January and February 2022 SubCriticalAppraisal Newsletter
With links on mRNA CAR T-cell therapy, deep-learning nuclear fusion, sanewashing, time-travel chess, and more.
This is the January and February 2022 issue of the SubCriticalAppraisal Newsletter (archives). Had too few links in January and too many in February, so you’re getting the two issues as one. Belated happy Chinese New Year!
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.
1. Writings
Nothing completed
2. Links
2.1 Medicine
Therapeutics:
CAR T cells produced in vivo to treat cardiac injury, Rurik et al. 2022: treating cardiac fibrosis by generating transient chimeric antigen receptor (CAR) T cells in vivo via mRNA in CD5–targeted lipid nanoparticles in mice
What is the medical evidence on non-therapeutic child circumcision?, Deacon et al. 2022: no benefit, rare harms; the most often cited benefit of HIV prevention is solely based on circumcision of adult males who were having unprotected heterosexual intercourse in sub-Saharan Africa; only 0.6% of boys suffering from pathological phimosis require circumcision so it’s nonsensical to circumcise dozens of boys just to prevent a latter circumcision; per 100 circumcisions needing to be performed to avoid 1 UTI, 10 boys would need antibiotics for post-operative wound infection
Managing Emotions: The Effects of Online Mindfulness Meditation on Mental Health and Economic Behavior, Shreekumar et al. 2022: economists find that (n=2,400) free access to mindfulness meditation app causes a 0.44 SD reduction(!) of symptoms of stress, anxiety depression; increases earnings on proofreading task by 2%; makes decision-making more stable across emotional states
Meta-medicine:
Effect of a Novel Mindfulness Curriculum on Burnout During Pediatric Internship: A Cluster Randomized Clinical Trial, Fraiman et al. 2022: mindfulness courses are completely useless compared to social lunches on the levels of emotional exhaustion, depersonalization, burnout, empathy, and mindfulness
Eliciting the Patient's Agenda- Secondary Analysis of Recorded Clinical Encounters, Ospina et al. 2018: (n=112) clinicians elicited patient’s agenda in 36% of encounter, more often in primary care (49%) than in specialty care (20%); shared decision-making tools did not affect the likelihood of eliciting the patient’s agenda
Epidemiology:
Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis, Bjornevik et al. 2022: multiple sclerosis is caused by EBV; risk of MS increased 32x with EBV infection from 955 cases in cohort of 10M in US military (mechanism still elusive)
A comprehensive map of genetic relationships among diagnostic categories based on 48.6 million relative pairs from the Danish genealogy, Athanasiadis et al. 2022: (n=6.7M) heritability estimates for mental disorders were consistently the highest across demographic cohorts, whereas estimates for cancers were the lowest:
Extensive identification of genes involved in congenital and structural heart disorders and cardiomyopathy, Spielmann et al. 2022: multicenter analysis of almost 4,000(!) KO mice that identified 705 mouse genes involved in cardiac function; using UK Biobank data to validate the DNAJC18 gene for cardiac homeostasis by showing that its loss of function is associated with altered left ventricular systolic function
French-fried potatoes consumption and energy balance: a randomized controlled trial, Smith et al. 2022: (n=180) daily French fries vs calorie-matched almond consumption finds no statistically significant differences in fat mass or glucoregulatory biomarker changes after 30 days
The energy balance model of obesity: beyond calories in, calories out, Hall et al. 2022
Do “Moderate” Drinkers Have Reduced Mortality Risk? A Systematic Review and Meta-Analysis of Alcohol Consumption and All-Cause Mortality, Stockwell et al. 2016: (n=4M) no significant reduction in mortality risk was observed for low-volume drinkers (RR = 0.97, 95% CI [0.88, 1.07])
Alcohol use and burden for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016, GBD 2016 Alcohol Collaborators: the level of alcohol consumption that minimised harm across health outcomes was zero (95% UI 0·0–0·8) standard drinks per week, largely because the estimated protective effects for ischaemic heart disease and diabetes in women are dwarfed by monotonic associations with cancer; see comment in No level of alcohol consumption improves health
Covid
