This is the March 2022 issue of the SubCriticalAppraisal Newsletter (archives).

The purpose of this newsletter is to be a more meaningful and summarised version of the RSS feed, complete with all my writings, site updates, interesting links, and reviews each month.

Feel free to email me with any and all suggestions or feedback. Without further ado:

1. Writings
2. Links
   1. Medicine
   2. Biology
   3. Physics/Computer Science
   4. Statistics/Meta-Science
   5. Psychology
   6. Politics/Religion
   7. Technology
   8. Economics/Business/Finance
   9. Philosophy/EA
   10. Miscellaneous

Writings

• Nothing completed

Links

Medicine

Therapeutics:

• Synthetic introns enable splicing factor mutation-dependent targeting of cancer cells, North et al. 2022: exploiting many cancer’s change-of-function mutation affecting RNA splicing, synthetic introns enables mutation-dependent killing of SF3B1-mutant leukaemia, breast cancer, uveal melanoma and pancreatic cancer cells in vitro while leaving wild-type cells unaffected
• Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial, Enebo et al. 2022: n=23 cagrilintide (long-acting amylin analogue) + semaglutide (GLP-1 analogue) vs n=24 placebo + semaglutide showed 6.0-7.4% additional weight loss

Diagnostics:

• Time to Retire the Concept of Transient Ischemic Attack, Easton et al. 2022: TIAs defined as ‘brief episodes of brain ischemia occurring rapidly enough to cause only transient symptoms and no permanent brain injury’ do not exist; all symptomatic focal cerebral ischemic events should be considered to be cerebral infarctions (it’s only a matter of degree), so TIAs are in fact mior ischemic strokes, and should be called acute ischemic cerebrovascular syndrome

Meta-medicine:

• Do Higher-Priced Hospitals Deliver Higher-Quality Care?, Cooper et al. 2022: receiving care from hospitals with two standard deviations higher inpatient prices leads to a 35% reduction in in-hospital mortality, or an additional $1 million on nondeferrable emergency cases for each life saved i.e. likely cost-effective, only if market is unconcentrated and no effect in concentrated markets; regulating hospital prices in unconcentrated markets may lead to a reduction in quality
• Are Medical Care Prices Still Declining? A Re-Examination Based on Cost‐Effectiveness Studies, Dunn et al. 2022: contra official statistics of 0.52% increase per year in medical care prices relative to economy-wide inflation from 2000 to 2017, quality-adjusted medical care prices actually declined by 1.33% per year

Epidemiology/pathophysiology:

• Prevention of MS Requires Intervention on the Causes of the Disease: Reconciling Genes, Epigenetics, and Epstein Barr Virus, Kearns et al. 2022: MS is 100% caused by genes and environment; due to EBV’s near ubiquity, the higher heritability in higher incidence populations reflects higher burden of environmental exposures (when everyone has a gun, knowing that the gun is the mechanistic cause of gun violence doesn’t explain the variation, rather it is explained by modifiable environmental factors ubiquitous in one population vs another)
• Continuous manipulation of mental representations is compromised in cerebellar degeneration, McDougle et al. 2022: ; (n=48 cerebellar disorder [CD] vs n=49 control) CD group showed impaired mental shape rotation and multiplication (arithmetic requiring memory retrieval) but unimpaired visual working memory and addition (arithmetic requiring iterative manipulation of number line); as with motor control, the cerebellum may be essential for coordinating dynamic movement-like transformations in a mental workspace

• The p Factor: One General Psychopathology Factor in the Structure of Psychiatric Disorders?, Gaspi et al. 2015: comorbidity rates are very high in psychiatry and conform roughly to the rule of 50% (half of patients who meet diagnostic criteria for one disorder meet that of a second disorder etc.); mental disorders have three dimensions: an Internalising liability to depression and anxiety; an Externalising liability to antisocial and substance-use disorders; and a Thought Disorder liability to symptoms of psychosis; underlying all three dimensions is the _p _factor:

  If _p is normally distributed (as you would expect from polygenic or even omnigenic traits), binary diagnosis of mental disorders e.g. Schizophrenia may become obsolete_

