657 research outputs found

    Is Incarceration a Contributor to Health Disparities? Access to Care of Formerly Incarcerated Adults

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    Despite the disproportionate prevalence of incarceration in communities of color, few studies have examined its contribution to health disparities. We examined whether a lifetime history of incarceration is associated with recent access to medical and dental care. We performed a secondary data analysis of the 2007 Los Angeles County Health Survey, a population-based random-digit-dialing telephone survey of county households. Any history of incarceration in a prison/jail/detention center as an adult was assessed for a random subsample. Bivariate and multivariate logistic regression analyses examined whether incarceration history was associated with access to care, controlling for other characteristics. Ten percent of our study population reported a history of incarceration. While persons with an incarceration history were similar to their peers with regard to health and insurance status, their access to medical and dental care was worse. Incarceration history was independently associated with disparities in access to care. Interventions to improve the health of communities affected by high rates of incarceration could include efforts that enable access to care for formerly incarcerated adults

    Gene-environment correlations and causal effects of childhood maltreatment on physical and mental health: a genetically informed approach.

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    BACKGROUND: Childhood maltreatment is associated with poor mental and physical health. However, the mechanisms of gene-environment correlations and the potential causal effects of childhood maltreatment on health are unknown. Using genetics, we aimed to delineate the sources of gene-environment correlation for childhood maltreatment and the causal relationship between childhood maltreatment and health. METHODS: We did a genome-wide association study meta-analysis of childhood maltreatment using data from the UK Biobank (n=143 473), Psychiatric Genomics Consortium (n=26 290), Avon Longitudinal Study of Parents and Children (n=8346), Adolescent Brain Cognitive Development Study (n=5400), and Generation R (n=1905). We included individuals who had phenotypic and genetic data available. We investigated single nucleotide polymorphism heritability and genetic correlations among different subtypes, operationalisations, and reports of childhood maltreatment. Family-based and population-based polygenic score analyses were done to elucidate gene-environment correlation mechanisms. We used genetic correlation and Mendelian randomisation analyses to identify shared genetics and test causal relationships between childhood maltreatment and mental and physical health conditions. FINDINGS: Our meta-analysis of genome-wide association studies (N=185 414) identified 14 independent loci associated with childhood maltreatment (13 novel). We identified high genetic overlap (genetic correlations 0·24-1·00) among different maltreatment operationalisations, subtypes, and reporting methods. Within-family analyses provided some support for active and reactive gene-environment correlation but did not show the absence of passive gene-environment correlation. Robust Mendelian randomisation suggested a potential causal role of childhood maltreatment in depression (unidirectional), as well as both schizophrenia and ADHD (bidirectional), but not in physical health conditions (coronary artery disease, type 2 diabetes) or inflammation (C-reactive protein concentration). INTERPRETATION: Childhood maltreatment has a heritable component, with substantial genetic correlations among different operationalisations, subtypes, and retrospective and prospective reports of childhood maltreatment. Family-based analyses point to a role of active and reactive gene-environment correlation, with equivocal support for passive correlation. Mendelian randomisation supports a (primarily bidirectional) causal role of childhood maltreatment on mental health, but not on physical health conditions. Our study identifies research avenues to inform the prevention of childhood maltreatment and its long-term effects. FUNDING: Wellcome Trust, UK Medical Research Council, Horizon 2020, National Institute of Mental Health, and National Institute for Health Research Biomedical Research Centre

    Transcriptional profiling of eosinophil subsets in interleukin-5 transgenic mice

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    Eosinophils are important in fighting parasitic infections and are implicated in the pathogenesis of asthma and allergy. IL-5 is a critical regulator of eosinophil development, controlling proliferation, differentiation, and maturation of the lineage. Mice that constitutively express IL-5 have in excess of 10-fold more eosinophils in the hematopoietic organs than their wild type (WT) counterparts. We have identified that much of this expansion is in a population of Siglec-F high eosinophils, which are rare in WT mice. In this study, we assessed transcription in myeloid progenitors, eosinophil precursors, and Siglec-F medium and Siglec-F high eosinophils from IL-5 transgenic mice and in doing so have created a useful resource for eosinophil biologists. We have then utilized these populations to construct an eosinophil trajectory based on gene expression and to identify gene sets that are associated with eosinophil lineage progression. Cell cycle genes were significantly associated with the trajectory, and we experimentally demonstrate an increasing trend toward quiescence along the trajectory. Additionally, we found gene expression changes associated with constitutive IL-5 signaling in eosinophil progenitors, many of which were not observed in eosinophils

    Multiple ITS Copies Reveal Extensive Hybridization within Rheum (Polygonaceae), a Genus That Has Undergone Rapid Radiation

