Tag: nevin manimala

JAMA Neurol. 2026 May 18. doi: 10.1001/jamaneurol.2026.1232. Online ahead of print.

ABSTRACT

IMPORTANCE: Disruptions in the sleep-wake cycle have been reported in the preclinical period of dementia; whether they contribute to dementia prediction remains unclear.

OBJECTIVE: To examine associations of accelerometer-derived sleep-wake cycle metrics with incident dementia and their contribution to dementia risk prediction in models containing age and known risk factors.

DESIGN, SETTING, AND PARTICIPANTS: This study included 2 prospective UK population-based cohort studies: (1) UK Biobank (derivation study) and (2) Whitehall II (validation study). A UK Biobank accelerometer substudy was undertaken from 2013 to 2015, yielding accelerometer data on 103 278 participants. A Whitehall II accelerometer substudy was undertaken from 2012 to 2013 that provided data on 4267 participants. Analyses were performed between August 2024 and November 2025. Included participants were 60 years and older, without dementia, and with valid accelerometer and covariate data.

EXPOSURES: Thirty-six accelerometer-derived sleep-wake cycle metrics were extracted. A machine learning approach identified and combined metrics predicting dementia risk.

MAIN OUTCOME AND MEASURE: Incident all-cause dementia, ascertained from electronic health records.

RESULTS: Analyses were based on 53 448 UK Biobank participants (mean [SD] age, 67.5 [4.2] years; 28 448 female [54.2%]; mean [SD] follow-up, 7.8 [1.1] years) and 3965 Whitehall II participants (mean [SD] age, 69.4 [5.7] years; 1025 female [25.9%]; mean [SD] follow-up, 10.6 [2.4] years). In UK Biobank, 9 sleep-wake cycle metrics were combined in 2 components. Higher values in component 1 represented shorter durations and less frequent bouts of moderate to vigorous physical activity, more time in low-intensity activity, lower diversity of activity intensities, and higher probabilities to transition from activity to rest during daytime. Higher component 2 corresponded to more extreme sleep durations, longer wake bouts during sleep, lower probabilities to transition from wake to sleep, and earlier waking time. Both components were associated with higher dementia risk (component 1: hazard ratio [HR], 1.43; 95% CI, 1.33-1.54; component 2: HR, 1.10; 95% CI, 1.04-1.17) and improved prediction of a model including sociodemographic, behavioral, and health-related factors (increase in C index = 0.018; 95% CI, 0.011-0.025). Results were confirmed in the Whitehall II cohort study. Compared with an age-only prediction model, adding the components led to an increase in C index equivalent to that for APOE genotype.

CONCLUSIONS AND RELEVANCE: Results of this cohort study show that accelerometer-derived sleep-wake cycle measures were associated with dementia, and made a modest, statistically significant contribution to its prediction. Future studies should evaluate their clinical utility as scalable markers alongside established predictors for early identification of individuals at risk of dementia.

PMID:42149581 | DOI:10.1001/jamaneurol.2026.1232

JAMA Intern Med. 2026 May 18. doi: 10.1001/jamainternmed.2026.1426. Online ahead of print.

ABSTRACT

IMPORTANCE: Most antibiotic prescribing takes place in primary care, driving antimicrobial resistance, a top-10 threat to global public health. There is considerable international interest in whether rapid multiplex microbiological point-of-care testing (RM-POCT) can safely reduce antibiotic prescribing in primary care.

OBJECTIVE: To investigate whether the use of a RM-POCT can safely reduce same-day antibiotic prescribing for children and adults presenting to primary care with respiratory infections.

DESIGN, SETTING, AND PARTICIPANTS: This parallel-group randomized clinical trial was conducted at 16 general practices in Southwest England between December 2022 and April 2024. Patients were eligible if they were aged 12 months or older, presented with any clinician-diagnosed acute (≤21 days) respiratory tract infection, and the patient or clinician believed antibiotic treatment was, or might be, necessary. Participants were randomized (1:1) to RM-POCT or usual care. The research team, including those conducting statistical analyses, were unaware of group allocation. Data were analyzed from November 21, 2024, to March 13, 2025.

INTERVENTION: Patients in the intervention group were tested with RM-POCT to indicate the presence or absence of 19 respiratory viral pathogens and 4 atypical bacteria in approximately 45 minutes.

MAIN OUTCOMES AND MEASURES: The primary outcome was same-day antibiotic prescribing. The safety outcome was patient-reported symptom severity on days 2 to 4.

