November and December 2021 SubCriticalAppraisal Newsletter
With links on microdosing, mitochondrial trafficking, qubit-entangled tardigrades, the value of time, and more.
This is the November and December 2021 issue of the SubCriticalAppraisal Newsletter (archives). I’ve been busy in the past two months, so you’re getting the two issues as one.
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. Happy new year!
1. Writings
2. Links
2.1 Medicine
Therapeutics:
Biologic and Clinical Efficacy of LentiGlobin for Sickle Cell Disease, Kanter et al. 2021: (n=35) one-time autologous transplantation of hematopoietic stem and progenitor cells transduced with the BB305 lentiviral vector encoding a modified β-globin gene resulted in sustained production of antisickling HbAT87Q in most red cells, leading to reduced hemolysis and complete(!) resolution of severe vaso-occlusive events
Psilocybin microdosing does not affect emotion-related symptoms and processing: A preregistered field and lab-based study, Marschall et al. 2021: yet again microdosing had no effect on affect emotion processing or symptoms of anxiety and depression compared with placebo
Use of placebo controls in the evaluation of surgery: systematic review, Wartolowska et al. 2014: in 39 out of 53 (74%) trials there was improvement in the placebo arm and in 27 (51%) trials the effect of placebo did not differ from that of surgery; in 26 (49%) trials, surgery was superior to placebo but the magnitude of the effect of the surgical intervention over that of the placebo was generally small; serious adverse events were reported in the placebo arm in 18 trials (34%) and in the surgical arm in 22 trials (41.5%)
Acupuncture: Does it alleviate pain and are there serious risks? A review of reviews, Ernst et al. 2011: reviews have little truly convincing evidence while serious adverse events including death continues to be reported
Antiaging diets: Separating fact from fiction, Lee et al. 2021, all diets (intermittent fasting, fasting-mimicking diets, ketogenic diets, time-restricted feeding, protein restriction, and dietary restriction of specific amino acids) fail to control for good ol’ caloric restriction, related: Comparison of Weight Loss Among Named Diet Programs in Overweight and Obese Adults: A Meta-analysis, Johnston et al. 2014: significant weight loss was observed with any low-carbohydrate or low-fat diet, also A Call for an End to the Diet Debates, Pagoto et al. 2013
More treatment but no less depression: The treatment-prevalence paradox, Ormel et al. 2021: (a) the published literature overestimates short- and long-term treatment efficacy, (b) treatments are considerably less effective as deployed in “real world” settings, and (c) treatment impact differs substantially for chronic-recurrent cases relative to non-recurrent cases
Diagnostics:
An In-Depth Analysis of a Piece of Shit: Distribution of Schistosoma mansoni and Hookworm Eggs in Human Stool, Krauth et al. 2012
Meta-medicine:
Reproducibility in Cancer Biology: Challenges for assessing replicability in preclinical cancer biology, Errington et al. 2021: it’s hard to assess whether reported findings are credible – the data needed to compute effect sizes and conduct power analyses was publicly accessible for just 4 of 193 experiments, 68% of where not available despite contacting original authors, 0 of 193 experiments had protocols detailed enough to repeat the experiments, related: Raise standards for preclinical cancer research, Begley et al. 2012
Alcohol, cardiovascular disease and industry funding: A co-authorship network analysis of systematic reviews, Golder et al. 2021, and The big alcohol study that didn't happen: My primal scream of rage
The Effects of Becoming a Physician on Prescription Drug Use and Mental Health Treatment, Anderson et al. 2021: becoming a physician is associated with a 20% increase in the chance of having been prescribed an anxiolytic (e.g. Xanax), a 25% increase in the chance of having been prescribed an opioid (e.g. Oxycodone), and a 61% chance of having been prescribed a sedative (e.g. Versed), especially for female doctor, note: in the Netherlands, medical school applicants are divided into 6 slots based on their high school GPA and are admitted by lottery
