1,771 research outputs found

    Nowhere to go: How stigma limits the options of female drug users after release from jail

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    Background Drug and alcohol using women leaving prison or jail face many challenges to successful re-integration in the community and are severely hampered in their efforts by the stigma of drug or alcohol use compounded by the stigma of incarceration. Methods This qualitative study is based on individual semi-structured interviews and focus groups with 17 women who had recently left jail about the challenges they faced on reentry. Results Our analysis identified three major themes, which are related by the overarching influence of stigma: survival (jobs and housing), access to treatment services, and family and community reintegration. Conclusion Stigma based on drug use and incarceration works to increase the needs of women for health and social services and at the same time, restricts their access to these services. These specific forms of stigma may amplify gender and race-based stigma. Punitive drug and social policies related to employment, housing, education, welfare, and mental health and substance abuse treatment make it extremely difficult for women to succeed

    Enrichment of Genetic Variants for Rheumatoid Arthritis within T-Cell and NK-Cell Enhancer Regions

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    To identify disease-causative variants, we intersected the published results of a metaanalysis of genome-wide association studies (GWAS) for rheumatoid arthritis (RA) with the set of enhancer regions for 71 primary cell types that was provided by the FANTOM consortium. We first retrieved all single nucleotide polymorphisms (SNPs) that are associated (P \u3c 5 x 10(8)) with RA in the GWAS meta-analysis and that are located in any of these enhancer regions. After excluding the major histocompatibility complex (MHC) region, we identified 50 such RA-associated SNPs that are located in enhancer regions. Enhancer sets from different cell types were then compared with each other for their number of RA-associated SNPs by permutation analysis. This analysis showed that RA-associated SNPs are preferentially located in enhancers from several immunological cell types. In particular, we see a strong relative enrichment in enhancer regions that are active in T cells (P \u3c 0.001) and NK cells (P \u3c 0.001). Several loci display multiple RA-associated SNPs in tight linkage disequilibrium that are located within the same or neighboring enhancers. These haplotypes may have a greater likelihood to influence enhancer activity than any SNP on its own. Taken together, these results support the hypothesis that RA-causative variants often act through altering the activity of immune cell enhancers. The enrichment in T-cell and NK-cell enhancer regions indicates that expression changes in these cell types are particularly relevant for the pathogenesis of RA. The specific SNPs that account for this enrichment can be used as a basis for focused genotype-phenotype studies of these cell types

    Understanding students’ motivation towards proactive career behaviours through goal-setting theory and the job demands–resources model

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    The graduate labour market is highly competitive but little is known about why students vary in their development of employability. This study contributes to the literature by applying goal-setting theory and the job demands–resources model to investigate how motivational processes influence students’ proactive career behaviours. We tested four hypotheses using structural equation modelling and moderation/mediation analysis using a nested model approach; 432 undergraduates from 21 UK universities participated in this cross-sectional study. The results showed that students higher in mastery approach had greater perceived employability mediated by two proactive career behaviours (skill development and network building). Students’ career goal commitment was associated with all four proactive career behaviours (career planning, skill development, career consultation and network building). Students’ academic and employment workloads did not negatively impact their proactive career behaviours. University tutors and career services should therefore encourage students to set challenging career goals that reflect mastery approach

    Disease variants in genomes of 44 centenarians

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    To identify previously reported disease mutations that are compatible with extraordinary longevity, we screened the coding regions of the genomes of 44 Ashkenazi Jewish centenarians. Individual genome sequences were generated with 30x coverage on the Illumina HiSeq 2000 and single-nucleotide variants were called with the genome analysis toolkit (GATK). We identified 130 coding variants that were annotated as pathogenic or likely pathogenic based on the ClinVar database and that are infrequent in the general population. These variants were previously reported to cause a wide range of degenerative, neoplastic, and cardiac diseases with autosomal dominant, autosomal recessive, and X-linked inheritance. Several of these variants are located in genes that harbor actionable incidental findings, according to the recommendations of the American College of Medical Genetics. In addition, we found risk variants for late-onset neurodegenerative diseases, such as the APOE epsilon4 allele that was even present in a homozygous state in one centenarian who did not develop Alzheimer\u27s disease. Our data demonstrate that the incidental finding of certain reported disease variants in an individual genome may not preclude an extraordinarily long life. When the observed variants are encountered in the context of clinical sequencing, it is thus important to exercise caution in justifying clinical decisions

