127 research outputs found

    Reduction of tilt rotor download using circulation control

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    The effect of boundary layer control blowing on the download of a wing in the wake of a hovering rotor was measured in a small scale experiment. The objective was to evaluate the potential of boundary layer control blowing for reducing tilt rotor download. Variations were made in rotor thrust coefficient, blowing pressure ratio, and blowing slot height. The effect of these parameter variations on the wing download and wing surface pressures is presented. The boundary layer control blowing caused reductions in the wing download of 25 to 55 percent

    Matted nodes: Poor prognostic marker in oropharyngeal squamous cell carcinoma independent of HPV and EGFR status

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    Background Despite better prognosis, there is a group of oropharyngeal squamous cell carcinoma (SCC) human papillomavirus (HPV)+ patients who experience treatment failure and succumb to distant metastasis. Methods Seventy‐eight previously untreated patients nested in a concurrent chemoradiation protocol were reviewed to correlate patterns of local‐regional tumor extent to distant metastasis. Biomarker assessment was: HPV in situ hybridization and epidermal growth factor receptor (EGFR) immunointensity. Results The 3‐year disease‐specific survival (DSS) for patients presenting with and without matted nodes was 69% and 94%, respectively ( p = .003). Matted nodes were a poor prognostic factor independent of T classification, HPV, EGFR, and smoking status. For patients who were HPV+, 7 of 11 died of distant metastasis and 6 of 7 with distant metastasis had matted nodes. Conclusion Matted nodes are a novel marker of poor prognosis in oropharyngeal SCC independent of established prognostic factors. Matted nodes may identify patients at risk for the development of distant metastasis who could benefit from systemic therapy, whereas patients without matted nodes may be candidates for de‐escalation of therapy. © 2012 Wiley Periodicals, Inc. Head Neck , 2012Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94456/1/21997_ftp.pd

    Evaluation Research and Institutional Pressures: Challenges in Public-Nonprofit Contracting

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    This article examines the connection between program evaluation research and decision-making by public managers. Drawing on neo-institutional theory, a framework is presented for diagnosing the pressures and conditions that lead alternatively toward or away the rational use of evaluation research. Three cases of public-nonprofit contracting for the delivery of major programs are presented to clarify the way coercive, mimetic, and normative pressures interfere with a sound connection being made between research and implementation. The article concludes by considering how public managers can respond to the isomorphic pressures in their environment that make it hard to act on data relating to program performance.This publication is Hauser Center Working Paper No. 23. The Hauser Center Working Paper Series was launched during the summer of 2000. The Series enables the Hauser Center to share with a broad audience important works-in-progress written by Hauser Center scholars and researchers

    The Impact of Advocacy Organizations on Low-Income Housing Policy in U.S. Cities

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    Financial support for affordable housing competes with many other municipal priorities. This work seeks to explain the variation in support for affordable housing among U.S. cities with populations of 100,000 or more. Using multivariate statistical analysis, this research investigates political explanations for the level of city expenditures on housing and community with a particular interest in the influence of housing advocacy organizations (AOs). Data for the model were gathered from secondary sources, including the U.S. Census and the National Center for Charitable Statistics. Among other results, the analysis indicates that, on average, the political maturity of AOs has a statistically significant, positive effect on local housing and community development expenditures

    Non-Neoplastic and Neoplastic Pleural Endpoints Following Fiber Exposure

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    Exposure to asbestos fibers is associated with non-neoplastic pleural diseases including plaques, fibrosis, and benign effusions, as well as with diffuse malignant pleural mesothelioma. Translocation and retention of fibers are fundamental processes in understanding the interactions between the dose and dimensions of fibers retained at this anatomic site and the subsequent pathological reactions. The initial interaction of fibers with target cells in the pleura has been studied in cellular models in vitro and in experimental studies in vivo. The proposed biological mechanisms responsible for non-neoplastic and neoplastic pleural diseases and the physical and chemical properties of asbestos fibers relevant to these mechanisms are critically reviewed. Understanding mechanisms of asbestos fiber toxicity may help us anticipate the problems from future exposures both to asbestos and to novel fibrous materials such as nanotubes. Gaps in our understanding have been outlined as guides for future research

    Towards evidence-based marketing: The case of childhood obesity

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    Contentious commodities such as tobacco, alcohol and fatty foods are bringing marketing under scrutiny from consumers and policymakers. Yet there is little agreement on whether marketing is harmful to society. Systematic review (SR), a methodology derived from clinical medicine, offers marketers a tool for providing resolution and allowing policymakers to proceed with greater confidence. This article describes how SR methods were applied for the first time to a marketing problem -- the effects of food promotion to children. The review withstood scrutiny and its findings were formally ratified by government bodies and policymakers, demonstrating that SR methods can transfer from clinical research to marketing

    Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors

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    CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We demonstrated that CD25 expression is largely restricted to tumor-infiltrating Treg cells in mice and humans. While existing anti-CD25 antibodies were observed to deplete Treg cells in the periphery, upregulation of the inhibitory Fc gamma receptor (FcγR) IIb at the tumor site prevented intra-tumoral Treg cell depletion, which may underlie the lack of anti-tumor activity previously observed in pre-clinical models. Use of an anti-CD25 antibody with enhanced binding to activating FcγRs led to effective depletion of tumor-infiltrating Treg cells, increased effector to Treg cell ratios, and improved control of established tumors. Combination with anti-programmed cell death protein-1 antibodies promoted complete tumor rejection, demonstrating the relevance of CD25 as a therapeutic target and promising substrate for future combination approaches in immune-oncology

    Mapping genomic loci implicates genes and synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60-80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies

    Introduction to special issue:New Times Revisited: Britain in the 1980s

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    The authors in this volume are collectively engaged with a historical puzzle: What happens if we examine the decade once we step out of the shadows cast by Thatcher? That is, does the decade of the 1980s as a significant and meaningful periodisation (equivalent to that of the 1960s) still work if Thatcher becomes but one part of the story rather than the story itself? The essays in this collection suggest that the 1980s only makes sense as a political period. They situate the 1980s within various longer term trajectories that show the events of the decade to be as much the consequence as the cause of bigger, long-term historical processes. This introduction contextualises the collection within the wider literature, before explaining the collective and individual contributions made

    Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

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    Schizophrenia has a heritability of 60–80%1, much of which is attributable to common risk alleles. Here, in a two-stage genome-wide association study of up to 76,755 individuals with schizophrenia and 243,649 control individuals, we report common variant associations at 287 distinct genomic loci. Associations were concentrated in genes that are expressed in excitatory and inhibitory neurons of the central nervous system, but not in other tissues or cell types. Using fine-mapping and functional genomic data, we identify 120 genes (106 protein-coding) that are likely to underpin associations at some of these loci, including 16 genes with credible causal non-synonymous or untranslated region variation. We also implicate fundamental processes related to neuronal function, including synaptic organization, differentiation and transmission. Fine-mapped candidates were enriched for genes associated with rare disruptive coding variants in people with schizophrenia, including the glutamate receptor subunit GRIN2A and transcription factor SP4, and were also enriched for genes implicated by such variants in neurodevelopmental disorders. We identify biological processes relevant to schizophrenia pathophysiology; show convergence of common and rare variant associations in schizophrenia and neurodevelopmental disorders; and provide a resource of prioritized genes and variants to advance mechanistic studies
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