Social Science & Medicine

Background Preventing sexually transmitted re-infections brings health benefits and can be significantly less costly than treating their sequelae. Safetxt is a potential novel digital intervention developed to promote safer sexual behaviours. However, a recent randomised controlled trial of safetxt found no effect on reinfection at 1 year (OR 1.13, 95%CI: 0.98-1.31). We investigated if safetxt's effect was mediated through sexually risky behaviours. Methods We used data from 6248 young people with STIs from 92 UK sexual health clinics. The direct and indirect effects of safetxt on reinfection were estimated using the counterfactual approach. Condom use at last sexual encounter, number of sexual partners and STI testing were assessed as mediators. These were analysed singly and together, using regression models and a formal weighting approach. The assumptions of each approach were considered and tested. Analyses were repeated in the subgroup showing the most promising effect of safetxt: men who have sex with men or with men and women (MSM/MSMW). Results No evidence was found for the total, indirect or direct effects differing from the null. Despite not being significant, for MSM/MSMW, some of safetxt's effect on reducing reinfection was identified as being offset through its effect on number of sexual partners. Conclusions There was no evidence that safetxt's effect on reinfection was mediated through changes in sexually risky behaviours. Adaptations to specifically target these behaviours are unlikely to improve safetxt's overall effect. However, improving safetxt's effect on the number of sexual partners a participant has may improve its effect for MSM/MSMW.

Background: Clinician-scientists translate clinical observation into discovery, trials, and policy, yet this workforce is shrinking across health systems worldwide. Integrated MB-PhD training, pausing medical training to complete a PhD before clinical exposure or specialisation, is one route into this career. We aimed to evaluate the long-term value of MB-PhD training and the barriers to clinical-academic careers these face after graduation. Methods: We evaluated all 131 graduates (29.8% female) who entered the University College London (UCL) MB-PhD programme over a 25-year period (1994-2018). Bibliometric outputs were collated via an inter-linked information system. Concurrently, all 131 graduates were invited to respond to open-ended questions on career benefits and structural barriers; 99 (75.6%) responded, and responses were independently coded into themes, which were then reviewed and confirmed by a Study Group of 107 individuals, including the 91 respondents who agreed to participate further. Results: Graduates produced 5,877 publications (1,141 first-author, 819 corresponding-author), attracting 350,754 citations, with a mean relative citation ratio of 3.30 {+/-} 0.47, approximately three times the field average and sustained across three decades of programme entry. Graduates secured an estimated $157.55 million across 99 grants, released 465 public datasets, and were named investigators on 31 clinical trials across five continents. Among the 99 survey respondents, 49.5% held consultant-grade posts, 72.7% remained research-active, and 25.3% had reached senior academic grade. Open-ended responses were coded into five recurring structural barriers, subsequently confirmed by the Study Group: insufficient protected research time (72.2% of responses), unsupportive training structures and limited career opportunities (36.7%, 24.4% of responses), funding and pay barriers (22.2% of responses), and lack of mentorship or geographical/family constraints (14.4%, 13.3% of responses). Conclusions: Integrated MB-PhD training generates sustained academic productivity and leadership, but structural barriers threaten retention of graduates within clinical-academic careers. Protecting research time, stabilising funding and pay, and reducing geographic instability are needed to retain the clinician-scientists that health systems have already invested in training.

Background: Previous trauma research includes many limitations, such as the scarcity of pretraumatic health measurements and assessment of traumatic experiences with a broad scope across the lifespan. To respond to these gaps, we aimed to develop a new, prospective, population-based trauma dataset from childhood to middle age. Methods: We used the Young Finns Study that is a population-based, multi-generational, prospective study (n = 3596 for the main generation). It has started in 1980 (baseline assessment) and includes follow-ups in 1983, 1986, 1989, 1992, 1997, 2001, 2007, 2011/2012, and 2018-2020. From the 38-year follow-up and ten measurement points of the YFS, we collected all relevant trauma variables, including both free-format and structured questions that both the participants and their parents responded to. By a data-driven case-to-case analysis, we developed a scale to numerically capture variation in the quality of the experiences. Results: Our final dataset captured a total of 7769 traumatic experiences. We also developed the Traumatic Experience Severity Scale (TESS), including six subscales such as shamefulness, rarity, danger to life or health, effects on everyday life, human-made physical threat, and whether the target person was within or outside one's household. We also preprocessed the dataset to be later easily interleaved with other psychological, cardiovascular, and epigenetic variables of the YFS. Conclusions: We believe this new trauma dataset with thousands of experiences across the lifespan provides new opportunities to multidisciplinary, lifelong trauma research.

