BMC Psychiatry

Objective: This study examined the prevalence of psychotic experiences (PE) and how early onset and persistence of PE contribute to risk and severity of mental disorders in adolescents at familial high-risk of schizophrenia (FHR-SZ) or bipolar disorder (FHR-BP) and adolescents from a population-based control group (PBC). Methods: This is the second follow-up of a nationwide cohort study including 522 children at FHR-SZ (N=202), FHR-BP (N=120), and PBC (N=200). Participants were assessed at ages 7, 11, and 15 using a semi-structured interview to evaluate PE and mental disorders. Results: At age 15, adolescents at FHR-SZ reported more PE than PBC over the past six months (current) and the past four years, while adolescents at FHR-BP only reported more current PE. PE reported at two or three timepoints (persistent PE) predicted any Axis I disorder in mid-adolescence, corresponding to three- (OR 2.9, 95% CI [1.5-5.7]) and 21-fold (OR 21.4, 95% CI [2.8-162.3]) increased risks, respectively. Persistent PE also predicted multimorbidity, with three- (OR 2.8, 95% CI [1.0-7.6]) and four-fold (OR 4.1, 95% CI [1.2-14.1]) increased risks, respectively. This was after adjustment for sex, early mental disorders, and familial risk. Conclusions: This study demonstrates a strong link between persistent PE and mid-adolescence mental disorders. Our findings emphasize PE as important risk markers for mental disorders during mid-adolescence and highlight the importance of monitoring children with PE before age 7 who develop persistent symptoms.

Objective: The Brief-cope questionnaire explore coping behavior. However, the underlying factor structure remains a subject of ongoing debate. Exploratory factor analyses (EFA) conducted across different populations have identified factor solutions ranging from two to fourteen factors. As of yet, the underlying factor structure of the Brief-cope has not been investigated in patients with seropositive rheumatoid arthritis (RA). Therefore, the aim of this study was to explore the underlying factor structure of the Brief-cope in a German population of seropositive RA. Methods: 216 outpatients with seropositive RA completed the Brief-cope. An EFA with principal axis factoring and Promax rotation was conducted. Results: EFA indicated a five-factor solution. The five-factor solution explained 51.95% of variance. The identified factors were: (1) problem-focused coping (Cronbach's = .851), (2) emotion-focused coping ( = .754), (3) maladaptive coping ( = .747), (4) religious coping ( = .851), and (5) substance-use coping ( = .869). Conclusion: A five-factor solution provided the most appropriate representation of the underlying factor structure of the Brief-cope in patients with seropositive RA. This factor structure may serve as a suitable basis for future analyses of Brief-cope data in comparable RA populations.

Background: Hippocampal sclerosis (HS) is a common cause of drug-resistant focal epilepsy (DRFE) and amenable to neurosurgical treatment. Detection relies on MRI but can be challenging. 7 Tesla (T) ultra-high field MRI and automated MRI post-processing tools have independently been shown to improve radiological diagnosis of HS. However, combining these approaches remains underexplored. This study evaluated whether AID-HS, a tool for HS detection developed using 3T MRI, generalises to 7T MRI data. Methods: We collated a dataset of paired 3T and 7T T1-weighted MRI from four epilepsy centres, including 23 patients with HS, 39 healthy controls, and 23 individuals with focal cortical dysplasia as disease controls. Histopathology served as the gold standard for defining HS where available (n=7), otherwise radiological findings (n=16). AID-HS was applied to images acquired at both field strengths, and sensitivity and specificity for detection and lateralisation of HS were compared. Additionally, agreement of hippocampal features across 3T and 7T was evaluated. Results: We found no evidence of a difference in performance of AID-HS between 3T and 7T. Sensitivity for detection of unilateral HS was 63% (12/19) at 3T and 68% (13/19) at 7T (McNemar's exact test p=1.0). Specificity in controls was 97% (60/62) at 3T and 100% (62/62) at 7T (p=0.5). Bilateral HS was correctly flagged in 3 of 4 cases using feature-based criteria, with high specificity in controls. Quantitative hippocampal features showed moderate to good agreement across field strengths (ICC 0.70 to 0.98), with small differences observed for volume and thickness estimates. Conclusion: AID-HS provides robust detection and lateralisation of HS across multiple 7T MRI centres, highlighting its potential to enhance lesion detection. Future work is needed to investigate whether models trained on 7T data can leverage the improved image quality for further gains in HS detection performance.