Covid

• Vaccination Rates and COVID Outcomes across US States, Barro 2022: a marginal cost around $5000(!) for 250 additional doses leads to 1 expected life saved
• BNT162b2 Vaccine-Associated Myo/Pericarditis in Adolescents: A Stratified Risk‐Benefit Analysis, Stevenson et al. 2022: (n=253) post 2 dose incidence in males aged 12-15 was 162.2 per million; males aged 16-17 93.0 per million; one dose carried more risk than benefit for boys with prior infection and no comorbidities; two doses uniformly favourable only in nonimmune girls with a comorbidity
• Humoral and cellular immune memory to four COVID-19 vaccines, Zhang et al. 2022
• Intracellular Reverse Transcription of Pfizer BioNTech COVID-19 mRNA Vaccine BNT162b2 In Vitro in Human Liver Cell Line, Aldén et al. 2022
• Far-UVC (222 nm) efficiently inactivates an airborne pathogen in a room-sized chamber, Eadie et al. 2022: krypton chloride excimer lamps (far-UVC) inactivates 98.4% of aerosolized _S. aureus _in full-size room i.e. additional 184 equivalent air changes
• SARS-CoV-2 is associated with changes in brain structure in UK Biobank, Douaud et al. 2022: (n=401 covid positive vs n=384 control) (i) greater reduction in grey matter thickness and tissue-contrast in the orbitofrontal cortex and parahippocampal gyrus, (ii) greater changes in markers of tissue damage in regions functionally-connected to the primary olfactory cortex, and (iii) greater reduction in global brain size
• Risk of Hospitalization, severe disease, and mortality due to COVID-19 and PIMS-TS in children with SARS-CoV-2 infection in Germany, Sorg et al. 2022: overall hospitalisation rate 35.9 per 10,000 children, ICU admission rate 1.7 per 10,000; case fatality 0.09 per 10,000; in children aged 5-11 ICU admission rate 0.2 per 10,000
• Secondary Attack Rates for Omicron and Delta Variants of SARS-CoV-2 in Norwegian Households, Jørgensen et al. 2022: Omicron 25.1%; Delta 19.4%
• Large-Scale Implementation of a Daily Rapid Antigen Testing Program in California for Detecting SARS-CoV-2, Ventura et al. 2022: 0.0036% false positives
• Large-scale implementation of rapid antigen testing system for COVID-19 in workplaces, Rosella et al. 2022
• Evaluation of science advice during the COVID-19 pandemic in Sweden, Brusselaers et al. 2022: the Swedish Public Health Agency dismissed scientific expertise as extreme positions, kept the public ignorant of basic facts e.g. covid is airborne, asymptomatic can still be contagious, and face mask is protective; elderly was administered morphine instead of oxygen despite available supplies; heads should roll
• The changing epidemiology of SARS-CoV-2, Koelle et al. 2022

Biology

Genetics:

• Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data, Wainschtein et al. 2022: estimated heritability of height increases from 0.53 to 0.68 and BMI from 0.18 to 0.3 when factoring in genomic relatedness matrices (GRMs) of minor allele frequencies (MAFs) of at least 0.01%, but still lower than estimates from twin studies (0.7-0.9 for height; 0.5-0.9 for BMI), which suggests the remaining missing heritability of complex traits and disease is found in variants with MAF <0.01%, which is consistent with negative selection
• Genome-wide meta-analysis of alcohol use disorder in East Asians, Zhou et al. 2022: largest-to-date in East Asians (n=13,600) confirmed the usual ADH1B and ALDH2 loci (ethanol metabolism) but no novel risk loci was observed
• The genetics of specific cognitive abilities, Procopio et al. 2022: (n=860,000) compared to g variance (.5 heritability) variance of 16 special cognitive abilities (e.g. fluid reasoning, processing speed, and quantitative knowledge) has heritability of .55 on average (.49 when corrected for g) but some abilities are more heritable than others (e.g. 40% for decision speed; 74% for processing speed) and unlike g doesn’t show dramatic increase with age
• A weakly structured stem for human origins in Africa, Ragsdale et al. 2022
• Reduced reproductive success is associated with selective constraint on human genes Gardner et al. 2022

Neuroscience:

• Reproducible brain-wide association studies require thousands of individuals, Marek et al. 2022: median neuroimaging study sample size is about 25, so unsurprisingly effect size is routinely inflated; reproduction rate improves as sample sizes grow into the thousands, noting that BWAS should be able to achieve reproducibility in relatively smaller samples than GWAS because of bigger effect sizes
• Decoding cognition from spontaneous neural activity, Liu et al. 2022: “representation-rich” approach (decoding task-related representations form spontaneous neural activity) combines the pros of both the “data-driven” approach (spontaneous but hard to establish causation) and the “intervention-based” approach (allows direct interference but disrupts spontaneity)
• Independence in ROI analysis: where is the voodoo?, Poldrack et al. 2009: on the fMRI voodoo controversy — Vye et al. were correct that non-independent region of interest (ROI) analyses result in bias (Bennet et al. 2009 scanned a dead salmon’s brain using an uncorrected threshold of P < 0.001 and 2-voxel extent threshold without strict control for multiple comparison, not uncommon methodology, to find ‘active’ brain area when ‘asked’ to perform an emotional judgement task), but incorrect in their suggestion that correlations between behaviour and imaging data in the 0.7–0.8 range are ‘impossibly high’
• An action potential initiation mechanism in distal axons for the control of dopamine release, Liu et al. 2022

