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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.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.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.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).

4 more claims

An observational atlas linked GLP-1 receptor agonists to dozens of outcomes beyond glucose, weight and the heart. We pooled the serious adverse events that 234 placebo-controlled trials, with 161309 participants, posted to ClinicalTrials.gov, coded blind to the results under a registered plan. Reports of serious bacterial infection (ratio 0.88, confidence interval 0.83 to 0.93) and pneumonia (0.87) were less frequent on the drugs, as were pneumonia counted in people and death. The reductions held under random effects, with any trial left out, if infection terms overlapped within participants as all serious events do in each comparison, and in trials not coded as recording only on treatment. Of the atlas's associations with enough events to test, the trials found three in its direction with no difference from it detected, contradicted none, and left most inconclusive, among them every neurological and psychiatric one; its large hazard of drug-induced pancreatitis concerns a subtype the trials don't separate.

• Published, Reproduced.Published, Reproduced: Of the 539 interventional studies of GLP-1 receptor agonists with results on ClinicalTrials.gov on 2026-10-12, 234 randomized trials compare a GLP-1 receptor agonist with placebo, in 257 comparisons with 161,309 participants in their adverse-event tables (93,765 on the drugs and 67,544 on placebo). In them, reports of serious gallbladder and biliary disease, counting a participant once for each of the outcome's terms they had, are more frequent on the drugs (Mantel-Haenszel ratio 1.38, 95% CI 1.21 to 1.57), and so are reports of serious nausea and vomiting (2.02, 1.52 to 2.68), as the trials' own publications and the drugs' labels lead one to expect.
• Published, Reproduced.Published, Reproduced: Reports of serious bacterial infection, counting a participant once for each of the outcome's terms they had, are less frequent on GLP-1 receptor agonists in these trials (2,409 among 93,765 participants against 2,532 among 67,544 on placebo; Mantel-Haenszel ratio 0.88, 95% CI 0.83 to 0.93, q < 0.001), and so are reports of serious pneumonia (1,442 against 1,568; 0.87, 0.81 to 0.93, q = 0.0020); both stay significant under random effects and with any single trial left out. Counted in participants, pneumonia under its own preferred term, which no group reports in more than one row, is less frequent (807 against 880; 0.86, 0.79 to 0.95). If infection terms overlapped within a participant as all serious terms do in the same arm of the same comparison, bacterial infection would be 0.89 (0.82 to 0.97).
• Published, Reproduced.Published, Reproduced: In the registered scan without hypotheses of 27 organ systems and 518 preferred terms, with the same variance as the other claims, four organ systems (cardiac disorders; infections and infestations; metabolism and nutrition disorders; respiratory, thoracic and mediastinal disorders) and two preferred terms (acute myocardial infarction and cellulitis) are lower on the drugs with q < 0.05 in a random half of the trials and p < 0.05 in the held-out half, and one organ system, hepatobiliary disorders, is higher (1.36 in the first half, 1.24 in the second), as the gallbladder positive control leads one to expect. Among those lower are serious infection reports as a whole (0.88 and 0.89) and cellulitis (0.64 and 0.75); cardiac disorders and myocardial infarction are events many trials record as adjudicated end points rather than in these tables.

6 more claims

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.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.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.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.

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.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.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.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.

1 more claim

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.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.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).

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.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.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.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).

Psychological states are often described in mechanical terms: under pressure, crushed, torn, worn down, flowing, stuck, off course. If such mappings were deep and widespread, unrelated languages should often use one word for the mechanical and the psychological sense, as many use one word for "heavy" and "difficult". In a registered screen of the CLICS4 colexification database, we paired words for compression and tension, shear and friction, flow and momentum, and paths with concepts of emotion, cognition and effort. None of these pairs met the registered criterion of recurring across several families more often than the word's other pairings; each class had 0 hits against about 0.477 to 0.719 expected for random concepts. Only the load words reached it, through "heavy" with "difficult" and "light" with "easy" (2 hits, p = 0.0633). Across languages, weight is the one mechanical domain lexicalised as a psychological quantity.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Weight words are the exception: 'heavy' and 'light (weight)' give 2 hits among five load words (with 'difficult' and 'easy'), against 0.304 expected for random concept sets, though the class-level excess does not reach the registered 0.05 level (p = 0.0633), so the class test has limited sensitivity.
• Published, Reproduced.Published, Reproduced: Across CLICS4 v1.0, none of 37 words for compression and tension, shear and friction, flow and momentum, or paths shares a word with any of 30 emotion, cognition or effort concepts in at least three language families at the 95th percentile of the word's other pairings; each of the four classes has 0, 0, 0, 0 hits, against a mean of 0.48 to 0.72 for random concept sets of the same size.

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.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.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.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.

4 more claims

The World Health Organization's 2020 guideline recommended giving mass azithromycin, which lowers child mortality in high-mortality settings of sub-Saharan Africa, only to infants, to limit antibiotic resistance; no trial had then tested that. Under a pre-registered plan we pooled every randomized trial by whom it treated. Treating all children under five lowered their mortality by 14.1% (CI 7.4% to 20.3%), consistently across trials. In the three trials that treated only infants, infant mortality was not detectably lower (rate ratio 0.971, CI 0.867 to 1.086), an interval that excludes the effect of treating all children. Infants had lower mortality when all children were treated, though a between-trial comparison of the two strategies fell short of significance, and giving azithromycin to individual infants at clinic visits showed no effect. The infant-only approach has not lowered mortality in any trial that tested it; treating all children under five has.

