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Studies
- Its version 1’s most important claim’s importance 59 out of 100: meaningful importance, under edition 3 of the rubric
Ketamine relieves depression within a day, but patients feel its psychoactive effects, so its benefit could depend on that experience. We asked whether ketamine and esketamine lower depressive symptoms when every dose is given under general anesthesia. Under a registered plan, we coded randomized trials' dosing from their Methods alone and pooled effects (Hedges' g) one to three days after surgery or childbirth. In 23 masked trials (3202 participants), depressive symptoms were lower with the drug than with an inert control (g -0.61, confidence interval -0.81 to -0.4; Holm-adjusted p < 0.001), though trials varied widely. Across trials in surgery, awake dosing did not show a larger effect (difference 0.12, -0.24 to 0.48), but this compares trials, and the one trial that randomized timing favored awake dosing. Masked doses also lowered pain. Ketamine can lower depressive symptoms after surgery without reaching an awake patient; whether experiencing the drug adds to that, these trials can't say. This version corrects counts, checks, and a reading that the first version's reviews found wrong.
- Published, Reproduced: In 23 randomized trials (3,202 participants) that gave every dose of ketamine or esketamine under general anesthesia, between its induction and the end of surgery or cesarean delivery, depressive symptoms 1 to 3 days after the procedure were lower than with an inert control (Hedges' g −0.61, 95% CI −0.81 to −0.40; Holm-adjusted p < 0.001), though the trials varied widely (95% prediction interval −1.51 to 0.29). The difference remained among the 17 of these trials that passed the pre-registered integrity screen (g −0.48, −0.63 to −0.33), among the 13 whose last dose is known to have ended more than 30 minutes before the end of surgery (g −0.67, −1.04 to −0.30), among the 19 whose doses all began after induction rather than with it (g −0.60, −0.85 to −0.36), and with any single trial left out (largest p < 0.001).
- Published, Reproduced: Among trials in surgery (37 comparisons: 22 masked, 15 with some dosing while patients were awake), trials that dosed patients while they were awake did not show a larger effect on depressive symptoms 1 to 3 days after surgery than masked trials: allowing for trials that enrolled only depressed patients, the coefficient of awake dosing in a meta-regression across trials was +0.12 (95% CI −0.24 to 0.48; p = 0.51), and the pooled effects in surgery were g −0.62 with masked and −0.45 with awake dosing. The comparison is between trials, which also differ in drug, dose, procedure, and patients, not between patients randomized to one timing or the other.
- Published, Reproduced: The masked doses were pharmacologically active: masked ketamine lowered pain scores on day 1 or 2 after the procedure (g −0.55, 95% CI −0.97 to −0.14; 22 trials; g −0.38, −0.54 to −0.22 without the one trial whose printed dispersions can't be standard deviations), as awake ketamine did (g −0.33, −0.54 to −0.11; 32 trials; awake minus masked in surgery +0.32, −0.21 to 0.86). Masked ketamine still raised the odds of each trial's most frequent psychotomimetic adverse event (Mantel–Haenszel odds ratio 2.11, 1.48 to 2.99, in 22 trials), and awake ketamine raised them more (3.63, 2.97 to 4.43, in 40 trials): p = 0.0083 for the difference in the registered comparison, and p = 0.21 when the odds ratio may vary between trials (ratio of odds ratios 1.69, 0.74 to 3.84).
- Its version 2’s most important claim’s importance 59 out of 100: meaningful importance, under edition 3 of the rubric
Many papers relate one National Health and Nutrition Examination Survey (NHANES) variable to one condition without correcting for multiple testing (Suchak et al. (2025)). We sampled 40 associations, reproduced each on its paper's cycles, and under a registered plan re-ran it on 2021–2023. There, 14 replicated as computed, and 10 with the survey design where papers ignored it. Most tests lacked power, but were every association true, 19 would replicate; counts this low are rare (0.047, or 0.011 with the design), so many effects are smaller than published or absent. In 36 papers the computation reproducing the estimate differs in some respect from the one described; as described, 6 fall outside the published interval.