Abstract Preventable neonatal deaths remain a major public health problem in Zimbabwe, where near-universal antenatal and facility-delivery coverage coexist with a rising neonatal mortality rate. This study evaluated whether institutionalising three core "vital signs" of the community health system (a trained village health worker (VHW) workforce, functional community governance structures, and modified women's and men's participatory learning and action groups) reduces preventable neonatal deaths in Mashonaland West Province. An embedded QUAN (qual) mixed-methods design was used, with a two-arm, parallel-group cluster-randomised controlled trial as the dominant strand. Fifty-two ward-level clusters were randomised 1:1 to the institutionalised community health system package or to standard Ministry of Health and Child Care community services, and 984 pregnant women were enrolled between 1 September 2020 and 31 October 2021, with each mother-infant pair followed to 28 days after delivery, yielding 973 mother-infant pairs for intention-to-treat analysis. The primary outcome was neonatal death within 28 days of life, expressed per 1,000 live births. The primary analysis used a three-level mixed-effects log-binomial regression model with cluster and community-health-worker random intercepts, adjusted for pre-specified covariates. Supervised machine-learning classifiers with leave-one-cluster-out cross-validation, Cox proportional-hazards regression, and multilevel logistic models were fitted as supplementary analyses. An embedded longitudinal process evaluation used key informant interviews and focus group discussions, which were analysed thematically and integrated with the quantitative findings. The neonatal mortality rate was 44.8 per 1,000 live births in the intervention arm versus 110.1 per 1,000 in the control arm. The adjusted risk ratio for neonatal death was 0.43 (95% CI 0.26-0.70; p < 0.001), a 57% relative reduction, with a number needed to treat of 16 mother-infant pairs (95% CI 11-29). Low birthweight (<2,500 g), birth interval under two years, and low community women's literacy were the strongest risk factors, while trained VHWs, functional community governance, early antenatal care, and sustained participatory group attendance were independently protective. The women's and men's groups were protective in a dose-dependent manner, becoming significant at four or more cycles (about 14 meetings) (adjusted odds ratio 0.71; 95% CI 0.60-0.85; p = 0.001). A random forest classifier discriminated against neonatal deaths with a cross-validated area under the curve of 0.842 and a sensitivity of 0.912. Qualitative findings converged with the trial results, identifying male engagement, earlier care-seeking, danger-sign literacy, social-network activation, and community death audits as the behavioural and structural mechanisms of change. Institutionalising the community health system package (trained VHWs, functional governance, early antenatal engagement, and sustained participatory groups) was associated with a substantial reduction in preventable neonatal deaths. The findings suggest that in high-coverage, high-mortality settings, the binding constraint is structural rather than clinical, and that scaling functional community governance and workforce infrastructure in the most disadvantaged communities may accelerate progress toward neonatal survival targets. The principal limitations are a one-year follow-up period, the rarity of neonatal death, and concurrent national programming that only partially reached the control clusters. Trial registration: Pan African Clinical Trials Registry, PACTR202607591142118 (https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=PACTR202607591142118); registered retrospectively on 7 July 2026.

Importance: Chronic stress may contribute to adverse health outcomes through cumulative physiologic dysregulation. Allostatic load (AL), a composite measure of multisystem physiologic burden, may capture biologic effects of structural, social, and psychosocial stress not reflected by self-reported measures. Objective: To evaluate racial and ethnic differences in AL among women with familial cancer risk and examine how socioeconomic status, psychosocial factors, clinical characteristics, and health behaviors contribute to variations in AL. Design: Cross-sectional study of underrepresented minority participants enrolled in the HERSTORY cohort from October 2023 through September 2025, with comparison participants from the UCLA ATLAS biobank. Setting: UCLA academic health system. Participants: The study included 303 racially and ethnically diverse female HERSTORY participants aged [&ge;]35 years with a family history of cancer and matched non-Hispanic White female ATLAS participants (n=709). Exposures: Race and ethnicity, age, neighborhood deprivation, cancer history and stage, depression, perceived stress, cancer worry, and physical activity. Main Outcomes and Measures: The primary outcome was AL, calculated from cardiometabolic and organ-function measures. A secondary index incorporated race- and ethnicity-specific neutrophil-to-lymphocyte ratio (NLR) derived from 326,826 women in the UCLA Health population. Multivariable regression models evaluated factors associated with elevated AL. Results: Compared with matched non-Hispanic White participants, Black and Asian/Pacific Islander HERSTORY participants had significantly higher AL after adjustment. Hispanic/Latina participants did not have significantly elevated AL. Older age, greater area-level socioeconomic deprivation, and depression were independently associated with higher AL. Prior cancer diagnosis, cancer worry and perceived stress were not significantly associated with AL, whereas regular physical activity was associated with lower AL. Among cancer patients, advanced stage was associated with greater AL. Conclusions and Relevance: This study demonstrates elevated AL among understudied racial/ethnic minority groups with familial cancer risk and identifies associations with neighborhood deprivation, depression, and physical activity. The association between cancer stage and AL suggests that physiologic stress may reflect variation in cancer burden. The lack of association with perceived stress and cancer worry further indicates that physiologic and self-reported psychosocial measures capture distinct dimensions of stress. The development of race/ethnicity-specific NLR thresholds derived from large population samples provide a benchmark for future studies.