The statistical properties of RCTs and a proposal for shrinkage, Zwet et al. 2020
Epidemiology:
24-Hour Urinary Sodium and Potassium Excretion and Cardiovascular Risk, Ma et al, 2021: gold-standard methods, using individual-level data rather than aggregate, adjusted for many possible confounders, found each daily increment of 1000 mg in sodium excretion was associated with an 18% increase in cardiovascular risk (hazard ratio, 1.18; 95% CI, 1.08 to 1.29), and each daily increment of 1000 mg in potassium excretion was associated with an 18% decrease in risk (hazard ratio, 0.82; 95% CI, 0.72 to 0.94)
Is everything we eat associated with cancer? A systematic cookbook review, Schoenfeld et al. 2021
Association between low density lipoprotein cholesterol and all-cause mortality: results from the NHANES 1999–2014, Liu et al. 2021: low LDL-C level (< 70 mg/dL) is associated with increased risk of all-cause mortality
Canaries in the coal mine: a cross-species analysis of the plurality of obesity epidemics, Klimentidis et al. 2010: increasing mid-life body weights in 8 species of animals (n=20,000) living with or around humans
Rebalancing the unbalanced aged immune system - a special focus on zinc, Baarz et al. 2021: zinc is key for the immune system and its levels reduce with age
COVID:
The effect of vitamin D supplementation on mortality and Intensive Care Unit admission of COVID‐19 patients. A systematic review, meta‐analysis and meta‐regression, Tentolouris et al. 2021: (n=2,078) 12.2% of the treated group were admitted to ICU vs 26.3% of the non-treated group; no effect on mortality
Miscellaneous:
Intercellular nanotubes mediate mitochondrial trafficking between cancer and immune cells, Saha et al, 2021: cancer cells grow nanotubes to absorb the mitochondria from immune cells like vampires
Related: Mitochondrial Capture by a Transmissible Cancer, Rebbeck et al. 2011: canine transmissible venereal tumour periodically acquire mitochondria from its host
Blood sugar level follows perceived time rather than actual time in people with type 2 diabetes, Park et al. 2021
Studies on the mechanism of general anesthesia, Pavel et al. 2020: inhaled anaesthetics (chloroform and isoflurane) activate TREK-1 through disruption of phospholipase D2 localization to lipid rafts and subsequent production of signalling lipid phosphatidic acid
Measles virus infection diminishes preexisting antibodies that offer protection from other pathogens, Mina et al. 2019: measles caused elimination of 11-73% of the antibody repertoire across unvaccinated children (n=77), and The dual-function CD150 receptor subfamily: the viral attraction, Sidorenko et al. 2003
Inventing the randomized double-blind trial: The Nürnberg salt test of 1835, Stolberg 2006, and The MRC randomized trial of streptomycin and its legacy: a view from the clinical front line, Crofton 2006
Direct voluntary control of pupil constriction and dilation: Exploratory evidence from pupillometry, optometry, skin conductance, perception, and functional MRI, Eberhardt et al. 2021
Stubbins Ffirth, a third-year medical student in 1804, smeared yellow-fever-infected vomit, blood, saliva, and urine into incisions in his arms, poured them onto his eyeballs, fried them to inhale the fumes, to prove that yellow fever was non-contagious; turns out he was right, but the samples he used for his experiments came from late-stage patients who were no longer contaminated with the virus
2.2 Biology
Molecular Biology:
RecA finds homologous DNA by reduced dimensionality search, Wiktor et al. 2021
De novo protein design by deep network hallucination, Anishchenko et al. 2021
Genetics:
Endogenous p53 expression in human and mouse is not regulated by its 3′UTR, Mitschka et al. 2021: dozens of published studies on regulation of p53 expression by mRNAs and RNA-binding proteins, all based on reporter gene experiments, all invalidated by CRISPR deletion of the endogenous 3' UTR "target"
