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Objective: Prior studies examining small samples of symptomatic former professional football players suggest that earlier age of first exposure (AFE) to American football is associated with adverse later life health outcomes. This study examined a larger, more representative sample of former professional American football players to assess associations between AFE before age 12 (AFE < 12) and clinical outcomes compared with those who started at age 12 or older (AFE 12 +)., Methods: Former professional American football players who completed a questionnaire were dichotomized into AFE < 12 and AFE 12 + . AFE groups were compared on outcomes including symptoms of depression and anxiety, perceived cognitive difficulties, neurobehavioral dysregulation, and self-reported health conditions (e.g., headaches, sleep apnea, hypertension, chronic pain, memory loss, dementia/Alzheimer's disease, and others)., Results: Among 4189 former professional football players (aged 52 ± 14 years, 39% self-reported as Black), univariable associations with negligible effect sizes were seen with AFE < 12, depressive symptoms (p = 0.03; η 2  = 0.001), and anxiety-related symptoms (p = 0.02; η 2  = 0.001) only. Multivariable models adjusting for age, race, body mass index, playing position, number of professional seasons, and past concussion burden revealed no significant relationships between AFE < 12 and any outcome. Linear and non-linear models examining AFE as a continuous variable showed similar null results., Conclusions: In a large cohort of former professional American-style football players, AFE was not independently associated with adverse later life outcomes. These findings are inconsistent with smaller studies of former professional football players. Studies examining AFE in professional football players may have limited utility and generalizability regarding policy implications for youth sports., (© 2024. The Author(s).)

Background: Childbirth posttraumatic stress disorder (PTSD) poses significant challenges, impacting both mothers and infants. This work investigates whether childbirth PTSD is less recognized than PTSD caused by other index events., Methods: In two preregistered experimens we investigated the public and professional perception of PTSD resulting from childbirth compared to other traumatic events (i.e., sexual assault, car accident, terror attack, and an earthquake)., Findings: Study 1, conducted among the general population in the U.S. revealed that a woman depicted as experiencing PTSD symptoms due to childbirth, was less likely to be recognized as suffering from PTSD than a woman with the same symptoms resulting from other traumatic events. Study 2 demonstrated that mental health professionals worldwide are also less inclined to diagnose PTSD when childbirth is the index event in comparison to other index events., Discussion: Due to the importance of social recognition in the treatment of PTSD, the findings underscore the urgent need for heightened awareness and education regarding childbirth PTSD to bridge the recognition gap among the general population and mental health professionals., Competing Interests: Declaration of Competing Interest We hereby declare that we have no potential conflicts of interest with respect to the authorship or the publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Beliefs that the US 2020 Presidential election was fraudulent are prevalent despite substantial contradictory evidence. Why are such beliefs often resistant to counter-evidence? Is this resistance rational, and thus subject to evidence-based arguments, or fundamentally irrational? Here we surveyed 1,642 Americans during the 2020 vote count, testing fraud belief updates given hypothetical election outcomes. Participants' fraud beliefs increased when their preferred candidate lost and decreased when he won, and both effects scaled with partisan preferences, demonstrating partisan asymmetry (desirability effects). A Bayesian model of rational updating of a system of beliefs-beliefs in the true vote winner, fraud prevalence and beneficiary of fraud-accurately accounted for this partisan asymmetry, outperforming alternative models of irrational, motivated updating and models lacking the full belief system. Partisan asymmetries may not reflect motivated reasoning, but rather rational attributions over multiple potential causes of evidence. Changing such beliefs may require targeting multiple key beliefs simultaneously rather than direct debunking attempts., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Importance: There are few studies assessing the association of tumor mutational burden (TMB) and clinical outcomes in a large cohort of patients with diverse advanced cancers., Objective: To clinically validate a TMB biomarker from a next-generation sequencing targeted gene panel assay., Design, Setting, and Participants: A prespecified cohort study using the deidentified clinicogenomic Tempus database of patients sequenced between 2018 and 2022, which contained retrospective, observational data originating from 300 cancer sites including 199 community sites and 101 academic sites. Patients with advanced solid tumors across 8 cancer types and more than 20 histologies, sequenced with Tempus xT who were treated with immune checkpoint inhibitors (ICIs) in the first-line or second-line setting were included. Data were analyzed from September 2018 to August 2022., Exposure: Treatment with US Food and Drug Administration (FDA)-approved antiprogrammed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) ICI and/or in combination with a cytotoxic T-lymphocyte-associated protein-4 ICI., Main Outcomes and Measures: The primary outcome was the association of tumor mutational burden (TMB) binary category (high [≥10 mut/mb] vs low) with overall survival (OS) in patients treated with ICIs. Secondary outcomes were progression-free survival (PFS), and time to progression (TTP)., Results: In the evaluable cohort of 674 patients, the median (IQR) age was 69.4 (28.6-89.8) years, 271 patients (40.2%) were female, and 435 patients (64.5%) were White. The most common advanced cancers were non-small cell lung cancer (330 patients [49.0%]), followed by bladder cancer (148 patients [22.0%]), and head and neck squamous cell carcinoma (96 patients [14.8%]). Median (IQR) follow-up was 7.2 (3.2-14.1) months. High TMB (TMB-H) cancers (206 patients [30.6%]) were significantly associated with longer OS than low TMB (TMB-L) cancers (hazard ratio [HR], 0.72; upper confidence bound [UCB], 0.91; P = .01). In a prospective subset of 403 patients treated with ICIs after TMB testing, TMB-H cancers (135 patients [33.5%]) were significantly associated with longer OS (HR, 0.61; UCB, 0.84; P = .005), PFS (HR, 0.62; UCB, 0.82; P = .003), and TTP (HR, 0.67; UCB, 0.92; P = .02) than TMB-L cancers. An overall survival benefit was seen regardless of the type of ICI used (pembrolizumab, 339 patients; HR, 0.67; UCB, 0.94; P = .03), other ICIs (64 patients; HR, 0.37; UCB, 0.85; P = .03), and after adjusting for PD-L1 and microsatellite stability status (403 patients; HR = 0.67; UCB, 0.92; P = .02)., Conclusions and Relevance: In this cohort study of patients with advanced solid tumors treated with ICIs in diverse clinics, TMB-H cancers were significantly associated with improved clinical outcomes compared with TMB-L cancers.

