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Studies
- Its version 1’s most important claim’s importance 62 out of 100: meaningful importance, under edition 3 of the rubric
Whether antidepressants raise suicidal behaviour in adults is disputed: the FDA's pooled trials found no increase past young adulthood, and re-analyses of approval data on newer drugs found more suicide attempts. We tested this in the serious adverse events placebo-controlled trials posted to ClinicalTrials.gov, under a registered plan. This version corrects the first, which counted a participant listed under two of an outcome's terms twice. With the posted tables and the trials' public reports, serious suicidal behaviour affected 43 adults on antidepressants and 17 to 18 on placebo (risk ratio 1.86 to 1.96): nominally significant, but at the least favourable count not after the registered correction for two endpoints. Without the trials the re-analyses also used, the excess is similar but less certain. Pediatric trials showed more serious suicidality on antidepressants, as the FDA found. These data lean toward more suicidal behaviour in adults but cannot establish it.
- Published, Reproduced: Of the 932 interventional studies naming an antidepressant with results posted on ClinicalTrials.gov on 2026-10-13, 393 randomized trials compare an antidepressant with placebo in 413 comparisons with 99,730 participants at risk in their adverse-event tables. In the 306 adult trials that randomized participants from the start (71,643 participants), nausea is more frequent on antidepressants in the 207 comparisons whose non-serious tables list it (57,580 participants; Mantel-Haenszel risk ratio 2.08, 95% CI 1.98 to 2.18), as these drugs' known side effects predict.
- Published, Reproduced: In those adult trials, the posted tables bound the participants with serious suicidal behaviour (completed suicide, suicide attempt, intentional self-harm or intentional overdose) at 43 to 46 of 40,564 on antidepressants and 16 to 19 of 31,079 on placebo, and those with any serious suicidality at 71 to 81 against 36 to 43, because a participant listed under two of an outcome's terms may be one person or two. Across every count the tables allow, the Mantel-Haenszel risk ratio is 1.76 to 2.20 for serious suicidal behaviour (p 0.0097 to 0.0502) and 1.29 to 1.73 for any serious suicidality (p 0.0078 to 0.20). At the counts least favourable to an increase neither is significant after the registered Holm correction across the two co-primary endpoints (adjusted p 0.10 and 0.20); at the most favourable both are (0.016 and 0.016).
- Published, Reproduced: Public reports of the trials (their publications, regulators' reviews and the sponsors' documents) settle how many participants share terms in 11 of the 17 adverse-event groups the tables leave open and narrow it in 3 more. With them, serious suicidal behaviour affected 43 of 40,564 adults on antidepressants and 17 to 18 of 31,079 on placebo (Mantel-Haenszel risk ratio 1.86 to 1.96; p 0.025 to 0.036), and any serious suicidality 72 to 77 against 40 to 41 (1.38 to 1.51; p 0.041 to 0.12). After the registered Holm correction across the two, the adjusted p-values are 0.071 and 0.12 at the counts least favourable to an increase and 0.0496 for both at the most favourable.
- 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: 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).
- Published, Reproduced: The masked effect was also present in the 7 masked trials that enrolled only patients with depression or depressive symptoms (g −0.78, 95% CI −1.24 to −0.31), and later after the procedure: on days 4 to 14 (g −0.51, −0.90 to −0.13; 18 trials) and days 15 to 90 (g −0.54, −0.75 to −0.33; 11 trials). Among the masked trials whose doses all began after induction, the days 4 to 14 interval included zero (g −0.61, −1.33 to 0.12; 10 trials).
- 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 38 out of 100: limited importance, under edition 3 of the rubric, being rated again
How sensitive is a focused meta-analysis of walking and jogging for depressive symptoms? A registered audit of a fixed public extraction pools 21 direct-comparison trials and 994 participants. Post-treatment Hedges g is -0.762, with a confidence interval from -1.203 to -0.321. Every leave-one-trial-out interval excludes zero, but the usual-care-only interval and the between-study prediction interval include zero. No included trial has an overall low-risk-of-bias rating. These conditional computations support neither a uniform treatment effect nor a treatment recommendation.
