| 1. |
- Linde, C, et al.
(författare)
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The Membership Committee of the ESC
- 2019
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Ingår i: Cardiovascular research. - : Oxford University Press (OUP). - 1755-3245 .- 0008-6363. ; 115:12, s. E130-E132
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Tidskriftsartikel (refereegranskat)
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| 2. |
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| 3. |
- Walsh, Roddy, et al.
(författare)
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Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls
- 2021
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Ingår i: Genetics in Medicine. - : Nature Publishing Group. - 1098-3600 .- 1530-0366. ; 23:1, s. 47-58
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 x 10(-18)) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 x 10(-13)). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
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| 4. |
- Becker, A, et al.
(författare)
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Practical Experiences from Existing Case Studies and Pilot River Basins
- 2010
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Ingår i: Water Framework Directive. - London : IWA Publishing. - 9781843392736 ; , s. 99-202
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Water resources planning and management and the development of appropriate policies requires methodologies and tools that are able to support systematic, integrative and multidisciplinary assessments at various scales. It also requires the quantification of various uncertainties in both data and models, and the incorporation of stakeholders participation and institutional mechanisms into the various tools and risk assessment methodologies, to help decision makers understand and evaluate alternative measures and decisions. This requirement has been explicitly recognised in the context of the European Union Water Framework Directive (WFD). This book is one of the concrete outcomes of the Harmoni-CA concerted action (supported by the European Commission). It provides a framework for model-supported participatory planning of measures at various river basin scales and practical guidance to water managers and other interested stakeholders on the model-supported implementation of the WFD. The objective of the book is to offer guidance to water managers on the model-supported implementation of the Water Framework Directive at the level of a river basin district and at other levels (such as sub-basins, national, or international scale in the case of international river basins). It should help water managers to better understand how models may be used for planning purposes, while special attention is given to the problem of predicting an uncertain future, one very likely to differ from the present. Six case studies from different parts of Europe are provided to illustrate the practical applicability of the planning framework in the WFD implementation. They are very important for illustrating how concepts from earlier parts of the document are applied to real-world situations. The case studies cover several aspects of mesoscale river basin management, water quantity and quality issues, and the role of modelling, with two case studies located in pilot river basins. This text is intended for use by water managers and hydrologists engaged in the implementation of the Water Framework Directive.
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