Neuroscience:
Irregular distribution of grid cell firing fields in rats exploring a 3D volumetric space, Grieves et al. 2021, and Locally ordered representation of 3D space in the entorhinal cortex, Ginosar et al. 2021: the mammalian brain maps 2D and 3D spaces fundamentally differently
Testing the structure of human cognitive ability using evidence obtained from the impact of brain lesions over abilities, Protzko et al. 2021
Neural population geometry: An approach for understanding biological and artificial neural networks, Chung et al. 2021
Single cortical neurons as deep artificial neural networks, Beniaguev et al. 2021
Physical principles for scalable neural recording, Marblestone et al. 2013
Longevity:
Loss of Epigenetic Information as a Cause of Mammalian Aging, Yang et al. 2021
Identification of the Adult Hematopoietic Liver as the Primary Reservoir for the Recruitment of Pro-regenerative Macrophages Required for Salamander Limb Regeneration, Debuque et al. 2021 and Heart regeneration in the salamander relies on macrophage-mediated control of fibroblast activation and the extracellular landscape, Godwin et al. 2017 and : axolotl completely regenerate their heart and limbs with macrophages from the liver
Small molecules for cell reprogramming: a systems biology analysis, Knyazer et al. 2021
Biotechnology:
Personalized phosphoproteomics identifies functional signaling, Needham et al. 2021
Lipid nanoparticles incorporating a GalNAc ligand enable in vivo liver ANGPTL3 editing in wild-type and somatic LDLR knockout non-human primates, Kasiewicz et al. 2021
Life, Uh, Finds A Way
The lungfish cocoon is a living tissue with antimicrobial functions, Heimroth et al. 2021
De novo evolution of macroscopic multicellularity, Bozdag et al. 2021
Tungsten in biological systems, Kletzin et al. 1996
Miscellaneous:
The TFAM-to-mtDNA ratio defines inner-cellular nucleoid populations with distinct activity levels, Brüser et al. 2021: the vast majority of mitochondrial DNA are inactive and serve as backup to counter mutations in the active nucleoid subpopulation
The geometry of decision-making in individuals and collectives, Sridhar et al. 2021
The energetics of genome complexity, Lane et al. 2010: by enabling oxidative phosphorylation across a wide area of internal membranes, mitochondrial genes enabled a roughly 200,000x rise in genome size compared with bacteria
Cancer risk across mammals, Vincze et al. 2021: Peto’s Paradox — cancer mortality risk is largely independent of both body mass and adult life expectancy across species
Osmosis is not driven by water dilution, Kramer et al. 2013 and Five popular misconceptions about osmosis, Kramer et al. 2011: the “concentration gradient” model of osmosis is wrong; instead, on side without solute, whenever a particle hits a pore it goes through; on side with solute, solute that hit a pore bounce back (rejected by pore), small momentum away from membrane shared among all nearby molecules due to viscous interactions between solute and water:
Individual quality: tautology or biological reality?, Bergeron et al. 2010
2.3 Physics/Computer Science
Entanglement between superconducting qubits and a tardigrade, Lee et al. 2021: a tardigrade in cryptobiosis was entangled with qubits, and the tardigrade came alive again after 420 hours at sub 10 mK temperatures and pressure of 6×10−6 mbar
Neural Tangent Kernel: Convergence and Generalization in Neural Networks, Jacot et al. 2021: NNs of infinite width converges to a kernel
Plenoxels: Radiance Fields without Neural Networks, Yu et al, 2021: 2x faster than NNs without loss in visual quality
Simulation Intelligence: Towards a New Generation of Scientific Methods, Lavin et al. 2021
Symbolic Behaviour in Artificial Intelligence, Santoro et al. 2021
Why AI is Harder Than We Think, Mitchel 2021