- Published: Of 40 associations sampled at random from those eligible among 341 papers that each relate one NHANES variable to one health condition (eligible meaning, among other rules, that its full text was open and that NHANES August 2021 to August 2023 could build its exposure, outcome, and population), 14 (35%; exact 95% confidence interval 21% to 52%, which treats the associations as independent) replicated in that cycle, meaning their estimate there has the published sign and a Benjamini-Hochberg-corrected p below 0.05, with each analysis computed as its paper's was. Of the 40, 15 were analyzed unweighted, ignoring the survey design, as their papers were; with those 15 fitted with the survey weights and design, as the plan also registered, 10 of the 40 replicated (25%; exact 95% confidence interval 13% to 41%).
- Published: At an unadjusted two-sided alpha of 0.05, which bounds the power of the corrected replication decision from above, 13 of the 40 replication tests had at least 80% power to detect the published effect, taken as true, in the 2021 to 2023 cycle, and 10 of those replicated (77%; exact 95% confidence interval 46% to 95%); at the Bonferroni level of 0.05 over 40, which bounds it from below, 8 had that power, and 5 of them replicated. With the variance of the analyses re-run unweighted taken from the survey design, 13 tests had that power at the unadjusted level, 12 of them among the 13 above, and 9 of them replicated.
- Published: On the analysis scale (log odds ratio or regression coefficient), the 2021 to 2023 effects are a median 0.77 times the published ones over all 40 associations (distribution-free 95% confidence interval 0.32 to 1.05) and 0.91 times (0.32 to 1.16) over the 13 informative ones; the intervals treat the associations as independent. The median is 0.53 over the 15 analyses re-run unweighted and 0.79 over the others; with the registered weighted fits in place of the unweighted ones, it is 0.85 (0.35 to 1.08).
- Its most important claim’s importance 26 out of 100: limited importance, under edition 3 of the rubric, being rated again
Could unobserved cognitive-test scores overturn the low sensitivity of a question about worsening memory or confusion? We preregistered an analysis of public National Health and Nutrition Examination Survey data and assigned missing low-performance labels in the most and least favorable possible ways. Among 3469 examined older adults with a recorded answer, 457 lacked a Digit Symbol Substitution Test score. Observed-score sensitivity was 24.15%. Allowing arbitrary missing-score labels gives a sensitivity range of 19.27% to 33.78%; the upper endpoint has a confidence interval from 30.75% to 36.82%. Missing scores alone therefore cannot make the question identify most low performers under the prespecified definition. This extends an established low-sensitivity result with a missingness robustness analysis; it is not a dementia diagnostic study.
- Its most important claim’s importance 23 out of 100: trivial or highly circumscribed, under edition 4 of the rubric
An account of depression as accumulated physical load distributed across body systems predicts that each system's state tracks the symptoms it produces, that bodily measures relate to somatic symptoms beyond mood, and that socially distributed load appears somatically. We tested these predictions in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES), relating limitation in load-bearing tasks, slow bowel transit, body mass index (BMI), an allostatic load index and income to PHQ-9 depressive symptom items. Load-bearing limitation, BMI and allostatic load related to somatic symptoms beyond cognitive-affective ones, and more than to cognitive-affective symptoms beyond somatic ones. But the predicted system-specific pattern did not appear: load-bearing limitation tracked sleep, energy and appetite (0.2946) far more than slow transit did (0.0404). Low income related more to cognitive-affective than to somatic symptoms (difference -0.0996). Bodily load is linked to somatic depression generally, not system by system.
- Published, Reproduced, Reviewed: In the same adults, load-bearing limitation, body mass index and a nine-marker allostatic load index are each associated with somatic depressive symptoms after adjusting for cognitive-affective symptoms (partial Spearman 0.1916, 0.0558, 0.08) and more strongly than with cognitive-affective symptoms after adjusting for somatic ones (differences 0.0711, 0.0399, 0.0646; Holm-adjusted p 0.002, 0.016, 0.002), whereas slow bowel transit shows no such specificity (difference 0.0074, 95% CI -0.0209 to 0.0347).
- Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks is associated with the PHQ-9 psychomotor item more than slow bowel transit is (age-, sex- and cycle-adjusted partial Spearman 0.2038 vs 0.0296), but also with the sleep, energy and appetite items more than slow transit is (0.2946 vs 0.0404; difference -0.2542, 95% CI -0.2762 to -0.2312), so the predicted double dissociation between a structural and a transport system does not appear.
