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- Poley, L., et al.
(författare)
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The ABC130 barrel module prototyping programme for the ATLAS strip tracker
- 2020
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Ingår i: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- For the Phase-II Upgrade of the ATLAS Detector [1], 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-250) [2, 3] 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.
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- Shrine, N, et al.
(författare)
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Multi-ancestry genome-wide association analyses improve resolution of genes and pathways influencing lung function and chronic obstructive pulmonary disease risk
- 2023
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 55:3, s. 410-
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Tidskriftsartikel (refereegranskat)abstract
- Lung-function impairment underlies chronic obstructive pulmonary disease (COPD) and predicts mortality. In the largest multi-ancestry genome-wide association meta-analysis of lung function to date, comprising 580,869 participants, we identified 1,020 independent association signals implicating 559 genes supported by ≥2 criteria from a systematic variant-to-gene mapping framework. These genes were enriched in 29 pathways. Individual variants showed heterogeneity across ancestries, age and smoking groups, and collectively as a genetic risk score showed strong association with COPD across ancestry groups. We undertook phenome-wide association studies for selected associated variants as well as trait and pathway-specific genetic risk scores to infer possible consequences of intervening in pathways underlying lung function. We highlight new putative causal variants, genes, proteins and pathways, including those targeted by existing drugs. These findings bring us closer to understanding the mechanisms underlying lung function and COPD, and should inform functional genomics experiments and potentially future COPD therapies.
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- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 8. |
- Shrine, Nick, et al.
(författare)
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New genetic signals for lung function highlight pathways and chronic obstructive pulmonary disease associations across multiple ancestries
- 2019
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 51:3, s. 481-493
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Tidskriftsartikel (refereegranskat)abstract
- Reduced lung function predicts mortality and is key to the diagnosis of chronic obstructive pulmonary disease (COPD). In a genome-wide association study in 400,102 individuals of European ancestry, we define 279 lung function signals, 139 of which are new. In combination, these variants strongly predict COPD in independent populations. Furthermore, the combined effect of these variants showed generalizability across smokers and never smokers, and across ancestral groups. We highlight biological pathways, known and potential drug targets for COPD and, in phenome-wide association studies, autoimmune-related and other pleiotropic effects of lung function-associated variants. This new genetic evidence has potential to improve future preventive and therapeutic strategies for COPD.
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- Shafer, Aaron B. A., et al.
(författare)
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Genomics and the challenging translation into conservation practice
- 2015
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Ingår i: Trends in Ecology & Evolution. - : Elsevier. - 0169-5347 .- 1872-8383. ; 30:2, s. 78-87
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Tidskriftsartikel (refereegranskat)abstract
- The global loss of biodiversity continues at an alarming rate. Genomic approaches have been suggested as a promising tool for conservation practice as scaling up to genome-wide data can improve traditional conservation genetic inferences and provide qualitatively novel insights. However, the generation of genomic data and subsequent analyses and interpretations remain challenging and largely confined to academic research in ecology and evolution. This generates a gap between basic research and applicable solutions for conservation managers faced with multifaceted problems. Before the real-world conservation potential of genomic research can be realized, we suggest that current infrastructures need to be modified, methods must mature, analytical pipelines need to be developed, and successful case studies must be disseminated to practitioners.
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- Gustafsson, U. O., et al.
(författare)
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Guidelines for Perioperative Care in Elective Colorectal Surgery : Enhanced Recovery After Surgery (ERAS®) Society Recommendations: 2018
- 2019
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Ingår i: World Journal of Surgery. - : Springer. - 0364-2313 .- 1432-2323. ; 43:3, s. 659-695
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Forskningsöversikt (refereegranskat)abstract
- Background: This is the fourth updated Enhanced Recovery After Surgery (ERAS®) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded recommendations for each ERAS item within the ERAS® protocol.Methods: A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.Results: All recommendations on ERAS® protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly.Conclusions: The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS® Society in this comprehensive consensus review.
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- Jasechko, S., et al.
(författare)
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Late-glacial to late-Holocene shifts in global precipitation delta O-18
- 2015
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 11:10, s. 1375-1393
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Tidskriftsartikel (refereegranskat)abstract
- Reconstructions of Quaternary climate are often based on the isotopic content of paleo-precipitation preserved in proxy records. While many paleo-precipitation isotope records are available, few studies have synthesized these dispersed records to explore spatial patterns of late-glacial precipitation delta O-18. Here we present a synthesis of 86 globally distributed groundwater (n = 59), cave calcite (n = 15) and ice core (n = 12) isotope records spanning the late-glacial (defined as similar to 50 000 to similar to 20 000 years ago) to the late-Holocene (within the past similar to 5000 years). We show that precipitation delta O-18 changes from the late-glacial to the late-Holocene range from -7.1% (delta O-18(late-Holocene) > delta O-18(late-glacial)) to + 1.7% (delta O-18(late-glacial) > delta O-18(late-Holocene)), with the majority (77 %) of records having lower late-glacial delta O-18 than late-Holocene delta O-18 values. High-magnitude, negative precipitation delta O-18 shifts are common at high latitudes, high altitudes and continental interiors (delta O-18(late-Holocene) > delta O-18(late-glacial) by more than 3 %). Conversely, low-magnitude, positive precipitation delta O-18 shifts are concentrated along tropical and subtropical coasts (delta O-18(late-glacial) > delta O-18(late-Holocene) by less than 2 %). Broad, global patterns of late-glacial to late-Holocene precipitation delta O-18 shifts suggest that stronger-than-modern isotopic distillation of air masses prevailed during the late-glacial, likely impacted by larger global temperature differences between the tropics and the poles. Further, to test how well general circulation models reproduce global precipitation delta O-18 shifts, we compiled simulated precipitation delta O-18 shifts from five isotope-enabled general circulation models simulated under recent and last glacial maximum climate states. Climate simulations generally show better intermodel and model-measurement agreement in temperate regions than in the tropics, highlighting a need for further research to better understand how inter-model spread in convective rainout, seawater delta O-18 and glacial topography parameterizations impact simulated precipitation delta O-18. Future research on paleo-precipitation delta O-18 records can use the global maps of measured and simulated late-glacial precipitation isotope compositions to target and prioritize field sites.
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| 14. |
- Schillemans, T., et al.
(författare)
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Conflictual Accountability: Behavioral Responses to Conflictual Accountability of Agencies
- 2021
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Ingår i: Administration & Society. - : SAGE Publications. - 0095-3997 .- 1552-3039. ; 53:8, s. 1232-1262
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Tidskriftsartikel (refereegranskat)abstract
- In contemporary public governance, leaders of public organizations are faced with multiple, and oftentimes conflictual, accountability claims. Drawing upon a survey of CEO's of agencies in seven countries, we explore whether and how conflictual accountability regimes relate to strategic behaviors by agency-CEO's and their political principals. The presence of conflictual accountability is experienced as a major challenge and is associated with important behavioral responses by those CEO's. This article demonstrates empirically how conflictual accountability is related to (a) controlling behaviors by principals, (b) constituency building behaviors by agencies, and (c) a general pattern of intensified contacts and information processing by both parties.
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