Longevity:

• Targeting aging mechanisms: pharmacological perspectives. Moskalev et al. 2022: even the most common anti-aging drug Resveratrol is basically useless preclinically

  

Biotechnology:

• Nonlinear Dynamics and Chaos in Conformational Changes of Mechanical Metamaterials, Kim et al. 2022: designing precise geometry of shape change in complex networks is not so complex afterall
• Characterizing cellular heterogeneity in chromatin state with scCUT&Tag-pro, Zhang et al. 2022

Life, Uh, Finds A Way

• Scaling laws in enzyme function reveal a new kind of biochemical universality, Gagler et al. 2022: genomic dataset from 12,000 metagenomes, 1,300 archaea, 12,000 bacteria, and 200 eukaryotic taxa show that all enzyme classes (EC) display scaling behaviour with positive exponents (k > 0) with the power law fit y = ax^k, such that the total number of unique functions in each EC systematically increases with an expanding total number of enzyme function, suggesting the possibility of universal constraints (not strictly dependent on evolutionary contingency) on biochemical architecture:

  

  The last universal common ancestor shares the same scaling law, but perhaps even at the origin of life and alien life.

• Precision of morphogen gradients in neural tube development, Vetter et al. 2022: single morphogen (encodes positional information during embryogenesis) gradient yields higher central progenitor domain boundaries accuracy than simultaneous readout of opposing gradients; position error of gradients in mouse neural tube has been overestimated

Miscellaneous:

• Differential mosquito attraction to humans is associated with skin-derived carboxylic acid levels, Obaldia et al. 2022: odour concentration from carboxylic acid is the primary factor in attractiveness
• Levantine overkill: 1.5 million years of hunting down the body size distribution, Dembitzer et al. 2022: mean hunted animal masses declined log-linearly in 10k years ago to only 1.7% of those 1.5 million years ago independent of climate change, suggesting that humans hunted the largest species until extinction and moved onto the next largest species

Physics/Computer Science

• Tensor Programs V: Tuning Large Neural Networks via Zero-Shot Hyperparameter Transfer, Yang et al. 2022: outperforming GPT-3 model with tuning cost only 7% of total pre-training cost
• Uncertainty Estimation for Language Reward Models, Gleave et al. 2022

Statistics/Meta-Science

• An Investigation of the Facts Behind Columbia’s U.S. News Ranking, Thaddeus 2022: putting his tenure to good use, the Columbia maths prof finds his college’s rise in rankings from 18th place to 2nd place is based on fraudulent data mainly by deflating class sizes, inflating instructional spending, and inflating the proportion of professors with PhDs

• Sci-Hub downloads per country again:

  

  Even US researchers who have paid access to journals use Sci-Hub just because its faster.

Psychology

• Who Believes the “50 Great Myths of Psychology”?, Meinz et al. 2022: replication (n=150 psychology students) of Furnham and Hughes (2014) that found adults (n=829) were only able to recognise 37% of 249 myths presented in 50 Great Myths of Popular Psychology
• Evaluating the Big Five as an Organizing Framework for Commonly Used Psychological Trait Scales, Bainbridge et al. 2021: 70-90% of commonly used psychological trait scales can be subsumed into Big Five
• What is an “Explanation” of Behavior?, Simon 1992

Politics/Religion

• The marketplace of rationalizations, Williams 2022: rationalisation markets provide epistemic support for beliefs that people what to hold for non-epistemic reasons (belief-based preferences driven by tribalism); the highest-quality rationalisations are presented as objective and impartial, and cannot be clear (to the consumer) misinformation (cannot be rationalised); rationalisations are hard to make excludable (hard to extract private profits from) and opaque (does not permit perfect competition) so the common way to profit is monopoly by brand (consumers evaluate source of rationalisation but not the rationalisation itself), and most rationalisation production is rewarded by attention and prestige instead of money; greater consumer choice and more polarised electorate increases production of more biassed media
• Ex Post Lobbying, You 2017: 40% of lobbying happens after the bill’s passage (ex post) and 50% of ex post lobbying targets members of Congress suggests collective action problem in lobbying — the more ex ante (before bill’s passage) lobbying the higher the collective benefits, the less specific the implementation the more ex post lobbying is required be a firm to secure the benefit; nonprofit advocacy groups and schools/colleges engage in more ex ante lobbying while agribusiness and energy/natural resources show higher ex post lobbying ratios; the bigger the firm the more balanced resource allocation between ex ante and ex post lobbying is but biassed towards ex ante; trade association engage in more ex ante lobbying than individual groups

