Job Coaching: A Means to Reduce Unemployment and Underemployment in the Deaf Community

Historically, vocational rehabilitation approaches to assisting deaf people to succeed in employment have been lacking. This contributes to unemployment and underemployment among the deaf community. This article discusses barriers to employment experienced by deaf people, the traditional role of vocational rehabilitation services, and service gaps related to job retention and advancement. A model for the provision of job coach services is provided that calls for the coach to be a member of a team providing routine ongoing services. Current and future efforts to develop coach training opportunities are described as well

The prospective relationship between loneliness, life satisfaction, and psychological distress before and during the Covid-19 pandemic in the UK

Aim: Mental wellbeing in the UK seems to have deteriorated significantly during the COVID-19 pandemic, with the rates of loneliness, life satisfaction and psychological distress taking longer to return to the pre-pandemic levels than elsewhere. Nevertheless, there is little knowledge about the interactions between these outcomes, or the factors that played a role in the rates of change. The current study aims to address this gap by simultaneously investigating changes in loneliness, life satisfaction and psychological distress in the UK from pre-pandemic levels to those between April and November 2020, while critically assessing the role of a range of social ecological influencing factors. Subject and Methods: Longitudinal data from Understanding Society (N=3475) were used to explore the changes in loneliness, life satisfaction and psychological distress from pre-pandemic levels (2017-2019) through November 2020, the interactions between these outcomes, and the role of individual, social, community and geographic factors in the rates of change, using multivariate latent growth curve model. Results: Loneliness, life satisfaction and psychological distress deteriorated minimally between April and November 2020, compared to the pre-pandemic levels (2017–2019), while the rate of change in each outcome influenced the rates of change in the other two. Key individual (age, gender, physical health), social (number of friends and similarity to them), and environmental (neighbourhood quality) variables influenced baseline scores and the rates of change. Conclusion: Considering significant dynamic associations between loneliness, life satisfaction and psychological distress, we argue that interventions to tackle any one of the outcomes may have beneficial effects on others, while highlighting malleable factors and individual and community-level interventions to tackle loneliness

Higher-Order Inter-chromosomal Hubs Shape 3D Genome Organization in the Nucleus

Eukaryotic genomes are packaged into a 3-dimensional structure in the nucleus. Current methods for studying genome-wide structure are based on proximity ligation. However, this approach can fail to detect known structures, such as interactions with nuclear bodies, because these DNA regions can be too far apart to directly ligate. Accordingly, our overall understanding of genome organization remains incomplete. Here, we develop split-pool recognition of interactions by tag extension (SPRITE), a method that enables genome-wide detection of higher-order interactions within the nucleus. Using SPRITE, we recapitulate known structures identified by proximity ligation and identify additional interactions occurring across larger distances, including two hubs of inter-chromosomal interactions that are arranged around the nucleolus and nuclear speckles. We show that a substantial fraction of the genome exhibits preferential organization relative to these nuclear bodies. Our results generate a global model whereby nuclear bodies act as inter-chromosomal hubs that shape the overall packaging of DNA in the nucleus

The Prognostic and Predictive Value of Melanoma-related MicroRNAs Using Tissue and Serum: A MicroRNA Expression Analysis

The overall 5-year survival for melanoma is 91%. However, if distant metastasis occurs (stage IV), cure rates are = 82%) when = 4 miRNAs were expressed. Moreover, the 'MELmiR-7' panel characterised overall survival of melanoma patients better than both serum LDH and S100B (delta log likelihood=11, p < 0.001). This panel was found to be superior to currently used serological markers for melanoma progression, recurrence, and survival; and would be ideally suited to monitor tumour progression in patients diagnosed with early metastatic disease (stages IIIa-c/IV M1a-b) to detect relapse following surgical or adjuvant treatment. (C) 2015 The Authors. Published by Elsevier B. V

Select Atrophied Regions in Alzheimer disease (SARA): An improved volumetric model for identifying Alzheimer disease dementia

INTRODUCTION: Volumetric biomarkers for Alzheimer disease (AD) are attractive due to their wide availability and ease of administration, but have traditionally shown lower diagnostic accuracy than measures of neuropathological contributors to AD. Our purpose was to optimize the diagnostic specificity of structural MRIs for AD using quantitative, data-driven techniques. METHODS: This retrospective study assembled several non-overlapping cohorts (total n = 1287) with publicly available data and clinical patients from Barnes-Jewish Hospital (data gathered 1990-2018). The Normal Aging Cohort (n = 383) contained amyloid biomarker negative, cognitively normal (CN) participants, and provided a basis for determining age-related atrophy in other cohorts. The Training (n = 216) and Test (n = 109) Cohorts contained participants with symptomatic AD and CN controls. Classification models were developed in the Training Cohort and compared in the Test Cohort using the receiver operating characteristics areas under curve (AUCs). Additional model comparisons were done in the Clinical Cohort (n = 579), which contained patients who were diagnosed with dementia due to various etiologies in a tertiary care outpatient memory clinic. RESULTS: While the Normal Aging Cohort showed regional age-related atrophy, classification models were not improved by including age as a predictor or by using volumetrics adjusted for age-related atrophy. The optimal model used multiple regions (hippocampal volume, inferior lateral ventricle volume, amygdala volume, entorhinal thickness, and inferior parietal thickness) and was able to separate AD and CN controls in the Test Cohort with an AUC of 0.961. In the Clinical Cohort, this model separated AD from non-AD diagnoses with an AUC 0.820, an incrementally greater separation of the cohort than by hippocampal volume alone (AUC of 0.801, p = 0.06). Greatest separation was seen for AD vs. frontotemporal dementia and for AD vs. non-neurodegenerative diagnoses. CONCLUSIONS: Volumetric biomarkers distinguished individuals with symptomatic AD from CN controls and other dementia types but were not improved by controlling for normal aging

The \u3cem\u3eChlamydomonas\u3c/em\u3e Genome Reveals the Evolution of Key Animal and Plant Functions

Chlamydomonas reinhardtii is a unicellular green alga whose lineage diverged from land plants over 1 billion years ago. It is a model system for studying chloroplast-based photosynthesis, as well as the structure, assembly, and function of eukaryotic flagella (cilia), which were inherited from the common ancestor of plants and animals, but lost in land plants. We sequenced the ∼120-megabase nuclear genome of Chlamydomonas and performed comparative phylogenomic analyses, identifying genes encoding uncharacterized proteins that are likely associated with the function and biogenesis of chloroplasts or eukaryotic flagella. Analyses of the Chlamydomonas genome advance our understanding of the ancestral eukaryotic cell, reveal previously unknown genes associated with photosynthetic and flagellar functions, and establish links between ciliopathy and the composition and function of flagella

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk.

Common variants in the hepatocyte nuclear factor 1 homeobox B (HNF1B) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on HNF1B gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the HNF1B locus to be associated with endometrial cancer, and now report extensive fine-mapping and in silico and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 (P = 8.4 × 10(-14), odds ratio = 0.86, 95% confidence interval = 0.82-0.89), located within HNF1B intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with HNF1B mRNA expression but not with HNF1B methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended HNF1B promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal HNF1B promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased HNF1B promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the HNF1B locus, and that risk is likely mediated via altered HNF1B gene expression