Inappropriate antibiotic use presents a major global health challenge, particularly in low-resource settings where access to quality care is limited but antibiotics remain relatively unrestricted. This study estimates the causal effect of frontline primary care quality on inappropriate community antibiotic use, combining detailed community-based data from approximately 100 rural villages in rural China with an instrumental variable (IV) approach embedded within a double/debiased machine learning (DML) framework. We linked objective measures of village doctor clinical practice quality, measured through unannounced standardized patient visits, to household-level antibiotic use data collected from the same villages. To identify the causal effect, we constructed multiple candidate instruments from extensive provider characteristics and used an ensemble of machine learning algorithms within a flexible DML-IV framework to approximate an optimal instrument, addressing a many-weak-instruments problem. We found that improving village provider clinical practice quality reduced both antibiotic receipt during healthcare encounters for common diseases and household antibiotic storage for future self-medication. Our findings suggest that strengthening frontline primary care quality can meaningfully reduce inappropriate community antibiotic use without restricting access to essential treatment. More broadly, this study illustrates how causal machine learning can strengthen conventional causal estimation in complex observational settings in global health economics research.

Purpose Despite the high documented prevalence of hunger and poor mental health in adolescent girls and young women (AGYW) in South Africa, this relationship remains understudied, with existing studies limited by their cross-sectional designs. This longitudinal study aimed to identify the association of hunger trajectories with anxiety and depressive symptoms, and hope in AGYW. Methods We used secondary data from the HIV Prevention Trials Network (HPTN) -068 conducted in rural Agincourt, South Africa. Complete data from 1779 AGYW collected at baseline (2011/12) and three annual follow-up visits were used. Hunger trajectories, measured using the Household Hunger Scale, were estimated via Group-Based Trajectory Modelling. Self-reported incident anxiety and depressive symptoms and hope were assessed based on AGYWs last two follow-up visits. Covariate adjusted modified Poisson regression models estimated the association between hunger trajectories and incident anxiety symptoms, incident depressive symptoms, and hope. Results Moderate-severe hunger was prevalent in 11.0%, 10.8%, and 6.0% of the households at baseline, follow-up 1, and 2, respectively. Incident anxiety symptoms were reported by 4.5%, incident depressive symptoms by 20.0% and hopelessness by 52.8% of the AGYW. Two hunger trajectories were identified- no hunger (82%) and marginal hunger (18%). Hunger trajectories were not associated with incident anxiety symptoms [RR:1.09, 95% CI: 0.55, 2.18], incident depressive symptoms [RR: 0.97; 95% CI: 0.72, 1.33] nor hope [RR: 1.00; 95% CI: 0.81, 1.23] in AGYW. Conclusion Better understanding of the factors that promote resiliency and mental health of AGYW in this setting is warranted to inform the design of interventions.

