Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Teaching Im/migration through an Ethnographic Portrait Project

The Im/migrant Ethnographic Portrait Project was designed for introductory cultural anthropology courses and has a threefold aim: 1) to familiarize students with research methods, 2) to facilitate students’ deeper understanding of migration by connecting course readings with a hands-on project, and 3) to humanize im/migrants by bringing students into one-on-one conversations where they will hear a person’s story in their own words. To support students’ success with this semester-long project and to ensure (as far as is possible) that no harm is done, we provide instruction and feedback through a series of progressive assignments. In this essay we explain each of these steps before concluding with remarks about the challenges and benefits of teaching this project.

Teaching Im/migration through an Ethnographic Portrait Project

The Im/migrant Ethnographic Portrait Project was designed for introductory cultural anthropology courses and has a threefold aim: 1) to familiarize students with research methods, 2) to facilitate students’ deeper understanding of migration by connecting course readings with a hands-on project, and 3) to humanize im/migrants by bringing students into one-on-one conversations where they will hear a person’s story in their own words. To support students’ success with this semester-long project and to ensure (as far as is possible) that no harm is done, we provide instruction and feedback through a series of progressive assignments. In this essay we explain each of these steps before concluding with remarks about the challenges and benefits of teaching this project.

Local host specialization, host-switching, and dispersal shape the regional distributions of avian haemosporidian parasites

The drivers of regional parasite distributions are poorly understood, especially in comparison with those of free-living species. For vector-transmitted parasites, in particular, distributions might be influenced by host-switching and by parasite dispersal with primary hosts and vectors. We surveyed haemosporidian blood parasites (Plasmodium and Haemoproteus) of small land birds in eastern North America to characterize a regional parasite community. Distributions of parasite populations generally reflected distributions of their hosts across the region. However, when the interdependence between hosts and parasites was controlled statistically, local host assemblages were related to regional climatic gradients, but parasite assemblages were not. Moreover, because parasite assemblage similarity does not decrease with distance when controlling for host assemblages and climate, parasites evidently disperse readily within the distributions of their hosts. The degree of specialization on hosts varied in some parasite lineages over short periods and small geographic distances independently of the diversity of available hosts and potentially competing parasite lineages. Nonrandom spatial turnover was apparent in parasite lineages infecting one host species that was well-sampled within a single year across its range, plausibly reflecting localized adaptations of hosts and parasites. Overall, populations of avian hosts generally determine the geographic distributions of haemosporidian parasites. However, parasites are not dispersal-limited within their host distributions, and they may switch hosts readily

Accommodating individual preferences in nurse scheduling via auctions and optimization

Nurse scheduling, Health care applications, Optimization, Auction,