Background: Substance use is common among individuals with depression. Transcranial magnetic stimulation (TMS) is an effective treatment for depression, but current clinical guidelines have discouraged TMS treatment for individuals with depression and co-occurring substance use given concerns for limited efficacy. However, limited data exists on whether substance use affects response to TMS. Methods: Using electronic health record data from patients who received a standard course of TMS for major depressive disorder at an academic medical center, we investigated associations between substance use frequency and response to TMS, defined as change in Patient Health Questionnaire-9 (PHQ-9) scores. Substance use frequency was extracted for alcohol, cannabis, nicotine, stimulants, benzodiazepines, opioids, inhalants, psychedelics, and other drugs. We performed ANCOVA and multiple regression analyses to predict change in PHQ-9 score based on substance use frequency, controlling for pre-TMS PHQ-9 score, age, sex, and number of TMS sessions received. Results: We extracted data from 219 TMS courses. Alcohol was the substance used most commonly (34.2%), followed by prescription benzodiazepines (28.3%), and prescription stimulants (21.0%). Across all substance categories, substance use was not associated with change in PHQ-9 score (all p > 0.05, Cohens d=0.00 to 0.30). In multiple regression models to compare individual levels of substance use frequency (e.g., daily use vs. no use), level of substance use was not associated with change in PHQ-9 score (all p > 0.05). The range of plausible effects of substance use frequency on PHQ-9 change was generally below the minimal clinically important difference for PHQ-9, suggesting substance use was unlikely to have a meaningful clinical effect on antidepressant response to TMS. Conclusions: Low to moderate substance use does not have a clinically significant effect on antidepressant response to TMS. Low-level substance use should not exclude individuals with depression from receiving TMS.

Aim: The Patient Safety Screener-3 (PSS-3) is a brief suicide-risk screening tool. Item 1 of this scale assesses depressive mood but is not included in the total score. We examined the association of item 1 with depressive symptom severity and characterized the suicide-related risk captured by PSS-3 total positivity. Methods: We conducted a nationwide cross-sectional survey among resident physicians in Japan. Associations between PSS-3 item 1 endorsement and Patient Health Questionnaire-9 (PHQ-9) scores were evaluated using the Wilcoxon rank-sum test. Diagnostic performance of item 1 was evaluated using PHQ-9 positivity ([&ge;]10) as reference standard. We also compared Short-form Scale for Suicide Ideation (SIS-6) scores according to PSS-3 total positivity and PHQ-9 item 9 positivity. Results: A total of 1,844 participants were included. PSS-3 item 1 was endorsed by 443 physicians (24.0%), and 47 (2.5%) met the criteria for PSS-3 total positivity. Item 1 showed 79.3% sensitivity and 79.5% specificity for PHQ-9 positivity. SIS-6 scores were higher in the PSS-3 total-positive group than in the total-negative group (median [IQR], 6 [5-9] vs 0 [0-1]; p<0.001). The SIS-6 showed a higher area under the receiver operating characteristic curve (AUC) and Youden index using PSS-3 total positivity (AUC, 0.961; optimal cutoff, 3) than PHQ-9 item 9 positivity (AUC, 0.907; optimal cutoff, 2). Discussion: PSS-3 may support brief, simultaneous screening for depressive symptoms and suicide-related risk. Compared with PHQ-9 item 9, PSS-3 may capture a more severe spectrum of suicide-related risk. PSS-3 may facilitate identification of individuals requiring further mental health assessment.