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    During adaptive radiation events, characters can arise multiple times due to parallel evolution, but transfer of traits through hybridization provides an alternative explanation for the same character appearing in apparently non-sister lineages. The signature of hybridization can be detected in incongruence between phylogenies derived from different markers, or from the presence of two divergent versions of a nuclear marker such as ITS within one individual.In this study, we cloned and sequenced ITS regions for 30 species of the genus Rheum, and compared them with a cpDNA phylogeny. Seven species contained two divergent copies of ITS that resolved in different clades from one another in each case, indicating hybridization events too recent for concerted evolution to have homogenised the ITS sequences. Hybridization was also indicated in at least two further species via incongruence in their position between ITS and cpDNA phylogenies. None of the ITS sequences present in these nine species matched those detected in any other species, which provides tentative evidence against recent introgression as an explanation. Rheum globulosum, previously indicated by cpDNA to represent an independent origin of decumbent habit, is indicated by ITS to be part of clade of decumbent species, which acquired cpDNA of another clade via hybridization. However decumbent and glasshouse morphology are confirmed to have arisen three and two times, respectively.These findings suggested that hybridization among QTP species of Rheum has been extensive, and that a role of hybridization in diversification of Rheum requires investigation

    Discrepancies between survey and administrative data on the use of mental health services in the general population: findings from a study conducted in Québec

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    <p>Abstract</p> <p>Background</p> <p>Population surveys and health services registers are the main source of data for the management of public health. Yet, the validity of survey data on the use of mental health services has been questioned repeatedly due to the sensitive nature of mental illness and to the risk of recall bias. The main objectives of this study were to compare data on the use of mental health services from a large scale population survey and a national health services register and to identify the factors associated with the discrepancies observed between these two sources of data.</p> <p>Methods</p> <p>This study was based on the individual linkage of data from the cycle 1.2 of the Canadian Community Health Survey (CCHS-1.2) and from the health services register of the Régie de l'assurance maladie du Québec (RAMQ). The RAMQ is the governmental agency managing the Quebec national health insurance program. The analyses mostly focused on the 637 Quebecer respondents who were recorded as users of mental health services in the RAMQ and who were self-reported users or non users of these services in the CCHS-1.2.</p> <p>Results</p> <p>Roughly 75%, of those recorded as users of mental health services users in the RAMQ's register did not report using mental health services in the CCHS-1.2. The odds of disagreement between survey and administrative data were higher in seniors, individuals with a lower level of education, legal or de facto spouses and mothers of young children. They were lower in individuals with a psychiatric disorder and in frequent and more recent users of mental health services according to the RAMQ's register.</p> <p>Conclusions</p> <p>These findings support the hypotheses that social desirability and recall bias are likely to affect the self-reported use of mental health services in a population survey. They stress the need to refine the investigation of mental health services in population surveys and to combine survey and administrative data, whenever possible, to obtain an optimal estimation of the population need for mental health care.</p

    Cornucopia: Temporal safety for CHERI heaps

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    Use-after-free violations of temporal memory safety continue to plague software systems, underpinning many high-impact exploits. The CHERI capability system shows great promise in achieving C and C++ language spatial memory safety, preventing out-of-bounds accesses. Enforcing language-level temporal safety on CHERI requires capability revocation, traditionally achieved either via table lookups (avoided for performance in the CHERI design) or by identifying capabilities in memory to revoke them (similar to a garbage-collector sweep). CHERIvoke, a prior feasibility study, suggested that CHERI’s tagged capabilities could make this latter strategy viable, but modeled only architectural limits and did not consider the full implementation or evaluation of the approach. Cornucopia is a lightweight capability revocation system for CHERI that implements non-probabilistic C/C++ temporal memory safety for standard heap allocations. It extends the CheriBSD virtual-memory subsystem to track capability flow through memory and provides a concurrent kernel-resident revocation service that is amenable to multi-processor and hardware acceleration. We demonstrate an average overhead of less than 2% and a worst-case of 8.9% for concurrent revocation on compatible SPEC CPU2006 benchmarks on a multi-core CHERI CPU on FPGA, and we validate Cornucopia against the Juliet test suite’s corpus of temporally unsafe programs. We test its compatibility with a large corpus of C programs by using a revoking allocator as the system allocator while booting multi-user CheriBSD. Cornucopia is a viable strategy for always-on temporal heap memory safety, suitable for production environments.This work was supported by the Defense Advanced Research Projects Agency (DARPA) and the Air Force Research Laboratory (AFRL), under contracts FA8750-10-C-0237 (“CTSRD”) and HR0011-18-C-0016 (“ECATS”). We also acknowledge the EPSRC REMS Programme Grant (EP/K008528/1), the ABP Grant (EP/P020011/1), the ERC ELVER Advanced Grant (789108), the Gates Cambridge Trust, Arm Limited, HP Enterprise, and Google, Inc

    Determining the impact of an artificial intelligence tool on the management of pulmonary nodules detected incidentally on CT (DOLCE) study protocol: a prospective, non-interventional multicentre UK study

