2,651 research outputs found

    Exoskeletons - Designing for Social Justice

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    Many engineering professionals believe that discussions surrounding diversity, equity, and inclusion (DEI), and social justice do not belong in engineering because engineering is supposed to be a neutral or objective field. Through an extensive review of the literature and a survey sent out to potential users, the need for DEI in engineering was examined. Many current engineering projects do not take into consideration social justice principles which leaves certain groups further marginalized and disempowered while empowering a select few. Engineering has the opportunity to be a field of service, but first risks and benefits must be weighed and the outcome of enhancing human capacities must be valued over monetary gain. For example, this project was dedicated to applying DEI efforts to engineering an upper limb exoskeleton. In this case, the exoskeleton enhances a person’s capabilities by enhancing their natural arm movement. In order to equitably design our exoskeleton we considered user needs from the very beginning through empathy mapping and surveying potential users. The results that we have gathered thus far suggest that potential users care foremost about cost and secondly about the comfort and fit of the device. Moving forward it is crucial that we implement design choices that reflect the value of the potential users to ensure that the device we create is attainable and usable while offering a sustainable solution to users

    Viral Reservoirs in Lymph Nodes of FIV-Infected Progressor and Long-Term Non-Progressor Cats during the Asymptomatic Phase.

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    BackgroundExamination of a cohort of cats experimentally infected with feline immunodeficiency virus (FIV) for 5.75 years revealed detectable proviral DNA in peripheral blood mononuclear cells (PBMCs) harvested during the asymptomatic phase, undetectable plasma viral RNA (FIV gag), and rarely detectable cell-associated viral RNA. Despite apparent viral latency in peripheral CD4+ T cells, circulating CD4+ T cell numbers progressively declined in progressor animals. The aim of this study was to explore this dichotomy of peripheral blood viral latency in the face of progressive immunopathology. The viral replication status, cellular immunophenotypes, and histopathologic features were compared between popliteal lymph nodes (PLNs) and peripheral blood. Also, we identified and further characterized one of the FIV-infected cats identified as a long-term non-progressor (LTNP).ResultsPLN-derived leukocytes from FIV-infected cats during the chronic asymptomatic phase demonstrated active viral gag transcription and FIV protein translation as determined by real-time RT-PCR, Western blot and in situ immunohistochemistry, whereas viral RNA in blood leukocytes was either undetectable or intermittently detectable and viral protein was not detected. Active transcription of viral RNA was detectable in PLN-derived CD4+ and CD21+ leukocytes. Replication competent provirus was reactivated ex vivo from PLN-derived leukocytes from three of four FIV-infected cats. Progressor cats showed a persistent and dramatically decreased proportion and absolute count of CD4+ T cells in blood, and a decreased proportion of CD4+ T cells in PLNs. A single long-term non-progressor (LTNP) cat persistently demonstrated an absolute peripheral blood CD4+ T cell count indistinguishable from uninfected animals, a lower proviral load in unfractionated blood and PLN leukocytes, and very low amounts of viral RNA in the PLN.ConclusionCollectively our data indicates that PLNs harbor important reservoirs of ongoing viral replication during the asymptomatic phase of infection, in spite of undetectable viral activity in peripheral blood. A thorough understanding of tissue-based lentiviral reservoirs is fundamental to medical interventions to eliminate virus or prolong the asymptomatic phase of FIV infection

    Synovial cell metabolism and chronic inflammation in rheumatoid arthritis

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    Metabolomic studies of body fluids show that immune-mediated inflammatory diseases such as rheumatoid arthritis (RA) are associated with metabolic disruption. This is likely to reflect the increased bioenergetic and biosynthetic demands of sustained inflammation and changes to nutrient and oxygen availability in damaged tissue. The synovial membrane lining layer is the principle site of inflammation in RA. Here the resident cells are the fibroblast-like synoviocytes (FLS) and the synovial tissue macrophages (STM), which are transformed toward overproduction of enzymes which degrade cartilage and bone, and cytokines which promote immune cell infiltration. Recent studies have shown metabolic changes in both FLS and macrophages from RA patients and these may be therapeutically targetable. However, as the origins and subset specific functions of synoviocytes are poorly understood and the signaling modules which control metabolic deviation in RA synovial cells are yet to be explored, significant additional research is needed to translate these findings toward clinical application. Furthermore, in many inflamed tissues, different cell types can forge metabolic collaborations through solute carriers (SLC) in their membranes, to meet a high demand for energy or biomolecules. Such relationships are likely to exist in the synovium and are yet to be explored. Finally, it is not yet known whether metabolic change is a consequence of disease or if primary changes to cellular metabolism might underlie or contribute to early stage disease pathogenesis. This article collates what is known about metabolism in synovial tissue cells and highlights future research directions in this area