Children and adolescents with hearing loss frequently encounter reduced auditory access and delayed language development, factors that may influence the maturation of executive functions. This study examined developmental differences in planning, a core executive function, in 98 children and adolescents with hearing loss or normal hearing aged 7 to18 years using the Tower of London task. Compared to normal hearing peers, participants with hearing loss made more unnecessary moves and rule violations and initiated problem-solving more rapidly, suggesting reduced preplanning efficiency and increased impulsivity. These group differences were most pronounced in adolescents, who showed faster initiation and greater movement inefficiency than age-matched normal hearing participants. Within the hearing loss group, adolescents displayed higher accuracy and longer initiation times than children, reflecting developmental improvements despite persistent gaps relative to hearing peers. Language development age did not alter the main effects. Findings indicate that reduced early auditory and language access may contribute to differences in planning development, highlighting the need for targeted executive functions support in educational and clinical settings for youth with hearing loss.

Background: Cognitive impairment is the leading cause of disability in schizophrenia with limited treatments. A major barrier to treatment development is the absence of reproducible, mechanistically grounded neural targets. Cross-sectional studies have identified dorsomedial prefrontal cortex (DMPFC)-somatomotor connectivity as a neural marker of cognitive performance on the Auditory Continuous performance task (ACPT), a measure of attention. To test the stability of this marker, we tested the relationship between DMPFC-somatomotor connectivity and ACPT performance in a longitudinal psychosis sample. Methods: Individuals with early psychosis (n=251) and matched controls (n=90) were enrolled and underwent resting-state neuroimaging and neurocognitive assessment. A subset completed longitudinal assessments over 2-4 years. We calculated DMPFC-somatomotor resting-state functional connectivity using a previously identified DMPFC region and a seed in the somatomotor cortex. We performed linear mixed effects models to predict ACPT performance based on connectivity, time, psychosis type, and their interaction. Results: In the psychosis sample, time (p=.0037) and affective psychosis diagnosis (p<.0001) predicted better ACPT performance. In a model predicting ACPT performance, we observed a significant interaction effect of DMPFC-somatomotor connectivity*psychosis subtype (p=.0079) such that DMPFC-somatomotor connectivity predicted ACPT performance only in individuals with non-affective psychosis (p=.0051). We then tested the specificity of this connectivity-cognitive performance relationship. In a model predicting DMPFC-somatomotor connectivity, only ACPT performance (p=.017), but not fluid cognition, was a significant predictor. Conclusions: DMPFC-somatomotor connectivity is longitudinally associated with cognitive performance in early psychosis. This relationship is strongest in nonaffective psychosis, suggesting a novel, reliable target for intervention for cognitive deficits in early psychosis.

The Autism Spectrum Quotient (AQ-50) is widely used to assess autistic traits, yet its Hungarian version has not been psychometrically evaluated. We assessed the reliability, factor structure, temporal stability, convergent validity, and clinical utility of the Hungarian AQ-50 and a revised translation (AQ-50-HU-R) in two samples (N1 = 1967; N2 = 423), including autistic and non-autistic participants. The AQ-50-HU-R showed high internal consistency and test-retest reliability. A bifactor model provided the best fit ({chi}2[1125] = 1650.433, p < 0.001; CFI = 0.991; TLI = 0.990; RMSEA = 0.033 [90% CI = 0.030-0.037]; SRMR = 0.083), with 71% of common variance attributable to a general autistic traits factor. The total score distinguished clinically verified autistic participants from participants reporting no ASD diagnosis (AUC = 0.906), with a cutoff of 25. Associations with ADOS scores were weak or nonsignificant. The AQ-50-HU-R is best interpreted as a reliable total-score screening measure, supporting referral for comprehensive autism assessment.

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.