The Sensory Neuron as a Transformer: Permutation-Invariant Neural Networks for Reinforcement Learning, Tang et al. 2021: everything is converging into transformers
John von Neumann: "with four parameters I can fit an elephant"; Real numbers, data science and chaos: How to fit any dataset with a single parameter, Boué 2021: hold my beer:
2.4 Statistics/Meta-Science
The h-index is no longer an effective correlate of scientific reputation, Koltun et al. 2021: e.g. the correlation of the h-index with scientific awards in physics has dropped from 0.34 in 2010 to 0.00 in 2019
What’s Another Year? The Lengthening Training and Career Paths of Scientists. Cheng 2021: since the 1960’s, a STEM Ph.D.’s probability of obtaining a tenure-track position has dropped from 42.8% to 25.2%:
Fast Lane to Slow Science, Frith 2021
Statistically Controlling for Confounding Constructs Is Harder than You Think, Westfall et al. 2016: try for yourself – incremental validity error rate calculator
Amateur hour: Improving knowledge diversity in psychological and behavioral science by harnessing contributions from amateurs, Mohlhenrich et al. 2021: name dropping Nielsen, Matuschak, Alexander, Guzey, Simler, LessWrong, Neuroskeptic, Very Bad Wizards
What Is Your Estimand? Defining the Target Quantity Connects Statistical Evidence to Theory, Lundberg et al. 2021
An Automated Approach to Causal Inference in Discrete Settings, Duarte et al. 2021
2.5 Psychology
Longitudinal Associations Between Parenting and Child Big Five Personality Traits, Ayoub et al. 2021: small to very small (<0.10)
Credibility and Incredulity in Milgram's Obedience Experiments: A Reanalysis of an Unpublished Test, Perry et al. 2019: is a modern psychology 101 textbook solely about landmark studies that have been debunked?
The Sphex story: How the cognitive sciences kept repeating an old and questionable anecdote, Keijzer et al. 2013
Reversals in psychology: no good evidence for many forms of priming, power pose, ego depletion, brain training, multiple intelligences, hungry judges, facial-feedback, depressive realism, “Mount Stupid” Dunning-Kruger effect, stereotype threat suppressing gir;s’maths scores, implicit bias testing for racism, Milgram experiments, Stanford prison “experiment”
Bullshit makes the art grow profounder, Turpin et al. 2019
The Experimental Generation of Interpersonal Closeness: A Procedure and Some Preliminary Findings, Aron et al. 1997: ehe same paper that gave us the famed "36 Questions To Fall In Love With Anyone" also has 36 control tasks i.e. "Small Talk Prompts to Avoid Ever Becoming Close With Anyone"
2.6 Politics/Religion
The State of Democracy in the United States, Ministry of Foreign Affairs of the People’s Republic of China, 2021
Quantifying social organization and political polarization in online platforms, Waller et al. 2021: Reddit political polarisation in 2016 was disproportionately driven by the arrival of new users, not individual-level polarisation
The rise and fall of rationality in language, Scheffer et al. 2021: in fictional and non-fictional text in English and Spanish, thinking words relating to technology and social organisation (experiment, gravity, weigh, cost, contract) become more common between 1850 and 1977 but since then thinking words have declined markedly and feeling words relating to belief, spirituality, sapience, and intuition (e.g. forgiveness, heal, feel) have become more common:
A social network perspective on the Bamboo Ceiling: Ethnic homophily explains why East Asians but not South Asians are underrepresented in leadership in multiethnic environments, Lu et al. 2021: East Asians but not South Asians are less likely than other ethnicities to emerge as leaders in multiethnic environments partly because East Asians socialise more with ethnic ingroup members
Revealing the Preferences Behind a Superstition, Invernizzi et al. 2021: the conforming nature of the majority that sustains the false beliefs of the minority
Arbitration supports reciprocity when there are frequent perception errors, Boyd et al. 2021
