Back

Journal of The Royal Society Interface

● The Royal Society

Preprints posted in the last 7 days, ranked by how well they match Journal of The Royal Society Interface's content profile, based on 235 papers previously published here. The average preprint has a 0.17% match score for this journal, so anything above that is already an above-average fit.

1
Reconstructing Dengue Exposure Dynamics and Assessing the Public Health Impact of Vaccination Scenarios Using Mathematical Models in Brazil

Ko, Y.; Santos, C.; Huang, A. T.; Salje, H.; Cummings, D. A.; Ko, A. I.

2026-10-16 epidemiology 10.64898/2026.10.15.26365586 medRxiv
Top 1%
3.2%
Show abstract

Brazil experienced its worst dengue epidemic in 2024, with an increase in severe outcomes among elderly individuals, highlighting the need for vaccination strategies informed by population immunity. We reconstructed state- and age-specific immune profiles by fitting an age-structured catalytic model to dengue surveillance data from 2000-2025. This inferred immune profile was incorporated into an SIR-type transmission model to project disease burden and to evaluate the public health impact of vaccine allocation strategies. We observed substantial spatial heterogeneity in accumulated immunity, which was closely associated with projected burden and optimal allocation. Strategies prioritizing states with lower historical incidence and larger susceptible populations yielded greater benefits. Under limited vaccine supply, targeting children resulted in the greatest reductions in DALYs, whereas targeting elderly populations achieved smaller DALY reductions but larger reductions in mortality. We further showed that accelerated vaccine supply markedly increased impact, while allocation choices remained critical when availability was constrained.

2
Vaccination and Non-School NPIs Shaped Ontario's Pre-Omicron COVID-19 Hospital Burden

Tuffaha, M. Z.; Dick, D. W.; Li, J.; Heffernan, J. M.

2026-10-16 epidemiology 10.64898/2026.10.14.26365553 medRxiv
Top 2%
2.1%
Show abstract

We develop an age- and immunity-structured COVID-19 model with setting-specific contacts, calibrated to Ontario incidence and hospital admissions before Omicron. We simulate counterfactual vaccination strategies and contact restrictions in schools, workplaces, and other community settings, evaluating projected severe-case demand against an illustrative healthcare-capacity benchmark. Vaccination combined with workplace and community contact restrictions keeps simulated demand within capacity. In contrast, relaxing restrictions in either setting produces large surges and repeated capacity threats, even when school restrictions remain. School-only changes produce smaller effects on severe disease. These findings highlight the value of vaccination and setting-specific contact restrictions that prioritize workplace and community settings for pathogens with adult-concentrated severe outcomes.

3
SARS-CoV-2 infection detection efficiency in Denmark before major vaccine impacts

Westfall, M. N.; Hoiby, N.; Rasmussen, S.; Ziock, H.-J.

2026-10-21 epidemiology 10.64898/2026.10.16.26364986 medRxiv
Top 2%
1.9%
Show abstract

To deal with the COVID-19 pandemic, Denmark implemented an aggressive program aimed at controlling the pandemic which included both testing and contact tracing programs. The large amount of data collected in Denmark on the pandemic and its integrated nature made it possible to investigate the effectiveness of the testing and contact tracing effort. The results of that investigation and a discussion of the effectiveness and limitations of the different control efforts are reported herein, as are lessons learned concerning possible improvements for the future. The analysis is limited to the period from the start of the COVID-19 pandemic in Denmark (late Feb. 2020) into May 2021, at which time the impact of vaccination intervention was already playing a role with ~25% of the Danish population at least partially vaccinated. From the available data sets we estimate the national Infection Detection Efficiency (IDE) starting around July 1, 2020, the time at which the national infection detection program started to be implemented in a more robust form. The results rely on daily COVID-19 hospital admissions, PCR test results, and anti-body prevalence values for the Danish population. We find that for the long-term average, the combined Danish national testing and contact tracing program identified on average about 55 to 60% of the infected individuals during the period from Sept. 1, 2020, into early May 2021. However, higher infection detection efficiencies were achieved in localized areas for short time intervals. Our investigations further indicate that the Danish testing and contact tracing program, which was among the most ambitious in the world, could have had a better balance between voluntary probing on the one hand and focused contact tracing and targeted testing on the other hand. As typically implemented, it proved to be largely ineffective in controlling the pandemic. However, in at least one case when it was implemented in an enhanced and focused mode, it was able to bring a large local outbreak that dominated the country's cases under control. We have compiled a list of lessons learned regarding the use of contact tracing procedures to control potential future pandemics before vaccinations become available.

4
Assessing the Competing Risks of Loss to Follow-up and Mortality Among Adults Receiving Antiretroviral Therapy in Northern Ghana: Application of the Fine-Gray Subdistribution Hazard Model

Abo, S. C.; Abdulai, M. Y.; Bavug, B. T.