RESULTS: Among 552 included patients (mean [SD] age, 40.0 [21.2] years; 349 [63%] female), 276 were randomized to the intervention group and 276 to usual care. Primary outcome data were available for all participants, and safety outcome data were available in 216 intervention participants (78%) and 203 usual care participants (74%). Same-day antibiotics were prescribed to 124 participants (45%) in each group (odds ratio [OR], 1.00 [95% CI, 0.71 to 1.41]; P > .99). Prespecified subgroup analyses showed evidence of differentially reduced antibiotic prescribing in participants from whom a virus was detected (OR, 0.35 [95% CI, 0.20 to 0.63]; P for interaction < .001) and those with chronic lung disease (OR, 0.55 [95% CI, 0.28 to 1.09]; P for interaction = .046) but not children younger than 16 years (OR, 1.75 [95% CI, 0.64 to 4.74]; P for interaction = .24), nor where patients and clinicians disagreed on antibiotic necessity (OR, 1.12 [95% CI, 0.63 to 1.98]; P for interaction = .53). There was no difference in symptom severity on days 2 to 4 between groups (difference in means, 0.09 [95% CI, -0.10 to 0.27]; P = .36).

CONCLUSIONS AND RELEVANCE: In this randomized clinical trial among patients with respiratory tract infections being considered for antibiotic treatment in primary care, use of an RM-POCT did not reduce same-day antibiotic prescribing or worsen patient outcomes.

TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN16039192.

PMID:42149561 | DOI:10.1001/jamainternmed.2026.1426

J Pers Soc Psychol. 2026 May 18. doi: 10.1037/pspa0000487. Online ahead of print.

ABSTRACT

When thinking about a task or goal feels difficult, people can interpret this as signaling self-relevant value (difficulty-as-importance) and a reminder to stop wasting time on self-irrelevant things (difficulty-as-impossibility). Identity-based motivation theory predicts that both interpretations are available in memory, vary in momentary accessibility, and shape action in part through activating action-relevant judgments. We note that in situations calling for task engagement, action-relevant judgment entails making sense of time, an abstract concept that people reason about metaphorically. We test this novel prediction that difficulty mindsets shape action in part by shaping how people reason metaphorically about time by examining associations (N = 941) and documenting effects of mindset accessibility (using an autobiographical recall task, N = 1,676) on how much people endorse the time-as-limited and time-as-expandable aspects of the time-as-resource metaphor. Indeed, across experiments, people more strongly endorsed time-as-limited, less strongly endorsed time-as-expandable and saw these aspects of the time-as-resource metaphor as more negatively correlated if randomized to the difficulty-as-impossibility (vs. difficulty-as-importance) recall condition. Supporting our novel prediction, the consequence of accessible difficulty mindsets on task engagement (Experiments 2-3) and performance (Experiments 4-5), confidence in goal progress and experienced time to make progress (the length of the line they drew to represent the semester or year, Experiments 6-7) occurred partly through the effect of accessible mindsets on momentary judgments of time-as-limited and time-as-expandable, as revealed in statistical mediation analyses. In situations requiring task engagement and assessing goal certainty, accessible difficulty mindsets matter in part by momentarily shifting judgments about having time. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:42149496 | DOI:10.1037/pspa0000487

Psychol Methods. 2026 May 18. doi: 10.1037/met0000834. Online ahead of print.

ABSTRACT

Although previous research has described that intervention effects vary across replication studies, less effort has been devoted to identifying causes of this effect heterogeneity with regard to differences in study implementations. However, knowing in which way study characteristics (such as population, measurement instrument, setting, or treatment implementation) impact the study results may not only help to better infer the impact of research practices but also provide evidence for theory building. Causal effects can be easily identified if all study characteristics but the one under investigation are kept constant across two studies. This is, however, not always possible in practice and unintended differences between the studies to be compared may confound the relationship of the study characteristic of interest and the treatment effect. In this article, we present a statistical approach for identifying effects of study characteristics on study-specific treatment effects from randomized experiments in cases in which unintended differences in study implementation across studies cannot be prevented. We present formal definitions of the causal effects of interest, identification assumptions, and derive respective causal estimands. The assumptions can more likely be fulfilled in prospective replication studies or many-lab studies, where researchers have more control over design and measurement of covariates in both studies. We also provide ways to test the assumptions and illustrate consequences of not meeting the assumptions. The approach is illustrated using an empirical example on the imagined intergroup contact effect in social psychology. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:42149494 | DOI:10.1037/met0000834

J Infect Dis. 2026 May 18:jiag193. doi: 10.1093/infdis/jiag193. Online ahead of print.

