94 research outputs found

    Translating the Devil: Religion and Modernity among the Ewe in Ghana

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    Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/91169/1/ae.2000.27.3.775.pd

    The Unheimlich Man‐Oeuvre

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136524/1/ae.2001.28.4.909.pd

    Development and assessment of the Alberta Context Tool

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    <p>Abstract</p> <p>Background</p> <p>The context of healthcare organizations such as hospitals is increasingly accepted as having the potential to influence the use of new knowledge. However, the mechanisms by which the organizational context influences evidence-based practices are not well understood. Current measures of organizational context lack a theory-informed approach, lack construct clarity and generally have modest psychometric properties. This paper presents the development and initial psychometric validation of the Alberta Context Tool (ACT), an eight dimension measure of organizational context for healthcare settings.</p> <p>Methods</p> <p>Three principles guided the development of the ACT: substantive theory, brevity, and modifiability. The Promoting Action on Research Implementation in Health Services (PARiHS) framework and related literature were used to guide selection of items in the ACT. The ACT was required to be brief enough to be tolerated in busy and resource stretched work settings and to assess concepts of organizational context that were potentially <it>modifiable</it>. The English version of the ACT was completed by 764 nurses (752 valid responses) working in seven Canadian pediatric care hospitals as part of its initial validation. Cronbach's alpha, exploratory factor analysis, analysis of variance, and tests of association were used to assess instrument reliability and validity.</p> <p>Results</p> <p>Factor analysis indicated a 13-factor solution (accounting for 59.26% of the variance in 'organizational context'). The composition of the factors was similar to those originally conceptualized. Cronbach's alpha for the 13 factors ranged from .54 to .91 with 4 factors performing below the commonly accepted alpha cut off of .70. Bivariate associations between instrumental research utilization levels (which the ACT was developed to predict) and the ACT's 13 factors were statistically significant at the 5% level for 12 of the 13 factors. Each factor also showed a trend of increasing mean score ranging from the lowest level to the highest level of instrumental research use, indicating construct validity.</p> <p>Conclusions</p> <p>To date, no completely satisfactory measures of organizational context are available for use in healthcare. The ACT assesses several core domains to provide a comprehensive account of organizational context in healthcare settings. The tool's strengths are its brevity (allowing it to be completed in busy healthcare settings) and its focus on dimensions of organizational context that are modifiable. Refinements of the instrument for acute, long term care, and home care settings are ongoing.</p

    Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

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    Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

    Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

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    This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

    Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

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    Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

    Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

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    Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

    Home-based chlamydia testing of young people attending a music festival - who will pee and post?

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    <p>Abstract</p> <p>Background</p> <p>Chlamydia is most common among young people, but only a small proportion of Australian young people are tested annually. Home-based chlamydia testing has been piloted in several countries to increase testing rates, but uptake has been low. We aimed to identify predictors of uptake of home-based chlamydia testing to inform future testing programs.</p> <p>Methods</p> <p>We offered home-based chlamydia testing kits to participants in a sexual behaviour cross-sectional survey conducted at a music festival in Melbourne, Australia. Those who consented received a testing kit and were asked to return their urine or vaginal swab sample via post.</p> <p>Results</p> <p>Nine hundred and two sexually active music festival attendees aged 16-29 completed the survey; 313 (35%) opted to receive chlamydia testing kits, and 67 of 313 (21%) returned a specimen for testing. One participant was infected with chlamydia (1% prevalence). Independent predictors of consenting to receive a testing kit included older age, knowing that chlamydia can make women infertile, reporting more than three lifetime sexual partners and inconsistent condom use. Independent predictors of returning a sample to the laboratory included knowing that chlamydia can be asymptomatic, not having had an STI test in the past six months and not living with parents.</p> <p>Conclusions</p> <p>A low proportion of participants returned their chlamydia test, suggesting that this model is not ideal for reaching young people. Home-based chlamydia testing is most attractive to those who report engaging in sexual risk behaviours and are aware of the often asymptomatic nature and potential sequelae of chlamydia infection.</p

    Ovarian and Breast Cancer Risks Associated With Pathogenic Variants in RAD51C and RAD51D.

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    BACKGROUND: The purpose of this study was to estimate precise age-specific tubo-ovarian carcinoma (TOC) and breast cancer (BC) risks for carriers of pathogenic variants in RAD51C and RAD51D. METHODS: We analyzed data from 6178 families, 125 with pathogenic variants in RAD51C, and 6690 families, 60 with pathogenic variants in RAD51D. TOC and BC relative and cumulative risks were estimated using complex segregation analysis to model the cancer inheritance patterns in families while adjusting for the mode of ascertainment of each family. All statistical tests were two-sided. RESULTS: Pathogenic variants in both RAD51C and RAD51D were associated with TOC (RAD51C: relative risk [RR] = 7.55, 95% confidence interval [CI] = 5.60 to 10.19; P = 5 × 10-40; RAD51D: RR = 7.60, 95% CI = 5.61 to 10.30; P = 5 × 10-39) and BC (RAD51C: RR = 1.99, 95% CI = 1.39 to 2.85; P = 1.55 × 10-4; RAD51D: RR = 1.83, 95% CI = 1.24 to 2.72; P = .002). For both RAD51C and RAD51D, there was a suggestion that the TOC relative risks increased with age until around age 60 years and decreased thereafter. The estimated cumulative risks of developing TOC to age 80 years were 11% (95% CI = 6% to 21%) for RAD51C and 13% (95% CI = 7% to 23%) for RAD51D pathogenic variant carriers. The estimated cumulative risks of developing BC to 80 years were 21% (95% CI = 15% to 29%) for RAD51C and 20% (95% CI = 14% to 28%) for RAD51D pathogenic variant carriers. Both TOC and BC risks for RAD51C and RAD51D pathogenic variant carriers varied by cancer family history and could be as high as 32-36% for TOC, for carriers with two first-degree relatives diagnosed with TOC, or 44-46% for BC, for carriers with two first-degree relatives diagnosed with BC. CONCLUSIONS: These estimates will facilitate the genetic counseling of RAD51C and RAD51D pathogenic variant carriers and justify the incorporation of RAD51C and RAD51D into cancer risk prediction models

    Integrated Genomic Analysis of the Ubiquitin Pathway across Cancer Types

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    Protein ubiquitination is a dynamic and reversibleprocess of adding single ubiquitin molecules orvarious ubiquitin chains to target proteins. Here,using multidimensional omic data of 9,125 tumorsamples across 33 cancer types from The CancerGenome Atlas, we perform comprehensive molecu-lar characterization of 929 ubiquitin-related genesand 95 deubiquitinase genes. Among them, we sys-tematically identify top somatic driver candidates,including mutatedFBXW7with cancer-type-specificpatterns and amplifiedMDM2showing a mutuallyexclusive pattern withBRAFmutations. Ubiquitinpathway genes tend to be upregulated in cancermediated by diverse mechanisms. By integratingpan-cancer multiomic data, we identify a group oftumor samples that exhibit worse prognosis. Thesesamples are consistently associated with the upre-gulation of cell-cycle and DNA repair pathways, char-acterized by mutatedTP53,MYC/TERTamplifica-tion, andAPC/PTENdeletion. Our analysishighlights the importance of the ubiquitin pathwayin cancer development and lays a foundation fordeveloping relevant therapeutic strategies
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