597 research outputs found

    The Efficacy of Functional Assessments in Rehabilitation Medicine

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    Functional assessment in rehabilitation medicine is not a new concept. Functional assessment measures have, however, experienced increased usage. Health insurance companies and clinicians are now focusing on functional outcomes in addition to objective tests. Certain measurement criteria must be satisfied before a measurement tool may be successfully implemented into the clinical setting. Variable standardization, reliability, and validity are necessary for accurate measurement. The term function, however, deals with many variables leading to definitional difficulty. The purpose of the functional assessment is to describe, screen and assess, and monitor. Although many functional assessments are available for clinical use, most lack scientific rigor. Consequently, few reliability and validity studies have been completed. Therefore, a critical analysis of three common functional measurement scales was completed. No scale demonstrated unequivocal superiority. Each scale has its own strengths and weaknesses. Scale selection depends on the clinical setting, the patient population, and the purpose for completing the assessment. Research in the area of definitional standardization, validity, and clinical feasibility is necessary to further substantiate the efficacy of functional assessment in rehabilitation medicine

    A Managerial Perspective on the Information Technology Needs of End-Users

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    The advancement in Information Technology (IT) has brought a tremendous impact on End-User Computing (EUC). Many organizations have partially decentralized information systems, and functional area managements are being held accountable for effective utilization of IT. This study investigates IT knowledge and skills which functional area managers identify as important for end-users. Since information systems managers\u27 views are also important, their perceptions are compared with non-information systems functional area managers\u27 perceptions. Results of this study suggest specific IT topics that business graduates should know and be able to apply. The topics identified should receive the most emphasis in the MIS curriculum for all business majors

    Dual Requirement for Yeast hnRNP Nab2p in mRNA poly(A) Tail Length Control and Nuclear Export

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    Recent studies of mRNA export factors have provided additional evidence for a mechanistic link between mRNA 3′‐end formation and nuclear export. Here, we identify Nab2p as a nuclear poly(A)‐binding protein required for both poly(A) tail length control and nuclear export of mRNA. Loss of NAB2 expression leads to hyperadenylation and nuclear accumulation of poly(A)+ RNA but, in contrast to mRNA export mutants, these defects can be uncoupled in a nab2 mutant strain. Previous studies have implicated the cytoplasmic poly(A) tail‐binding protein Pab1p in poly(A) tail length control during polyadenylation. Although cells are viable in the absence of NAB2 expression when PAB1 is overexpressed, Pab1p fails to resolve the nab2Δ hyperadenylation defect even when Pab1p is tagged with a nuclear localization sequence and targeted to the nucleus. These results indicate that Nab2p is essential for poly(A) tail length control in vivo, and we demonstrate that Nab2p activates polyadenylation, while inhibiting hyperadenylation, in the absence of Pab1p in vitro. We propose that Nab2p provides an important link between the termination of mRNA polyadenylation and nuclear export

    The TolC Protein of Legionella pneumophila Plays a Major Role in Multi-Drug Resistance and the Early Steps of Host Invasion

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    Pneumonia associated with Iegionnaires's disease is initiated in humans after inhalation of contaminated aerosols. In the environment, Legionella pneumophila is thought to survive and multiply as an intracellular parasite within free-living amoeba. In the genome of L. pneumophila Lens, we identified a unique gene, tolC, encoding a protein that is highly homologous to the outer membrane protein TolC of Escherichia coli. Deletion of tolC by allelic exchange in L. pneumophila caused increased sensitivity to various drugs. The complementation of the tolC mutation in trans restored drug resistance, indicating that TolC is involved in multi-drug efflux machinery. In addition, deletion of tolC caused a significant attenuation of virulence towards both amoebae and macrophages. Thus, the TolC protein appears to play a crucial role in virulence which could be mediated by its involvement in efflux pump mechanisms. These findings will be helpful in unraveling the pathogenic mechanisms of L. pneumophila as well as in developing new therapeutic agents affecting the efflux of toxic compounds

    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

    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

    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

    A Landscape Plan Based on Historical Fire Regimes for a Managed Forest Ecosystem: the Augusta Creek Study

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    The Augusta Creek project was initiated to establish and integrate landscape and watershed objectives into a landscape plan to guide management activities within a 7600-hectare (19,000-acre) planning area in western Oregon. Primary objectives included the maintenance of native species, ecosystem processes and structures, and long-term ecosystem productivity in a federally managed landscape where substantial acreage was allocated to timber harvest. Landscape and watershed management objectives and prescriptions were based on an interpreted range of natural variability of landscape conditions and disturbance processes. A dendrochronological study characterized fire patterns and regimes over the last 500 years. Changes in landscape conditions throughout the larger surrounding watershed due to human uses (e.g., roads in riparian areas, widespread clearcutting, a major dam, and portions of a designated wilderness and an unroaded area) also were factored into the landscape plan. Landscape prescriptions include an aquatic reserve system comprised of small watersheds distributed throughout the planning area and major valley-bottom corridor reserves that connect the small-watershed reserves. Where timber harvest was allocated, prescriptions derived from interpretations of fire regimes differ in rotation ages (100 to 300 years), green-tree retention levels (15- to 50-percent canopy cover), and spatial patterns of residual trees. General prescriptions for fire management also were based on interpretations of past fire regimes. All these prescriptions were linked to specific blocks of land to provide an efficient transition to site-level planning and project implementation. Landscape and watershed conditions were projected 200 years into the future and compared with conditions that would result from application of standards, guidelines, and assumptions in the Northwest Forest Plan prior to adjustments resulting from watershed analyses. The contrasting prescriptions for aquatic reserves and timber harvest (rotation lengths, green-tree retention levels, and spatial patterns) in these two approaches resulted in strikingly different potential future landscapes. These differences have significant implications for some ecosystem processes and habitats. We view this management approach as a potential post watershed analysis implementation of the Northwest Forest Plan and offer it as an example of how ecosystem management could be applied in a particular landscape by using the results of watershed analysis
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