2026-10-20 hiv aids 10.64898/2026.10.15.26365612 medRxiv
Top 2%
1.7%
Show abstract

Retention in antiretroviral therapy (ART) programmes remains a major public health challenge in HIV care, with loss to follow-up (LTFU) and death threatening treatment success. Because these outcomes are competing events, conventional survival methods may yield biased estimates of their incidence and associated risk factors. To estimate the cumulative incidence of LTFU and mortality and identify factors associated with these outcomes among adults receiving ART in Northern Ghana using a competing-risks framework. We conducted a retrospective cohort study of 329 adults living with HIV who initiated ART at Nalerigu Baptist Medical Centre, Ghana, between January 2013 and December 2019. Fine--Gray subdistribution hazard models were used to evaluate predictors of LTFU and death while accounting for competing risks. Cause-specific Cox proportional hazards models were fitted as a sensitivity analysis. The incidence rates were 2.2 per 100 person-months (95% CI: 1.9--2.6) for LTFU and 0.74 per 100 person-months (95% CI: 0.57--0.98) for death. At 36 months, the cumulative incidence was 50.2% for LTFU and 16.0% for death. Patients residing closer to the clinic had a lower cumulative incidence of LTFU than those living farther away (SHR = 0.68, 95% CI: 0.49--0.93), whereas higher baseline weight was associated with increased LTFU (SHR = 1.02 per kg, 95% CI: 1.00--1.04). Mortality was lower among patients receiving efavirenz-based regimens (SHR = 0.27, 95% CI: 0.15--0.50), females (SHR = 0.39, 95% CI: 0.18--0.85), and those with higher baseline weight (SHR = 0.93 per kg, 95% CI: 0.90--0.96). Findings were broadly consistent in cause-specific Cox models. LTFU was substantially more frequent than mortality among adults receiving ART in Northern Ghana. Travel distance to the treatment facility was an important barrier to retention, while ART regimen, sex, and baseline weight were associated with mortality. Expanding access to ART services through decentralized and community-based models may improve retention and support efforts to achieve HIV control targets.

5
The Effect of Regionalization of Thoracic Surgery on Blood Transfusion at the Ottawa Hospital

Smith, J.; Smith, B.; Pittman, T.

2026-10-19 health economics 10.64898/2026.10.15.26365639 medRxiv
Top 3%
1.4%
Show abstract

This paper examines the impact of Cancer Care Ontario's regionalization of lung cancer surgery on blood transfusion use for thoracic surgery at The Ottawa Hospital. Using aggregate data scraped from the paper ''Changing trends in blood transfusion: an analysis of 244,013 hospitalizations'' by Shehata et al. (2014) we estimated the effect regionalization on the log mean number of blood transfusions among thoracic surgeons (who treat lung cancer), utilizing other surgical specialties as controls. We found that the average number of blood transfusions increased significantly among thoracic surgeons following the opening of a new cancer care centre at the hospital in December 2009, while control specialties showed no parallel change. Contextualizing these results in a modified ''population level'' treatment threshold model, it is argued that the main driver of this increase in blood transfusions among thoracic surgeons was due to the influx of less skilled thoracic surgeons to The Ottawa Hospital, and the closing of thoracic surgery units at smaller hospitals which was part of the broader regionalization process.

6
Autistic Adults' Perceptions of the Adequacy of their Supports and Disability-Related Information: Instrument Validation & Preliminary Correlates

Schuck, R. K.; Moura, I.; Baker-Ericzen, M. J.; Yang, L.-Q.; McDonald, K.; Kapp, S.; Uljarevic, M.; Love, J.; Vera, J. W.; Horner-Johnson, W.; Kripke-Ludwig, R.; Siddeek, Z.; Nicolaidis, C.

2026-10-21 psychiatry and clinical psychology 10.64898/2026.10.19.26365938 medRxiv
Top 3%
1.1%
Show abstract

Autistic adults face considerable challenges in receiving adequate support, from both paid/formal (such as from disability services) and unpaid/informal (for example, from friends and family) sources. Having adequate support can lead to better health and well-being outcomes. However, most instruments designed to assess adequacy of support were not made specifically for/with autistic adults. This paper presents a psychometric validation of the AASPIRE Adequacy of Supports and Information Scale (AASIS), a community-informed adaptation of a previously developed instrument (the Quality of Care and Support scale; Lucas-Carrasco et al., 2011), designed to be relevant and accessible to autistic adults. We also used the AASIS to explore correlates of perceptions of support in a sample of 798 autistic adults. Our confirmatory factor analysis supported a two factor structure for the AASIS (factor one: Supports; factor two: Information). Further testing confirmed the instrument was invariant across several groups, including race/ethnicity, gender, intellectual disability, communication fluency, and self versus proxy-report. Regression analyses suggested that the way in which participants joined the study (i.e., through community advertisements or via established healthcare/disability services) impacted whether they viewed their support as adequate. Additionally, a higher number of adverse childhood events and greater experience of discrimination were related to worse perceptions of support adequacy across both factors. Our findings support the preliminary validity of the AASIS across a variety of autistic people, though further testing is warranted. Findings also point to the importance of addressing the needs of autistic people who are minoritized and/or who have complex trauma histories.

