165 research outputs found

    A preliminary appraisal of the mineral potential of Venda based on a reconnaissance geochemical soil sampling survey and literature review

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    A reconnaissance soil sampling survey was carried out over Venda by Cycad (Pty) Ltd and the samples were analysed for 36 elements using XRF techniques, by Anglo American Research Laboratories in Johanuesburg. The data resulting from this survey forms the basis for the present interpretive study. Initially the sample positions were co-ordinated, then the geological, soil and sample types were allocated to each point. Twelve lithological groupings were chosen which incorporated most of the available data, retained significant geological characteristics and consisted of statistically significant sample populations. Statistical manipulation was undertaken for each of the lithological groups. Using a final population of 5768 samples, means were determined and anomalous values were identified using a threshold of mean plus two standard deviations. Due to time and budgetary constraints, 24 of the 36 elements were chosen for statisical manipulation and fourteen of these, with particular economic significance, were chosen for plotting, wherever significant numbers of anomalies were present. The element overlays were plotted so as to coincide with 18 of the 25, 1:50 000 topographic sheets covering Venda , the remaining 7 having inadequate sample coverage to yield meaningful contours. In this way a total of 175 element overlay sheets were plotted, each showing contoured element levels, with selected anomalous values. The treatment of the vast body of information made available by the Cycad sampling programme has thus been selective and has continually been aimed at highlighting and concentrating attention on the areas of greatest indicated mineralization potential, rather than on specific anomalies. In this regard it is felt that the present study has been successful, in spite of limited sample coverage in some areas. Combining the results of this study with a modern tectonically-based appraisal of mineralization potential and a knowledge of the local geology and previously known mineralization gleaned from an extensive literature review, the following types of mineralization are considered to have the highest potential in Venda: i) Nickel-copper-platinum mineralization as well as magnesite, in the olivine dolerite sills which intrude the base of the Karoo Sequence in Northern Venda. ii) Coal in the basal Karoo Sequence sediments in a broad zone from Jazz 715 MS in the west, and along the Klein Tshipise fault from Amonda 159 MT to the Mutale Copper Fields then east of these to the Kruger National Park. Where intrusives invade these lower Karoo sed iments the potential exists for amorphous graphite. iii) Hydrothermal copper and possibly gold and silver concentrations, in Nzhelele and Sibasa Formation rocks, particularly those associated with faults known to have been active in post-Soutpansberg times. iv) Sediment-hosted massive sulphide deposits (Cu-Pb -Zn) close to basin margin faults, near intersections with cross cutting faults that have resulted in localized basin formation. These are most likely in the Soutpansberg sediments. v) Martle, flake-graphite and late stage skarn mineralization (including lead, zinc, gold and tungsten), in calcareous rocks of the Gumbu Formation

    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

    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

    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

    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

    American Thoracic Society and National Heart, Lung, and Blood Institute Implementation Research Workshop Report

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    To advance implementation research (IR) in respiratory, sleep, and critical care medicine, the American Thoracic Society and the Division of Lung Diseases from the NHLBI cosponsored an Implementation Research Workshop on May 17, 2014. The goals of IR are to understand the barriers and facilitators of integrating new evidence into healthcare practices and to develop and test strategies that systematically target these factors to accelerate the adoption of evidence-based care. Throughout the workshop, presenters provided examples of IR that focused on the rate of adoption of evidence-based practices, the feasibility and acceptability of interventions to patients and other stakeholders who make healthcare decisions, the fidelity with which practitioners use specific interventions, the effects of specific barriers on the sustainability of an intervention, and the implications of their research to inform policies to improve patients’ access to high-quality care. During the discussions that ensued, investigators’ experience led to recommendations underscoring the importance of identifying and involving key stakeholders throughout the research process, ensuring that those who serve as reviewers understand the tenets of IR, managing staff motivation and turnover, and tackling the challenges of scaling up interventions across multiple settings

    Updated guidance on the management of COVID-19:from an American Thoracic Society/European Respiratory Society coordinated International Task Force (29 July 2020)

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    BACKGROUND: Coronavirus disease 2019 (COVID-19) is a disease caused by severe acute respiratory syndrome-coronavirus-2. Consensus suggestions can standardise care, thereby improving outcomes and facilitating future research. METHODS: An International Task Force was composed and agreement regarding courses of action was measured using the Convergence of Opinion on Recommendations and Evidence (CORE) process. 70% agreement was necessary to make a consensus suggestion. RESULTS: The Task Force made consensus suggestions to treat patients with acute COVID-19 pneumonia with remdesivir and dexamethasone but suggested against hydroxychloroquine except in the context of a clinical trial; these are revisions of prior suggestions resulting from the interim publication of several randomised trials. It also suggested that COVID-19 patients with a venous thromboembolic event be treated with therapeutic anticoagulant therapy for 3 months. The Task Force was unable to reach sufficient agreement to yield consensus suggestions for the post-hospital care of COVID-19 survivors. The Task Force fell one vote shy of suggesting routine screening for depression, anxiety and post-traumatic stress disorder. CONCLUSIONS: The Task Force addressed questions related to pharmacotherapy in patients with COVID-19 and the post-hospital care of survivors, yielding several consensus suggestions. Management options for which there is insufficient agreement to formulate a suggestion represent research priorities.status: Published onlin

    Integrated genomic characterization of oesophageal carcinoma

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    Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies
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