• Published, Reproduced.Published, Reproduced: In 5 placebo-controlled comparisons from 3 cluster-randomized trials (MORDOR in Niger, Malawi and Tanzania; AVENIR in Niger; CHAT in Burkina Faso), twice-yearly mass azithromycin to every child 1 to 59 months old lowered mortality among children 1 to 59 months by 14.1% (rate ratio 0.859, 95% CI 0.797 to 0.926; Holm-corrected p = 0.015; I² = 0%), and the reduction held with a common-effect model (0.859, 0.813 to 0.908) and with any one comparison left out (largest p = 0.044).
• Published, Reproduced.Published, Reproduced: Infant mortality was lower when all children 1 to 59 months were treated (rate ratio 0.823, 95% CI 0.707 to 0.958; 3 comparisons) than when only infants were (0.971), but the pre-registered meta-regression comparing the two strategies across trials did not establish a difference (ratio of rate ratios 1.187, 95% CI 0.974 to 1.447; p = 0.074; Holm-corrected p = 0.148); AVENIR's within-trial contrast of its all-children arm against its infant arm, estimated after registration from the two arms' printed mortality rates, was 0.830 (0.717 to 0.959).
• Published, Reproduced.Published, Reproduced: Across the 8 mass-distribution comparisons against placebo, mortality fell more where the control arm's mortality rate was higher: the log rate ratio changed by -0.078 per unit of the log control rate (95% CI -0.144 to -0.013; p = 0.027), allowing for strategy, in a pre-specified descriptive analysis resting on few comparisons, one of whose rates comes from birth histories.

4 more claims

Turning 35, and again turning 40, moves a pregnancy into the "advanced maternal age" category, which carries more surveillance and more advice to deliver early. Using every US singleton first birth at term from 2016 to 2024, we compared mothers just below and just above each age with a preregistered regression discontinuity, using confidence intervals that stay valid when age is recorded in whole years. Labor induction jumps by 1.19 percentage points at 35 (honest 95% CI 0.7 to 1.68). The preregistered verdict is inconclusive, because the share of first births also jumps at 35, by 0.4 points. At 40, induction jumps by 2.86 points (2.05 to 3.67), and that secondary test meets its confirm rule. Delivery at 39 weeks rises at both ages. Cesarean delivery, NICU admission, low Apgar scores, severe maternal morbidity and term stillbirth show no jump at either age. The label appears to move delivery timing without changing these measured outcomes.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Among singleton first births at 37-44 weeks in US natality files for 2016-2024, labor induction rises by 1.19 percentage points at maternal age 35 (honest 95% CI 0.70 to 1.68, bias bound 0.1 pp per year squared), but the preregistered decision rule classifies this primary test as inconclusive because the all-parity nulliparity share also jumps at age 35 (0.40 pp, Holm-adjusted p = 0.023).
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In the same population, labor induction rises by 2.86 percentage points at maternal age 40 (honest 95% CI 2.05 to 3.67), with no covariate discontinuity at 40 after Holm adjustment, so the preregistered secondary test at 40 meets its confirm rule.
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Delivery at 39 weeks rises by 1.00 percentage points at maternal age 35 (honest 95% CI 0.52 to 1.48) and by 3.64 percentage points at age 40 (honest 95% CI 2.85 to 4.44) among singleton first births at 37-44 weeks.

2 more claims

Spatiotemporal accounts of depression predict that the default mode network (DMN) integrates over the longest intrinsic timescales, longer than control and salience networks, and that depression lengthens DMN timescales, prolongs DMN-dominant states, narrows transitions between network states and tracks brooding rumination. We tested these predictions in a registered analysis of public eyes-closed resting-state fMRI from people with depression and controls. Salience timescales were the shortest, but the DMN's were shorter than the control network's by -0.0416 s (CI -0.07 to -0.0125), opposite to the predicted order. Depression did not change DMN timescales (AUC 0.4015, CI 0.2708 to 0.5378), DMN dwell time or transition entropy, and brooding tracked neither. These data do not support the tested predictions.

• Published.Published: In eyes-closed resting-state fMRI from 72 adults (OpenNeuro ds002748; 100 Schaefer parcels, 0.01-0.1 Hz band-pass, TR 2.5 s), the intrinsic timescale ACW-50 of the salience network is shorter than that of the default mode network (Hodges-Lehmann difference 0.0391 s, 95% CI 0.0057 to 0.0731) and of the control network (0.0751 s, 0.0397 to 0.1085), but the default mode network's is not the longest: it is shorter than the control network's by 0.0416 s (95% CI 0.0125 to 0.07).
• Published.Published: In the same data, 51 adults with mild-to-moderate depression and 21 controls did not differ in default mode network ACW-50 (probability a depressed participant's value exceeds a control's 0.4015, 95% CI 0.2708 to 0.5378), in mean dwell time of default-mode-dominant states (0.5131, 0.3679 to 0.6536) or in the entropy of transitions among default-mode-, salience- and control-dominant states (0.549, 0.3987 to 0.6975); the design had 80% power only for differences near an AUC of 0.70.
• Published.Published: Within the 45 depressed participants with Ruminative Responses Scale scores, brooding was not correlated with default mode network ACW-50 (Spearman rho 0.1065, 95% CI -0.1848 to 0.3812) or with default-mode-dominant dwell time (rho -0.2063, -0.4732 to 0.0887).