SARS-CoV-2 emergence very likely resulted from at least two zoonotic events, Pekar et al. 2022, and The Huanan market was the epicenter of SARS-CoV-2 emergence, Worobey et al. 2022: SARS-CoV-2 genomic diversity early in the COVID-19 pandemic points to emergence via repeated zoonotic events; geographical clustering of the earliest known COVID-19 cases and the proximity of positive environmental samples to live-animal vendors suggest that the Huanan Seafood Wholesale Market in Wuhan was the site of origin of the COVID-19 pandemic; the remaining open question is how it got to the market, from an animal who passed it to people or from a person who got infected at the lab and took it to the market
Long-term cardiovascular outcomes of COVID-19, Xie et al. 2022: n= 12M
mRNA-1273 or mRNA-Omicron boost in vaccinated macaques elicits comparable B cell expansion, neutralizing antibodies and protection against Omicron, Gagne et al. 2022: an Omicron boost may not provide greater immunity or protection compared to a boost with the current mRNA-1273 vaccine
Myocarditis Cases Reported After mRNA-Based COVID-19 Vaccination in the US From December 2020 to August 2021, Oster et al. 2022: n=1626 cases of myocarditis, rates were highest after the second vaccination dose in adolescent males aged 12 to 15 years (70.7 per million doses of the BNT162b2 vaccine), in adolescent males aged 16 to 17 years (105.9 per million doses of the BNT162b2 vaccine), and in young men aged 18 to 24 years (52.4 and 56.3 per million doses of the BNT162b2 vaccine and the mRNA-1273 vaccine, respectively)
The Long Long Covid Post: I’m glad Zvi did the hard work so I don’t have to:
Long Covid is real, but less common than many worry it is
Reports of Long Covid are often people who have symptoms, then blame them on Long Covid whether or not they even had Covid, the exception is loss of taste and smell
Long Covid severity and risk is proportional to Covid severity and risk.
If you didn’t notice you had Covid, you’re at very very low risk for developing Long Covid
Vaccination is thus highly but incompletely protective against Long Covid
Children are thus at minimal risk
Omicron is thus less likely to cause serious Long Covid than Delta
My current estimate of the forward-looking-practical-use chance of a healthy non-elderly person getting serious, life-impacting Long Covid from a case of Omicron is about 0.2%, or 1 in 500. This number will decline further once Paxlovid is readily available
Long Covid remains the primary downside of contracting Covid while young and healthy
Diseases often have long-term negative health effects. Long Covid is not fundamentally so different from Long Other Disease. If you are worried going forward about Long Covid you should consider things like permanently not living in a city to avoid diseases
A lot of people are in poor health; it is likely worthwhile to treat your health a lot more seriously than most people do, irrespective of Covid
The Precautionary Principle carries some weight in all this
Remember that the chance of preventing a Covid case via additional Covid prevention, going forward, even with extreme measures, is not all that high.
If you compare the potential costs of Long Covid to the costs of Long Covid Prevention, it is obvious the second is a bigger threat
Short-term additional vigilance is reasonable but rapidly becoming less reasonable
Using Long Covid as a reason for not returning to normal once case levels come down would not be reasonable
2.2 Biology
Molecular Biology:
RNA velocity unraveled, Gorin et al. 2022: rigorous and thorough analysis of RNA velocity methods
Genetics:
“Reports of My Death Were Greatly Exaggerated”: Behavior Genetics in the Postgenomic Era, Harden 2021: excellent overview, same author as The Genetic Lottery that bravely argues against the liberal dogma that says genes do not matter, and that any progressive policy needs to take genetics into account to have any chance of working
Two decades since Pinker published The Blank Slate, all nurture no nature is still the politically-correct stance, except for causes of homosexualism and transgenderism. The Fourth Law of Behavior Genetics, Chabris et al. 2015:
1. All human behavioural traits are heritable.
2. The effect of being raised in the same family is smaller than the effect of genes.
3. A substantial portion of the variation in complex human behavioural traits is not accounted for by the effects of genes or families.
4. A typical human behavioural trait is associated with very many genetic variants, each of which accounts for a very small percentage of the behavioural variability.
Turns out effects (OR) of variants and traits are correlated across populations.
