Common variants at the MHC locus and at chromosome 16q24.1 predispose to Barrett's esophagus

Barrett's esophagus is an increasingly common disease that is strongly associated with reflux of stomach acid and usually a hiatus hernia, and it strongly predisposes to esophageal adenocarcinoma (EAC), a tumor with a very poor prognosis. We report the first genome-wide association study on Barrett's esophagus, comprising 1,852 UK cases and 5,172 UK controls in the discovery stage and 5,986 cases and 12,825 controls in the replication stage. Variants at two loci were associated with disease risk: chromosome 6p21, rs9257809 (P(combined) = 4.09 × 10(-9); odds ratio (OR) = 1.21, 95% confidence interval (CI) =1.13-1.28), within the major histocompatibility complex locus, and chromosome 16q24, rs9936833 (P(combined) = 2.74 × 10(-10); OR = 1.14, 95% CI = 1.10-1.19), for which the closest protein-coding gene is FOXF1, which is implicated in esophageal development and structure. We found evidence that many common variants of small effect contribute to genetic susceptibility to Barrett's esophagus and that SNP alleles predisposing to obesity also increase risk for Barrett's esophagus.

The Ties That Bind Us: Ritual, Fusion, and Identification

Most social scientists endorse some version of the claim that participating in collective rituals promotes social cohesion. The systematic testing and evaluation of this claim, however, has been prevented by a lack of precision regarding the nature of both ‘ritual’and ‘social cohesion’ as well as a lack of integration between the theories and findings of the social and evolutionary sciences. By directly addressing these challenges, we argue that a systematic investigation and evaluation of the claim that ritual promotes social cohesion is achievable.

We present a general and testable theory of the relationship between ritual, cohesion, and cooperation that more precisely connects particular elements of ‘ritual,’ such as causal opacity and emotional arousal, to two particular forms
of ‘social cohesion’: group identification and identity fusion. Further, we ground this theory in an evolutionary account of why particular modes of ritual practice would be adaptive for societies with particular resource acquisition strategies. In setting out our conceptual framework we report numerous ongoing investigations that test our hypotheses against data from controlled psychological experiments as well as from theethnographic, archaeological, and historical records.

BRCA1 is an essential mediator of vinorelbine-induced apoptosis in mesothelioma

Therapeutic options for malignant pleural mesothelioma (MPM) are limited despite the increasing incidence globally. The vinca alkaloid vinorelbine exhibits clinical activity; however, to date, treatment optimization has not been achieved using biomarkers. BRCA1 regulates sensitivity to microtubule poisons; however, its role in regulating vinorelbine-induced apoptosis in mesothelioma is unknown. Here we demonstrate that BRCA1 plays an essential role in mediating vinorelbine-induced apoptosis, as evidenced by (1) the strong correlation between vinorelbine sensitivity and BRCA1 expression level; (2) induction of resistance to vinorelbine by BRCA1 using siRNA oligonucleotides; (3) dramatic down-regulation of BRCA1 following selection for vinorelbine resistance; and (4) the re-activation of vinorelbine-induced apoptosis following re-expression of BRCA1 in resistant cells. To determine whether loss of BRCA1 expression in mesothelioma was potentially relevant in vivo, BRCA1 immunohistochemistry was subsequently performed on 144 primary mesothelioma specimens. Loss of BRCA1 protein expression was identified in 38.9% of samples. Together, these data suggest that BRCA1 plays a critical role in mediating apoptosis by vinorelbine in mesothelioma, warranting its clinical evaluation as a predictive biomarker.

The Northern Ireland early onset psychosis study:Phenomenology and co-morbidity in the first 25 cases

Diagnosing psychotic disorders in young people is difficult. High rates of co-morbidity may be one reason for this difficulty, but it may also be the case that current diagnostic categories are not the most useful when approaching the care of young people with psychotic symptoms. The Northern Ireland Early Onset Psychosis Study is the first study to investigate psychotic disorders in children and adolescents in this region. Young people presenting with psychotic symptoms with onset before their 18th birthday were prospectively ascertained over a three-year period (2001-2004). Those who provided informed consent were subject to a diagnostic interview using the Kiddie-Schedule for Affective Disorders and Schizophrenia - Present and Lifetime Version. Twenty-five young people have completed the full assessment process to date. Ten young people met criteria for schizophrenia, 11 for affective psychosis, two for schizoaffective disorder and two for schizophreniform disorder. Twenty-one (80%) subjects also fulfilled criteria for at least one other DSM-IV diagnosis. In conclusion, whilst all subjects met criteria for one or other psychotic disorder, co-morbidity was common in this clinical sample. Greater awareness of the difficulties encountered when trying to reach a diagnosis in this age group may help to improve treatment outcomes.