ABSTRACT

Infectious disease trials have long used ordinal outcomes, or ranked categorical scales, to capture the full spectrum of response to an intervention. We review 2 summary statistics for ordinal outcomes: the proportional odds ratio (pOR) and the win probability. The pOR asks: How much more likely is a treated participant to be in an improved category compared with control? The win probability asks: In a random treatment-control pair, what is the chance the treated participant fares better? We also introduce visual companions, the stacked-bar chart and bubble plot, to make ordinal trial results more accessible and interpretable.

PMID:42149490 | DOI:10.1093/infdis/jiag193

J Psychopathol Clin Sci. 2026 May 18. doi: 10.1037/abn0001113. Online ahead of print.

ABSTRACT

The stress generation model posits that depression and other psychopathology elevate risk that individuals create or select into stressful life events. Although decades of research support stress generation theory, life stress is inherently challenging to assess and model as an outcome variable, and prior studies follow inconsistent methodological standards. Toward a vision of elevated “next generation” research, we present expert consensus methodological guidelines for conducting stress generation research. A panel of researchers with diverse expertise delineates best practice, acceptable, and nonrecommended methods across 6 areas: stressor operationalizations, assessment, longitudinal study design (including intensive longitudinal design), statistical analysis, openness/transparency, and avoiding stigmatizing language. For example, the review covers modeling stressors as formative variables, statistically comparing effect sizes for predicting independent and dependent stress, and using life stress interviews versus questionnaires, among other methodological concerns pertinent to stress generation research. Following these guidelines will allow future investigators to construct a research base with greater rigor, transparency, and reproducibility, providing a firmer foundation to improve understanding of stress generation. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:42149474 | DOI:10.1037/abn0001113

Psychol Trauma. 2026 May 18. doi: 10.1037/tra0002167. Online ahead of print.

ABSTRACT

OBJECTIVE: The Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) characterizes posttraumatic stress disorder (PTSD) by intrusion, avoidance, negative cognition, and hyperarousal symptom clusters. These clusters may reflect distinct underlying pathologies. There is a strong bidirectional relationship between PTSD and sleep disturbances, but sleep’s associations with individual symptom clusters remain unclear. This study examines these relationships and may be the first relating sleep architecture to the negative cognition cluster. We investigated subjective and physiological sleep measures across the spectrum of PTSD symptom cluster severities.

METHOD: This Research Domain Criteria-design study included participants (N = 133) who experienced a Criterion-A trauma within the past 2 years but not the previous month; 68 met PTSD criteria and 65 qualified as resilient or subthreshold PTSD using the Clinician-Administered PTSD Scale for DSM-5. Sleep was assessed via 14-days of sleep diaries and one night of ambulatory polysomnography following an acclimation night. Multiple linear regression models analyzed sleep quality measures (sleep onset latency, total sleep time, sleep midpoint, and wake after sleep onset), while stepwise regression models explored sleep architecture (sleep macroarchitecture, rapid eye movement sleep, and slow-wave sleep microarchitecture).

RESULTS: Sleep quality measures had varying relationships with total PTSD Checklist for DSM-5 and symptom cluster scores. Sleep architecture and rapid eye movement sleep-specific and slow-wave sleep-specific features demonstrated unique relationships with PTSD symptom clusters.

CONCLUSIONS: Findings suggest the utility of dimensional approaches, potential symptom-specific intervention targets, and highlight possible distinct contributions of sleep in PTSD cluster pathophysiology. (PsycInfo Database Record (c) 2026 APA, all rights reserved).

PMID:42149467 | DOI:10.1037/tra0002167

Int Urol Nephrol. 2026 May 18. doi: 10.1007/s11255-026-05193-2. Online ahead of print.

ABSTRACT

AIM AND OBJECTIVES: This study aimed to evaluate perirenal and epicardial fat thickness and examine their associations with oxidative stress, inflammation, and metabolic markers in pre-dialysis CKD patients (diabetic and non-diabetic) compared with healthy controls.

