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.

Polymorphisms near TBX5 and GDF7 are associated with increased risk for Barrett's esophagus

BACKGROUND & AIMS: Barrett's esophagus (BE) increases the risk of esophageal adenocarcinoma (EAC). We found the risk to be BE has been associated with single nucleotide polymorphisms (SNPs) on chromosome 6p21 (within the HLA region) and on 16q23, where the closest protein-coding gene is FOXF1. Subsequently, the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) identified risk loci for BE and esophageal adenocarcinoma near CRTC1 and BARX1, and within 100 kb of FOXP1. We aimed to identify further SNPs that increased BE risk and to validate previously reported associations.

METHODS: We performed a genome-wide association study (GWAS) to identify variants associated with BE and further analyzed promising variants identified by BEACON by genotyping 10,158 patients with BE and 21,062 controls.

RESULTS: We identified 2 SNPs not previously associated with BE: rs3072 (2p24.1; odds ratio [OR] = 1.14; 95% CI: 1.09-1.18; P = 1.8 × 10(-11)) and rs2701108 (12q24.21; OR = 0.90; 95% CI: 0.86-0.93; P = 7.5 × 10(-9)). The closest protein-coding genes were respectively GDF7 (rs3072), which encodes a ligand in the bone morphogenetic protein pathway, and TBX5 (rs2701108), which encodes a transcription factor that regulates esophageal and cardiac development. Our data also supported in BE cases 3 risk SNPs identified by BEACON (rs2687201, rs11789015, and rs10423674). Meta-analysis of all data identified another SNP associated with BE and esophageal adenocarcinoma: rs3784262, within ALDH1A2 (OR = 0.90; 95% CI: 0.87-0.93; P = 3.72 × 10(-9)).

CONCLUSIONS: We identified 2 loci associated with risk of BE and provided data to support a further locus. The genes we found to be associated with risk for BE encode transcription factors involved in thoracic, diaphragmatic, and esophageal development or proteins involved in the inflammatory response.

A Scalable Runtime for the ECOSCALE Heterogeneous Exascale Hardware Platform

Exascale computation is the next target of high performance computing. In the push to create exascale computing platforms, simply increasing the number of hardware devices is not an acceptable option given the limitations of power consumption, heat dissipation, and programming models which are designed for current hardware platforms. Instead, new hardware technologies, coupled with improved programming abstractions and more autonomous runtime systems, are required to achieve this goal. This position paper presents the design of a new runtime for a new heterogeneous hardware platform being developed to explore energy efficient, high performance computing. By combining a number of different technologies, this framework will both simplify the programming of current and future HPC applications, as well as automating the scheduling of data and computation across this new hardware platform. In particular, this work explores the use of FPGAs to achieve both the power and performance goals of exascale, as well as utilising the runtime to automatically effect dynamic configuration and reconfiguration of these platforms. 

Collective synchrony increases prosociality towards non-performers and out-group members

Previous research has found that behavioural synchrony between people leads to greater prosocial tendencies towards co-performers. In this study we investigated the scope of this prosocial effect: does it extend beyond the performance group to an extended in-group (extended parochial prosociality) or even to other people in general (generalized prosociality)? Participants performed a simple rhythmic movement either in time (synchrony condition) or out of time (asynchrony condition) with each other. Before and during the rhythmic movement, participants were exposed to a prime that made salient an extended in-group identity. After the task, half the participants had the opportunity to help an extended in-group member; the other half had the opportunity to help an out-group member. We found a main effect of our synchrony manipulation across both help targets suggesting that the prosocial effects of synchrony extend to non-performers. Furthermore, there was a significantly higher proportion of participants willing to help an out-group member after moving collectively in synchrony. This study shows that under certain intergroup contexts synchrony can lead to generalized prosociality with performers displaying greater prosociality even towards out-group members.

A relação terapêutica como pacto de cuidados (Perspectiva de Paul Ricoeur)

O capítulo é dedicado à reflexão, partindo de Ricoeur, sobre alguns aspectos que podem fornecer alicerce à tematização dos problemas do cuidar da Pessoa em vários níveis da Enfermagem. Importa-nos, acima de tudo, que, na procura da racionalidade própria da vida humana, as questões éticas da decisão do agir não fiquem soterradas por normas ou preceitos deontológicos adoptados acrítica e mecanicamente. Julgamos, então, necessário um esforço reflexivo práxico, pois sem reflexão orientada para a acção sairá malogrado o ideal de cuidar, que é, ao mesmo tempo, ideal de compreender, de respeitar e de servir responsavelmente o Outro, através do cultivo de relações interpessoais competentes, em termos científicos, técnicos e éticos.

Análise custo benefício de gestões alternativas do paúl de Lagos pelo método dos preços hedónicos/contigenciais com recursos a análise ANOVA sic: valorização do paul de Lagos

Dissertação mest., Gestão e Conservação da Natureza, Universidade do Algarve, 2009