93 research outputs found

    Multi-domain design assessment for aerospace components including weld accessibility

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    AbstractAeroengine manufacturers need to better include assessment of risk and cost for realising the novel products needed to meet the ambitions sustainability driven targets for air transport. Radical technologies are needed that simultaneously require critical manufacturing processes to be assessed already in conceptual design.In this paper, a multi-domain framework for conceptual design and evaluation is proposed that provide the ability to interactively explore the concepts that simultaneously allow a wider range of architectures can be assessed and still include weldability of the concepts.It has been demonstrated how high level, and function driven conceptual design alternatives can be modelled and evaluated to analyse risk and resilience of architectures. Geometrical concepts generated for the most interesting regimes using design of experiments covering a desired design space. For each CAD-model the welding process can be simulated to assess feasibility and lead time for welding, and return quantified results to be included in an integrated results data set for interactive decision making. The paper is the first report from a research project that improve concurrent design of product and production concepts.Clean Sky 2 Joint Undertaking under the European Union’s Horizon 2020 research and innovation programme. Grant agreement No 887174

    Recruitment and retention of women in a large randomized control trial to reduce repeat preterm births: the Philadelphia Collaborative Preterm Prevention Project

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    <p>Abstract</p> <p>Background</p> <p>Recruitment and retention of patients for randomized control trial (RCT) studies can provide formidable challenges, particularly with minority and underserved populations. Data are reported for the Philadelphia Collaborative Preterm Prevention Project (PCPPP), a large RCT targeting risk factors for repeat preterm births among women who previously delivered premature (< 35 weeks gestation) infants.</p> <p>Methods</p> <p>Design of the PCPPP incorporated strategies to maximize recruitment and retention. These included an advanced database system tracking follow-up status and assessment completion rates; cultural sensitivity training for staff; communication to the community and eligible women of the benefits of participation; financial incentives; assistance with transportation and supervised childcare services; and reminder calls for convenient, flexibly scheduled appointments. Analyses reported here: 1) compare recruitment projections to actual enrollment 2) explore recruitment bias; 3) validate the randomization process 4) document the extent to which contact was maintained and complete assessments achieved 5) determine if follow-up was conditioned upon socio-economic status, race/ethnicity, or other factors.</p> <p>Results</p> <p>Of eligible women approached, 1,126 (77.7%) agreed to participate fully. Of the 324 not agreeing, 118 (36.4%) completed a short survey. Consenting women were disproportionately from minority and low SES backgrounds: 71.5% consenting were African American, versus 38.8% not consenting. Consenting women were also more likely to report homelessness during their lifetime (14.6% vs. 0.87%) and to be unmarried at the time of delivery (81.6% versus 47.9%). First one-month postpartum assessment was completed for 83.5% (n = 472) of the intervention group (n = 565) and 76% (426) of the control group. Higher assessment completion rates were observed for the intervention group throughout the follow-up. Second, third, fourth and fifth postpartum assessments were 67.6% vs. 57.5%, 60.0% vs. 48.9%, 54.2% vs. 46.3% and 47.3% vs. 40.8%, for the intervention and control group women, respectively. There were no differences in follow-up rates according to race/ethnicity, SES or other factors. Greater retention of the intervention group may reflect the highly-valued nature of the medical and behavior services constituting the intervention arms of the Project.</p> <p>Conclusion</p> <p>Findings challenge beliefs that low income and minority women are averse to enrolling and continuing in clinical trials or community studies.</p

    Eculizumab improves fatigue in refractory generalized myasthenia gravis

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    The use of race, ethnicity and ancestry in human genetic research