Background: Cardiovascular disease (CVD) disproportionately burdens underserved communities, where social determinants of health (SDOH) perpetuate persistent disparities. Family-based interventions leveraging social support represent a promising yet understudied approach. We describe the rationale, design, and methods of the Skills-based Educational strategies for the Reduction of Vascular Events in Orange County (SERVE OC) RCT and present baseline characteristics of enrolled families. Methods: SERVE OC is a 2-arm RCT of 190 Latino and Vietnamese families (486 individuals) randomized to the family-based intervention or individual self-management. The intervention was grounded in social network theory while employing community engaged strategies. Primary outcomes include achieving ideal cardiovascular health (CVH) defined by AHA Life's Essential 8 (LE8) and systolic blood pressure reduction at 12, 24, and 36 months. Baseline assessments include demographics, LE8, psychosocial factors, food security, and SDOH. Descriptive statistics and regression analyses examined cohort characteristics and associations between SDOH, food security, and LE8. Results: Over 83% of participants had suboptimal LE8 scores. Average adult total LE8 scores were 66.61 {plus minus}11.96, with physical activity as the weakest domain, compared to an average of 76.52{plus minus}10.15 in children. Greater SDOH burden and food security were associated with significantly lower odds of ideal CVH and lower LE8 scores respectively. Conclusions: SERVE OC demonstrates the feasibility of enrolling families in community-engaged RCT targeting CVD disparities in underserved population. Baseline findings confirm substantial CVD risk and SDOH burden underscoring the need for multi-level, culturally tailored interventions. Trials results will inform scalable, family-focused strategies for CVD prevention across the life course. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/; Unique Identifier: NCT05641519.

Background There has been a proliferation of new person-centered and human rights-based contraception measures in recent years, though their application in research remains limited. Improved measures offer an opportunity to examine how contraceptive decision-making agency relates to individuals ability to act in line with their contraceptive preferences. We sought to assess the association between contraceptive agency and subsequent Preference-aligned Fertility Management (PFM) over 12 months in a cohort of women in rural Uganda. Methods We analyzed data from a prospective cohort study conducted in five largely rural Ugandan districts from 2022 to 2024. Data were collected at baseline, 6 and 12 months from a convenience sample of women who were new users of contraception or not using contraception. We used mixed-effects logistic regression models to examine the association between baseline Agency in Contraceptive Decisions Scale overall and subscale scores and future PFM Index scores at 6 and 12 months, assessing whether associations varied over time using interaction terms for follow-up time point. We used interactions between agency scores and follow-up visit to assess whether associations differed between the 6- and 12-month visits. We assessed effect modification by age group and baseline contraceptive method category using three-way interaction terms and predicted probabilities. Results The analytic sample comprised 2,227 women. The percentage of women practicing PFM increased from 85.7% at baseline to 93.3% at 12 months. A one-unit increase in Agency in Contraceptive Decisions Scale score was associated with higher odds of subsequent PFM (aOR: 1.68, 95% CI: 1.10-2.54). Subscales 3 (knowledge aligned with preferences) and 4 (control over use or non-use) of the Agency in Contraceptive Decisions Scale were significantly associated with future PFM (aOR: 1.31, 95% CI: 1.04-1.66 and aOR: 1.27, 95% CI: 1.06-1.51, respectively). The association between overall contraceptive agency and PFM did not differ between the 6- and 12-month visits. Three-way interaction tests suggested that the associations between the overall Agency in Contraceptive Decisions Scale score and the PFM outcomes varied jointly by age group and baseline contraceptive method category: overall PFM Index (p<0.001), PFM1 (p=0.011), and PFM2 (p<0.001). Conclusion Our findings suggest that higher levels of contraceptive agency may help women act in line with their contraceptive preferences. Increasing womens knowledge and control over contraceptive use may be particularly essential for preferred contraceptive use. The findings also suggest that the association between contraceptive agency and PFM may vary by womens age group and the method of choice, though further exploration is necessary to examine this influence.

Disseminating study results to participants is an ethical responsibility for researchers but remains uncommon in low- and middle-income countries, and participants preferences for receiving study results are poorly understood. This study examined study result dissemination preferences among pregnant women in a phase III malaria prevention trial in Papua New Guinea (PNG). Participants completed an interviewer-administered questionnaire (survey) assessing their interest in and motivation for receiving trial results and preferences for dissemination methods and content. Associations between participants characteristics and dissemination preferences were explored using multivariable logistic regression analysis. Of 1172 trial participants, 96.0% (1125/1172) completed the survey, and of these 99.6% (1121/1125) wanted to learn about the trial results. The main motivation factors driving participants interest were an acknowledgment of their contribution to research (51.7%; n=579) and a better understanding of the study (45.0%; n=505). Most participants (78.9%; n=884) wanted to learn about the trial findings through written summary and a group meeting with other participants at the nearest clinic (31.1%, n=349). Multivariable regression analysis indicated that participants from rural/peri-urban clinics were more likely to choose non-electronic media dissemination approaches such as a group meeting as compared to urban-dwelling participants. Frequently selected items (>50% of participants) for content included information regarding good results of the study, purpose of the study, medical treatment advances, results specific to me, and how study was conducted. There was heterogenicity in the preference for dissemination content: compared to urban clinics rural clinics are less likely to want to learn about how and why study was conducted and medical and scientific advances. Overall, the majority wanted to learn about trial results, highlighting the importance of integrating dissemination into research activities in PNG. Variation in preferences for mode and content of dissemination between study clinics suggests that dissemination activities could be tailored to local context and preferences.