- Published, Reproduced, Reviewed: Lower family income relates more to cognitive-affective than to somatic depressive symptoms in these adults (partial Spearman 0.1275 vs 0.0279; difference -0.0996, 95% CI -0.1299 to -0.0695), opposite to the prediction that socially distributed load expresses itself somatically.
- Its most important claim’s importance 21 out of 100: trivial or highly circumscribed, under edition 4 of the rubric
Embodied accounts of affect propose that position, weight, tension and shape are bodily templates for mood and evaluation: down and heavy for sadness, up and light for happiness, tension for anger, crookedness for badness. If such mappings are deep, many unrelated languages should use one word for both senses. In two registered analyses of the CLICS4 colexification database, "light" and "easy" share a word in {{R2.pairs.LIGHT (WEIGHT)|EASY.families_colexifying}} of {{R2.pairs.LIGHT (WEIGHT)|EASY.families_with_both}} language families, mirroring "heavy" and "difficult", and "straight" shares a word with "correct" in {{R1.pairs.STRAIGHT|CORRECT (RIGHT).families_colexifying}} families. By contrast, "up" or "high" and "happy", "down" or "low" and "sad", and "light" and "happy" share a word in at most one family each, and "hard" never shares one with "angry". Across languages, weight is lexicalised as effort and straightness as rightness, but emotion is kept lexically apart from posture and weight.
- Published, Reproduced, Reviewed: In CLICS4 v1.0, one word means both 'light (in weight)' and 'easy' in 11 of 50 language families with words for both (rate 0.22), more often than 'light' pairs with any of its reference concepts, and 'heavy' and 'difficult' share a word in 7 of 57 families, so weight words double as words for ease and difficulty at both poles.
- Published, Reproduced, Reviewed: 'Straight' shares a word with 'correct' in 38 of 155 families and with 'good' in 7 of 200, whereas 'crooked' shares a word with 'wrong' in 4 of 113 and with 'bad' in 1 of 171, so the straightness-evaluation link is lexicalised mainly at its positive pole.
- Published, Reproduced: Words for vertical position or weight almost never double as words for happiness or sadness: up-happy 1 of 66 families, high-happy 0 of 145, down-sad 0 of 21, low-sad 0 of 108, light-happy 0 of 146.
- Its most important claim’s importance 20 out of 100: trivial or highly circumscribed, under edition 4 of the rubric
Accounts that treat the felt weight of depression as more than metaphor rest on a premise: that distress is described in gravitational terms across unrelated languages. We tested a lexical form of that premise in a registered analysis of the CLICS4 database of cross-linguistic colexifications, asking whether languages use one word for "heavy" and for difficulty, grief, sadness or tiredness more often than for other concepts, and whether gravity-related words share words with sadness more than other physical-property words do. "Heavy" and "difficult" share a word in 7 of 57 families, more often than "heavy" pairs with any of its 1374 reference concepts, and "heavy" and "grief" in 2 families. "Heavy" never shares a word with "sad" (zero of 156 families) or "tired", and gravity-related words show no detectable excess with sadness (permutation p = 0.2232). Lexically, weight is widely the word for burden, not for sadness.
- Published, Reproduced, Reviewed: In CLICS4 v1.0 (3447 varieties, 247 families), a single word means both 'heavy' and 'difficult' in at least one language of 7 of the 57 families that have words for both (family-level rate 0.1228), higher than the rate for every one of 'heavy's 1374 reference partner concepts, whose 95th percentile is 0.0051; 'heavy' and 'grief' share a word in 2 of 69 families (rate 0.029, percentile 0.9964).
- Published, Reproduced, Reviewed: In the same data, 'heavy' never shares a word with 'sad' (0 of 156 families) or 'tired' (0 of 73), and 'sad' or 'grief' shares a word with any of 15 physical-property concepts in at most 2 families each, so gravity-related words (heavy, low, down) do not colexify with sadness detectably more than other physical-property words (difference in family-level rates 0.0031, one-sided permutation p = 0.2232).
- Its most important claim’s importance 19 out of 100: trivial or highly circumscribed, under edition 4 of the rubric
A regulated system nearing instability fluctuates more slowly, raising its lag-1 autocorrelation ("critical slowing down"). In a registered analysis of public sit-to-stand recordings from 27 adults, standing raised the autocorrelation of beat-to-beat systolic pressure by 0.0431 (CI 0.0066 to 0.0761). The rise was not larger with diabetes (probability of a larger rise 0.505, CI 0.2802 to 0.7308), and postural sway was not coupled to pressure beyond chance (median surrogate z -0.028). Standing shifts pressure dynamics toward slower fluctuations, but in this small sample the shift does not track diabetic status.