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    Post-Human Genome Project progress has enabled a new wave of population genetic research, and intensified controversy over the use of race/ethnicity in this work. At the same time, the development of methods for inferring genetic ancestry offers more empirical means of assigning group labels. Here, we provide a systematic analysis of the use of race/ethnicity and ancestry in current genetic research. We base our analysis on key published recommendations for the use and reporting of race/ethnicity which advise that researchers: explain why the terms/categories were used and how they were measured, carefully define them, and apply them consistently. We studied 170 population genetic research articles from high impact journals, published 2008–2009. A comparative perspective was obtained by aligning study metrics with similar research from articles published 2001–2004. Our analysis indicates a marked improvement in compliance with some of the recommendations/guidelines for the use of race/ethnicity over time, while showing that important shortfalls still remain: no article using ‘race’, ‘ethnicity’ or ‘ancestry’ defined or discussed the meaning of these concepts in context; a third of articles still do not provide a rationale for their use, with those using ‘ancestry’ being the least likely to do so. Further, no article discussed potential socio-ethical implications of the reported research. As such, there remains a clear imperative for highlighting the importance of consistent and comprehensive reporting on human populations to the genetics/genomics community globally, to generate explicit guidelines for the uses of ancestry and genetic ancestry, and importantly, to ensure that guidelines are followed

    Consistent improvement with eculizumab across muscle groups in myasthenia gravis

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    Pathologic and Phenotypic Alterations in a Mouse Expressing a Connexin47 Missense Mutation That Causes Pelizaeus-Merzbacher–Like Disease in Humans

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    Gap junction channels are intercellular conduits that allow diffusional exchange of ions, second messengers, and metabolites. Human oligodendrocytes express the gap junction protein connexin47 (Cx47), which is encoded by the GJC2 gene. The autosomal recessive mutation hCx47M283T causes Pelizaeus-Merzbacher–like disease 1 (PMLD1), a progressive leukodystrophy characterized by hypomyelination, retarded motor development, nystagmus, and spasticity. We introduced the human missense mutation into the orthologous position of the mouse Gjc2 gene and inserted the mCx47M282T coding sequence into the mouse genome via homologous recombination in embryonic stem cells. Three-week-old homozygous Cx47M282T mice displayed impaired rotarod performance but unchanged open-field behavior. 10-15-day-old homozygous Cx47M282T and Cx47 null mice revealed a more than 80% reduction in the number of cells participating in glial networks after biocytin injections into oligodendrocytes in sections of corpus callosum. Homozygous expression of mCx47M282T resulted in reduced MBP expression and astrogliosis in the cerebellum of ten-day-old mice which could also be detected in Cx47 null mice of the same age. Three-month-old homozygous Cx47M282T mice exhibited neither altered open-field behavior nor impaired rotarod performance anymore. Adult mCx47M282T expressing mice did not show substantial myelin alterations, but homozygous Cx47M282T mice, additionally deprived of connexin32, which is also expressed in oligodendrocytes, died within six weeks after birth and displayed severe myelin defects accompanied by astrogliosis and activated microglia. These results strongly suggest that PMLD1 is caused by the loss of Cx47 channel function that results in impaired panglial coupling in white matter tissue

    Racial and ethnic differences in general health status and limiting health conditions among American children: parental reports in the 1999 National Survey of America's Families

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    Working PaperObjectives: This research investigates the association between race/ethnicity and child health and examines the role of family structure, family SES, and healthcare factors in this association. Five major racial/ethnic groups in the United States are studied. Two child health outcomes including parent-rated health and limiting health condition are examined. The analysis is stratified into three age groups: age 0 to 5, age 6 to 11, and age 12 to 17. Design: Cross-sectional study using data from a large nationally representative sample collected in 1999 in the United States. Results: For general health, older age groups tend to exhibit larger racial/ethnic disparities. With few exceptions, minority groups showed higher risk of poor health relative to Whites among children age 6 to 17. In the youngest group (age 0 to 5), only Latinos have significant health disadvantage. As to limiting health condition, black children prior to adolescence are slightly disadvantaged, Native American adolescents are significantly more likely to have limiting conditions, whereas Asian adolescents are better off than Whites. Family SES explains some black, Latino, and Native American effects but not all; and SES does not explain the Asian effects. Family structure and healthcare factors generally do not contribute much to the racial/ethnic differences but they can have significant effects on child health in their own right. We also find that economic resources play a more salient role in child health than parental education especially in younger children. And healthcare factors to some extent explain why children from higher SES family fare better. Conclusion: Racial/ethnic disparities in health start early in life. Except for Asians, class explains a substantial amount but not all of these disparities. Healthcare factors play a prominent role in explaining disparities by class. Structural solution is needed to reduce disparities by race and ethnicity particularly in younger children
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