Genome-wide association study of perioperative myocardial infarction after coronary artery bypass surgery.

OBJECTIVES: Identification of patient subpopulations susceptible to develop myocardial infarction (MI) or, conversely, those displaying either intrinsic cardioprotective phenotypes or highly responsive to protective interventions remain high-priority knowledge gaps. We sought to identify novel common genetic variants associated with perioperative MI in patients undergoing coronary artery bypass grafting using genome-wide association methodology. SETTING: 107 secondary and tertiary cardiac surgery centres across the USA. PARTICIPANTS: We conducted a stage I genome-wide association study (GWAS) in 1433 ethnically diverse patients of both genders (112 cases/1321 controls) from the Genetics of Myocardial Adverse Outcomes and Graft Failure (GeneMAGIC) study, and a stage II analysis in an expanded population of 2055 patients (225 cases/1830 controls) combined from the GeneMAGIC and Duke Perioperative Genetics and Safety Outcomes (PEGASUS) studies. Patients undergoing primary non-emergent coronary bypass grafting were included. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome variable was perioperative MI, defined as creatine kinase MB isoenzyme (CK-MB) values ≥10× upper limit of normal during the first postoperative day, and not attributable to preoperative MI. Secondary outcomes included postoperative CK-MB as a quantitative trait, or a dichotomised phenotype based on extreme quartiles of the CK-MB distribution. RESULTS: Following quality control and adjustment for clinical covariates, we identified 521 single nucleotide polymorphisms in the stage I GWAS analysis. Among these, 8 common variants in 3 genes or intergenic regions met p<10(-5) in stage II. A secondary analysis using CK-MB as a quantitative trait (minimum p=1.26×10(-3) for rs609418), or a dichotomised phenotype based on extreme CK-MB values (minimum p=7.72×10(-6) for rs4834703) supported these findings. Pathway analysis revealed that genes harbouring top-scoring variants cluster in pathways of biological relevance to extracellular matrix remodelling, endoplasmic reticulum-to-Golgi transport and inflammation. CONCLUSIONS: Using a two-stage GWAS and pathway analysis, we identified and prioritised several potential susceptibility loci for perioperative MI.

THE COMPLETE PRELUDES OF ALEXANDER SCRIABIN: THE EVOLUTION OF HIS REVOLUTIONARY COMPOSITIONAL STYLE

During the second half of the nineteenth century, a series of remarkable advances in musical composition emerged in the works of such innovative spirits as Franz Liszt, Hector Berlioz and Richard Wagner. Their pioneering works exerted an extraordinary impact on the music of the subsequent generation of composers--of disparate nationalities-who were active at the dawn of the 20th century: Including most notably Claude-Achille Debussy, Gustav Mahler, Richard Strauss, and Alexander Nikolayevich Scriabin. These important musical figures, each one leaving an indelible and formative imprint on late-nineteenth century Romantic style, together launched the modern era in music. Scriabin stands alone as a transcendental visionary: His music, initiated in the fashion of Chopin and Liszt, wanders through the realms of Debussy and Wagner, and, ultimately abandoning late Romantic tradition, unlocks the heretofore unforeseen power of atonality, bitonality, polyrhythms and key-signature free compositions. Arguably, Scriabin's compositions count among the most innovative, idiosyncratic and bewitching of all time. The development of Scriabin's groundbreaking compositional style is best understood by means of his piano works, which comprise the majority of his oeuvre. Beyond the larger works-his twelve sonatas, a concerto and a fantasy-Scriabin's piano explorations are also represented by miniature gems: The mazurkas, impromptus, waltzes, poems, a polonaise, etudes, nocturnes, morceaux and, in particular, the preludes. Scriabin's 90 preludes for piano, arranged in several opus numbers, richly exemplify the striking evolution of his ingenious music, his idiosyncratic philosophy and his provocative personality.

Translating Nietzsche, mediating literature: Alexander Tille and the limits of Anglo-German intercultural transfer

Dr. Alexander Tille (1866–1912) was one of the key-figures in Anglo-German intercultural transfer towards the end of the 19th century. As a lecturer in German at Glasgow University he was the first to translate and edit Nietzsche’s work into English. Writers such as W. B. Yeats were influenced by Nietzsche and used Tille’s translations. Tille’s social Darwinist reading of the philosopher’s oeuvre, however, had a narrowing impact on the reception of Nietzsche in the Anglo-Saxon world for decades. Through numerous publications Tille disseminated knowledge about British authors (e.g., Robert Louis Stevenson, William Wordsworth) in Germany and about German authors (e.g., Johann Wolfgang von Goethe) in Britain. His role as mediator also extended into areas such as history, religion, and industry. During the Boer war, however, Tille’s outspoken pro-German nationalism brought him in conflict with his British host society. After being physically attacked by his students he returned to Germany and published a highly anglophobic monograph. Tille personifies the paradox of Anglo-German relations in the pre-war years, which deteriorated despite an increase in intercultural transfer and knowledge about the respective Other. [From the Author]