Background Global labor migration from LMIC to higher-income destinations has expanded rapidly, placing increasing pressure on destination-country health. Existing research on cross-border migrant workers has focused largely on occupational health, general healthcare utilization, and disease-specific risks, while there is considerably less evidence on their sexual and reproductive health. This study contributes to this understudied field by examining the policy and health-system factors that shape the sexual and reproductive health services for migrant workers in Taiwan. Methods A qualitative study was conducted in Taiwan between November 2025 and August 2026. 22 stakeholders were purposively recruited from academia, healthcare, nongovernmental organizations, government, labor brokerage, and employers. Data were collected through semi-structured interviews and small focus groups. Interviews were conducted in Mandarin Chinese, transcribed verbatim, and translated into English. Data were analyzed using framework analysis combining deductive coding based on the AAAQ framework with inductive coding of implementation and contextual themes. Results Gaps were identified across all four AAAQ dimensions. Participants described limited migrant-responsive SRH programming; physical, financial, administrative, social, and information barriers; shortcomings in linguistic and cultural responsiveness; and weaknesses in interpretation, coordination, and continuity of care, despite generally favorable views of Taiwan's clinical quality. Conclusions Our findings show that broad insurance coverage and strong clinical capacity do not by themselves ensure the realization of migrant workers' SRHR. In Taiwan, rights were mediated through labor brokerage, gendered live-in work arrangements, and fragmented governance across health, labor, immigration, and social-welfare systems. Improving migrant SRHR therefore requires stronger implementation of existing protections, reduced dependence on informal intermediaries, and more integrated institutional responsibility for cross-sector migrant health needs.

The analysis uses a global 2010-2023 panel comprising 3,038 economy-years across 217 economies. It explicitly separates between-economy and within-economy estimands and tests the longitudinal interpretation using an identical-sample temporal analysis with cluster-aware coefficient contrasts, a formal isometric log-ratio sensitivity analysis, independent fixed-effects replication, and wild-cluster-bootstrap inference. The central finding is deliberately calibrated: cross-economy agreement cannot validate national sugar availability for longitudinal obesity surveillance. The study identifies temporal and construct instability without claiming that sugar is protective or that the mechanisms producing the instability have been identified. The manuscript aligns well with PLOS ONEs emphasis on technically sound, transparent and reproducible research of broad relevance. All data required to reproduce the findings, complete metadata, executable code, full-precision results, diagnostic outputs and a completed STROBE checklist are provided as S1-S5. Figures are provided separately as compliant 350-dpi TIFF files. The study used only publicly available, aggregated economy-year statistics and involved no individual participants, identifiable information or biological specimens; institutional ethics review and consent were therefore not required. This is original work; it is not under consideration elsewhere, and the sole author has approved the submission and accepts responsibility for its content. Funding and competing-interest declarations will be entered accurately in the submission portal. An Academic Editor with expertise in nutritional epidemiology, global health metrics, longitudinal panel methods, or food-system surveillance would be well placed to assess the work.

Background and Objectives: Preterm infants are commonly transfused, yet direct cardiorespiratory effects of red blood cell (RBC) transfusions remain poorly understood. We explored the feasibility of using multicentre electronic health data (EHD) to study such cardiorespiratory responses. Methods: Highly granular routine EHD were collected from preterm infants born <32 weeks gestational age at three European centres. Heart rate, oxygen saturation, and respiratory rate were evaluated 12 hours before and after the RBC transfusion. Results: A total of 321 transfusions in 164 infants were analysed. Overall, there was no significant change in the rate of bradycardia and apnoea following transfusion. Cardiorespiratory parameters varied substantially between infants; e.g. 20% of transfusions were associated with an unexpected, significant increase in heart rate. Respiratory rate and oxygen saturation exhibited similarly heterogenous patterns following transfusion. In sub-group analysis, the proportion of transfusions with increased heart rate was significantly higher within the first two weeks than later (32% vs 13%, p=0.0019). Conclusions: Multicentre EHD extraction allows to identify otherwise masked short-term effects of RBC transfusions on cardiorespiratory parameters, possibly indicating cardiac or pulmonary overload. Such effects may vary with adaptation to anaemia. Analysing EHD may ultimately enable personalized transfusion practice.