7
Epidemiologic shifts predict spatial patterns of measles re-emergence in the United States

Kumar, C. K.; Stoffel, L. A.; Warren, J. L.; Blumberg, S.; Schechter, R.; Bubar, K. M.; Fattah, M.; Kiang, M. V.; Maldonado, Y.; Mordecai, E. A.; Hotez, P. J.; Lipsitch, M.; Lo, N. C.

2026-10-16 epidemiology 10.64898/2026.10.14.26365590 medRxiv
Top 3%
1.1%
Show abstract

Globally, measles is re-emerging in countries that have previously achieved elimination, including the United States. As immunization rates decline, characterizing the dynamics and evolving spatial pattern of measles re-emergence is critical to inform the public health response. We analyze annual county-level measles cases and vaccine coverage data in the United States (US) from 2011-2025 and find a shift in measles epidemiology in recent years indicative of re-emergence. While outbreak risk is spatially concentrated, we find that outbreaks are increasingly spreading throughout the broader population and across counties, but targeted interventions are predicted to prevent re-emergence nationwide. During the first decade of this period (2011-2020), outbreaks were only weakly associated with county-level vaccine coverage and predominantly isolated to single counties; however, recently (2021-2025), vaccine coverage has become strongly associated with outbreak size and spread across neighboring counties has increased. These findings suggest that measles transmission is increasingly sustained across the broader population rather than only in socially clustered communities. We developed a spatial statistical model to predict outbreak risk and size in all US counties with validation over 2021-2025; the model predicted counties with [≥]10 cases with a sensitivity of 95% (range across 2021-2025: 75-100%) and specificity of 83% (64-98%). Mechanistic models based on county vaccine coverage alone had worse performance, particularly in predicting larger outbreaks. Using the spatial statistical model, we find that prioritizing interventions in the areas of greatest model-predicted risk (e.g., top decile of US counties) was more impactful than state-level interventions (e.g., top five states) or targeting based on low vaccine coverage alone. Achieving even modest (5 percentage point) increases in vaccine coverage in counties in the top decile of model-predicted risk reduced long-term measles risk nationwide by over 90%. Together, these findings demonstrate that predictive risk modeling to inform spatially targeted interventions can likely mitigate the re-emergence of vaccine-preventable diseases.

8
Towards Early Warning Systems for Shigellosis in Africa: Multi-Horizon Forecasting of Incidence in Rural Western Kenya Using Statistical State-Space and Machine Learning Models

Ogwel, B.; Onyando, B. O.; Nyawanda, B. O.; Awuor, A. O.; Ogutu, J.; Ochieng, J. B.; Garcia Quesada, M.; Pavlinac, P. B.; Lau, M.; Omore, R.; Rogawski McQuade, E. T.

2026-10-21 infectious diseases 10.64898/2026.10.19.26365895 medRxiv
Top 3%
1.1%
Show abstract

Introduction Despite the significant burden of Shigellosis, routine surveillance systems in resource-limited settings lack predictive capabilities to guide proactive public health responses. Consequently, we developed and evaluated the accuracy, uncertainty and computational cost of multi-horizon forecasting models for Shigella incidence among children <5 years in rural western Kenya using 16-year longitudinal incidence time-series. Methods We estimated monthly Shigella incidence using data from three pediatric enteric studies (2008-2024), supplemented with Kenya Health Information System during inter-study gaps. Incidence estimates incorporated sampling, healthcare-seeking, stool-testing, and pathogen-specific weights, with bootstrap-derived 95% confidence intervals. Predictors included Google Trends health-related indicators, climate, temporal trends, and seasonality. Forecasts at 1-, 3-, and 6-month horizons were evaluated using rolling-origin validation. Following horizon-specific predictor selection using Boruta, 14 state-space, machine-learning, and hybrid models were compared using point-forecast and probabilistic metrics, bootstrap confidence intervals, and Model Confidence Sets. Adaptive conformal prediction recalibrated prediction intervals, while Shapley Additive exPlanations assessed predictor contributions. Results Mean monthly Shigella incidence was 2.51 per 100 child-years (standard deviation=1.85). Shigella dynamics in Kenya can be forecast beyond seasonal persistence alone for up to six months reducing absolute errors by ~ 33%. However, optimal model architectures and predictor sets shift systematically across forecasting horizons. Temporal trend and recent incidence were the dominant predictors, while predictor importance shifted with forecast horizon toward syndromic, pharmaceutical, seasonal, and lagged environmental signals. Extreme Gradient Boosting performed best at 1 month (Root mean squared error [RMSE]=1.86), remained competitive at 3 months (RMSE=1.89), whereas exponential smoothing (ETS) performed best at 6 months (RMSE=2.05). Forecast accuracy declined with increasing horizon. ETS and TBATS provided the best-calibrated prediction intervals, whereas machine-learning models generally under-covered. Model Confidence Sets demonstrated horizon-dependent model distinguishability. Conclusion Horizon-specific model selection balancing predictive accuracy, uncertainty calibration, and computational feasibility could strengthen operational early warning systems for shigellosis.

9
Occupational burnout in the UK film and television industry: A cross-sectional survey of mental health, job quality, perceived stigma, and sexual harassment

Caldwell, M. S.; Chamberlain, R.; Rippon, D.