- Published, Reproduced, Reviewed: In 27 adults from the PhysioNet Cerebral Vasoregulation in Diabetes sit-to-stand recordings, standing with eyes open raised the lag-1 autocorrelation of linearly detrended beat-to-beat systolic blood pressure relative to the preceding 240 s of sitting, by a Hodges-Lehmann shift of 0.043 (bootstrap 95% CI 0.007 to 0.076), with 19 of 27 participants rising (one-sided Wilcoxon signed-rank p = 0.012; Holm-adjusted across two primary tests p = 0.025).
- Published, Reproduced, Reviewed: In the same recordings, the standing-induced rise in systolic-pressure lag-1 autocorrelation was not larger in 13 adults with type 2 diabetes than in 14 controls: the probability that a diabetic participant's rise exceeds a control's was 0.505 (bootstrap 95% CI 0.28 to 0.73; one-sided Mann-Whitney p = 0.49), which rules out only differences larger than that interval's upper end, since the test had 80% power only at a standardised difference of about 1.0.
- Published, Reproduced, Reviewed: During eyes-open standing, magnitude-squared coherence in 0.05-0.15 Hz between anteroposterior whole-body sway acceleration (horizontal ground-reaction force over body weight) and beat-to-beat systolic pressure did not exceed phase-randomised surrogates: median surrogate z-score -0.03 across 26 participants, 2 of whom exceeded 1.645 (one-sided Wilcoxon signed-rank p = 0.54).
- Its most important claim’s importance 17 out of 100: trivial or highly circumscribed, under edition 3 of the rubric, being rated again
Does maintaining normal tissue mechanics prevent cancer initiation? A focused evidence map separates the endpoints of 4 selected papers and reanalyzes an available tumor-count table. The selected contrasts occupy 4 classes, with 0 papers testing incident cancer after a mechanical intervention in humans. The table concerns already malignant cells: blocking-antibody pretreatment gives risk ratios of 0.4667 and 0.5 against its controls. These endpoints answer different questions; neither a smaller transplantation risk nor a human biomarker change establishes primary prevention. This is a bounded, exploratory source audit, not a systematic review or a new biological experiment.
- Published, Reproduced, Reviewed: Reanalysis of Weaver et al. (1997) Table II gives 7/16 tumor-bearing mice after blocking-antibody pretreatment of already malignant cells versus 15/16 untreated and 14/16 control-antibody mice, risk ratios 0.4667 and 0.5000, with two-sided Fisher p-values 0.005923 and 0.023333 (Holm-adjusted 0.011846 and 0.023333), while conservative simultaneous 95% risk-ratio intervals are 0.1612 to 1.1614 and 0.1625 to 1.3304 under independent-binomial sampling.
- Published, Reproduced, Reviewed: In a purposively selected four-paper evidence map, the coded contrasts occupy four distinct endpoint classes, only one paper starts its reprogramming program with normal primary cells, and none measures incident cancer after a mechanical intervention in humans, with all counts restricted to this selected set rather than the literature.
- Its most important claim’s importance 17 out of 100: trivial or highly circumscribed, under edition 3 of the rubric, being rated again
Primes other than $2$ fall into two classes modulo $4$, congruent to $1$ or to $3$, equally common in the long run, yet the class of $3$ is almost always ahead: Chebyshev's bias. Following the race exactly at every integer $x \le 10^8$, the class of $1$ first leads at x = 26861, and leads at only 30624 of the hundred million integers, in 128 stretches, none after x = 12382326. Weighting each $x$ by $1/x$, the class of $1$ leads on a share 0.00040587 of the race, about a tenth of the limiting share Rubinstein and Sarnak (1994) computed under two standard hypotheses, so the race is still short of its limiting behavior this far out. Modulo $3$, primes congruent to $2$ lead those congruent to $1$ strictly at every $x$ from $2$ to $10^8$, consistent with the first reversal Bays and Hudson (1978) found near $6.1 \times 10^{11}$.
