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- Brownstein, Catherine A., et al.
(författare)
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An international effort towards developing standards for best practices in analysis, interpretation and reporting of clinical genome sequencing results in the CLARITY Challenge
- 2014
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Ingår i: Genome Biology. - : Springer Science and Business Media LLC. - 1465-6906 .- 1474-760X. ; 15:3, s. R53-
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is tremendous potential for genome sequencing to improve clinical diagnosis and care once it becomes routinely accessible, but this will require formalizing research methods into clinical best practices in the areas of sequence data generation, analysis, interpretation and reporting. The CLARITY Challenge was designed to spur convergence in methods for diagnosing genetic disease starting from clinical case history and genome sequencing data. DNA samples were obtained from three families with heritable genetic disorders and genomic sequence data were donated by sequencing platform vendors. The challenge was to analyze and interpret these data with the goals of identifying disease-causing variants and reporting the findings in a clinically useful format. Participating contestant groups were solicited broadly, and an independent panel of judges evaluated their performance. Results: A total of 30 international groups were engaged. The entries reveal a general convergence of practices on most elements of the analysis and interpretation process. However, even given this commonality of approach, only two groups identified the consensus candidate variants in all disease cases, demonstrating a need for consistent fine-tuning of the generally accepted methods. There was greater diversity of the final clinical report content and in the patient consenting process, demonstrating that these areas require additional exploration and standardization. Conclusions: The CLARITY Challenge provides a comprehensive assessment of current practices for using genome sequencing to diagnose and report genetic diseases. There is remarkable convergence in bioinformatic techniques, but medical interpretation and reporting are areas that require further development by many groups.
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| 2. |
- Ramasamy, Adaikalavan, et al.
(författare)
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Genome-Wide Association Studies of Asthma in Population-Based Cohorts Confirm Known and Suggested Loci and Identify an Additional Association near HLA
- 2012
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Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 7:9, s. e44008-
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Asthma has substantial morbidity and mortality and a strong genetic component, but identification of genetic risk factors is limited by availability of suitable studies. Objectives: To test if population-based cohorts with self-reported physician-diagnosed asthma and genome-wide association (GWA) data could be used to validate known associations with asthma and identify novel associations. Methods: The APCAT (Analysis in Population-based Cohorts of Asthma Traits) consortium consists of 1,716 individuals with asthma and 16,888 healthy controls from six European-descent population-based cohorts. We examined associations in APCAT of thirteen variants previously reported as genome-wide significant (P < 5x10(-8)) and three variants reported as suggestive (P < 5 x 10(-7)). We also searched for novel associations in APCAT (Stage 1) and followed-up the most promising variants in 4,035 asthmatics and 11,251 healthy controls (Stage 2). Finally, we conducted the first genome-wide screen for interactions with smoking or hay fever. Main Results: We observed association in the same direction for all thirteen previously reported variants and nominally replicated ten of them. One variant that was previously suggestive, rs11071559 in RORA, now reaches genome-wide significance when combined with our data (P = 2.4x10(-9)). We also identified two genome-wide significant associations: rs13408661 near IL1RL1/IL18R1 (PStage1+Stage2 = 1.1x10(-9)), which is correlated with a variant recently shown to be associated with asthma (rs3771180), and rs9268516 in the HLA region (PStage1+Stage2 = 1.1x10(-8)), which appears to be independent of previously reported associations in this locus. Finally, we found no strong evidence for gene-environment interactions with smoking or hay fever status. Conclusions: Population-based cohorts with simple asthma phenotypes represent a valuable and largely untapped resource for genetic studies of asthma.
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| 3. |
- Troch, Peter A., et al.
(författare)
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The importance of hydraulic groundwater theory in catchment hydrology : The legacy of Wilfried Brutsaert and Jean-Yves Parlange
- 2013
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Ingår i: Water resources research. - : American Geophysical Union (AGU). - 0043-1397 .- 1944-7973. ; 49:9, s. 5099-5116
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Forskningsöversikt (refereegranskat)abstract
- Based on a literature overview, this paper summarizes the impact and legacy of the contributions of Wilfried Brutsaert and Jean-Yves Parlange (Cornell University) with respect to the current state-of-the-art understanding in hydraulic groundwater theory. Forming the basis of many applications in catchment hydrology, ranging from drought flow analysis to surface water-groundwater interactions, hydraulic groundwater theory simplifies the description of water flow in unconfined riparian and perched aquifers through assumptions attributed to Dupuit and Forchheimer. Boussinesq (1877) derived a general equation to study flow dynamics of unconfined aquifers in uniformly sloping hillslopes, resulting in a remarkably accurate and applicable family of results, though often challenging to solve due to its nonlinear form. Under certain conditions, the Boussinesq equation can be solved analytically allowing compact representation of soil and geomorphological controls on unconfined aquifer storage and release dynamics. The Boussinesq equation has been extended to account for flow divergence/convergence as well as for nonuniform bedrock slope (concave/convex). The extended Boussinesq equation has been favorably compared to numerical solutions of the three-dimensional Richards equation, confirming its validity under certain geometric conditions. Analytical solutions of the linearized original and extended Boussinesq equations led to the formulation of similarity indices for baseflow recession analysis, including scaling rules, to predict the moments of baseflow response. Validation of theoretical recession parameters on real-world streamflow data is complicated due to limited measurement accuracy, changing boundary conditions, and the strong coupling between the saturated aquifer with the overlying unsaturated zone. However, recent advances are shown to have mitigated several of these issues. The extended Boussinesq equation has been successfully applied to represent baseflow dynamics in catchment-scale hydrological models, and it is currently considered to represent lateral redistribution of groundwater in land surface schemes applied in global circulation models. From the review, it is clear that Wilfried Brutsaert and Jean-Yves Parlange stimulated a body of research that has led to several fundamental discoveries and practical applications with important contributions in hydrological modeling.
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| 4. |
- Wilson, Catherine M., et al.
(författare)
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Violence Against Teachers : Prevalence and Consequences
- 2011
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Ingår i: Journal of Interpersonal Violence. - : SAGE Publications. - 0886-2605 .- 1552-6518. ; 26:12, s. 2353-2371
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Tidskriftsartikel (refereegranskat)abstract
- Data collected from 731 teachers were used to examine the consequences of violence directed toward teachers while in the workplace. Analyses showed that the majority of respondents (n = 585, 80.0%) had experienced school-related violence-broadly defined-at one point in their careers. Serious violence (actual, attempted, or threatened physical violence) was less common, but still common enough to be of concern (n = 202, 27.6%). Violence predicted physical and emotional effects, as well as teaching-related functioning. In addition, a model with fear as a potential mediator revealed that both fear and violence were independently predictive of these negative outcomes. Finally, analyses showed that, in general, women reported higher levels of physical symptoms compared to men. We discuss the implications of violence against teachers in terms of personal consequences and the implications for mental health professionals working in an educational setting.
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