A body of research suggests that autistic individuals are less likely to drink alcohol than neurotypicals. However, emerging studies support a link between autism and alcohol use. This complex relationship is also reflected in studies that have examined the genetic overlap between the two traits. However, it is unclear whether there is a direct causal relationship between them. To explore this, we applied a combination of polygenic score and Mendelian randomisation analyses using publicly available genome-wide summary statistics and phenotypic measures of autism and alcohol consumption from UK Biobank. LD score regression analyses did not provide evidence of a genetic correlation between genetic liability for autism and drinks consumed per week (rg=-0.08; CI95%=-0.19, 0.03). Further, findings from polygenic score analyses did not support an association between genetic liability for autism and overall monthly alcohol intake. Univariable Mendelian randomisation analyses showed little evidence for a total effect of autism, attention deficit hyperactivity disorder (ADHD) or depression on overall monthly alcohol consumption. Multivariable Mendelian randomisation analyses also showed little evidence of a direct effect of autism on drinks per week when controlling for ADHD and depression. It is plausible that genetic liability for autism does not directly increase the amount of alcohol consumed but instead operates via commonly co-occurring difficulties in the autistic community. However, our findings may be due to methodological shortcomings, including weak instruments biasing effects towards to the null. Consequently, results should be interpreted with caution and further research conducted to address these issues.

Objective To measure the accuracy of clinical coding, clinician review, and a locally deployed large language model (LLM) in identifying alcohol, drug, and self-harm involvement in emergency department (ED) attendances, and quantify prevalence. Design Two-phase diagnostic accuracy study. In a validation week, the identification strategies were assessed against a conflict-adjudicated reference standard (n=2,256); the LLM was then applied to n=105,096 annual attendances at the same site. Setting UK Type 1 Emergency Department treating patients [&ge;]16yrs. Main outcome measures Prevalence quantification compared with the reference standard; sensitivity, specificity, and balanced accuracy of each strategy; monthly identification rates and adjusted annual prevalence. Results The reference standard identified 12.1% of attendances as involving alcohol, drugs, or self-harm (coding 6.0%; clinician 10.0%, LLM 15.6%). LLM balanced accuracy matched or outperformed clinician review in all three domains (alcohol 0.942 v 0.930, p=0.635; drug 0.959 v 0.791, p<0.001; self-harm 0.982 v 0.908, p=0.004). Coding recorded 1.07 domains per identified patient against 1.32 in the reference standard. Adjusted annual prevalence corresponded to 12,890 domain involvements per year not identifiable in coded data. Subdomain classification found at least 81.6% of self-harm attendances required medical assessment for injury or overdose before psychiatric review. Conclusions Clinical coding identified fewer than half of presentations involving alcohol, drugs, and self-harm and rarely captured co-occurring domains; under-recording was present across a full year. A locally deployed LLM generated more complete structured data from existing clinical text within NHS infrastructure, at a scale which is not feasible for manual review.

Background: Bipolar disorder is associated with persistent social, cognitive, and functional impairment during euthymia, yet the neural mechanisms underlying these deficits remain unclear. Alterations to self-referential processing are a candidate mechanism, but existing electrophysiological studies rely on emotionally valenced paradigms that potentially confound self-processing with emotional biases. Methods: We analysed electroencephalography from 28 patients with bipolar disorder (type I or II) and 28 age- and sex-matched healthy controls during an emotionally neutral colour judgment task with self-related (preference) and non-self-related (similarity) conditions. Late positive potentials, temporal generalisation decoding, and frequency band decoding (theta, alpha, beta) were used to characterise the temporal dynamics and oscillatory correlates of self versus non-self processing. Results: Controls showed higher overall event-related potential amplitudes and greater self versus non-self differentiation than patients (condition by group interaction, 337 to 946 ms). Broadband temporal generalisation decoding revealed extensive cross-temporal generalisation of the self versus non-self representation in controls, spanning most of the trial, but no significant generalisation in patients. Frequency analyses showed that alpha and beta carried self versus non-self information in both groups, with broader extent in controls, and that anterior theta carried this information in patients but not controls. Exploratory correlations linked decoding measures to rumination and anxiety but not to manic symptoms. Conclusions: The neural representation distinguishing self-referential from externally guided processing was both smaller in amplitude and less temporally sustained in bipolar disorder. Reduced persistence is not detectable by conventional amplitude analyses, and may bear on the self-related and social cognitive difficulties reported in this population.