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    \ua9 Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. INTRODUCTION: In a small percentage of patients, pulmonary nodules found on CT scans are early lung cancers. Lung cancer detected at an early stage has a much better prognosis. The British Thoracic Society guideline on managing pulmonary nodules recommends using multivariable malignancy risk prediction models to assist in management. While these guidelines seem to be effective in clinical practice, recent data suggest that artificial intelligence (AI)-based malignant-nodule prediction solutions might outperform existing models. METHODS AND ANALYSIS: This study is a prospective, observational multicentre study to assess the clinical utility of an AI-assisted CT-based lung cancer prediction tool (LCP) for managing incidental solid and part solid pulmonary nodule patients vs standard care. Two thousand patients will be recruited from 12 different UK hospitals. The primary outcome is the difference between standard care and LCP-guided care in terms of the rate of benign nodules and patients with cancer discharged straight after the assessment of the baseline CT scan. Secondary outcomes investigate adherence to clinical guidelines, other measures of changes to clinical management, patient outcomes and cost-effectiveness. ETHICS AND DISSEMINATION: This study has been reviewed and given a favourable opinion by the South Central-Oxford C Research Ethics Committee in UK (REC reference number: 22/SC/0142).Study results will be available publicly following peer-reviewed publication in open-access journals. A patient and public involvement group workshop is planned before the study results are available to discuss best methods to disseminate the results. Study results will also be fed back to participating organisations to inform training and procurement activities. TRIAL REGISTRATION NUMBER: NCT05389774

    Place preference induced by nucleus accumbens amphetamine is impaired by local blockade of Group II metabotropic glutamate receptors in rats

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    BACKGROUND: The nucleus accumbens (NAc) plays a critical role in amphetamine-produced conditioned place preference (CPP). In previous studies, NAc basal and amphetamine-produced DA transmission was altered by Group II mGluR agents. We tested whether NAc amphetamine CPP depends on Group II mGluR transmission. RESULTS: NAc injections (0.5 μl/side) of the Group II mGluR antagonist (2 S)- a-ethylglutamic acid (EGLU: 0.01–0.8 μg but not 0.001 μg) impaired CPP. The drug did not block the acute locomotor effect of amphetamine. CONCLUSION: Results suggest that Group II mGluRs may be necessary for the establishment of NAc amphetamine-produced CPP. These receptors may also mediate other forms of reward-related learning dependent on this structure

    Cold gas accretion in galaxies

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    Evidence for the accretion of cold gas in galaxies has been rapidly accumulating in the past years. HI observations of galaxies and their environment have brought to light new facts and phenomena which are evidence of ongoing or recent accretion: 1) A large number of galaxies are accompanied by gas-rich dwarfs or are surrounded by HI cloud complexes, tails and filaments. It may be regarded as direct evidence of cold gas accretion in the local universe. It is probably the same kind of phenomenon of material infall as the stellar streams observed in the halos of our galaxy and M31. 2) Considerable amounts of extra-planar HI have been found in nearby spiral galaxies. While a large fraction of this gas is produced by galactic fountains, it is likely that a part of it is of extragalactic origin. 3) Spirals are known to have extended and warped outer layers of HI. It is not clear how these have formed, and how and for how long the warps can be sustained. Gas infall has been proposed as the origin. 4) The majority of galactic disks are lopsided in their morphology as well as in their kinematics. Also here recent accretion has been advocated as a possible cause. In our view, accretion takes place both through the arrival and merging of gas-rich satellites and through gas infall from the intergalactic medium (IGM). The infall may have observable effects on the disk such as bursts of star formation and lopsidedness. We infer a mean ``visible'' accretion rate of cold gas in galaxies of at least 0.2 Msol/yr. In order to reach the accretion rates needed to sustain the observed star formation (~1 Msol/yr), additional infall of large amounts of gas from the IGM seems to be required.Comment: To appear in Astronomy & Astrophysics Reviews. 34 pages. Full-resolution version available at http://www.astron.nl/~oosterlo/accretionRevie

    The impact of negative selection on thymocyte migration in the medulla

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    Developing thymocytes are screened for self-reactivity before they exit the thymus, but how thymocytes scan the medulla for self antigens is unclear. Using two-photon microscopy, we observed that medullary thymocytes migrated rapidly and made frequent, transient contacts with dendritic cells. In the presence of a negative selecting ligand, thymocytes slowed, became confined to areas of approximately 30 mum in diameter and had increased contact with dendritic cells surrounding confinement zones. One third of polyclonal medullary thymocytes also showed confined, slower migration and may correspond to autoreactive thymocytes. Our data suggest that many autoreactive thymocytes do not undergo immediate arrest and death after encountering a negative selecting ligand but instead adopt an altered migration program while remaining in the medullary microenvironment
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