222 research outputs found

    Adaptive stiffness in lattice metastructures through tensile-buckling inspired topology morphing

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    This paper explores the use of simultaneous tensile buckling of unit cells to induce a transformation in lattice topology. Under tension, unit cells undergo passive transformation from a rectangle-like to a triangle-/pentagon-like topology, with an associated change in the effective stiffness properties. This behaviour is investigated through finite element analysis and experiments, with analytical results providing insights into the observed behaviour. The analysis identifies (i) that the initial unit cell topology (rectangular) is dominated by membrane effects, (ii) the transformation phase is associated with negative stiffness, and (iii) once formed, the new topology (triangular/pentagonal) exhibits increased stiffness in both compression and tension. Finite element analysis confirms that the unit cell behaviour is also preserved in lattices. Under tension, the lattice undergoes a seven-fold increase in stiffness as it transitions from its initial to the new topology, with a regime of negative stiffness during this transformation accounting for approximately 82% of its total elastic deformation. This new approach to elastically tailor the nonlinear response of (meta-)materials/structures has the potential to contribute to the development of novel tensile energy absorbers

    Plasma-derived proteomic biomarkers in human leukocyte antigen-haploidentical or human leukocyte antigen-matched bone marrow transplantation using post-transplantation cyclophosphamide

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    Recent studies have suggested that plasma-derived proteins may be potential biomarkers relevant for graft-versus-host disease and/or non-relapse mortality occurring after allogeneic blood or marrow transplantation. However, none of these putative biomarkers have been assessed in patients treated either with human leukocyte antigen-haploidentical blood or marrow transplantation or with post-transplantation cyclophosphamide, which has been repeatedly associated with low rates of severe acute graft-versus-host disease, chronic graft-versus-host disease, and non-relapse mortality. We explored whether seven of these plasma-derived proteins, as measured by enzyme-linked immunosorbent assays, were predictive of clinical outcomes in post-transplantation cyclophosphamide-treated patients using plasma samples collected at serial predetermined timepoints from patients treated on prospective clinical studies of human leukocyte antigen-haploidentical (n=58; clinicaltrials.gov Identifier: 00796562) or human leukocyte antigen-matched-related or -unrelated (n=100; clinicaltrials.gov Identifiers: 00134017 and 00809276) T-cell-replete bone marrow transplantation. Day 30 levels of interleukin-2 receptor α, tumor necrosis factor receptor 1, serum STimulation-2 (IL1RL1 gene product), and regenerating islet-derived 3-α all had high areas under the curve of 0.74–0.97 for predicting non-relapse mortality occurrence by 3 months post-transplant in both the human leukocyte antigen-matched and human leukocyte antigen-haploidentical cohorts. In both cohorts, all four of these proteins were also predictive of subsequent non-relapse mortality occurring by 6, 9, or 12 months post-transplant and were significantly associated with non-relapse mortality in univariable analyses. Furthermore, day 30 elevations of interleukin-2 receptor α were associated with grade II–IV and III–IV acute graft-versus-host disease occurring after day 30 in both cohorts. These data confirm that plasma-derived proteins previously assessed in other transplantation platforms appear to retain prognostic and predictive utility in patients treated with post-transplantation cyclophosphamide

    Special and inclusive education in the Republic of Ireland: reviewing the literature from 2000 to 2009

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    Provision for pupils with special educational needs in Ireland has undergone considerable change and review in the first decade of the twenty first century. In response to international demands for a more equitable education system which recognises diversity and considers how schools might address the needs of pupils who have been previously marginalised, Irish legislation has focused upon the development of inclusive schooling. Researchers during this period have endeavoured to understand how responses to the demand for greater inclusion have impacted upon the perceived need for change. This paper reviews the research literature for this period and identifies four key themes under which research has been conducted. The literature pertaining to these themes is explored and a possible agenda for future researchers identifie

    What works for wellbeing in culture and sport? Report of a DELPHI process to support coproduction and establish principles and parameters of an evidence review

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    Aims: There is a growing recognition of the ways in which culture and sport can contribute to wellbeing. A strong evidence base is needed to support innovative service development and a 3-year research programme is being undertaken to capture best evidence of wellbeing impacts and outcomes of cultural and sporting activities in order to inform UK policy and practice. This article provides an overview of methods and findings from an initial coproduction process with key stakeholders that sought to explore and agree principles and parameters of the evidence review for culture, sport and wellbeing (CSW). Methods: A two-stage DELPHI process was conducted with a purposeful sample of 57 stakeholders between August and December 2015. Participants were drawn from a range of culture and sport organisations and included commissioners and managers, policy makers, representatives of service delivery organisations (SDOs) and scholars. The DELPHI 1 questionnaire was developed from extensive consultation in July and August 2015. It explored definitions of wellbeing, the role of evidence, quality assessment, and the culture and sport populations, settings and interventions that are most likely to deliver wellbeing outcomes. Following further consultation, the results, presented as a series of ranked statements, were sent back to participants (DELPHI 2), which allowed them to reflect on and, if they wished, express agreement or disagreement with the emerging consensus. Results: A total of 40 stakeholders (70.02%) responded to the DELPHI questionnaires. DELPHI 1 mapped areas of agreement and disagreement, confirmed in DELPHI 2. The exercise drew together the key priorities for the CSW evidence review. Conclusion: The DELPHI process, in combination with face-to-face deliberation, enabled stakeholders to engage in complex discussion and express nuanced priorities while also allowing the group to come to an overall consensus and agree outcomes. The results will inform the CSW evidence review programme until its completion in March 2018