2026-10-20 occupational and environmental health 10.64898/2026.10.15.26365611 medRxiv
Top 4%
1.0%
Show abstract

Recent industry surveys have reported widespread concern about mental health, working conditions, and harassment in the UK film and television industry, but no peer-reviewed empirical study has examined the determinants of occupational burnout in this workforce. The present study tested whether physical health, mental wellbeing, perceived public stigma, intrinsic job quality, and sexual harassment exposure predict burnout in industry professionals. A cross-sectional online survey was completed by 415 individuals across more than 100 job titles, with 286 also completing an optional harassment module. Mental wellbeing sat well below population norms, with 68% scoring in the range indicative of probable depressive symptoms and 82% in the high-exhaustion range on the Maslach Burnout Inventory General Survey. Mental wellbeing and intrinsic job quality were the strongest predictors of burnout (R2 = .56), with meaningfulness accounting for most of the job-quality effect. Working hours independently predicted emotional exhaustion. Harassment exposure was associated with burnout in women but not men, approximately 30% mediated by mental wellbeing; sexist behaviour directly predicted exhaustion in women. Workers with a disability reported higher stigma. Burnout was strongly associated with intent to leave, and the findings collectively indicate an industry-wide occupational health concern requiring structural rather than individual-level intervention.

10
Biological aging markers in South African women with HIV and variable exposure to childhood maltreatment

Maloka, K. M. S.; Spies, G.; du Plessis, S.; Hemmings, S. M. J.; Letendre, S.; Seedat, S.; Womersley, J. S.

2026-10-16 hiv aids 10.64898/2026.10.15.26365601 medRxiv
Top 4%
0.9%
Show abstract

Introduction: HIV and childhood maltreatment (CM) are both chronic stressors that disproportionately affect women, with each contributing to accelerated biological aging. Whether biological aging markers are convergent and associate with HIV and CM is unclear. Methods: We studied 238 women (122 with HIV), characterised for CM severity, and assessed biological aging using absolute telomere length (aTL), mitochondrial DNA copy number (mtDNAcn), magnetic resonance imaging-based brain-predicted age difference (MRI-BPAD), and DNA methylation age (DNAmAge) clocks. CM was measured with the Childhood Trauma Questionnaire-Short Form total score. We examined intercorrelations among biological aging markers to assess convergence and conducted linear regression models to test moderation by HIV status and CM severity. Results: PWH had shorter aTL, lower MRI-BPAD, and higher Horvath age acceleration (HorvathAA), HannumAA, PhenoAA, and extrinsic epigenetic age acceleration (EEAA). CM had limited associations with biological aging markers. Absolute TL correlated weakly with mtDNAcn (p = 0.36), PhenoAA (p = -0.18), and EEAA (p = -0.18), while MRI-BPAD correlated weakly with PhenoAA (r = 0.20). DNAmAge clocks were moderately to strongly intercorrelated (r = 0.35 - 0.93). No robust two- or three-way moderation effects were observed after false discovery rate correction. Conclusion: Our findings support a multidimensional pattern of biological aging, with substantial convergence among epigenetic aging measures but limited relationships across different markers, largely independent of HIV status and CM severity. Longitudinal approaches are needed to clarify how distinct biological aging markers relate to one another and to health outcomes over time in vulnerable populations.

11
Prognosis after a new episode of musculoskeletal pain in children and young people, 2005-21: population-based study

Mason, K. J.; Jordan, K. P.; Thomas, M. J.; Bailey, J.; Mughal, F.; Protheroe, J.; Jowett, S.; Saxne Jöud, A.; Snell, K. I.; Dunn, K. M.

2026-10-16 pediatrics 10.64898/2026.10.15.26365290 medRxiv
Top 4%
0.9%
Show abstract

Objective: to estimate reconsultation risk and trajectories after a new episode of musculoskeletal pain in children and young people (CYP), and to determine routinely recorded prognostic factors associated with reconsultation. Design: Population based retrospective cohort study. Setting: Clinical Practice Research Datalink (CPRD) Aurum, 2005-2021. Participants: CYP aged 8-18 years consulting primary care for a new musculoskeletal pain episode (no musculoskeletal consultation in prior 12-months). Main Outcome Measures: Musculoskeletal pain reconsultation within 12-months, and 3-year musculoskeletal reconsultation trajectories derived using latent class growth analysis. Prognostic factors selected from a literature search and two-year symptom histories (sample prevalence >1%) were examined using regression models (conditional logistic; multinomial). Results: Among 313,830 CYP with >12 months' follow-up, 32% reconsulted for musculoskeletal pain within 12 months. Among 240,384 CYP with >3 years' follow-up, three trajectories were observed: single episode (62%), early reconsultation (18%), and persistent reconsultation (20%). Older age; female gender; hip, knee, multisite and back pain on index; previous headache; previous abdominal pain; and analgesic prescribing were associated with higher reconsultation risk. Asian or Black ethnicity, and residing in more deprived areas, were associated with lower recorded reconsultation. Conclusion: Most CYP had no further recorded consultation, but 38% followed early or persistent reconsultation trajectories. Routinely recorded prognostic factors, particularly index pain side and prior pain/symptom history, may differentiate groups who could benefit from proactive follow-up. Lower recorded reconsultation among Asian and Black individuals, and living in more deprived areas, should not imply lower need and warrants equity-sensitive monitoring of access, health-seeking, and coding.