Background Respiratory infections remain the leading infectious cause of death among children and adolescents, yet the share of these deaths that could be averted with currently feasible care is not routinely quantified. Existing amenable-mortality frameworks rely on cause lists and population-level mortality benchmarks and do not exploit information on how many episodes occur. We propose an episode-fatality-ratio (EFR) frontier approach and apply it to lower respiratory infections (LRI), whooping cough (pertussis) and upper respiratory infections (URI) in 204 countries, 1990-2023. Methods For each cause, country and year we computed EFR = deaths/incident episodes using Global Burden of Disease (GBD) 2023 estimates for ages 0-19 years. The frontier was defined as the 10th-percentile country EFR within each GBD super-region, cause and year; avoidable deaths = max(0, deaths - episodes x frontier EFR). Primary estimates are deterministic; 95% uncertainty intervals (UIs) come from 2,000 Monte Carlo draws. Sensitivity analyses varied the frontier percentile, applied an aspirational global frontier, constructed pertussis counterfactuals, and recomputed all estimates within the single under-5 age band. Results In 2023, 333,803 childhood deaths from lower respiratory infections (95% UI 289,123-417,460; 46.9% of LRI deaths) were avoidable. Summing the three causes deterministically gives 391,034 avoidable deaths (46.5% of 840,444); the combined figure is a deterministic sum, and a UI is available for the LRI component only. The pertussis (43,958; 39.0%) and URI (13,273; 81.0%) estimates are secondary: their deterministic point values fall below their own Monte Carlo intervals and the underlying death estimates carry very wide uncertainty (global pertussis UI 12,545-321,874). Avoidable deaths fell from 1,050,468 (44.9%) in 1990, but between 2019 and 2023 the avoidable share for LRI+URI barely moved (48.7% to 47.7%) while absolute avoidable deaths fell 14.5%, a pattern consistent with stalled convergence to the frontier. Sub-Saharan Africa plus South Asia held 73.1% of avoidable deaths in 2023 versus 41.8% in 1990; ten countries accounted for 59.1%. Conclusion Nearly half of childhood respiratory-infection deaths remain avoidable relative to within-region best practice, and the residual burden is increasingly concentrated in low-income settings. In the pertussis counterfactual, most countries kept pace with their regional frontier, so further gains require advancing the frontier itself through quality-of-care improvements.

Neighbourhood deprivation is one of the few potential policy-modifiable risk factors for psychiatric and neurological disorders, but the neurobiological pathways underlying these associations remain unclear. We investigated these relationships across three cohorts spanning the life span: the Healthy Brain and Child Development (HBCD) Study (n = 84, aged 0 to 4 weeks postnatal), the Adolescent Brain Cognitive Development (ABCD) Study (n = 4,792, aged 9 to 10 years), and the UK Biobank (UKB; approximately 500,000 adults, aged 44 to 87 years). Neighbourhood deprivation was associated with elevated disease risk, and individual lifestyle factors accounted for only a small fraction of this burden, indicating that the much larger residual effect reflects broader contextual characteristics of deprived environments rather than individual behaviours alone. Across all cohorts, greater deprivation consistently predicted lower cortical and subcortical brain volume, with effects detectable in early development and substantially stronger in adulthood. Across disorders, regional brain volume emerged as a consistent neuroanatomical mediator linking neighbourhood deprivation to neuropsychiatric disease. We further showed that deprivation preferentially affects brain regions intrinsically vulnerable to neuropsychiatric disorders. Spatial decoding analyses implicated dopaminergic and serotonergic neurotransmitter systems together with specific excitatory and inhibitory neuronal classes. Importantly, both the deprivation effects and their neuroanatomical mediation patterns were replicated across independent populations. Our study delivers a translational framework linking neighbourhood deprivation to brain health, which could inform public health policies and preventive interventions.

