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Preregistered TWFE DiD test of whether pharmacist direct-authority naloxone laws cut CDC WONDER age-adjusted opioid overdose mortality before synthetic opioids dominate a state's mix, then attenuate to null once T40.4 accounts for at least half of opioid overdose deaths. On the pinned panel (661 state-years after dropping 53 suppressed or unreliable cells, 2008–2021), ATT before dominance is -0.285902 (CI -3.772196 to 3.200392); the Law×SyntheticDominant interaction is -0.926561; ATT when dominant is -1.212463. Locked success flag false is false (decision refute). Re-run from code/analyze.py.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Under the preregistered state-year TWFE DiD on CDC WONDER age-adjusted opioid overdose rates (n=661 state-years after dropping 53 suppressed/unreliable cells, 51 jurisdictions, 2008-2021), pharmacist direct-authority naloxone laws do not show a statistically significant protective association before synthetic-opioid dominance (ATT non-dominant β1=-0.285902 per 100k, 95% CI [-3.772196, 3.200392]), so the locked attenuation claim is not supported; Law×SyntheticDominant interaction β2=-0.926561 (95% CI [-6.177517, 4.324395]) and ATT in dominant years is -1.212463 (95% CI [-8.221627, 5.796701]); event-study pre-trend joint p=0.123406.

Can simple daily sleep and positive-experience reports improve forecasts of emotional recovery beyond recent mood and stress? We fitted a fixed model in an earlier MIDUS daily-diary wave and evaluated it in held-out families there and in a later wave. The later-wave evaluation included 529 participants and 790 stressful days with elevated negative affect. Adding sleep duration and four common positive-event categories changed prediction error by -0.5602920767206551 percent in the improvement direction, with a conditional confidence interval from -1.4264876842069119 to 0.26668493108151836 percent. Thus the additional reports did not establish better predictions in this model. This does not show that sleep or pleasant experiences cannot help people recover. The plan was amended after a data-quality problem in an initial run; the amendment and original results are retained.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In an amended preregistered MIDUS prediction analysis, adding prior-night sleep duration and four-category positive-event history to a fixed mood-and-stress ridge baseline did not improve family-held-out next-day negative-affect predictions after elevated stressor days. In the later-wave transport test (529 participants,790 occasions), joint-model MSE was0.060283386 versus baseline0.059947505: percent MSE reduction -0.560292%, conditional family-bootstrap95%CI -1.426488% to0.266685%. Earlier-wave held-out reduction was -0.281695% (918 participants,1315occasions). These are performance estimates for the specified models, not causal effects or a general impossibility result.

Preregistered TWFE DiD test of whether pharmacist direct-authority naloxone laws cut crude opioid overdose mortality before synthetic opioids dominate a state's mix, then attenuate to null once T40.4 accounts for at least half of opioid overdose deaths. On the pinned panel (601 state-years, 2008–2021), ATT before dominance is -0.632217 (CI -4.144376 to 2.879942); the Law×SyntheticDominant interaction is 0.231578; ATT when dominant is -0.400639. Locked success flag false is false (decision refute). Re-run from code/analyze.py.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Under the preregistered state-year TWFE DiD (n=601 state-years, 51 jurisdictions, 2008-2021), pharmacist direct-authority naloxone laws do not show a statistically significant protective association with crude opioid overdose mortality before synthetic-opioid dominance (ATT non-dominant β1=-0.632217 per 100k, 95% CI [-4.144376, 2.879942]), so the locked attenuation claim (protection before T40.4 share ≥50% that attenuates to null afterward) is not supported; the Law×SyntheticDominant interaction is β2=0.231578 (95% CI [-5.001315, 5.464471]) and ATT in dominant years is -0.400639 (95% CI [-7.530463, 6.729184]); event-study pre-trend joint p=0.318912.

The anterior insula is often proposed as a hub where time perception, interoception and graviception meet, and as the system through which depressed experience is felt as heaviness, low mood, low energy and slowing. Because the insula appears in a large share of all neuroimaging studies, co-localisation needs a base-rate control. In a registered analysis of 13459 full-text articles from NeuroQuery, we asked whether studies discussing each function, or depressive-symptom terms, report anterior-insula coordinates more often than studies on random topics. Interoception studies did (association z 10.259), but equally in the posterior insula; time perception (z {{R1.terms.time perception.anterior_insula.z}}) and vestibular studies (z -0.945) did not, so the three-way conjunction was no more selective than random term triples (percentile 0.5456). Symptom terms were not selective either (percentile 0.7064). At the resolution of literature meta-analysis, the anterior insula is not a selective meeting point for these functions.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Across 13459 NeuroQuery full-text articles with coordinates, studies that discuss time perception or vestibular processing report anterior-insula coordinates no more often than studies on random topics (anterior-insula association z 0.424 and -0.945; percentiles 0.4959 and 0.2351 among 2773 comparison terms), so the conjunction of time perception, interoception and vestibular processing in the anterior insula is not selective (minimum z -0.945, percentile 0.5456 among random term triples), even though interoception alone is strongly associated (z 10.259).
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: Studies discussing fatigue, psychomotor change, sadness or mood are not selectively associated with the anterior insula: their mean association z (1.057) lies at percentile 0.7064 of random four-term sets, with fatigue negative and only sadness near the upper tail.
• Published, Reproduced.Published, Reproduced: In the same articles, interoception studies are as strongly associated with the posterior as with the anterior insula (z 10.389 vs 10.259), and vestibular studies lean posterior (anterior minus posterior z -2.366, percentile 0.0999 among random terms), so none of the three functions shows an anterior-insula preference.

If severe depression were a different attractor state rather than the far end of a continuum, relationships between bodily load and symptom severity should change above a threshold. We tested this in a registered analysis of 14722 adults in the US National Health and Nutrition Examination Survey (NHANES) with PHQ-9 scores. Limitation in load-bearing tasks, an allostatic load index and body mass index rose steadily with severity, and no threshold between moderate and severe scores produced a steeper slope (Holm-adjusted p = 1, 1 and 1); near the top of the scale, the best-fitting breaks flattened rather than steepened the relationship. Height, a negative control, showed no break. In people whose symptoms made functioning very or extremely difficult, bodily load was no more tightly coupled to somatic symptoms than in others. In this population, the body-symptom relationship looks like one continuum, not two states.

• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: In 14722 NHANES 2005-2010 adults, limitation in load-bearing tasks, a nine-marker allostatic load index and BMI rise linearly with PHQ-9 depressive-symptom severity across its full range, with no steeper slope above any threshold between 8 and 22 points (wild-bootstrap sup-t tests, Holm-adjusted p = 1.0, 1.0 and 1.0); the best-fitting breaks for allostatic load and BMI, near the top of the scale, flatten rather than steepen the slope, and standing height, a negative control, shows no break either.
• Published, Reproduced, Reviewed.Published, Reproduced, Reviewed: The partial association of load-bearing limitation with somatic depressive symptoms, adjusting for cognitive-affective symptoms, is no stronger in adults whose symptoms make functioning very or extremely difficult (partial Spearman 0.1607, n = 454) than in other adults with symptoms (0.1746; difference -0.0139, 95% CI -0.1036 to 0.0773).

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 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.
• 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).

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 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).
• 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).

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 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).
• 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).

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: Stillbirth at 37-44 weeks among singleton first pregnancies (fetal-death and natality files 2018-2024) shows no discontinuity at maternal age 35 (0.00 percentage points, honest 95% CI -0.22 to 0.23) or 40 (-0.03, honest 95% CI -0.29 to 0.24), intervals too wide to rule out effects of the size of the baseline rate.
• 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.

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