Petabase-scale sequence alignment catalyses viral discovery, Edgar et al. 2022: expanding known RNA viruses by 10x with Serratus, an open-source cloud-computing infrastructure that enables ultra-high-throughput sequence alignment at the petabase scale
Relationship between rice farming and polygenic scores potentially linked to agriculture in China, Zhu et al. 2021
cube3d.dna: step-by-step tutorial on how to implement an actual 3D engine in DNA code
Neuroscience:
Power failure: why small sample size undermines the reliability of neuroscience, Button et al. 2013: the median statistical power of neuroscience studies is 18%
Controllability of structural brain networks, Gu et al. 2022: white matter microstructure network differences between cognitive circuits dictate the distinct roles in controlling trajectories of cognitive function; and Warnings and caveats in brain controllability, Tu et al. 2018: no statistical evidence brain networks are controllable from a single region; relation between nodes controllability and degree is not specific for real brain networks, but holds also for random ones; resting state networks defined with fMRI do not play a specific role in brain controllability
Communication consumes 35 times more energy than computation in the human cortex, but both costs are needed to predict synapse number, Levy et al. a neuron’s computation cost is larger than the best possible bits per joule by a factor of 108; cortical computation only uses 0.1 W of ATP rather than the oft-quoted 20 W of glucose; long-distance communication costs are 35-fold greater i.e. 3.5 W
Longevity:
Caloric restriction in humans reveals immunometabolic regulators of health span, Spadaro et al. 2022: lifespan extension by 40% caloric restriction in mice and 14% over 2 years in humans show improved thymic function possibly by suppressing gene Pla2g7 encoding platelet activating factor acetylhydrolase (PLA2G7)
In vivo CRISPR screening identifies BAZ2 chromatin remodelers as druggable regulators of mammalian liver regeneration, Jia et al. 2022: in vivo CRISPR screening identified BAZ2 proteins that suppress liver regeneration; inhibiting BAZ2 with GSK2801 and BAZ2-ICR accelerate tissue regeneration by increasing ribosomal components Rpl10a or Rpl24
Acute multidrug delivery via a wearable bioreactor facilitates long-term limb regeneration and functional recovery in adult Xenopus laevis, Murugan et al. 2022
Targeting aging mechanisms: pharmacological perspectives, Moskalev et al. 2022
An open science study of ageing in companion dogs, Creevy et al. 2022
Life, Uh, Finds A Way
MicroRNAs are deeply linked to the emergence of the complex octopus brain, Zolotarov et al. 2022
Meta-analysis reveals an extreme “decline effect” in the impacts of ocean acidification on fish behavior, Clements et al. 2022: smells fishy
Cause of Cambrian Explosion - Terrestrial or Cosmic? Steele et al. 2018: I want to believe so badly that the octopus is seeded on Earth by life-bearing comets
2.3 Physics/Computer Science
Magnetic control of tokamak plasmas through deep reinforcement learning, Degrave et al. 2022: tokamak (plasma donut) feedback control in magnetic confinement to achieve nuclear fusion — yet another instance of NNs more or less solving boundary value/control problems; if it updates its weights and biases everytime a nuclear catastrophe happens, it really adds a whole new meaning to the exploding gradient problem; DeepMind’s “solve intelligence, which solves everything else” slogan looks less ridiculous every year
Burning plasma achieved in inertial fusion, Zylstra et al. 2022: the burning plasma state has never been achieved in a controlled way before; it's extremely hard to simulate so this is crucial step to directly observe and much better understand that state
Relentless and complex transits from a planetesimal debris disc, Farihi et al. 2022: a white dwarf with maybe 65 regularly spaced moon-sized objects in its habitable zone screams "artificial megastructure"
Brains and algorithms partially converge in natural language processing, Caucheteux et al. 2022
2.4 Statistics/Meta-Science
Countries by Sci-Hub paper downloads in the last 30 days:
Surprised to see Hong Kong so high. The Business of Extracting Knowledge from Academic Publications: extracting, structuring or synthesising "insights" from papers or building knowledge bases from a domain corpus of literature has negligible value in industry; close to nothing of what makes science actually work is published as text on the web
SMTM on The Scientific Virtues: stupidity, arrogance, laziness, carefreeness, beauty, rebellion, humour
Why the Father of Modern Statistics Didn't Believe Smoking Caused Cancer
2.5 Psychology
Personality Psychology, Roberts et al. 2022: have we literally wasted millions of dollars pursuing underpowered, uninformative research out of a misplaced wish to find a biological root to our phenotypes?