Generalization is a key cognitive process that allows humans to flexibly apply prior knowledge to guide new behaviors. Difficulties with generalization and flexibility are observed across neurodevelopmental disorders, especially autism, limiting adaptive function and quality of life. Cognitive-behavioral treatment benefits some but not all autistic individuals. As treatment requires application of learned skills to everyday life, variability in generalization ability may limit intervention success in autism. While cognitive substrates of learning and generalization are well established, their potential for explaining clinical outcomes is not known. Here, we combined a category learning task with computational modelling to distinguish two learning strategies underlying generalization -- prototype abstraction vs. exemplar memorization -- and tested whether individual differences in these learning strategies predicted real-world intervention outcomes in autistic youth. Fifty-four participants completed the category learning task at two pre-intervention timepoints, and then completed Unstuck and On Target:14-22 intervention targeting flexible problem solving, goal setting, and planning. We found that participants who consistently relied on prototype abstraction (N=26) were subsequently more likely to benefit from the intervention, showing improvement in parent- and self-reported flexibility. These findings identify prototype abstraction as a clinically relevant cognitive capacity that may help explain individual differences in intervention response and support the tailoring of interventions. More broadly, they demonstrate the value of linking basic cognitive mechanisms to clinical outcomes and may inform strategies to enhance the effectiveness of cognitive-behavioral interventions for youth with developmental disabilities.

Background: Major depressive disorder (MDD) is a severe mental illness associated with severe clinical consequences and substantial societal burden. It's characterized by immune-inflammatory dysregulation and immune sensitization. Objective: To determine whether in vitro ketamine attenuates phytohemagglutinin (PHA)/lipopolysaccharide (LPS)-induced immune sensitization in patients with MDD and healthy controls (HCs). Methods: Whole blood from 18 patients with MDD and 18 HCs was stimulated with PHA/LPS and exposed to ketamine (0.3 M, 0.6 M, and 6 M) for 72 hours. Cytokines, chemokines, growth factors, and composite immune profiles, including M1/M2 macrophages, T helper (Th)1/2/17, the immune-inflammatory response system (IRS), and compensatory immunoregulatory system (CIRS), were synthesized and determined. Results: Under PHA and LPS stimulation in vitro, the MDD group exhibited markedly elevated immune profiles, including M1, M2, Th1, Th2, Th17, IRS, CIRS, chemokines, and growth factors, consistent with immune sensitization. Significant group-by-treatment interactions were observed for Th1-Th2, M2, growth factors, IL-12(p70), M1, and chemokines. Ketamine produced minimal changes in HCs but broader suppression in MDD, particularly at the highest concentration, without normalizing the sensitized immune phenotype. Among the immune markers with no notable group-by-treatment interactions, ketamine exerted diagnosis-independent effects, decreasing MIP-1{beta}, IL-1&{beta}, Th1, TNF-{beta} IRS, IFN-{gamma}, and IL-2 compared to the control condition. Conclusions: Ketamine exhibited two distinct immunoregulatory patterns: selective, disease-dependent attenuation of sensitized immune pathways and broader, diagnosis-independent suppression of the stimulated immune response, predominantly at higher concentrations. However, these effects were insufficient to normalize the immune-sensitized phenotype of MDD.