• Richer (and Holier) Than Thou? The Effect of Relative Income Improvements on Demand for Redistribution, Karadja et al. 2017: people prefer redistribution less when they realise they are relatively richer than they thought they were

  

  70% of Swedes believe they are poorer than other Swedes than they actually are (underestimate by more than 10%)

• The Outcomes of International Trade Conflicts: The US and South Korea, 1960-1981, Odell 1985: the US has won most of the 13 substantial conflict over commerce between the US and South Korean governments

Technology

• Technical reasoning bolsters cumulative technological culture through convergent transformations, Osiurak, 2022: technology evolved through accumulated modifications transmitted not by blind copying as current theories propose, but instead by technical reasoning as a reconstruction mechanism that allows recovery from partial information obtained through social learning, thus guaranteeing the high-fidelity transmission of advantageous technologies

Economics/Business/Finance

• The Quality and Efficiency of Public and Private Firms: Evidence from Ambulance Services, Knutsson et al. 2022: Swedish private ambulances reduce costs and perform better than public ones (patients ~randomly assigned) on contracted measures such as response time, but perform worse on noncontracted measures such as mortality (1.4% higher risk of death within 3 years) by cutting costs at the expense of ambulance staff quality
• Drink…then Drive Away: The Effects of Lowering the BAC in Utah, Portillo et al. 2022: lowering legal blood alcohol content for driving from 0.08 to 0.05 g/dL in Utah resulted in a fall of 0.674 accidents per 1000 residents in urban counties (mostly property damage, some fatalities, not injury) most significantly on weekdays
• Let’s Take the Con Out of Randomized Control Trials in Development: The Puzzles and Paradoxes of External Validity, Empirically Illustrated, Pritchet et al. 2021: RCTs can’t be crucial to development because many countries became highly developed RCTs they mattered; the highest observed economic growth in human history (the East Asian economic miracle) happened before RCTs became fashionable; past RCTs have little influence of policy; practitioner objections about external validity that are technically right about the unreliability of RCTs for making context-specific predictions while academics are wrong, and this in the technical domain that supposedly is the academicians comparative advantage

• Accounting for the Great Divergence: Recent findings from historical national accounting, Broadberry 2021: there was a European Little Divergence as Britain and the Netherlands overtook Italy and Spain, and an Asian Little Divergence as Japan overtook China and India; the Great Divergence occurred because Japan grew more slowly than Britain and the Netherlands starting from a lower level, and because of a strong negative growth trend in Qing dynasty China:

  

  GDP per capita in Europe and Asia, 1000-1870 (1990 international dollars).

• Money and monetary stability in Europe, 1300–1914, Karaman et al. 2020: northwestern Europe stabilised their monetary units by the 17th and 18th centuries while southern and eastern Europe continued to depreciate their monetary units to generate short-term seigniorage (“inflation tax” on the public) revenue until at least 1914 (end of sample); increase in fiscal capacity allows states to pursue more predatory monetary policies but after a certain point allows states to stabilise their monetary units which predicts long-run economic growth rates; technology innovations (e.g. fiat money) and mechanical innovations (e.g. silver/gold standard) ultimately don’t explain as much as monetary politics (executive constraint stablises; warfare destabilised):

  

  History of European monetary standards and technologies, 1500–1914

• The Imperial and Transpacific Origins of Chinese Capitalism, Hamilton 2020: Hong Kong as the origin of Chinese capitalism
• The Perils of Partial Attribution: Let’s All Play for Team Development, Pritchet 2017: ‘rigorous, evidence-based’ developmental economics inevitable leads donors and external development actors to focus on individual actions that produce at best mere millions but for which they can receive credit (like Wilt Chamberlain), rather than more indirect systemic actions that produce billions but can only receive partial credit (like Bill Russel)

Philosophy/EA

• Dual use of artificial-intelligence-powered drug discovery, Urbina et al. 2022: as a proof of concept, a machine learning model predicting new therapeutic inhibitors was driven towards the nerve agent VX (6-10mg is fatal), in less than 6 hours designed VX and 40,000 other molecules that are even more toxic than VX
• “Taste typicality” is a foundational and multi-modal dimension of ordinary aesthetic experience, Chen et al. 2022: (n=100 + n=100 replication) the more typical one’s taste was for visual stimuli, the more typical one’s taste was for environmental sounds; taste typicality was the primary way people’s aesthetic preferences differed from each other, with no other factor explaining even one fourth as much variance

