45 research outputs found

    Rapid Fabrication of Flat Plate Cavity Phosphor Thermography Test Models for Shuttle Return-to-Flight Aero-Heating

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    Methods, materials and equipment are documented for fabricating flat plate test models at NASA Langley Research Center for Shuttle return-to-flight aeroheating experiments simulating open and closed cavity interactions in Langley s hypersonic 20-Inch Mach 6 air wind tunnel. Approximately 96 silica ceramic flat plate cavity phosphor thermography test models have been fabricated using these methods. On one model, an additional slot is machined through the back of the plate and into the cavity and vented into an evacuated plenum chamber to simulate a further opening in the cavity. After sintering ceramic to 2150 F, and mounting support hardware, a ceramic-based two-color thermographic phosphor coating is applied for global temperature and heat transfer measurements, with fiducial markings for image registration

    Do current methods of measuring the impact of chronic pain on work reflect the experience of working-age adults? : An integrated mixed methods systematic narrative review

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    The authors would like to acknowledge contributions to the QUICK study by members of the study advisory group: Patrice Forget, Siladitya Bhattacharya, Peter Goadsby, Cathy Price, David Coggon, Maureen McAllister, Stephen Bevan. The work presented in this manuscript was funded by the Medical Research Council (grant MR/V020676/1).Peer reviewe

    PDBe: improved accessibility of macromolecular structure data from PDB and EMDB

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    © 2015 The Authors. Published by OUP. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.1093/nar/gkv1047The Protein Data Bank in Europe (http://pdbe.org) accepts and annotates depositions of macromolecular structure data in the PDB and EMDB archives and enriches, integrates and disseminates structural information in a variety of ways. The PDBe website has been redesigned based on an analysis of user requirements, and now offers intuitive access to improved and value-added macromolecular structure information. Unique value-added information includes lists of reviews and research articles that cite or mention PDB entries as well as access to figures and legends from full-text open-access publications that describe PDB entries. A powerful new query system not only shows all the PDB entries that match a given query, but also shows the 'best structures' for a given macromolecule, ligand complex or sequence family using data-quality information from the wwPDB validation reports. A PDBe RESTful API has been developed to provide unified access to macromolecular structure data available in the PDB and EMDB archives as well as value-added annotations, e.g. regarding structure quality and up-to-date cross-reference information from the SIFTS resource. Taken together, these new developments facilitate unified access to macromolecular structure data in an intuitive way for non-expert users and support expert users in analysing macromolecular structure data.The Wellcome Trust [88944, 104948]; UK Biotechnology and Biological Sciences Research Council [BB/J007471/1, BB/K016970/1, BB/M013146/1, BB/M011674/1]; National Institutes of Health [GM079429]; UK Medical Research Council [MR/L007835/1]; European Union [284209]; CCP4; European Molecular Biology Laboratory (EMBL). Funding for open access charge: The Wellcome Trust.Published versio

    Racial Exclusion and the Political Economy of the Subprime Crisis

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    Abstract Th is paper develops a political economic explanation of the 2007-9 US subprime crisis which focuses on one of its central causes: the transformation of racial exclusion in US mortgagemarkets. Until the early 1990s, racial minorities were systematically excluded from mortgagefi nance due to bank-redlining and discrimination. But, then, racial exclusion in credit-markets was transformed: racial minorities were increasingly given access to housing-credit under terms far more adverse than were off ered to non-minority borrowers. Th is paper shows that the emergence of the subprime loan is linked, in turn, to the strategic transformation of banking in the 1980s, and to the unique global circumstances of the US macro-economy. Th us, subprime lending emerged from a combination of the long US history of racial exclusion in credit-markets, the crisis of US banking, and the position of the US within the global economy. From the viewpoint of the capitalist accumulation-process, these loans increased the depth of the fi nancial expropriation of the working class by fi nancial capital. Th e crisis in subprime lending then emerged when subprime loans with exploitative terms became more widespread and were made increasingly on an under-collateralised basis -that is, when housing-loans became not just extortionary but speculative

    A Pilot Study of IL-2Rα Blockade during Lymphopenia Depletes Regulatory T-cells and Correlates with Enhanced Immunity in Patients with Glioblastoma

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    Preclinical studies in mice have demonstrated that the prophylactic depletion of immunosuppressive regulatory T-cells (T(Regs)) through targeting the high affinity interleukin-2 (IL-2) receptor (IL-2Rα/CD25) can enhance anti-tumor immunotherapy. However, therapeutic approaches are complicated by the inadvertent inhibition of IL-2Rα expressing anti-tumor effector T-cells.To determine if changes in the cytokine milieu during lymphopenia may engender differential signaling requirements that would enable unarmed anti-IL-2Rα monoclonal antibody (MAbs) to selectively deplete T(Regs) while permitting vaccine-stimulated immune responses.A randomized placebo-controlled pilot study was undertaken to examine the ability of the anti-IL-2Rα MAb daclizumab, given at the time of epidermal growth factor receptor variant III (EGFRvIII) targeted peptide vaccination, to safely and selectively deplete T(Regs) in patients with glioblastoma (GBM) treated with lymphodepleting temozolomide (TMZ).Daclizumab treatment (n = 3) was well-tolerated with no symptoms of autoimmune toxicity and resulted in a significant reduction in the frequency of circulating CD4+Foxp3+ TRegs in comparison to saline controls (n = 3)( p = 0.0464). A significant (p<0.0001) inverse correlation between the frequency of TRegs and the level of EGFRvIII specific humoral responses suggests the depletion of TRegs may be linked to increased vaccine-stimulated humoral immunity. These data suggest this approach deserves further study.ClinicalTrials.gov NCT00626015

    The establishment, maintenance, and adaptation of high- and low-impact chronic pain: a framework for biopsychosocial pain research

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    We present a framework for the study of states of chronic pain and transitions between those states. We capture in the framework the dynamic nature of pain: people live with pain that changes over time. First, we offer definitions of both acute and chronic pain and explore the contextual considerations related to the common use of this temporal dichotomy. Second, we promote the importance of incorporating the impact pain has on a person's life. Finally, we discuss the challenges and opportunities inherent in implementing this common approach. Our goal is to produce a framework for the study of the development, maintenance, and resolution of chronic pain. Whether a single brief event or a constant feature of life, pain interrupts to prioritise protection, interferes with activity, reduces quality of life, and can alter identity.44 Protection is achieved by escape from harm, avoidance of perceived danger, withdrawal for respite and repair, and communication of incapacity and environmental risk; longer-term protection is achieved by learning the cues for pain and injury.53 From this perspective, pain is most usefully considered a need state, fundamentally a motivational drive to protect.49 This approach centres our attention on the consequences of pain for the person in their context, on its duration and its impact

    The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

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    Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care
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