One model for the learning of language, Yang et al. 2022: Chomskyans are wrong: a domain-general Bayesian learner can construct grammar and other computational devices with just a tiny amount of positive evidence
The daily association between affect and alcohol use: A meta-analysis of individual participant data, Dora et al. 2022: (n=12,000) people consume more alcohol on days high in positive than on days high in negative effect
Big Five personality traits and academic performance: A meta-analysis, Mammadov et al. 2021: (n=410,000) the combined effect of cognitive ability and personality traits explained 27.8% of the variance in academic performance; cognitive ability’s relative importance was 64%; conscientiousness accounted for 28% of the explained variance; openness, extraversion, neuroticism and agreeableness not so much
The Child as Hacker, Rule et al. 2020
Predicting mid-life capital formation with pre-school delay of gratification and life-course measures of self-regulation, Benjamin et al. 2020: (n=113 of the original Marshmallow Test participants) no evidence of more predictive power for self-regulation reported later in life; waiting 40 years to do a follow-up study is the real Marshmallow Test
2.6 Politics/Religion
Survival of the Weakest: Why the West Rules, Levine et al. 2022: the reason that the West “rules” can be traced back to two events both taking place in China: the invention of the cannon, which made possible the survival of the weakest in Europe; and the arrival of Genghis Khan, which led to the survival of the strongest in China
The Psychology of Online Political Hostility: A Comprehensive, Cross-National Test of the Mismatch Hypothesis, Bor et al. 2021: hostile political discussions are the result of status-driven individuals who are drawn to politics and are equally hostile both online and offline; online discussions feel more hostile because the behaviour of such individuals is more visible online than offline
Behind the numbers: The RSS puts the statistical skills of MPs to the test, Royal Statistical Society 2022: only half of MPs answered 25% when asked about the probability of getting two heads if you toss a coin twice; only two-thirds of MPs were able to identify the mean and mode of a dice roll
Judging job applicants by their politics: Effects of target–rater political dissimilarity on discrimination, cooperation, and stereotyping, Sinclair et al. 2022: (n=973) both Democrats and Republicans negatively stereotype job applicants with opposing political orientations
The wisdom of polarized crowds, Shi et al. 2019: political polarisation in Wikipedia editing teams increases article quality
On the Frequency Distribution of Retweets, Lu et al. 2014: retweeting distribution is described by a power-law function with the exponent form 0.6 to 0.7
/r/antiwork: A Tragedy of Sanewashing and Social Gentrification: a case study in how movements evolve when normies join your cause
Richard Hanania on Women's Tears Win in the Marketplace of Ideas: against asymmetric warfare created by feminization; just as men should be purged from public discourse if they swing their fists, women should be purged from public discourse if they start crying
The dangers of high status, low wage jobs: journalists living in Brooklyn are a homogeneous monolith of progressive cosplay, surviving off zero-sum status returns of living in a bubble of mutual-affirmation and shared anxiety, alas status can’t pay rent; Makowsky’s law of career planning: never bet your entire future on doing something other people will happily do for free
More than 1 in 5 Gen Z adults in US now identify as LGBTQ:
Ukraine: Regathering of the Russian Lands, Miscellanea: Understanding the War in Ukraine, and Thoughts on Shitpost Diplomacy
2.7 Technology
A Sociological History of the Neural Network Controversy, Olazaran 1993: the Perceptrons controversy only worked because lack of compute had already killed connectionism — it was beating a dead horse
Austin Vernon on Why is the Nuclear Power Industry Stagnant?