An Ethical Production of Place:A Case for Economy in Architectural Design

Architects typically interpret Heidegger to mean that dwelling in the Black Forest, was more authentic than living in an industrialised society however we cannot turn back the clock so we are confronted with the reality of modernisation. Since the Second World War production has shifted from material to immaterial assets. Increasingly place is believed to offer resistance to this fluidity, but this belief can conversely be viewed as expressing a sublimated anxiety about our role in the world – the need to create buildings that are self-consciously contextual suggests that we may no longer be rooted in material places, but in immaterial relations.
This issue has been pondered by David Harvey in his paper From Place to Space and Back Again where he argues that the role of place in legitimising identity is ultimately a political process, as the interpretation of its meaning is dependent on whose interpretation it is. Doreen Massey has found that different classes of people are more or less mobile and that mobility is related to class and education rather than to nationality or geography. These thinkers point to a different set of questions than the usual space/place divide – how can we begin to address the economic mediation of spatial production to develop an ethical production of place? Part of the answer is provided by the French architectural practice Lacaton Vassal in their book Plus. They ask themselves how to produce more space for the same cost so that people can enjoy a better quality of life. Another French practitioner, Patrick Bouchain, has argued that architect’s fees should be inversely proportional to the amount of material resources that they consume. These approaches use economics as a starting point for generating architectural form and point to more ethical possibilities for architectural practice

Prostate stereotactic ablative body radiotherapy using a standard linear accelerator:toxicity, biochemical, and pathological outcomes

Biological dose escalation through stereotactic ablative radiotherapy (SABR) holds promise of improved patient convenience, system capacity and tumor control with decreased cost and side effects. The objectives are to report the toxicities, biochemical and pathologic outcomes of this prospective study.

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.

When terror hits home: Identity Fused Americans who saw Boston bombing victims as “family” provided aid

When tragedy strikes a group, only some group members characteristically rush to the aid of the victims. What motivates the altruism of these exceptional individuals? Here, we provide one set of answers based on data collected before and shortly after the 15 April 2013, Boston Marathon bombings. The results of three studies indicated that Americans who were strongly “fused” with their country were especially inclined to provide various forms of support to the bombing victims. Moreover, the degree to which participants reported perceiving fellow Americans as psychological kin statistically mediated links between fusion and pro-group outcomes. Together, these findings shed new light on relationships between personal and group identity, cognitive representations of group members, and personally costly, pro-group actions.

The Nature of Religious Diversity: A Cultural Ecosystem Approach

Studies of religious and other cultural groups tend to be particularistic or focus on one or more axes of variation. In this article we develop a more comprehensive approach to studying cultural diversity that emulates the study of biological diversity. We compare our cultural ecosystem approach with the axis approach, using the distinction between “tight” and “loose” cultures as an example. We show that while the axis approach is useful, the cultural ecosystem approach adds considerable value to the axis approach. We end by advocating the establishment of field sites for the study of religious and cultural diversity, comparable to biological field sites.

Magnetic mirror cavities as terahertz radiation sources and a means of quantifying radiation friction

We propose a radiation source based on a magnetic mirror cavity. Relativistic electrons are simulated entering the cavity and their trajectories and resulting emission spectra are calculated. The uniformity of the particle orbits is found to result in a frequency comb in terahertz range, the precise energies of which are tunable by varying the electron's gamma-factor. For very high energy particles, radiation friction causes the spectral harmonics to broaden and we suggest this as a possible way to verify competing classical equations of motion.

Ultrahigh Brilliance Multi-MeV γ-Ray Beams from Nonlinear Relativistic Thomson Scattering

We report on the generation of a narrow divergence (θγ<2.5mrad), multi-MeV (Emax≈18MeV) and ultrahigh peak brilliance (>1.8×1020photonss-1mm-2mrad-2 0.1% BW) γ-ray beam from the scattering of an ultrarelativistic laser-wakefield accelerated electron beam in the field of a relativistically intense laser (dimensionless amplitude a0≈2). The spectrum of the generated γ-ray beam is measured, with MeV resolution, seamlessly from 6 to 18 MeV, giving clear evidence of the onset of nonlinear relativistic Thomson scattering. To the best of our knowledge, this photon source has the highest peak brilliance in the multi-MeV regime ever reported in the literature.