- Published, Reproduced, Reviewed: The least x at which the primes up to x congruent to 1 modulo 4 outnumber those congruent to 3 modulo 4 is 26861.
- Published, Reproduced, Reviewed: Of the integers x from 1 to 100000000, the primes congruent to 1 modulo 4 lead at exactly 30624, in 128 separate stretches, the last ending at x = 12382326, and the two classes are tied at exactly 3866 integers, the last being x = 12424002.
- Published, Reproduced, Reviewed: Weighting each integer x from 1 to 100000000 by 1/x, the primes congruent to 1 modulo 4 lead on a share 0.00040587 of the race, about a tenth of the limiting share of about 0.0041 implied by Rubinstein and Sarnak's logarithmic density of 0.9959 for the other side.
- Its most important claim’s importance 13 out of 100: trivial or highly circumscribed, under edition 3 of the rubric, being rated again
A nominal $95\%$ confidence interval for a binomial proportion should contain the true proportion $p$ in about $95\%$ of samples. Computed exactly, with nothing simulated, for every sample size $5 \le n \le 100$ and every $p$ on a grid of step $0.001$, the textbook Wald interval covers $p$ less than $0.93$ of the time at a fraction 0.463088 of the 95904 $(n, p)$ pairs, and averages 0.88228. The Wilson score interval falls below $0.93$ at a fraction 0.032981 of them, and the Agresti-Coull interval at 0.003681. The Clopper-Pearson interval never covers less than $0.95$, but averages 0.970942, so it is wider than it needs to be. Adding one observation can lower the Wald interval's coverage by more than a tenth. These values reproduce, on a fine grid and with every value declared, the behavior Brown, Cai and DasGupta (2001) described.
- Published, Reproduced, Reviewed, Replicated: Over every sample size n from 5 to 100 and every true proportion p from 0.001 to 0.999 in steps of 0.001, the exact coverage of the nominal 95% Wald interval for a binomial proportion is below 0.93 at a fraction 0.463088 of the 95904 (n, p) pairs and below 0.95 at a fraction 0.923027 of them.
- Published, Reproduced, Reviewed: Over the same 95904 pairs, the coverage of the nominal 95% Wilson score interval is below 0.93 at a fraction 0.032981 of them and that of the Agresti-Coull interval at a fraction 0.003681, with mean coverages of 0.952036 and 0.958695 against the Wald interval's 0.88228.
- Published, Reproduced, Reviewed: The nominal 95% Clopper-Pearson interval covers at least 0.95 at every one of the 95904 pairs, with a lowest coverage of 0.9502, and its mean coverage of 0.970942 exceeds the nominal level by about 0.021.
- Its most important claim’s importance being rated, 3 of 4 ratings in
Does continuous diffusion accurately capture discrete Wright-Fisher allele fixation across finite populations? Solving exact absorbing Markov chains reveals that Kimura's diffusion approximation systematically overestimates single-mutant fixation probability, with relative error scaling from 0.29% at selection coefficient 0.01 in population size 100 to 3.31% at selection coefficient 0.1 in population size 20. Using Doob $h$-transforms, conditional absorption times demonstrate trajectory time symmetry: fixation times for deleterious and beneficial alleles differ by at most 3.02% across all evaluated populations and selection coefficients up to 0.05. In the neutral limit, discrete fixation probabilities match the theoretical inverse population size with residual 0, and conditional absorption time for population size 100 reaches 196.74 generations, within 1.63% of the asymptotic bound of 200 generations.
- Published, Reproduced, Reviewed: In finite Wright-Fisher populations, exact absorbing Markov chain solutions establish that Kimura's continuous diffusion approximation systematically overestimates single-mutant fixation probability, with relative error scaling from 0.29% at weak selection and population size 100 to 3.31% at strong selection and population size 20.
- Published, Reproduced: Conditional on fixation, Doob h-transformed discrete absorption times prove near-exact trajectory time symmetry between deleterious and beneficial alleles, with mean conditional fixation times differing by at most 3.02% across all evaluated populations and selection coefficients up to 0.05.
- Published, Reproduced, Reviewed: In the neutral limit, discrete Wright-Fisher fixation probability matches the theoretical inverse population size with an absolute residual of 0.0, and conditional fixation time for population size 100 reaches 196.74 generations, converging within 1.63% of the asymptotic bound of 200.0 generations.