Stretching the IR theoretical spectrum on Irish neutrality: a critical social constructivist framework

In a 2006 International Political Science Review article, entitled "Choosing to Go It Alone: Irish Neutrality in Theoretical and Comparative Perspective," Neal G. Jesse argues that Irish neutrality is best understood through a neoliberal rather than a neorealist international relations theory framework. This article posits an alternative "critical social constructivist" framework for understanding Irish neutrality. The first part of the article considers the differences between neoliberalism and social constructivism and argues why critical social constructivism's emphasis on beliefs, identity, and the agency of the public in foreign policy are key factors explaining Irish neutrality today. Using public opinion data, the second part of the article tests whether national identity, independence, ethnocentrism, attitudes to Northern Ireland, and efficacy are factors driving public support for Irish neutrality. The results show that public attitudes to Irish neutrality are structured along the dimensions of independence and identity, indicating empirical support for a critical social constructivist framework of understanding of Irish neutrality

Queer Asian Subjects: Transgressive Sexualities and Heteronormative Meanings

This special issue of Asian Studies Review explores comparatively the production and transformation of gender and sexual subjectivities across and beyond South and Southeast Asia. More specifically, papers in this special issue disclose the complex intersections of ethnicity, race, class, gender, religion and nationality through which sexual subjectivities are formed and subject positions inhabited within and across these regions. By tracing the transnational movement of people and the circulation of images and ideas, their appropriations and effects, the papers in this volume reveal mutable and multiple sexual subjectivities that are no longer fixed in place, even as state discourses, hegemonic meanings and individual actors work to attach specific meanings to particular bodies. In this special issue we ask, what are the effects of migration, forced and chosen, on forms and formulations of gender and sexuality for people's embodied and discursive entanglements? How do spatial and temporal, as well as religious, economic and political changes alter and foreclose some kinds of intimacies and subjectivities even as they open and enable others? What are the social and cultural processes through which heteronormativity is articulated, enforced, transgressed and challenged

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Endoscopist-Directed Administration of Propofol: A Worldwide Safety Experience

Background & Aims: Endoscopist-directed propofol sedation (EDP) remains controversial. We sought to update the safety experience of EDP and estimate the cost of using anesthesia specialists for endoscopic sedation. Methods: We reviewed all published wor

Analyses of non-coding somatic drivers in 2,658 cancer whole genomes.

The discovery of drivers of cancer has traditionally focused on protein-coding genes1-4. Here we present analyses of driver point mutations and structural variants in non-coding regions across 2,658 genomes from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium5 of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). For point mutations, we developed a statistically rigorous strategy for combining significance levels from multiple methods of driver discovery that overcomes the limitations of individual methods. For structural variants, we present two methods of driver discovery, and identify regions that are significantly affected by recurrent breakpoints and recurrent somatic juxtapositions. Our analyses confirm previously reported drivers6,7, raise doubts about others and identify novel candidates, including point mutations in the 5' region of TP53, in the 3' untranslated regions of NFKBIZ and TOB1, focal deletions in BRD4 and rearrangements in the loci of AKR1C genes. We show that although point mutations and structural variants that drive cancer are less frequent in non-coding genes and regulatory sequences than in protein-coding genes, additional examples of these drivers will be found as more cancer genomes become available