- 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 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 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 12 out of 100: trivial or highly circumscribed, under edition 3 of the rubric, being rated again
What are the exact finite-sample distributions of longest increasing subsequence lengths in random permutations, and how rapidly do their moments approach the limiting Tracy-Widom law? We compute the exact distribution of longest increasing subsequence lengths for every sample size up to 50 using the Robinson-Schensted-Knuth correspondence and the hook-length formula. At the largest sample size, the exact expected length is 11.309389 with variance 1.94134, corresponding to a normalized centered mean of -1.475863 and normalized variance of 0.526961. Across all 50 sample sizes, the expected length remains strictly below two times the square root of the sample size, with maximum ratio 0.799695. Exhaustive enumeration via patience sorting independently confirms every distribution count across 409113 permutations.
- Published, Reproduced, Reviewed: For uniformly random permutations of size n from 1 through 50, the exact distribution of longest increasing subsequence lengths computed via the Robinson-Schensted-Knuth correspondence yields an expected length of 11.309389 at n=50, with all expected lengths strictly bounded below 2*sqrt(n).
- Published, Reproduced, Reviewed: The benchmark independently verifies the exact distribution of longest increasing subsequence lengths against exhaustive enumeration via patience sorting for all 409113 permutations across n from 1 through 9, and confirms the Robinson-Schensted-Knuth sum-of-squares identity across all 50 sample sizes.
- Its most important claim’s importance 12 out of 100: trivial or highly circumscribed, under edition 3 of the rubric, being rated again
Adding floating-point numbers one after another loses a little at each step, and how much depends on the order of the additions. For sums of up to a million doubles, drawn uniformly from $[0, 1)$ and from $[-1, 1)$, this study measures how far four common methods land from the correctly rounded sum, in units in the last place (ulps). Adding left to right, the error averages 196.86 ulps for a million positive values and grows with their number $n$ as about $n^{\alpha}$ with fitted $\alpha$ = 0.545, close to the square root that independent rounding errors predict. Pairwise summation stays within 2 ulps at every length. Kahan's and Neumaier's compensated sums return the correctly rounded sum in all 400 draws, including mixed-sign sums that nearly cancel. Every value is reproducible exactly, on any machine and Python version.
- Published, Reproduced, Reviewed: Adding 1000000 doubles drawn uniformly from [0, 1) from left to right lands a mean of 196.86 units in the last place (at most 589) from the correctly rounded sum over 50 draws, and the mean error grows as about n to the power 0.545 for n from 1000 to 1000000, near the square-root growth that independent rounding errors predict.
- Published, Reproduced, Reviewed: Pairwise summation of the same positive draws stays within 2 units in the last place of the correctly rounded sum in all 200 draws for n from 1000 to 1000000, with a mean error of 0.4 units at n = 1000000.
- Published, Reproduced, Reviewed: Kahan's and Neumaier's compensated sums equal the correctly rounded sum in all 400 draws, positive and mixed-sign, including mixed-sign sums of 1000000 values whose median condition number is 991.
- Its most important claim’s importance being rated, 0 of 4 ratings in
Guaranteed income, regular cash with no conditions, has been tested in many American cities and in national pilots, and its advocates expect it to improve mental health without reducing work. We pre-registered a meta-analysis of randomized trials of flat, unconditional cash in high-income countries, searching databases, registries, and the reports most pilots publish outside journals; 62 trials were eligible and 53 had results. About a year into payments, mental health was better in the cash arms by 0.09 standard deviations (CI 0.041 to 0.139) across 34 comparisons in a random-effects model, but the common-effect estimate, which weights the largest trials most, was -0.002 (-0.023 to 0.018), and smaller trials reported larger effects. Employment changed by 0.599 percentage points (-2.533 to 3.731), and the mental-health effect did not fade during payments. Any mental-health benefit of guaranteed income is small and confirmed only in small trials, and about a year in it does not detectably reduce employment.