12
Pickleball injuries, search interest, and participation in the United States, 2014-2023: an ecological time series study

Kim, D. S.; Lobelo, F.; Durieux, J. C.; Colovos, C.

2026-10-16 epidemiology 10.64898/2026.10.14.26365555 medRxiv
Top 4%
0.6%
Show abstract

OBJECTIVE: To describe (1) US emergency department-treated pickleball injury burden and the injury-to-participation measure among total players, with burden among adults aged 60 to 79 years as a descriptive subgroup, and (2) determine whether general internet search interest for 'pickleball' is also associated with total pickleball-related injuries. DESIGN: Ecological time series study, United States, 2014 to 2023. DATA SOURCES: National Electronic Injury Surveillance System (NEISS) emergency department microdata yielded 1,738 adjudicated pickleball cases, 921 of them orthopedic, weighted to an estimated 101,450 injuries nationally. Google Trends, English Wikipedia pageviews, and GDELT news volume served as general pickleball attention signals, with the Trends index for 'sourdough' as a negative control. Sports and Fitness Industry Association (SFIA) participation estimates supplied a total player denominator. MAIN OUTCOME MEASURES: Annual national injury estimates with design-based 95 percent confidence intervals; injury-to-participation measures; and correlations between total pickleball-related injuries and general pickleball attention signals before and after removing trend and seasonality. RESULTS: Estimated emergency department-treated pickleball injuries rose 17.5-fold, from 1,391 in 2014 (highly unstable) to 24,294 in 2023. 70 percent of adjudicated cases involved adults aged 60 to 79. During 2017-2023, injury estimates rose 4.0-fold and participation rose about 4.4-fold. No temporal trend was detected in the injury-to-participation measure (P=0.59). Search interest looked like an excellent proxy: in annual levels it correlated with total pickleball-related injuries at R=0.96, and Pickleball Wikipedia pageviews at R=0.98. However, so did searches for "sourdough", at R=0.76. Removing trend and seasonality left little (monthly residual R=0.084; year-on-year R=0.28 over 96 months, 2015-2023), and the seasons ran opposite, with injuries peaking in February and searches in July, such that, on 12-month mean profiles, the sourdough negative control fitted the injury season (R=0.96) while pickleball ran against it (R=-0.40). General pickleball search interest and pickleball news coverage remained correlated in year-on-year changes in 2017-2023 (R=0.64), whereas their corresponding correlations with total pickleball-related injuries in 2017-2023 were 0.25 and 0.20. CONCLUSIONS: The absolute burden of emergency department-treated pickleball injury has grown substantially, but the available surveillance data cannot resolve whether the sport has become more hazardous per participant. The observed rise is consistent with growth in exposure alone. The strong correlation between search interest and injury counts was not specific, the association was substantially attenuated after detrending, and the seasonal patterns were opposed. These descriptive results do not establish that search interest can substitute for injury surveillance, and series that rise together should not be assumed to be related.

13
Quantifying Fine-scale Vegetation Associated with Ixodes scapularis Density to Inform Public Health Programming, Western Massachusetts

Tsalah, J. M.; Bobskill, V.; Ravenhurst, J.; Ross, K.; Gardner, A.; Landesman, W.; Lover, A. A.

2026-10-20 epidemiology 10.64898/2026.10.14.26363243 medRxiv
Top 4%
0.6%
Show abstract

Vegetation plays a critical role in shaping fine-scale tick density by structuring local microclimates, habitat resources, and host interactions that largely determine tick survival and activity, with implications for tick-borne disease transmission. Tick burden in the United States continues to increase, with annual reported tick-borne disease cases more than doubling from 2004 through 2019. These trends call for a broader scope of tick-mitigation strategies that go beyond traditional prevention measures that focus on personal protection; and there is an opportunity to inform habitat-level interventions. Here, we quantify fine-scale vegetation structure across 48 subplots at tick surveillance sites in Western Massachusetts to assess local habitat features associated with Ixodes scapularis density and potential for human-tick contact risk. In assessing understory and overstory vegetation attributes, this study identified life stage-specific differences in predicted tick density, with higher adult densities in areas with deeper leaf litter and presence of invasive plant species and nymphs associated with high presence of ferns. Both adult and nymphal Ix. scapularis were predicted at higher densities in relatively low basal area forests (18.9 to 26.9 m2/hectare). This study design provides a simple, low-cost framework for organizations looking to incorporate tick-informed forest measurement ecology into their public health tick surveillance protocols with minimal training.

14
Combining Randomized and Observational Data: The Case of Postnatal Prophylaxis Against HIV

Yin, D. E.; Zivich, P. N.; Giganti, M. J.; Wu, D.; Edwards, J. K.; Cole, S. R.