Miscellaneous

• Studies so hardcore the authors were the subjects:
  • A human experiment in nerve division, Rivers et al. 1908: cutting and suturing all cutaneous branches of his own radial nerve at the left elbow sparing all muscular innervations to observe pattern of recovery over the next 4 years
  • Innsbruck Google Experiments: wearing reversing mirrors, prismatic and half prismatic goggles, and colored half goggles for long periods e.g. top-down reversing goggles for 24 hours a day for 124 days
  • Effects of Sexual Activity on Beard Growth in Man, Anonymous 1970: measured beard growth over 2 years to find beard growth rate increases just before he goes leaves remote island to see his girlfriend, published in Nature
  • Scrotal asymmetry in man and in ancient sculpture, McManus 1976: measured the scrotal asymmetry in 107 sculptures to find artists correctly placing the right testicle higher than the left, but incorrectly rendering the left as the bigger/heavier one, also published in Nature
  • Paralysis of the awake human: visual perceptions, Stevens et al. 1976: giving themselves total paralysis to report visual disturbances
  • Three-dimensional acceleration of the tibia during walking and running, Lafortune et al. 1991: inserted a metal rod (Steinmann pin) into the right tibia to measure acceleration
  • Maintenance of Foreign Language Vocabulary and the Spacing Effect, Bahrick et al. 1993: testing their own retention of learning 300 English-foreign language word pairs over 9 years
  • Does knuckle cracking lead to arthritis of the fingers?, Unger 1998: cracked his left knuckle over 36,500 times over 5 decades to find no difference in arthritis risk
  • The 2005 Nobel Prize in Physiology or Medicine awarded to Barry J. Marshall for discovering H. pylori as the cause of gastric and peptic ulcer disease by self-administering the bacterium in 1985
  • A few goodmen: surname-sharing economist coauthors, Goodmen et al. 2014: first paper to have four economist coauthors sharing the same surname (Goodmens) unrelated by marriage, blood, or current campus
  • MyConnectome: 3 MRIs and 1 blood collection per week of one guy over a year and a half, the data from which resulted in 28 papers
  • The cortisol awakening response predicts same morning executive function: results from a 50-day case study: Law et al. 2015: collecting saliva samples and completing an attention-switching index of executive function for 50 days to find that cortisol-awakening response predicts executive function
  • Brain mechanisms of recovery from pure alexia: A single case study with multiple longitudinal scans, Cohen et al. 2016: 17 behavioural, 9 anatomical, and 9 fMRI studies over 9 years of author who suffers pure alexia (impaired reading; preserved writing) after stroke
  • Precision Functional Mapping of Individual Human Brains, Gordon et al. 2017: their own 5 hr of RSFC data, 6 hr of task fMRI, multiple structural MRIs, and neuropsychological tests
  • Functional reorganization of brain networks across the human menstrual cycle, Pritschet et al. 2020: MRI and venipuncture of author for 30 consecutive days to find oestrogen and progesterone fluctuation change cortical network dynamics
  • SAYCam: A Large, Longitudinal Audiovisual Dataset Recorded From the Infant’s Perspective, Sullivan et al. 2021: strapped a headcam onto their infants aged 6-32 months 2 hours per week for 2.5 years to produce 415 hours of child-perspective videos
  • The 1983 American Urology Society meeting: once upon a time, the greatest debate in urology was on whether erectile dysfunction was caused by impaired contraction (cannot hold blood in) or impaired relaxation, so a respected British neurophysiologist Giles Brindley decided to settle the debate once and for all by showing slides of an erecting penis courtesy of a phenoxybenzamine (vasodilatory) injection, the phallic glory is of course Brindley’s own, with little fanfare he turns sideways to reveal his pronounced bulge that arose from another injection just before his talk, he then said, “Oh hell” and pulled his pants down and offered AUA members and their wives to touch his experiment and changed urology forever
• Ramzan Kadyrov: economists overstepping — the Chechen warlord has a PhD in economics

• Phone tones in musical notation: phone tones are deliberately dissonant to be more distinguishable; dial tones and busy signal too;

  

• Related: Beau Geste hypothesis in wolves: dissonant pitch modulation in “choral howl” make enemies think wolf pack is more numerous than they are; probably where the Wolf interval got its name from

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