Background: Stress research in nursing education has largely focused on distress, stressors, and negative outcomes, although challenging experiences may also support motivation, confidence, learning, and growth when appraised positively. Objective: To develop and evaluate the psychometric properties of the Nursing Student Positive Stress Scale (NSPSS). Design: A methodological instrument development and psychometric evaluation study. Methods: The NSPSS was developed using a deductive, theory-driven approach informed by the transactional theory of stress and coping and positive psychology perspectives. Content validity was assessed by an international nursing expert panel. Psychometric evaluation used national survey data from nursing students in New Zealand. Of 539 responses, 507 were analysed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted using separate subsamples. Internal consistency was assessed using Cronbach's alpha and McDonald's omega, and convergent validity through correlation with Perceived Stress Scale-10 scores. Results: Content validity was strong (I-CVI = .88-1.00; S-CVI/Ave = .975; S-CVI/UA = .800). EFA identified a dominant factor explaining 41.38% of variance (loadings = .528-.735). CFA supported a two-context Academic and Clinical Positive Stress model with correlated residuals between five parallel item pairs, chi-square(29) = 60.49, CFI = .970, TLI = .954, RMSEA = .063, SRMR = .065. Internal consistency was good (alpha = .839; omega = .843). NSPSS scores correlated negatively with PSS-10 scores (r = -.298, p < .001). Conclusion: The NSPSS demonstrated strong content validity, preliminary evidence of structural and convergent validity, and good internal consistency reliability for assessing positive stress appraisal among nursing students. Further validation in independent samples is warranted.

Health facilities (HFs) routinely administer medicines and are expected to ensure patient safety by detecting, reporting, investigating, and analysing adverse events following exposure to drugs (AEFED). This study aimed to assess the implementation of pharmacovigilance activities in referral and regional health facilities in Cameroon and to identify pharmacovigilance training needs among healthcare personnel (HP). This was a cross-sectional descriptive study targeting referral and regional health facilities and healthcare personnel involved in patient care and pharmacovigilance activities in Cameroon. Health facilities were selected using stratified purposive sampling, while healthcare personnel were selected through exhaustive sampling. Data were collected using semi-structured electronic questionnaires administered face-to-face by trained enumerators. The questionnaires assessed the organization, resources, and implementation of pharmacovigilance activities at health facilities, as well as healthcare personnel knowledge of pharmacovigilance concepts, previous training, and perceived training needs. Of the 14 eligible health facilities, 10 (71.4%) consented to participate in the study. Of the 10 health facilities, 4 (40.0%) had an established pharmacovigilance unit, while 3 (30.0%) reported conducting neither detection nor notification activities. Among the 261 healthcare personnel approached, 214 (81.9%) participated. Only 41.6% had needed knowledge to detect an adverse event, while 72.9% were aware of adverse event notification procedures. Previous exposure to pharmacovigilance training was reported by 37.9% of healthcare personnel, and all participants expressed a need for additional training, particularly on national pharmacovigilance regulations (69.2%), organization of the pharmacovigilance system (67.3%), and adverse event detection (67.3%). The main reported challenges by healthcare personnel in the implementation of pharmacovigilance activities included insufficient budget allocation, limited access to pharmacovigilance training, lack of pharmacovigilance guidelines and insufficient qualified human resources. Pharmacovigilance implementation in referral and regional health facilities in Cameroon remains limited, with gaps in organizational structures, resources, healthcare personnel knowledge, and training. Strengthening pharmacovigilance systems through improved facility capacity, availability of essential tools, and targeted healthcare personnel training is needed to enhance drug safety surveillance.