    Narrowing the Range of Future Climate Projections Using Historical Observations of Atmospheric CO2

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    This is the final version. Available from American Meteorological Society via the DOI in this recordUncertainty in the behavior of the carbon cycle is important in driving the range in future projected climate change. Previous comparisons of model responses with historical CO2 observations have suggested a strong constraint on simulated projections that could narrow the range considered plausible. This study uses a new 57-member perturbed parameter ensemble of variants of an Earth system model for three future scenarios, which 1) explores a wider range of potential climate responses than before and 2) includes the impact of past uncertainty in carbon emissions on simulated trends. These two factors represent a more complete exploration of uncertainty, although they lead to a weaker constraint on the range of future CO2 concentrations as compared to earlier studies. Nevertheless, CO2 observations are shown to be effective at narrowing the distribution, excluding 30 of 57 simulations as inconsistent with historical CO2 changes. The perturbed model variants excluded are mainly at the high end of the future projected CO2 changes, with only 8 of the 26 variants projecting RCP8.5 2100 concentrations in excess of 1100 ppm retained. Interestingly, a minority of the high-end variants were able to capture historical CO2 trends, with the large-magnitude response emerging later in the century (owing to high climate sensitivities, strong carbon feedbacks, or both). Comparison with observed CO2 is effective at narrowing both the range and distribution of projections out to the mid-twenty-first century for all scenarios and to 2100 for a scenario with low emissions.This work was supported by the Joint U.K. DECC/DEFRA Met Office Hadley Centre Climate Programme (GA01101). Chris Jones’s contribution was supported by the CRESCENDO project under the European Union's Horizon 2020 research and innovation programme, Grant Agreement 641816. Jo House was supported by a Leverhulme Early Career Fellowship and EU FP7 Project LUC4C (603542). Stephen Sitch was supported by the EU FP7 through Project LUC4C (GA603542)

    New first trimester crown-rump length's equations optimized by structured data collection from a French general population

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    --- Objectives --- Prior to foetal karyotyping, the likelihood of Down's syndrome is often determined combining maternal age, serum free beta-HCG, PAPP-A levels and embryonic measurements of crown-rump length and nuchal translucency for gestational ages between 11 and 13 weeks. It appeared important to get a precise knowledge of these scan parameters' normal values during the first trimester. This paper focused on crown-rump length. --- METHODS --- 402 pregnancies from in-vitro fertilization allowing a precise estimation of foetal ages (FA) were used to determine the best model that describes crown-rump length (CRL) as a function of FA. Scan measures by a single operator from 3846 spontaneous pregnancies representative of the general population from Northern France were used to build a mathematical model linking FA and CRL in a context as close as possible to normal scan screening used in Down's syndrome likelihood determination. We modeled both CRL as a function of FA and FA as a function of CRL. For this, we used a clear methodology and performed regressions with heteroskedastic corrections and robust regressions. The results were compared by cross-validation to retain the equations with the best predictive power. We also studied the errors between observed and predicted values. --- Results --- Data from 513 spontaneous pregnancies allowed to model CRL as a function of age of foetal age. The best model was a polynomial of degree 2. Datation with our equation that models spontaneous pregnancies from a general population was in quite agreement with objective datations obtained from 402 IVF pregnancies and thus support the validity of our model. The most precise measure of CRL was when the SD was minimal (1.83mm), for a CRL of 23.6 mm where our model predicted a 49.4 days of foetal age. Our study allowed to model the SD from 30 to 90 days of foetal age and offers the opportunity of using Zscores in the future to detect growth abnormalities. --- Conclusion --- With powerful statistical tools we report a good modeling of the first trimester embryonic growth in the general population allowing a better knowledge of the date of fertilization useful in the ultrasound screening of Down's syndrome. The optimal period to measure CRL and predict foetal age was 49.4 days (9 weeks of gestational age). Our results open the way to the detection of foetal growth abnormalities using CRL Zscores throughout the first trimester