2026-10-16 hiv aids 10.64898/2026.10.15.26365628 medRxiv
Top 4%
0.6%
Show abstract

The efficacy of current antiretroviral interventions for prevention of vertical HIV transmission is both a triumph and a challenge for future efficacy studies of novel agents, including long-acting antiretroviral agents. Given the effectiveness of current antiretroviral interventions, standard randomized controlled trials to assess novel interventions targeted towards further reducing vertical HIV transmission may be infeasible due to required sample sizes. To address this study design challenge, we propose a novel augmented clinical trial design, where a randomized trial with an active comparator is augmented with a concurrent observational cohort to supplement the standard-of-care arm. The proposed design and analysis can overcome sampling biases, and an associated diagnostic can evaluate potential biases from unmeasured covariates. The proposed trial design is illustrated with an example and studied further using a simulation study. In the illustrative example, an augmented trial with a 3:1 allocation ratio in the trial component yielded an unbiased treatment effect estimate, as compared to the trial component alone, and the standard error was reduced substantially. Although the total sample size of the augmented trial was larger than a similarly powered 1:1 standard trial, the sample size of the augmented trial's trial component was half the size of the standard trial and within the range of historically similar trials, thereby providing both feasibility and potential cost advantages. Although limitations with this design remain, many of these limitations can be mitigated by careful study planning and coordination. Augmented trials provide a potentially applicable solution to studying the efficacy of long-acting antiretrovirals for infant postnatal prophylaxis against HIV.

15
Title Mapping the brain signature of dyslexia risk onto histamine, acetylcholine and glutamate receptor systems

Celik, M. C.; Cicek, Y.; Sakiroglu, M. A.; Aslan, D.; Altunc, A. T.; Velioglu, H. A.

2026-10-20 psychiatry and clinical psychology 10.64898/2026.10.18.26365830 medRxiv
Top 5%
0.6%
Show abstract

The brain differences of dyslexia are well described and its genetic risk is now measurable; the brain systems that connect the two are unknown. That link decides which measures complement one another in early identification and which systems intervention research should examine. Here we compared large-scale polygenic score maps of brain structure in dyslexia with normative maps of brain neurotransmitter systems. The structural signature of genetic liability aligned with the cortical distribution of neurotransmitter systems. The strongest and most consistent alignment appeared for the histamine H3 receptor, the vesicular acetylcholine transporter (VAChT) and the N-methyl-D-aspartate (NMDA) glutamate receptor. The alignment was most pronounced in cingulate, medial and superior frontal cortex and the paracentral lobule. The H3 alignment held after adjustment for cortical position and for metabolic and cognitive reference maps. Once the component common to all nineteen maps and position were removed together, no individual system remained significant, while the shared component itself aligned with liability. The signature therefore follows the topography these systems share. In 169 children, per-person alignment with the H3 map related to reading skill with the opposite sign to liability. To our knowledge, this is the first study to relate the structural signature of genetic liability for dyslexia to normative maps of neurotransmitter receptor and transporter density. It places that signature within the shared geography of the systems that set attention, arousal and synaptic plasticity during learning, and gives the genetics of dyslexia a testable biological axis.

16
Anatomically optimised structural connectome derivation for the neonatal brain

Hew, C. K. W.; Leserri, S.; Aydogan, D. B.; Bastin, M. E.; Bonthrone, A. F.; Paterson, K.; Barclay, G.; Jardine, C.; Smith, K. M.; Thrippleton, M. J.; Marioni, R. P.; Boardman, J. P.; Blesa Cabez, M.

2026-10-21 pediatrics 10.64898/2026.10.20.26366012 medRxiv
Top 5%
0.5%
Show abstract

Structural connectomics provides a means of characterising white matter (WM) network organisation using diffusion MRI (dMRI), but reconstructing neonatal structural connectomes remains challenging due to the immature and heterogeneous nature of the developing brain. Although recent neonatal studies have increasingly adopted approaches beyond conventional diffusion tensor imaging (DTI), there remains scope to incorporate more advanced tractography and streamline post-processing approaches within neonatal pipelines. Here, we propose a neonatal structural connectome pipeline integrating surface-based anatomical constraints, ensemble tractography, hierarchical anatomical refinement of pathways (HARP) filtering, and spherical-deconvolution informed filtering (SIFT2) reweighting. We acquired 3T MRI data from 300 neonates (185 preterm, 115 term-born) to assess the impact of pipeline configuration on network organisation. Mean gestational age (GA) at birth was 29.31 (23.43-32.86) weeks in preterm infants and 39.52 (37.00-42.43) weeks in term infants. At scan, mean GA was 40.85 (36.29-49.00) weeks in preterm infants and 42.06 (38.29-48.00) weeks in term infants. Four connectome variants were generated: raw surfaced-based tractograms, HARP-filtered, SIFT2-weighted, and combined HARP+SIFT2. Pipeline performance was primarily evaluated using an existing brain age prediction model: connectome-based predictive model (CPM) and our derived connectomes to estimate GA at scan in term and preterm infants. In addition, global graph theoretical metric analyses were conducted to provide a complementary assessment of pipeline configuration differences in network organisation. In total, seven graph theoretical metrics were calculated and evaluated: global efficiency, local efficiency, transitivity, modularity, assortativity, degree variance and statistical complexity. Across all configurations, connectomes supported accurate brain age prediction, with mean absolute errors (MAE) of 0.76-0.79 weeks in term infants and 1.00-1.06 weeks in preterm infants. Prediction error and brain age gap variability were greater in preterm than term infants across configurations, with HARP+SIFT2 achieving the lowest preterm MAE (1.00 weeks) and brain age gap (BAG) variability (SD = 1.38 weeks). However, differences in prediction performance across configurations were minimal, suggesting limited influence of pipeline choice on brain age prediction. However, analysis of global network metrics demonstrated that pipeline choice significantly influenced downstream measures of network organisation, with HARP+SIFT2 being the only configuration to identify significant preterm vs. term differences across all seven metrics examined. These findings demonstrate the importance of considering tractography and streamline-processing choices when constructing neonatal structural connectomes and provide a framework for more anatomically informed investigation of early brain development.