- Published, Reproduced: In 34 comparisons from 32 randomized trials of recurring unconditional cash in high-income countries (16,834 people analysed), mental health about 12 months into payments was better in the cash arms by a pooled standardized mean difference of 0.090 (95% CI 0.041 to 0.139; Holm-corrected p = 0.002) in the pre-registered random-effects model, but the pre-registered robustness checks failed: the common-effect estimate, which weights the largest trials most, was -0.002 (-0.023 to 0.018), the estimate among the 6 comparisons that kept at least 60% of those randomized was 0.043 (-0.077 to 0.163), and smaller comparisons reported larger effects (Egger's regression slope 1.54, 95% CI 0.75 to 2.33; p < 0.001).
- Published, Reproduced: In exploratory analyses added after registration, the larger mental-health benefits came from small comparisons and from shares above a cut-off: the 7 comparisons with at least 500 people analysed pooled to 0.041 standard deviations (95% CI -0.079 to 0.161) against 0.107 (0.052 to 0.163) for the other 27, and estimates from scale scores pooled to 0.051 (0.007 to 0.096) against 0.233 (0.084 to 0.381) for shares above a cut-off converted to standard deviations (difference 0.147, 0.037 to 0.258).
- Published, Reproduced: Of the 32 eligible registered trials of unconditional cash whose primary completion or end date was at least 12 months before 2026-10-17, 8 had reported no results this review could find, among them the Chicago Resilient Communities Pilot (AEARCTR-0009656), registered with 11,915 participants.
- Its most important claim’s importance being rated, 2 of 4 ratings in
How much does scheduling a daily batch by historical grid intensity help when computing capacity and idle power are explicit? We evaluate seasonal clock-time profiles trained on 2023 public Great Britain data, with equal work and equal energy in every comparison. At 50% utilization, assigned carbon falls by 11.63% in 2024 and 12.81% in 2025 relative to uniform processing. Setting idle power to 50% of maximum power reduces these advantages to 3.88% and 4.27%. Some dates have higher assigned carbon after shifting. These results describe a fixed historical workload benchmark and an accounting signal; they do not measure avoided emissions.
- Its most important claim’s importance being rated, 3 of 4 ratings in
Does adaptive therapy consistently outperform continuous maximum tolerated dose treatment? Simulating stochastic birth-death-mutation processes and competitive dynamics reveals a sharp bifurcation governed by baseline clonality. Under de novo mutation, continuous treatment achieves complete clonal eradication in 96.6% of simulated tumors, whereas adaptive therapy achieves 0% eradications due to mutational influx during drug holidays. Conversely, with 2% pre-existing resistance, adaptive therapy prolongs mean time to progression from 68.6 days to 74.8 days while reducing cumulative drug exposure by 18.1%. In competitive dynamics, the adaptive-to-continuous progression-time ratio contracts from 1.11 under a 20% fitness cost to 1.09 under neutral resistance. Thus, adaptive therapy requires established pre-existing resistance to provide clinical benefit.
- Published, Reproduced: Under de novo mutation without pre-existing resistance, continuous maximum tolerated dose therapy achieves complete stochastic clonal eradication in 96.6% of simulated tumors, whereas adaptive therapy achieves 0.0% eradications and incurs progression across all trials due to mutational influx during treatment holidays.
- Published, Reproduced, Reviewed: In the presence of 2.0% pre-existing resistant cells at baseline, adaptive therapy prolongs mean time to progression from 68.6 days to 74.8 days while reducing cumulative drug exposure by 18.1% compared to continuous therapy.
- Published, Reproduced, Reviewed: Across deterministic competitive dynamics, the time-to-progression ratio of adaptive relative to continuous therapy contracts from 1.11 at a resistant fitness cost of 0.20 to 1.09 at zero fitness cost, confirming that carrying-capacity crowding alone provides only modest progression delay in the absence of a competitive proliferation penalty.