    Two-years Postradiotherapy Biopsies: Lessons from MRC RT01 Trial

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    Background: The importance of 2-yr postradiotherapy prostate biopsy status remains uncertain. Objective: To assess the value of 2 year post treatment biopsies in a randomised trial of radiotherapy dose escalation. Design, setting, and participants: Between 1998 and 2001, 843 men with localised prostate cancer were randomised to receive either control-64 Gy or escalated-74 Gy conformal radiotherapy (CFRT) in the MRC RT01 trial in combination with 3–6-mo neoadjuvant androgen deprivation therapy. Prostate biopsies were planned at 2 yr from start of CFRT in suitable men. Outcome measurements and statistical analysis: Prostate biopsy results and prostate-specific antigen (PSA) levels performed at 2 yr post-CFRT were evaluated with long-term biochemical progression free survival (bPFS) and overall survival. Outcome measures were timed from the 2-yr biopsy using a landmark approach. Results and limitations: A 2-yr biopsy was performed in 312/843 patients. One hundred and seventy-seven patients were included in the per-protocol group with median follow-up of 7.8 yr from biopsy. Median PSA at biopsy was 0.5 ng/ml. Sixty-four bPFS events were reported: 46/145 (32%) in patients with negative, 6/18 (33%) suspicious, and 12/14 (86%) positive biopsies. A positive biopsy was prognostic of worse bPFS, going forward, compared with negative and suspicious biopsies, hazard ratio (HR) = 4.81 (95% confidence interval [CI]: 2.50–9.26, p < 0.001). The estimate for survival was HR = 1.58 (95% CI: 0.52–4.78, p = 0.42). PSA values at 2 yr between 1.01 ng/ml and 2.09 ng/ml were also associated with subsequent PSA failures (HR = 2.71, 95% CI: 1.98–3.71), bPFS events (HR = 2.45, 95% CI: 1.81–3.32), and prostate cancer-specific survival (HR = 2.87, 95% CI: 1.08–7.64) compared with PSA ≤1.0 ng/ml. Conclusions: Two-year postradiotherapy prostate biopsies have limited value in patients with PSA control but both positive biopsy and higher PSA status are strongly associated with future bPFS events. A policy of selected biopsy may provide an opportunity for early salvage interventions. Patient summary: Routine 2-yr postradiotherapy biopsy is not recommended but can be considered in selected patients with unfavourable post-treatment prostate-specific antigen levels who are suitable for early salvage treatments

    Defining clinically important perioperative blood loss and transfusion for the Standardised Endpoints for Perioperative Medicine (StEP) collaborative: a protocol for a scoping review

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    INTRODUCTION: 'Standardised Endpoints for Perioperative Medicine' (StEP) is an international collaboration undertaking development of consensus-based consistent definitions for endpoints in perioperative clinical trials. Inconsistency in endpoint definitions can make interpretation of trial results more difficult, especially if conflicting evidence is present. Furthermore, this inconsistency impedes evidence synthesis and meta-analyses. The goals of StEP are to harmonise definitions for clinically meaningful endpoints and specify standards for endpoint reporting in clinical trials. To help inform this endeavour, we aim to conduct a scoping review to systematically characterise the definitions of clinically important endpoints in the existing published literature on perioperative blood loss and transfusion. METHODS AND ANALYSIS: The scoping review will be conducted using the widely adopted framework developed by Arksey and O'Malley, with modifications from Levac. We refined our methods with guidance from research librarians as well as researchers and clinicians with content expertise. The electronic literature search will involve several databases including Medline, PubMed-not-Medline and Embase. Our review has three objectives, namely to (1) identify definitions of significant blood loss and transfusion used in previously published large perioperative randomised trials; (2) identify previously developed consensus-based definitions for significant blood loss and transfusion in perioperative medicine and related fields; and (3) describe the association between different magnitudes of blood loss and transfusion with postoperative outcomes. The multistage review process for each question will involve two reviewers screening abstracts, reading full-text articles and performing data extraction. The abstracted data will be organised and subsequently analysed in an iterative process. ETHICS AND DISSEMINATION: This scoping review of the previously published literature does not require research ethics approval. The results will be used to inform a consensus-based process to develop definitions of clinically important perioperative blood loss and transfusion. The results of the scoping review will be published in a peer-reviewed scientific journal

    Current quark mass dependence of nucleon magnetic moments and radii

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    A calculation of the current-quark-mass-dependence of nucleon static electromagnetic properties is necessary in order to use observational data as a means to place constraints on the variation of Nature's fundamental parameters. A Poincare' covariant Faddeev equation, which describes baryons as composites of confined-quarks and -nonpointlike-diquarks, is used to calculate this dependence The results indicate that, like observables dependent on the nucleons' magnetic moments, quantities sensitive to their magnetic and charge radii, such as the energy levels and transition frequencies in Hydrogen and Deuterium, might also provide a tool with which to place limits on the allowed variation in Nature's constants.Comment: 23 pages, 2 figures, 4 tables, 4 appendice
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