    Hundreds of variants clustered in genomic loci and biological pathways affect human height

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    Most common human traits and diseases have a polygenic pattern of inheritance: DNA sequence variants at many genetic loci influence the phenotype. Genome-wide association (GWA) studies have identified more than 600 variants associated with human traits, but these typically explain small fractions of phenotypic variation, raising questions about the use of further studies. Here, using 183,727 individuals, we show that hundreds of genetic variants, in at least 180 loci, influence adult height, a highly heritable and classic polygenic trait. The large number of loci reveals patterns with important implications for genetic studies of common human diseases and traits. First, the 180 loci are not random, but instead are enriched for genes that are connected in biological pathways (P = 0.016) and that underlie skeletal growth defects (P < 0.001). Second, the likely causal gene is often located near the most strongly associated variant: in 13 of 21 loci containing a known skeletal growth gene, that gene was closest to the associated variant. Third, at least 19 loci have multiple independently associated variants, suggesting that allelic heterogeneity is a frequent feature of polygenic traits, that comprehensive explorations of already-discovered loci should discover additional variants and that an appreciable fraction of associated loci may have been identified. Fourth, associated variants are enriched for likely functional effects on genes, being over-represented among variants that alter amino-acid structure of proteins and expression levels of nearby genes. Our data explain approximately 10% of the phenotypic variation in height, and we estimate that unidentified common variants of similar effect sizes would increase this figure to approximately 16% of phenotypic variation (approximately 20% of heritable variation). Although additional approaches are needed to dissect the genetic architecture of polygenic human traits fully, our findings indicate that GWA studies can identify large numbers of loci that implicate biologically relevant genes and pathways.

    The impact of ADHD on the health and well-being of ADHD children and their siblings

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    Childhood attention-deficit/hyperactivity disorder (ADHD) has been associated with reduced health and well-being of patients and their families. The authors undertook a large UK survey-based observational study of the burden associated with childhood ADHD. The impact of ADHD on both the patient (N = 476) and their siblings (N = 337) on health-related quality of life (HRQoL) and happiness was quantified using multiple standard measures [e.g. child health utility-9D (CHU-9D), EuroQol-5D-Youth]. In the analysis, careful statistical adjustments were made to ensure a like-for-like comparison of ADHD families with two different control groups. We controlled for carers' ADHD symptoms, their employment and relationship status and siblings' ADHD symptoms. ADHD was associated with a significant deficit in the patient's HRQoL (with a CHU-9D score of around 6 % lower). Children with ADHD also have less sleep and were less happy with their family and their lives overall. No consistent decrement to the HRQoL of the siblings was identified across the models, except that related to their own conduct problems. The siblings do, however, report lower happiness with life overall and with their family, even when controlling for the siblings own ADHD symptoms. We also find evidence of elevated bullying between siblings in families with a child with ADHD. Overall, the current results suggest that the reduction in quality of life caused by ADHD is experienced both by the child with ADHD and their siblings

    Factors Associated With Sexual Coercion in a Representative Sample of Men in Australian Prisons

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    Very little research has focused on men or prisoners as victims of sexual violence. This study provides the first population-based analysis of factors associated with sexual coercion of men in Australian prisons, and the first to use a computer-assisted telephone interview to collect this information in a prison setting. A random sample of men in New South Wales and Queensland prisons were surveyed using computer-assisted telephone interviewing. We asked participants about sexual coercion, defined as being forced or frightened into doing something sexually that was unwanted while in prison. Associations between sexual coercion in prison and sociodemographics, sexual coercion history outside of prison, and prison-related factors were examined. Logistic regression was used to estimate adjusted odds ratios in examining factors associated with sexual coercion in prisons. Of 2626 eligible men, 2000 participated. Participants identifying as non-heterosexual and those with a history of sexual coercion outside prison were found to be most at risk. Those in prison for the first time and those who had spent more than 5 years in prison ever were also more likely to report sexual coercion. Although prison policies and improving prison officer training may help address immediate safety and health concerns of those at risk, given the sensitivity of the issue and likely under-reporting to correctional staff, community-based organizations and prisoner peer-based groups arguably have a role too in providing both preventive and trauma-focused support

    The EC-Earth3 Earth system model for the Coupled Model Intercomparison Project 6

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    The Earth system model EC-Earth3 for contributions to CMIP6 is documented here, with its flexible coupling framework, major model configurations, a methodology for ensuring the simulations are comparable across different high-performance computing (HPC) systems, and with the physical performance of base configurations over the historical period. The variety of possible configurations and sub-models reflects the broad interests in the EC-Earth community. EC-Earth3 key performance metrics demonstrate physical behavior and biases well within the frame known from recent CMIP models. With improved physical and dynamic features, new Earth system model (ESM) components, community tools, and largely improved physical performance compared to the CMIP5 version, EC-Earth3 represents a clear step forward for the only European community ESM. We demonstrate here that EC-Earth3 is suited for a range of tasks in CMIP6 and beyond.Peer reviewe
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