Pneumococcal conjugate vaccines (PCVs) have been used in the United States since 2000. To assess the cumulative 20-year effect of PCVs on invasive pneumococcal disease (IPD) incidence among children <5 years of age, we analyzed Active Bacterial Core Surveillance data, conducted a literature review, and modeled expected and observed disease. We found that PCVs have averted >282,000 cases of IPD, including ≈16,000 meningitis, ≈172,000 bacteremia, and ≈55,000 bacteremic pneumonia cases. In addition, vaccination has prevented 97 million healthcare visits for otitis media, 438,914-706,345 hospitalizations for pneumonia, and 2,780 total deaths. IPD cases declined 91%, from 15,707 in 1997 to 1,382 in 2019. Average annual visits for otitis media declined 41%, from 78 visits/100 children before PCV introduction to 46 visits/100 children after PCV13 introduction. Annual pneumonia hospitalizations declined 66%-79%, from 110,000-175,000 in 1997 to 37,000 in 2019. These findings confirm the substantial benefits of PCVs for preventing IPD in children.

Background: Rheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients., Methods: Medicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models., Results: 30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46-3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%. Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10-0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001-0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models., Conclusion: A prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.

Previous studies suggested that the 2016 presidential elections gave rise to pathological levels of election-related distress in liberal Americans; however, it has also been suggested that the public discourse and the professional discourse have increasingly overgeneralized concepts of trauma and psychopathology. In light of this, in the current research, we utilized an array of big data measures and asked whether a political loss in a participatory democracy can indeed lead to psychopathology. We observed that liberals report being more depressed when asked directly about the effects of the election; however, more indirect measures show a short-lived or nonexistent effect. We examined self-report measures of clinical depression with and without a reference to the election (Studies 1A & 1B), analyzed Twitter discourse and measured users' levels of depression using a machine-learning-based model (Study 2), conducted time-series analysis of depression-related search behavior on Google (Study 3), examined the proportion of antidepressants consumption in Medicaid data (Study 4), and analyzed daily surveys of hundreds of thousands of Americans (Study 5), and saw that at the aggregate level, empirical data reject the accounts of "Trump Depression." We discuss possible interpretations of the discrepancies between the direct and indirect measures. The current investigation demonstrates how big-data sources can provide an unprecedented view of the psychological consequences of political events and sheds light on the complex relationship between the political and the personal spheres. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Repetitive mild traumatic brain injury in American football players has garnered increasing public attention following reports of chronic traumatic encephalopathy, a progressive tauopathy. While the mechanisms underlying repetitive mild traumatic brain injury-induced neurodegeneration are unknown and antemortem diagnostic tests are not available, neuropathology studies suggest a pathogenic role for microvascular injury, specifically blood-brain barrier dysfunction. Thus, our main objective was to demonstrate the effectiveness of a modified dynamic contrast-enhanced MRI approach we have developed to detect impairments in brain microvascular function. To this end, we scanned 42 adult male amateur American football players and a control group comprising 27 athletes practicing a non-contact sport and 26 non-athletes. MRI scans were also performed in 51 patients with brain pathologies involving the blood-brain barrier, namely malignant brain tumours, ischaemic stroke and haemorrhagic traumatic contusion. Based on data from prolonged scans, we generated maps that visualized the permeability value for each brain voxel. Our permeability maps revealed an increase in slow blood-to-brain transport in a subset of amateur American football players, but not in sex- and age-matched controls. The increase in permeability was region specific (white matter, midbrain peduncles, red nucleus, temporal cortex) and correlated with changes in white matter, which were confirmed by diffusion tensor imaging. Additionally, increased permeability persisted for months, as seen in players who were scanned both on- and off-season. Examination of patients with brain pathologies revealed that slow tracer accumulation characterizes areas surrounding the core of injury, which frequently shows fast blood-to-brain transport. Next, we verified our method in two rodent models: rats and mice subjected to repeated mild closed-head impact injury, and rats with vascular injury inflicted by photothrombosis. In both models, slow blood-to-brain transport was observed, which correlated with neuropathological changes. Lastly, computational simulations and direct imaging of the transport of Evans blue-albumin complex in brains of rats subjected to recurrent seizures or focal cerebrovascular injury suggest that increased cellular transport underlies the observed slow blood-to-brain transport. Taken together, our findings suggest dynamic contrast-enhanced-MRI can be used to diagnose specific microvascular pathology after traumatic brain injury and other brain pathologies., (© The Author(s) (2020). Published by Oxford University Press on behalf of the Guarantors of Brain.)