BACKGROUND: We used anthropometric data from electronic health records (EHRs) of Swiss childrens hospitals to evaluate growth references and estimate centile curves. METHODS: We received EHRs extracted from seven Swiss childrens hospitals and analysed two samples: all children with a height, weight, body mass index (BMI), or head circumference recording, and a subsample restricted to children without diseases potentially affecting growth, weighted to represent the general population. We calculated mean z-scores based on the World Health Organization growth references adopted for Switzerland in 2011 (CH-WHO 2011) and current Swiss growth references (Swiss 2026). We estimated sex-specific centile curves in the subsample using generalised additive models for location, scale, and shape. RESULTS: We included 213,868 children with height, 448,002 with weight, 209,244 with BMI, and 67,397 with head circumference recordings. Mean z-scores in the all children sample were (CH-WHO 2011; Swiss 2026): height (0.10; -0.19), weight (0.16; -0.09), BMI (0.04; -0.07), head circumference (-0.28, -0.28); and in the subsample: height (0.34; 0.00), weight (0.27; 0.01), BMI (0.18; 0.05), and head circumference (0.04; 0.01). The 50th height, weight, BMI, and head circumference centiles of girls and boys in the subsample closely followed those of Swiss 2026, with slightly wider 3rd and 97th centiles in infancy and adolescence. CONCLUSION: Height, weight, BMI, and head circumference centiles aligned well with the Swiss 2026 growth references in Switzerland, demonstrating that hospital EHRs could contribute to future growth references.

The distribution of fat-soluble compounds (including antioxidants) in follicular fluid (FF) remains sparsely documented in relation to in vitro fertilization (IVF) outcomes and existing studies have reported diverging associations. This study aimed to describe plasma and FF concentrations of fat-soluble micronutrients in women undergoing IVF and to analyze their adjusted associations with ovarian function, embryo development and pregnancy outcomes. In 2021-2022, plasma and FF samples were collected from 82 women (first IVF cycle) at oocyte puncture, along with lifestyle data covering the three preceding months. Eleven compounds (two tocopherols, three xanthophylls, five carotenes and retinol) were quantified. All compounds were detected in both compartments (lowest in FF) except phytoene, undetectable in FF. Plasma and FF -tocopherol concentrations were positively associated with plasma estradiol levels before oocyte puncture (both p<0.01) while FF -carotene and lycopene were inversely associated with plasma progesterone concentrations (p=0.01 and 0.02, respectively). Plasma phytofluene and phytoene were positively associated with mature oocyte rate (p=0.03 and p=0.01, respectively), while FF retinol was negatively associated (p=0.03). Carotenes, tocopherols and retinol were inversely associated with later IVF outcomes: fertilization rate (p<0.001 for plasma g-tocopherol, 0.02 for FF retinol), top-quality embryo (p=0.02 for plasma phytofluene), biochemical pregnancy at day 7 post-embryo transfer (p=0.05 for plasma -tocopherol, 0.02 for plasma -carotene), clinical pregnancy (p=0.03 for plasma -tocopherol, 0.01 for plasma phytoene) and live birth (p=0.04 for plasma -tocopherol, 0.02 for plasma phytoene). Plasma and FF g-tocopherol were positively associated with embryo fragmentation (both p<0.05). Finally, among xanthophylls, only plasma {beta}-cryptoxanthin was positively associated with plasma progesterone concentrations (p=0.02). Our findings of heterogeneous associations between tocopherols, carotenes, retinol and IVF outcomes across the stages of IVF suggest a beneficial effect limited to early outcomes and support a complex and context-dependent role of these compounds in female reproduction. This manuscript has been submitted to PlosOne on August 19, 2026.

Background. Cardiovascular-kidney-metabolic (CKM) syndrome affects nearly 90% of US adults, yet most individuals at early, modifiable stages remain unidentified outside clinical care. Blood donation centers offer a scalable, non-clinical venue for CKM screening, but the potential benefit of screening in this context remains unclear. We projected the population-level impact of effective digital return of results (ROR) to inform the design of a pragmatic trial. Methods. We developed a Monte Carlo simulation (100,000 iterations) of the incident major adverse cardiovascular events (MACE), end-stage renal disease (ESRD), and type 2 diabetes (T2DM) preventable by ROR-prompted, guideline-concordant follow-up among donors in CKM Stages 1-2. The estimand counts only events averted by donors who act because of ROR; the intervention effect was modeled directly on strictly positive support, and action was translated into prevented events through a hazard-based cumulative-incidence difference that counts each donor at most once. We evaluated 18 design cells (donor volumes 300,000, 1 million, and 8 million/year; 5- and 10-year horizons; action-rate gains of +10, +20, and +30 percentage points [pp]) and, in a complementary two-arm simulation, the assurance (expected power) of detecting the effect in a single deployment. Results. Under the primary +20 pp scenario, ROR at a single large blood center (300,000 donors/year) is projected to prevent a median of 2,201 events (95% uncertainty interval [UI], 1,099-4,364) over 10 years, scaling to 58,526 (29,154-116,769) at the national donor pool. All 18 design cells had strictly positive 95% lower bounds. The number needed to screen was 136 and the screening cost $2,045 per event prevented (at $15/donor), both invariant to donor volume. Impact scaled linearly with volume and effect size but sub-linearly with the horizon. Detection of the effect was effectively certain at gains of +20 pp or larger (assurance [&ge;]99.6% in every cell and >99.9% in all but the smallest 5-year cell). Conclusions. Even under the conservative scenario, digital CKM ROR at blood donation centers is projected to prevent hundreds to tens of thousands of incident cardiometabolic events at a screening cost per event well within accepted prevention benchmarks, providing prospective, quantitative justification for a pragmatic, randomized evaluation of digital ROR in non-clinical screening settings.