Communities exposed to flooding can experience markedly different mental health outcomes, yet conventional resilience indicators capture only part of the social and contextual conditions that may explain this variation. This study develops a multilevel and predictive framework for examining community resilience and depressive symptoms following flood exposure in Indonesia. Data were drawn from 20,303 respondents aged 15 years and older nested within 312 communities in the Indonesia Family Life Survey (IFLS-5). Depressive symptoms were assessed using the 10-item Centre for Epidemiologic Studies Depression Scale (CES-D-10), with Rasch Partial Credit Model calibration used to examine measurement properties. Bayesian multilevel models quantified between-community heterogeneity and assessed how far observable structural resources accounted for this variation. Community resilience was represented through two complementary constructs: structural resilience, based on observable socioeconomic and social-capital resources, and Latent Community Protective Capacity (LCPC), a model-derived proxy for residual contextual variation in depressive-symptom risk. Approximately 6 percent of variation was attributable to between-community differences, while observable structural resources explained only part of this heterogeneity. Structural resilience and LCPC were weakly correlated (r = 0.155). Moderation analyses provided no clear evidence that structural resilience altered the flood-depression association, while LCPC showed a directionally consistent but uncertain buffering pattern. Predictive models incorporating community-level information improved discrimination, with the best-performing model reaching an ROC-AUC of approximately 0.71. The findings suggest that observable resource-based indices provide an incomplete account of community-level mental health vulnerability and that residual contextual measures may provide complementary information, while requiring cautious interpretation and independent validation.

Background: The Centiloid (CL) scale standardizes global amyloid PET quantification and is widely used to define amyloid positivity. As a global summary measure, however, CL may not fully reflect the regional distribution of amyloid deposition, which can carry additional prognostic information about the rate of cognitive decline. Objective: To develop and externally validate a fixed, regional amyloid PET composite score that complements CL for predicting cognitive decline in Alzheimer's disease. Methods: The Regional Amyloid PET Score (RAPS) was derived from 82 FreeSurfer regions using machine learning with bootstrap stability selection to predict the rate of change in CDR-Sum of Boxes (CDR-SB) in 433 amyloid-positive ADNI [18F]florbetapir participants. The fixed nine-region weights were applied without retraining in a cross-tracer ADNI [18F]florbetaben subset (N = 71; largely overlapping the discovery participants) and two external validation cohorts, NACC SCAN (N = 1531; four tracers) and OASIS-3 (N = 428). Results: RAPS comprised nine regions. In ADNI, RAPS correlated more strongly with CDR-SB slope than CL and showed higher discrimination of rapid decliners (AUC 0.813 vs 0.713). Performance was directionally consistent across validation cohorts; in NACC SCAN, RAPS and CL independently predicted clinical progression. Cross-cohort meta-analysis of the three independent cohorts supported incremental discrimination beyond CL (pooled {Delta}AUC +0.066; I2 = 0%). Conclusions: RAPS, a fixed regional amyloid PET-derived score, may complement CL for prognostic stratification in Alzheimer's disease research.

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.

Objectives: To estimate the prevalence of Post-Exertional Malaise (PEM) among adults with prior COVID-19 and associated mental health and disability outcomes. Methods: We conducted a cross-sectional analysis of data from a survey of 9,620 adults with prior COVID-19 in New York City, collected May - June 2024. PEM was measured with the DePaul Symptom Questionnaire - Post Exertional Malaise, categorized by symptom duration (< 14 vs. [&ge;]14 hours). Weighted prevalence estimates were stratified by socio-demographic and clinical characteristics. Modified Poisson regression was used to assess the association of PEM with depression, anxiety, and disability. Results: The prevalence of PEM symptoms was 20.9% overall and 4.0% with symptom duration [&ge;]14 hours, representing over 800,000 New Yorkers affected and over 150,000 who meet a diagnostic criterion for ME/CFS. PEM prevalence was higher among women, transgender and non-binary adults, people of color, and lower educational attainment, chronic comorbidities, or disabilities. PEM was associated with 3 - 4 times higher prevalence of mental health outcomes and 4 - 5 times higher disability scores. Conclusions: PEM symptoms were common and strongly associated with disability and adverse mental health. Screening, pathways to care, and supportive policies are needed to mitigate long-term consequences, particularly among marginalized populations.