MATERIAL AND METHODS: This cross-sectional study included 90 participants (30 diabetic CKD, 30 non-diabetic CKD, and 30 controls). Perirenal fat thickness was assessed by ultrasonography and epicardial fat thickness by echocardiography. Biochemical parameters including renal function, lipid profile, hs-CRP, malondialdehyde (MDA), and ferric reducing antioxidant power (FRAP) were measured. Statistical analysis was performed using parametric or non-parametric tests based on data distribution, with multivariate regression adjusting for age, sex, and BMI.

RESULTS: DKD patients had significantly higher perirenal (32.1 ± 5.0 mm) and epicardial (8.72 ± 1.89 mm) fat thickness compared to non-DKD patients and controls. DKD patients also exhibited increased oxidative stress (MDA 4.65 ± 3.39 µmol/L) and decreased antioxidant capacity (FRAP 0.25 ± 0.16 mmol/L). The inflammatory marker hs-CRP was significantly elevated in DKD patients [8.53 (12.64) mg/L]. No significant differences were observed in lipid profiles or atherogenic indices between groups; however, visceral adiposity showed significant positive correlations with atherogenic indices.

CONCLUSION: Pre-dialysis CKD patients, particularly those with diabetes, exhibit increased visceral adiposity along with higher oxidative stress and inflammation. Although atherogenic indices were not significantly different between groups, their association with visceral fat suggests a potential role of regional adiposity as a marker of metabolic risk; however, longitudinal studies are required to establish the prognostic significance.

PMID:42149464 | DOI:10.1007/s11255-026-05193-2

Methods Mol Biol. 2026;3031:377-398. doi: 10.1007/978-1-0716-5253-4_29.

ABSTRACT

Shaped by evolution, human skin cells have acquired a remarkable capacity to detect and react to sunlight photons through a wide array of photochemical processes. These reactions trigger intricate intracellular signaling cascades, ultimately resulting in photobiological effects that help regulate skin cell homeostasis. Some of these photobiological responses (also so-called photobiomodulation or low-level light therapy) are capable of initiating profound and beneficial therapeutic effects. To identify the regimes for these light-based therapeutic solutions, one needs to carefully decipher the physical, optical, biological, and chemical conditions that all need to be fulfilled to facilitate such positive photobiological effects. Here, we provide the protocols specifically developed to investigate multidimensional parameter space driving photobiological interactions triggered by light in the cells of human integumentary system. The approach also includes the so-called design of experiment (DoE), a statistical method, which allows for the investigation of multidimensional parameters landscapes. This goes hand in hand with sharing practical tips for the design of light-based devices for experimental work. We illustrate practical applications of our methods and light-based devices by sharing comprehensive experimental datasets, highlighting both the robustness and reproducibility of the results.

PMID:42149463 | DOI:10.1007/978-1-0716-5253-4_29

Ophthalmic Physiol Opt. 2026 May 18. doi: 10.1007/s44402-026-00093-5. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate systematically the effect of different concentrations of atropine eye drops on accommodative amplitude and binocular visual function in children and adolescents with myopia.

METHODS: A systematic review and meta-analysis of randomised controlled trials was conducted in accordance with PRISMA 2020 guidelines and registered in PROSPERO (registration number: CRD420261297760). PubMed, Web of Science and Scopus were searched up to January 15, 2025. Eligible studies compared atropine eye drops (0.01-1%) with placebo, single-vision correction or no treatment and reported accommodative or binocular vision outcomes. The primary outcome was the change in accommodative amplitude. Secondary outcomes included accommodative lag, stereoacuity, heterophoria and fusional vergence. Mean differences (MD) with 95% confidence intervals (CI) were pooled using fixed- or random-effects models based on heterogeneity.

RESULTS: Thirteen randomised controlled trials were included, most of which were conducted in Asian populations. Low-dose atropine (0.01%) was associated with a small but statistically significant reduction in accommodative amplitude (MD: -0.84 D, 95% CI: -1.50 to -0.18), with substantial heterogeneity and no consistent effects at individual follow-up time points. Intermediate concentrations (0.02-0.03%) showed variable and heterogeneous effects. Atropine 0.05% produced a consistent and clinically meaningful reduction in accommodative amplitude (MD: -1.96 D, 95% CI: -2.36 to -1.57) and measurable changes in binocular parameters. Higher concentrations (≥0.1%) resulted in marked cycloplegic effects.

CONCLUSIONS: The effects of atropine on accommodation and binocular visual function are dose-dependent. Low-dose atropine demonstrates a favourable functional safety profile, while higher concentrations are associated with clinically relevant accommodative impairment.

PMID:42149424 | DOI:10.1007/s44402-026-00093-5