Purpose: This study assesses the association between colorectal cancer (CRC) screening and a validated, housing-based measure of individual-level socioeconomic status (SES, called HOUSES hereafter) within rural communities and determines whether HOUSES-integrated geospatial analysis can be used to tailor interventions. Methods: We used CRC screening data from a subset of Mayo Clinic Midwest patients living in cities without ready access to routine care in the Mayo Clinic Health System in 2019 to represent rural communities. At the individual level, we assessed the association between CRC screening rates and the HOUSES index, adjusting for age, sex, race/ethnicity, comorbidity, distance from home address to clinic, and area deprivation index, using a multilevel mixed-effects logistic regression model. Additionally, we conducted geospatial analysis to examine the correlation between hotspots of 1) lower CRC screening rates and 2) lower SES of the subject population (HOUSES quartile 1). Findings: Among 34,489 individuals (median age 64.0 years, 52.4% female), those with the lowest SES (HOUSES Q1) had 37% lower odds of being CRC screening adherent than those with the highest SES (HOUSES Q4) (adj. OR [95% CI]: 0.63 [0.58-0.69]). In the 14 identified HOUSES Q1 hotspots, there was a significant correlation in counts of HOUSES Q1 and low CRC screening (correlation coefficient=0.81). Conclusion: Lower SES was significantly associated with lower CRC screening among rural populations. HOUSES-enabled geospatial analysis identified geographic hotspots with lower CRC screening rates for targeted interventions to address disparities in CRC screening in rural communities. HOUSES may be a useful digital tool for cancer preventive care and research.

Postnatal care (PNC) is essential for reducing preventable maternal and neonatal deaths, but its utilization remain low across sub-Saharan Africa. Intimate Partner Violence (IPV) may be an under-recognized barrier to PNC utilization, particularly in Tanzania, where direct evidence shows that IPV is linked to limited utilization of PNC. Therefore, this study assessed the association between IPV and PNC utilization within 42 days postpartum among women in Tanzania. This study conducted a secondary analysis of the 2022 Tanzania Demographic and Health Survey (TDHS), a nationally representative cross-sectional survey. The analysis included 2,674 women aged 15-49 years who had a live birth in the five years preceding the survey and were selected for the domestic violence module. IPV (any, physical, sexual, and emotional) was the primary exposure, and PNC utilization within 42 days postpartum was the outcome. Modified Poisson regression was used to estimate crude and adjusted prevalence ratios (cPR/aPR) with 95% confidence intervals (CI) because the prevalence of the outcome was common. The prevalence of PNC utilization within 42 days postpartum was 42.0%, and the overall prevalence of IPV was 33.6% (physical 26.1%, emotional 21.8% and sexual 7.3%). Women who experienced any IPV had 16% lower PNC utilization than those who did not (aPR=0.84; 95% CI: 0.74-0.96). Physical IPV (16%, aPR=0.84; 95% CI: 0.73-0.96) and sexual IPV (25%, aPR=0.75; 95% CI: 0.57-0.98) were significantly associated with lower PNC utilization, while emotional IPV was not. Maternal education, partners age, travel time to the nearest health facility, and media exposure were also other covariates associated with PNC utilization. Intimate partner violence is associated with low utilization of PNC within 42 days postpartum in Tanzania. Integrating IPV screening and survivor support into postnatal care services, alongside addressing structural barriers to access, may improve postpartum care coverage and maternal-neonatal outcomes.