    Benzo-fused Tri[8]annulenes as Molecular Models of Cubic Graphite

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    Cyclotrimerization of 9,10‐dibromo‐9,10‐dihydrodibenzo[3,4:7,8]cycloocta[1,2‐l]phenanthrene with potassium tert‐butoxide in the presence of a transition‐metal catalyst afforded two polycyclic aromatic hydrocarbon stereoisomers consisting of three cyclooctatetraene (COT) moieties connected via a central benzene ring. Both isomeric tri[8]annulenes were obtained selectively through the choice of the catalyst: The α,α,α‐form (Ru catalyst) displayed a threefold symmetrywith the COT subunits forming the side walls of a (chiral) molecular cup. In the thermodynamically more stable α,α,ÎČ‐isomer (Pd catalyst), one of the three boat‐shaped COTs was flipped over and faced the opposite molecular hemisphere with respect to the central benzene ring as evidenced by crystal structure analysis. Both title compounds are small segments of “cubic graphite”, an elusive carbon allotrope

    Nodal dynamics, not degree distributions, determine the structural controllability of complex networks

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    Structural controllability has been proposed as an analytical framework for making predictions regarding the control of complex networks across myriad disciplines in the physical and life sciences (Liu et al., Nature:473(7346):167-173, 2011). Although the integration of control theory and network analysis is important, we argue that the application of the structural controllability framework to most if not all real-world networks leads to the conclusion that a single control input, applied to the power dominating set (PDS), is all that is needed for structural controllability. This result is consistent with the well-known fact that controllability and its dual observability are generic properties of systems. We argue that more important than issues of structural controllability are the questions of whether a system is almost uncontrollable, whether it is almost unobservable, and whether it possesses almost pole-zero cancellations.Comment: 1 Figures, 6 page

    The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia : further evidence and meta-analysis

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    NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ. interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our strongest finding was the NOS1 promoter SNP rs41279104, yielding an odds ratio of 1.29 in the meta-analysis. As findings from heterologous cell systems have suggested that the risk allele decreases gene expression, we studied the effect of the variant on NOS1 expression in human post-mortem brain samples and found that the risk allele significantly decreases expression of NOS1 in the prefrontal cortex. Bioinformatic analyses suggest that this might be due the replacement of six transcription factor binding sites by two new binding sites as a consequence of proxy SNPs. Taken together, our data argue that genetic variance in NOS1 resulting in lower prefrontal brain expression of this gene contributes to schizophrenia liability, and that NOS1 interacts with NOS1AP in doing so. The NOS1-NOS1AP PDZ interface may thus well constitute a novel target for small molecules in at least some forms of schizophrenia. PostprintPeer reviewe

    Combinatorial synthesis of (YxGd1-x)Ba2Cu3Ox superconducting thin films

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    Environmentally friendly water-based YBa2Cu3Ox (YBCO) and GdBa2Cu3Ox (GdBCO) precursor solutions were synthesized to realize thin films by chemical solution deposition. Pure YBCO and GdBCO precursor solutions were used for ink plotting on SrTiO3 substrates and subsequent thermal treatment at the corresponding crystallization temperature. Phase formation of Gd123 requires a higher crystallization temperature of 840 °C compared to the Y123 phase. The critical temperature of YBCO films is about 92 K with a sharp transition into the superconducting state. Micro liter sized ink volumes of YBCO and GdBCO were successfully mixed for two-dimensional ink plotting of a (YxGd1-x)Ba2Cu3Ox film library. A homogeneous surface and no indication of a-axis growth were found in all mixed films
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