enabled accountant's to design and carry out the procedures in the Nazi death camps, Zimbardo performed an experiment on Stanford Students, some of whom were randomly made prisoners and others guards.   The result was that within a few days (the experiment had to be stopped after 6 days of the scheduled 15) the guards were mis-treating the prisoners in ways seen recently at Abu Ghraib in Iraq. 

    Zimbardo's experiment demonstrated that evil actions can be induced by systematic processes.  Hence the legal arguement for punishing the militiary police at Abu Ghriab is seen as scapegoating.  Zimbardo acted as an expert witness showing the social issues to the Judges at Abu Graib trials but they ignored his arguements.  Zimbardo concludes that the Military Courts are acting to scapegoat the guards to protect the real perpetrators, who he indicated as Defense Secretary Rumsfeld and maybe higher. 

    The social processes of inducing the evil actions is to:

    • Dehumanize the prisoners.  Put them in uniform, with numbers and no distinguishing marks. 
    • Put the guards in uniforms, with mechanisms to induce annonimity such as dark glasses.