Bartosz Ciechanowski on GPS: his interactive essays are works of art
Google Search Is Dying: funny how appending ‘reddit’ to search is the only way to salvation
Their Bionic Eyes Are Now Obsolete and Unsupported: the most compelling argument against transhumanism isn’t philosophical — merely that biotech startups will cease firmware support the moment venture capital runs dry
2.8 Economics/Business/Finance
Education, Income and Mobility: Experimental Impacts of Childhood Exposure to Progresa after 20 Years, Araujo et al. 2022: new result from the Mexican conditional cash transfer program — children whose parents received cash transfers 20 years ago earn 15% more than those who didn't
Launching with a parachute: The gig economy and new business formation, Barrios et al. 2022: arrival of Uber and Lyft is associated with 5% increase in the number of new business registrations in the local area, and a correspondingly increase in small business lendings; introduction of the gig economy creates fallback opportunities for would-be entrepreneurs that reduce risk and encourage new business formation
For Want of a Cup: The Rise of Tea in England and the Impact of Water Quality on Mortality, Antman 2022: British tea drinking really did power the Industrial Revolution… by accidentally increasing consumption of boiled water which lowered mortality rates by 25% in lower water-quality areas
A Skeptic's Guide to Modern Monetary Theory, Mankiw et al. 2020: while the government can always print money to pay its bills, it doesn’t free the government from its intertemporal budget constraint; while the economy normally operates with excess capacity, it doesn’t mean policymakers only rarely need to worry about inflationary pressures; in a world of pervasive market power, government price setting might improve private price setting as a matter of economic theory, but it doesn’t imply that actual governments in actual economies can increase welfare by inserting themselves extensively in the price-setting process
Bryan Caplan on No One Cared About My Spreadsheets: quantitative social science is barely relevant in the real world — and almost every social scientist covertly agrees
Not Boring on Replit: Remix the Internet and The Value Chain of the Open Metaverse
The Economics of Data Businesses: data businesses have impregnable network effects moats; data follows Sturgeon’s law so only non-obvious data assets are left to be captured, but category creation is very hard
Kevin Kwok on Making Uncommon Knowledge Common: Rich Barton’s playbook for winning in consumer markets (Expedia, Zillow, Glassdoor) through data content loops
John Luttig on Don't forget Microsoft
Dissecting startup failure rates by stage:
Startups are hard, getting from seed to series A is remarkably hard.
2.9 Philosophy/EA
Psychedelics alter metaphysical beliefs, Timmermann et al. 2021: (n=866) significant shifts away from ‘physicalist’ or ‘materialist’ views, and towards panpsychism and fatalism; all changes except fatalism persist after 6 months
Has the pandemic changed views on human extinction? Bees dying out is 6th highest:
Brain Efficiency: Much More than You Wanted to Know: the brain is about as efficient as any conventional learning machine can be, given an energy budget of 10W, thermodynamic cooling constrained surface power density similar to that of earth's surface (1kW/m2) i.e. 10 cm radius, and a total training dataset of about 10 billion precepts or 'steps'; the future of AGI is to become more like the brain, not less
Kevin Simler on Consciousness: An Outside View: epidemiology of contagious consciousness states
Katja Grace on Beyond fire alarms: freeing the groupstruck
2.10 Miscellaneous
Word prevalence norms for 62,000 English lemmas, Brysbaert et al. 2018: words better known by males than females (left) and vice versa (right):
The Cognitive Style of PowerPoint, Tufte 2006
The unsuccessful self-treatment of a case of “writer's block”, Upper 1974
Dan Luu on Cocktail party ideas: people generally don't know what sub-problems need to be solved to solve the problem they're trying to address, making their solution hopeless; the root cause is generally that many people who have a superficial understanding of topic assume that the topic is as complex as their understanding of the topic
1985 MOVE bombing: 500 Philadelphia police officers attempted to clear the MOVE (a communal organisation combining Black Panthers ideology and animal rights) building and execute the arrest warrants; the police used tear gas, MOVE members fired back with semi-automatic firearms; the police returned fire with 10,000 rounds before dropping two bombs on the rooftop from a helicopter; the fire department let the subsequent fire burn out of control which destroyed 61 homes; a total of 6 adults and 5 died
Food crimes committed against Italian cuisine by the rest of the world:
Worst offender is Hong Kong.
