23 research outputs found

    The ABC130 barrel module prototyping programme for the ATLAS strip tracker

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    For the Phase-II Upgrade of the ATLAS Detector, its Inner Detector, consisting of silicon pixel, silicon strip and transition radiation sub-detectors, will be replaced with an all new 100 % silicon tracker, composed of a pixel tracker at inner radii and a strip tracker at outer radii. The future ATLAS strip tracker will include 11,000 silicon sensor modules in the central region (barrel) and 7,000 modules in the forward region (end-caps), which are foreseen to be constructed over a period of 3.5 years. The construction of each module consists of a series of assembly and quality control steps, which were engineered to be identical for all production sites. In order to develop the tooling and procedures for assembly and testing of these modules, two series of major prototyping programs were conducted: an early program using readout chips designed using a 250 nm fabrication process (ABCN-25) and a subsequent program using a follow-up chip set made using 130 nm processing (ABC130 and HCC130 chips). This second generation of readout chips was used for an extensive prototyping program that produced around 100 barrel-type modules and contributed significantly to the development of the final module layout. This paper gives an overview of the components used in ABC130 barrel modules, their assembly procedure and findings resulting from their tests.Comment: 82 pages, 66 figure

    Common, low-frequency, rare, and ultra-rare coding variants contribute to COVID-19 severity

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    The combined impact of common and rare exonic variants in COVID-19 host genetics is currently insufficiently understood. Here, common and rare variants from whole-exome sequencing data of about 4000 SARS-CoV-2-positive individuals were used to define an interpretable machine-learning model for predicting COVID-19 severity. First, variants were converted into separate sets of Boolean features, depending on the absence or the presence of variants in each gene. An ensemble of LASSO logistic regression models was used to identify the most informative Boolean features with respect to the genetic bases of severity. The Boolean features selected by these logistic models were combined into an Integrated PolyGenic Score that offers a synthetic and interpretable index for describing the contribution of host genetics in COVID-19 severity, as demonstrated through testing in several independent cohorts. Selected features belong to ultra-rare, rare, low-frequency, and common variants, including those in linkage disequilibrium with known GWAS loci. Noteworthily, around one quarter of the selected genes are sex-specific. Pathway analysis of the selected genes associated with COVID-19 severity reflected the multi-organ nature of the disease. The proposed model might provide useful information for developing diagnostics and therapeutics, while also being able to guide bedside disease management. © 2021, The Author(s)

    Genetic mechanisms of critical illness in Covid-19.

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    Host-mediated lung inflammation is present,1 and drives mortality,2 in critical illness caused by Covid-19. Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development.3 Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study(GWAS) in 2244 critically ill Covid-19 patients from 208 UK intensive care units (ICUs). We identify and replicate novel genome-wide significant associations, on chr12q24.13 (rs10735079, p=1.65 [Formula: see text] 10-8) in a gene cluster encoding antiviral restriction enzyme activators (OAS1, OAS2, OAS3), on chr19p13.2 (rs2109069, p=2.3 [Formula: see text] 10-12) near the gene encoding tyrosine kinase 2 (TYK2), on chr19p13.3 (rs2109069, p=3.98 [Formula: see text] 10-12) within the gene encoding dipeptidyl peptidase 9 (DPP9), and on chr21q22.1 (rs2236757, p=4.99 [Formula: see text] 10-8) in the interferon receptor gene IFNAR2. We identify potential targets for repurposing of licensed medications: using Mendelian randomisation we found evidence in support of a causal link from low expression of IFNAR2, and high expression of TYK2, to life-threatening disease; transcriptome-wide association in lung tissue revealed that high expression of the monocyte/macrophage chemotactic receptor CCR2 is associated with severe Covid-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms, and mediators of inflammatory organ damage in Covid-19. Both mechanisms may be amenable to targeted treatment with existing drugs. Large-scale randomised clinical trials will be essential before any change to clinical practice

    Integrating employability resources to strengthen student – personal tutor partnerships

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    The Teaching Excellence Framework has resulted in an increased focus on personalised learning, as part of the wider learning environment, and on graduate employment, as an indicator of student outcomes and learning gain. One element of the academic role which is fundamental to both these considerations is that of the personal tutor. The benefits of an effective personal tutoring system include promoting the development of transferable skills, improving student retention and progression, and strengthening career awareness and employability (McFarlane, 2016). Inconsistencies in the implementation of this important element of individualised student support may be partly due to staff uncertainties about the scope of their responsibilities, concerns about the boundaries between pastoral and academic elements of the role, and the lack of readily available resources and tools for the personal tutor. (Race 2010; Luck 2010; Gardner and Lane 2010; Barlow and Antoniou 2007; Levy et al. 2009). Moreover, students can have variable experiences of personal tutoring (Thomas 2006a; Hixenbaugh, Pearson and Williams, 2006), which result in them viewing it as poorly organised and perhaps unnecessary. This presentation will explore the challenges involved in the creation of a tool designed to help personal tutors facilitate student reflection on their progress and to signpost them to a range of employability resources and opportunities, and the strategies used to overcome these. There were four contributory elements to this development. An exploration of staff and students’ experiences of personal tutoring included focus group discussions and semi-structured interviews with students and staff across five different Departments which included sciences, geography and engineering. The findings of an institutional survey into student readiness for employability highlighted the proportion of students who did not appear to be considering the importance of in-course preparation for future graduate employment. Two examples of initiatives in which personal tutoring had been successfully embedded into curricula were then considered, from geography and health programmes. One of these had involved embedding personal tutoring within a core module and the other incorporated several mandatory individual meetings scheduled between students and personal tutors throughout an undergraduate programme. Lessons learned from all these elements were discussed with personal tutor coordinators, and the Director of Placements and Employability who advised about local, national and regional resources and opportunities, both at Faculty and University level. Building on these elements, a tool for personal tutors was developed and distributed to colleagues. The aim of the tool was to provide them with easily accessible resources which could be used at meetings with their personal tutees. It included elements of the work and toolkit developed by Winston, Nash, Parker and Rowntree (2017), created to encourage students to optimise the use of their assessment feedback, and reflect on their personal development. Alongside this, it highlighted the whole range of employability opportunities which might enable students to better consider their future following graduation. Feedback from colleagues was very positive and it was disseminated across the institution. Comments from colleagues who were new to Higher Education indicated that some were quite daunted as it highlighted the scope of their role as personal tutor, but that the tool was helpful in adapting to this responsibility
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