17
Readiness to start long acting injectable HIV treatment and prevention and conditions for acceptance among clinic clients in Uganda

Olet, S. C.; Muluga, W. U.; Musoki, D.; Kihumuro, B. R.; Muluga, F.; Ssebandeke, I.; Among, F.; Stecher, C. D.; Musoke, D.

2026-10-15 hiv aids 10.64898/2026.10.14.26365499 medRxiv
Top 5%
0.5%
Show abstract

Long-acting injectable human immunodeficiency virus (HIV) medicines expand treatment and prevention choices, but willingness to use them does not establish readiness to begin. We examined readiness to start these options, associated factors and conditions for acceptance among people living with HIV and pre-exposure prophylaxis (PrEP)-service clients in Uganda. This cross-sectional study analysed 225 participants at Mildmay Hospital and Kajjansi Health Centre IV in central Uganda. Readiness meant preferring initiation immediately or within three months. Modified Poisson regression estimated adjusted prevalence ratios (aPRs) and 95% confidence intervals (CIs), including age-by-service-group interaction. Separate models examined informational, perceptual and financial factors, adjusting for service group, age and sex. Logistic marginal standardisation checked demographic and expanded age comparisons. Overall, 108 participants (48.0%) were ready to start injectable HIV treatment or prevention, 111 (49.3%) wanted more information about these options, and six (2.7%) preferred initiation in six to twelve months. Readiness was 80.8% among people living with HIV aged 15-24 years and 34.4% among those aged 25 years or older (aPR 2.35, 95% CI 1.63-3.38). Corresponding proportions among PrEP-service clients were 39.2% and 41.4% (aPR 0.95, 95% CI 0.60-1.50; interaction p=0.002). In separate adjusted models, clinic-staff information (aPR 1.94, 95% CI 1.42-2.66), belief in greater effectiveness (2.00, 1.43-2.80) and a one-point increase in benefit score (3.27, 2.36-4.55) were associated with higher readiness. A one-point increase in concern score (0.70, 0.60-0.80) and financial difficulty sometimes or more often (0.68, 0.48-0.96) were associated with lower readiness. Fewer side effects was the leading condition for accepting injectable HIV treatment or prevention across service and readiness groups. Nearly half of participants were ready to start, while a similar proportion wanted further information about injectable options. Programmes should assess intended initiation timing alongside willingness and address safety, appointment flexibility, privacy and affordability through counselling and service planning.

18
Spatial variation and correlates of raised blood pressure in Cambodia: a Gaussian-process geostatistical analysis of the 2023 STEPwise survey

Um, S.; Chhea, C.; Phy, M.; Haruyama, R.

2026-10-15 epidemiology 10.64898/2026.10.13.26365387 medRxiv
Top 6%
0.4%
Show abstract

Introduction: Raised blood pressure is an important cardiovascular risk factor in Cambodia; however, national averages may obscure substantial local geographic heterogeneity. We assessed the spatial distribution of raised blood pressure and its demographic, metabolic, behavioural, built-environment, and environmental correlates using the 2023 Cambodia STEPwise approach to noncommunicable disease (NCD) risk factor surveillance (STEPS) survey. Methods: We analysed 289 georeferenced primary sampling units (PSUs) from the 2023 Cambodia STEPS Survey. PSU-level case counts and numbers of adults with valid blood pressure data were modelled using a frequentist binomial generalised additive model with a two-dimensional Gaussian-process smooth. An explanatory model included selected PSU-level and contextual covariates; a separate mapping model used spatially continuous predictors to generate predictions on a 5-km grid. Design-based national and residence-specific prevalence estimates were calculated separately using the survey design and Step-2 weights. Results: Among 4,225 adults with valid blood pressure data, unweighted prevalence of raised blood pressure was 28.6%, compared with 18.8% after Step-2 weighting; weighted prevalence was 17.5% in rural areas and 21.7% in urban/suburban areas. Mean observed unweighted PSU-level prevalence was 29.0%. In the adjusted spatial explanatory model, the proportion aged 60-69 years ({beta}=1.969, SE=0.327; p<0.001) and overweight/obesity prevalence ({beta}=0.996, SE=0.265; p<0.001) were positive ecological correlates. The spatial model had lower Akaike information criterion and residual deviance than its non-spatial counterpart, although Bayesian information criterion was higher. Prediction uncertainty was greater in some sparsely sampled areas. Conclusions: Raised blood pressure showed significant geographic heterogeneity across Cambodia. Older age composition and overweight/obesity prevalence were positive PSU-level correlates, not individual-level causal effects. Predicted prevalence should be interpreted alongside uncertainty and should complement, rather than replace, design-based STEPS prevalence estimates for geographically informed NCD planning.