The Psychology of Online Political Hostility: A Comprehensive, Cross-National Test of the Mismatch Hypothesis, Bor et al. 2021
Levitating the Pentagon: Exorcism as Politics, Politics as Exorcism, Laylock 2011: that time hippies tried to levitate the Pentagon to protest the Vietnam War; the organisers asked for a permit to lift it 300 feet in the air, and was authorised only 10 feet
The Subjection of Women: John Stuart Mill was ahead of his time
2.7 Technology
Almost Wikipedia: Eight Early Encyclopedia Projects and the Mechanisms of Collective Action, Hill 2013: Wikipedia succeeded because of its familiar end-product (online collaboration to produce a traditional encyclopaedia), low barrier to contribution and no publicly credited author
2.8 Economics/Business/Finance
Large Learning Gains in Pockets of Extreme Poverty: Experimental Evidence from Guinea Bissau, Fazzio et al. 2021: the Gambian parateachers they trained sued for higher wages, so the researchers decided to hire already-certified teachers to run 16 schools parallel to government ones for 4 years, finding treatment to be ~5 SDs better than control (the biggest effect I’ve ever seen in an education RCT), showing ultimately that in some countries kids are in school and simply not learning to read or even recognize numbers, and that's an fixable problem in principle for ~$425/kid/year:
RCTs to Scale: Comprehensive Evidence from Two Nudge Units, DelleVigna et al. 2021: in published papers, the average nudge has an 8.7% take-up effect, a 33.5% increase over the average control; in the Nudge Unit trials, the average impact is only at 1.4%, an 8.1% increase
Why Do We Think That Inflation Expectations Matter for Inflation? (And Should We?), Rudd 2021
The Economic Consequences of Sir Robert Peel: A Quantitative Assessment of the Repeal of the Corn Laws, Irwin et al. 2021: bottom 90% gained, while wealthy landowners lost out (sounds like repealer propaganda was justified):
Evaluating replicability of laboratory experiments in economics, Camerer et al. 2016: average replicated effect size of 66% of the original
Forced Entrepreneurs, Hacamo et al. 2021
Crisis Innovation Policy from World War II to COVID-19, Gross et al. 2021
The Value of Time in the United States: Estimates from Nationwide Natural Field Experiments, Goldszmidt et al. 2020: using Lyft data the value of time (VOT) is $19 per hour i.e. 75% (100%) of the after-tax mean (median) wage rate, which is higher than the VOT estimate currently used by the US government, suggesting under-investment in time-saving infrastructure
Do We Really Need Another Meeting? The Science of Workplace Meetings, Mroz et al. 2018
Prospect Theory: An Analysis of Decision under Risk, Kahneman et al. 1979
A Theory of Interstellar Trade, Krugman 1978
2.9 Philosophy/EA
2021 AI Alignment Literature Review and Charity Comparison, Larks 2021
A Soul's View of the Optimal Population Problem, de la Croix et al. 2021
Solar Superstorms: Planning for an Internet Apocalypse, Jyothi 2021
The Inconsistency in Gödel's Ontological Argument: A Success Story for AI in Metaphysics, Benzmüller et al. 2016: the higher-order theorem prover Leo-II automatically detected the inconsistency of the axioms used in Gödel’s ontological argument
2.10 Fiction
The emotional arcs of stories are dominated by six basic shapes, Reagan et al. 2016: ‘Rags to riches’ (rise); ‘Tragedy’, or ‘Riches to rags’ (fall); ‘Man in a hole’ (fall-rise); ‘Icarus’ (rise-fall); ‘Cinderella’ (rise-fall-rise); ‘Oedipus’ (fall-rise-fall).
2.11 Miscellaneous
Octopuses, crabs and lobsters to be recognised as sentient beings under UK law
Circassian genocide: the Russian Empire's systematic mass murder, ethnic cleansing, and expulsion of 800,000–1,500,000 Muslim Circassians (minimum 80–97% of the total population) from their homeland Circassia in the aftermath of the Russo-Circassian War (1763–1864)
Higher than the Shoulders of Giants; Or, a Scientist's History of Drugs: the Great Stagnation Is due to… the 1970 Controlled Substances Act?
Becoming A Whorelord: The Overly Analytical Guide To Escorting