Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility.

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings

T. S. Eliot and the Cultural Divide

The modernist poet T. S. Eliot has been applauded and denounced for decades as a staunch champion of high art and an implacable opponent of popular culture. But Eliot’s elitism was never what it seemed. T. S. Eliot and the Cultural Divide refurbishes this great writer for the twenty-first century, presenting him as the complex figure he was, an artist attentive not only to literature but to detective fiction, vaudeville theater, jazz, and the songs of Tin Pan Alley. David Chinitz argues that Eliot was productively engaged with popular culture in some form at every stage of his career, and that his response to it, as expressed in his poetry, plays, and essays, was ambivalent rather than hostile. He shows that American jazz, for example, was a major influence on Eliot’s poetry during its maturation. He discusses Eliot’s surprisingly persistent interest in popular culture both in such famous works as The Waste Land and in such lesser-known pieces as Sweeney Agonistes. And he traces Eliot’s long, quixotic struggle to close the widening gap between high art and popular culture through a new type of public art: contemporary popular verse drama. What results is a work that will persuade adherents and detractors alike to return to Eliot and find in him a writer who liked a good show, a good thriller, and a good tune, as well as a “great” poem.https://ecommons.luc.edu/facultybooks/1245/thumbnail.jp

Six Countries, six health reform models? health care reform in Chile, Israel, Singapore, Switzerland, Taiwan and The Netherlands

10.1080/13876980903076237Journal of Comparative Policy Analysis: Research and Practice121-275-11