19
Intersectional inequalities in youth mental health measurement and outcomes: population-representative evidence from the UK Millennium Cohort Study

Moreno-Agostino, D.; Steare, T.; Evans, C. R.; Fitzsimons, E.; Phoenix, A.; Ploubidis, G. B.; Abid, U.; Nawaz, Y.; Pant, H.; Fisher, H. L.; Patalay, P.

2026-10-21 psychiatry and clinical psychology 10.64898/2026.10.19.26365893 medRxiv
Top 6%
0.4%
Show abstract

Background. Population-representative evidence on social inequalities in youth mental health from an intersectional perspective is limited. We investigated inequalities across multiple mental health outcomes among young adults and examined whether measures operated equivalently across social and intersectional groups. Methods. Cross-sectional analyses were conducted with 9,675 participants aged 23 years from the nationally representative UK Millennium Cohort Study (born 2000-2002). Self-reported outcomes included psychological distress (Kessler-6), probable serious psychological distress/'caseness' (Kessler-6 score [&ge;]13), psychological wellbeing (Short Warwick-Edinburgh Mental Well-Being Scale; SWEMWBS), past-year self-harm, and lifetime suicide attempts. Measurement invariance analyses assessed comparability of the Kessler-6 and SWEMWBS across groups. Intersectional MAIHDA examined inequalities by sex assigned at birth, ethnic identity/background, sexual identity, and childhood poverty. Young people with lived experience of mental ill-health and/or social discrimination contributed to study design, interpretation, and reporting. Findings. Large inequalities were observed across all outcomes, with the largest disparities by sexual identity, followed by sex assigned at birth, childhood poverty history, and ethnic identity/background. Across intersectional strata, predicted psychological distress ranged from -0.27 to 1.32 SDs, and psychological wellbeing from -0.54 to 0.11 SDs. Predicted prevalence varied 6.99-fold (9.81% to 68.55%) for psychological distress 'caseness', 6.84-fold (8.60% to 58.79%) for self-harm, and 22.10-fold (1.96% to 43.32%) for suicide attempts. Young people at the intersection of sexual minority status, female birth sex, childhood poverty, and some ethnic minority identities/backgrounds experienced particularly poor outcomes. Most inequalities showed cumulative patterns consistent with additive expectations, although some intersectional groups experienced better or worse outcomes than expected. Accounting for measurement differences revealed inequalities that were otherwise undetected. Interpretation. Findings highlight the large extent of mental health inequalities when multiple dimensions of social (dis)advantage are considered, and the need to address both the social conditions generating these inequalities and the methodological assumptions shaping how they are measured and understood.

20
Patterns of Influenza Vaccine Uptake by Age Group and Product Type in Michigan, 2017-2021

Zhou, Z.; Malosh, R.; Sudan, S.; Wagner, A.; Eisenberg, M. C.; Monto, A.; Martin, E. T.

2026-10-21 epidemiology 10.64898/2026.10.19.26365920 medRxiv
Top 6%
0.4%
Show abstract

Background Influenza vaccines have seen many changes over recent years in terms of both policy recommendations and product types. Immune responses and vaccine effectiveness vary by vaccine strain composition and product type. This study aimed to explore this variation on a regional level through examining spatial and temporal autocorrelations of vaccine uptake of different product types within Michigan from 2017 to 2021. Methods Influenza vaccine administration data from the 2017/18 to 2021/22 seasons were obtained from the Michigan Care Improvement Registry. Population size estimates for 2017 and 2019 were obtained from the Michigan Department of Health and Human Services. Age-standardized and age-stratified vaccination rates were computed. Disparate county-level vaccine uptake clusters were constructed using spatial autocorrelation indicators and spatiotemporal clusters were identified using scan statistics. Linear mixed effect models were used to study the impact of social vulnerability and urbanicity level on seasonal influenza vaccination rate. Results Vaccination incidence rates for adjuvanted, recombinant, and nasal sprays vaccines and for any vaccines increased significantly through the study period. County-level spatiotemporal clusters of type-specific uptake rates were identified. Most notably, we identified an emerging cluster with high uptake of adjuvanted vaccine radiating from Ottawa County, located in suburban Grand Rapids, and the disappearance of high uptake cluster for high-dose vaccine uptake in the area. Vaccination rates by any product type were found to vary seasonally and showed weak negative association with more rural regions. The overall vaccination rates appear to be lower among counties with higher social vulnerability in certain urbanicity levels, but social vulnerability and urbanicity were not significantly associated with overall vaccination rate during the study period. Conclusions Vaccine type-specific uptake was spatially and temporally diverse in Michigan between 2017 and 2022. Mid and Northern Michigan had consistently relatively lower vaccination rate compared to other regions in Michigan.