2 resultados para meta-analytical study

em Worcester Research and Publications - Worcester Research and Publications - UK


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This paper aims to reflect upon the potential analytical utility of the political discourse analysis framework proposed by Isabela Fairclough and Norman Fairclough (2012). This framework represents the most recent substantive development upon Norman Fairclough's past work situated within the wider school of Critical Discourse Analysis, building upon his influential position this methodological tradition. Central to this development is the additional emphasis placed upon the necessity to conceptualise all political discourse as 'argumentative' in nature, given that political actors are ultimately proposing or refuting particular courses of concrete future action. This paper will therefore apply Fairclough and Fairclough's model to provisional data derived from an ongoing doctoral thesis which considers the nature of political discourse relating to sport, the Glasgow 2014 Commonwealth Games and Scottish independence, with an ultimate aim of critically considering the benefits and limitations of applying this analytical framework as a methodological tool within this ongoing study.

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Lithium is the mainstay prophylactic treatment for bipolar disorder (BD), but treatment response varies considerably across individuals. Patients who respond well to lithium treatment might represent a relatively homogeneous subtype of this genetically and phenotypically diverse disorder. Here, we performed genome-wide association studies (GWAS) to identify (i) specific genetic variations influencing lithium response and (ii) genetic variants associated with risk for lithium-responsive BD. Patients with BD and controls were recruited from Sweden and the United Kingdom. GWAS were performed on 2698 patients with subjectively defined (self-reported) lithium response and 1176 patients with objectively defined (clinically documented) lithium response. We next conducted GWAS comparing lithium responders with healthy controls (1639 subjective responders and 8899 controls; 323 objective responders and 6684 controls). Meta-analyses of Swedish and UK results revealed no significant associations with lithium response within the bipolar subjects. However, when comparing lithium-responsive patients with controls, two imputed markers attained genome-wide significant associations, among which one was validated in confirmatory genotyping (rs116323614, P=2.74 × 10-8). It is an intronic single-nucleotide polymorphism (SNP) on chromosome 2q31.2 in the gene SEC14 and spectrin domains 1 (SESTD1), which encodes a protein involved in regulation of phospholipids. Phospholipids have been strongly implicated as lithium treatment targets. Furthermore, we estimated the proportion of variance for lithium-responsive BD explained by common variants ('SNP heritability') as 0.25 and 0.29 using two definitions of lithium response. Our results revealed a genetic variant in SESTD1 associated with risk for lithium-responsive BD, suggesting that the understanding of BD etiology could be furthered by focusing on this subtype of BD.