A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus

Esophageal adenocarcinoma is a cancer with rising incidence and poor survival. Most such cancers arise in a specialized intestinal metaplastic epithelium, which is diagnostic of Barrett's esophagus. In a genome-wide association study, we compared esophageal adenocarcinoma cases (n = 2,390) and individuals with precancerous Barrett's esophagus (n = 3,175) with 10,120 controls in 2 phases. For the combined case group, we identified three new associations. The first is at 19p13 (rs10419226: P = 3.6 × 10(-10)) in CRTC1 (encoding CREB-regulated transcription coactivator), whose aberrant activation has been associated with oncogenic activity. A second is at 9q22 (rs11789015: P = 1.0 × 10(-9)) in BARX1, which encodes a transcription factor important in esophageal specification. A third is at 3p14 (rs2687201: P = 5.5 × 10(-9)) near the transcription factor FOXP1, which regulates esophageal development. We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma.

Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture

Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.

The Limits of Local Accommodation: Why Contentious Events Remain Prone to Conflict in Northern Ireland

This article examines the difficulties of finding local solutions to the problem of contentious events in contemporary Northern Ireland. In so doing, it offers a sociological perspective on fundamental divisions in Northern Ireland: between classes and between communities. It shows how its chosen case study—parades and associated protests in north Belfast—exemplifies the most fundamental problem that endures in post-Agreement Northern Ireland, namely that political authority is not derived from a common civic culture (as is the norm in Western liberal democracy) but rather that legitimacy is still founded on the basis of the culture of either one or the other community. Haugaard’s reflections on authority and legitimacy are used to explore Northern Ireland’s atypical experience of political conflict vis-`a-vis the Western liberal democratic model. The Bourdieusian concepts of field illusio and doxa help to explain why it is that parading remains such an important political and symbolic touchstone in this society.

Defining the role of common variation in the genomic and biological architecture of adult human height

Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different numbers of variants in independent studies, we show that the most strongly associated 1/42,000, 1/43,700 and 1/49,500 SNPs explained 1/421%, 1/424% and 1/429% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/I 2-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.

Multimedia Resource Allocation in mmWave 5G Networks

The 5G network infrastructure is driven by the evolution of today's most demanding applications. Already, multimedia applications such as on-demand HD video and IPTV require gigabit- per-second throughput and low delay, while future technologies include ultra HDTV and machine-to-machine communication. Mm-Wave technologies such as IEEE 802.15.3c and IEEE 802.11ad are ideal candidates to deliver high throughput to multiple users demanding differentiated QoS. Optimization is often used as a methodology to meet throughput and delay constraints. However, traditional optimization techniques are not suited to a mixed set of multimedia applications. Particle swarm optimization (PSO) is shown as a promising technique in this context. Channel-time allocation PSO (CTA-PSO) is successfully shown here to allocate resource even in scenarios where blockage of the 60 GHz signal poses significant challenges.

The Business of Building Peace: Private Sector Cooperation across the Irish Border

The sustainability of cross-border peacebuilding initiatives is increasingly pertinent in a context of reduced public funding (national and European), yet the potential contribution to be made to this from private sector cooperation remains under-explored. This paper brings together quantitative data on cross-border trade with qualitative evidence from business leaders in the Irish border region in order to examine the nature of cross-border cooperation within the private sector and its possible connections to peacebuilding. This evidence is analysed in the light of three theses: spillover, contact and business-based peacebuilding. The first part of this paper assesses the conditions for cross-border business cooperation in Ireland, including funding support for economic development, European integration, and (post-Agreement) institutional change. The second part examines the particular contributions made by the private sector to peace, centring upon consciously non-political motivations (such as pragmatism and profit), networking and leadership.

Deliberative Democracy in Northern Ireland: Opportunities and challenges for consensus in a consociational system

The 1998 Multiparty Agreement established a consociational system that contains within it an explicit dualism: unionist/nationalist, north and south of Ireland, and British and Irish. But although this formula has facilitated relatively stable and devolved governance, it is based on a distorted representation of a society in which there are much more complex divisions and, indeed, many common problems. Citizen-led efforts towards deliberative democracy since the 1980s have demonstrated both the will and the capacity for alternative, consensual political expressions. This chapter examines the challenges and opportunities facing these citizen-led initiatives in a political environment which, despite the significant decline in violence and terror, seems stubbornly resistant to the idea of broadening the various means of democratic participation.

Ireland after Rapid Immigration:The consequences of neglect

Essay review of:
Immigration and Schooling in the Republic of Ireland: Making a Difference?, by Dympna Devine . Manchester, UK: Manchester University Press, 2012. 186pp. $24.95 paper. ISBN: 9780719081026.
Immigration and Social Cohesion in the Republic of Ireland, by Bryan Fanning . Manchester, UK: Manchester University Press, 2011. 202pp. $24.95 paper. ISBN: 9780719084799.
Understanding Immigration in Ireland: State, Capital and Labour in a Global Age, by Steven Loyal . Manchester, UK: Manchester University Press, 2011. 283pp. $24.95 paper. ISBN: 9780719078316.

European Border Regions in Comparison: Overcoming Nationalistic Aspects or Re-Nationalization?

Essay Review of Katarzyna Stokłosa and Gerhard Besier (eds) (2014) European Border Regions in Comparison: Overcoming Nationalistic Aspects or Re-Nationalization? (London: Routledge)

New genetic loci link adipose and insulin biology to body fat distribution

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.