The Degree of Segmental Aneuploidy Measured by Total Copy Number Abnormalities Predicts Survival and Recurrence in Superficial Gastroesophageal Adenocarcinoma

Abstract Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC

The degree of segmental aneuploidy measured by total copy number abnormalities predicts survival and recurrence in superficial gastroesophageal adenocarcinoma

Background: Prognostic biomarkers are needed for superficial gastroesophageal adenocarcinoma (EAC) to predict clinical outcomes and select therapy. Although recurrent mutations have been characterized in EAC, little is known about their clinical and prognostic significance. Aneuploidy is predictive of clinical outcome in many malignancies but has not been evaluated in superficial EAC. Methods: We quantified copy number changes in 41 superficial EAC using Affymetrix SNP 6.0 arrays. We identified recurrent chromosomal gains and losses and calculated the total copy number abnormality (CNA) count for each tumor as a measure of aneuploidy. We correlated CNA count with overall survival and time to first recurrence in univariate and multivariate analyses. Results: Recurrent segmental gains and losses involved multiple genes, including: HER2, EGFR, MET, CDK6, KRAS (recurrent gains); and FHIT, WWOX, CDKN2A/B, SMAD4, RUNX1 (recurrent losses). There was a 40-fold variation in CNA count across all cases. Tumors with the lowest and highest quartile CNA count had significantly better overall survival (p = 0.032) and time to first recurrence (p = 0.010) compared to those with intermediate CNA counts. These associations persisted when controlling for other prognostic variables. Significance: SNP arrays facilitate the assessment of recurrent chromosomal gain and loss and allow high resolution, quantitative assessment of segmental aneuploidy (total CNA count). The non-monotonic association of segmental aneuploidy with survival has been described in other tumors. The degree of aneuploidy is a promising prognostic biomarker in a potentially curable form of EAC. © 2014 Davison et al

Unjamming and cell shape in the asthmatic airway epithelium

From coffee beans flowing in a chute to cells remodelling in a living tissue, a wide variety of close-packed collective systems— both inert and living—have the potential to jam. The collective can sometimes flow like a fluid or jam and rigidify like a solid. The unjammed-to-jammed transition remains poorly understood, however, and structural properties characterizing these phases remain unknown. Using primary human bronchial epithelial cells, we show that the jamming transition in asthma is linked to cell shape, thus establishing in that system a structural criterion for cell jamming. Surprisingly, the collapse of critical scaling predicts a counter-intuitive relationship between jamming, cell shape and cell–cell adhesive stresses that is borne out by direct experimental observations. Cell shape thus provides a rigorous structural signature for classification and investigation of bronchial epithelial layer jamming in asthma, and potentially in any process in disease or development in which epithelial dynamics play a prominent role

The Crowdsourced Replication Initiative: Investigating Immigration and Social Policy Preferences. Executive Report.

In an era of mass migration, social scientists, populist parties and social movements raise concerns over the future of immigration-destination societies. What impacts does this have on policy and social solidarity? Comparative cross-national research, relying mostly on secondary data, has findings in different directions. There is a threat of selective model reporting and lack of replicability. The heterogeneity of countries obscures attempts to clearly define data-generating models. P-hacking and HARKing lurk among standard research practices in this area.This project employs crowdsourcing to address these issues. It draws on replication, deliberation, meta-analysis and harnessing the power of many minds at once. The Crowdsourced Replication Initiative carries two main goals, (a) to better investigate the linkage between immigration and social policy preferences across countries, and (b) to develop crowdsourcing as a social science method. The Executive Report provides short reviews of the area of social policy preferences and immigration, and the methods and impetus behind crowdsourcing plus a description of the entire project. Three main areas of findings will appear in three papers, that are registered as PAPs or in process

Comparison of Boundary Element and Finite Element Approaches to the EEG Forward Problem

International audienceThe accurate simulation of the electric fields evoked by neural activity is crucial for solving the inverse problem of EEG. Nowadays, boundary element methods (BEM) are frequently applied to achieve this goal, usually relying on the simpli-fication of approximating the human head by three nested compartments with isotropic conductivities (skin, skull, brain). Here, including the highly-conducting cerebrospinal fluid (CSF) is a difficult task due to the complex geomet-rical structure of the CSF, demanding a high number of additional nodes for an accurate modeling and thus a strongly increased computational effort. Though, CSF conductivity is well-known and nearly not varying inter-individually and its significant influence on EEG forward simulation has been shown. The CSF can be included at negligible computational costs when applying finite element (FE) forward approaches. In this study we compare the accuracy and performance of state-of-the-art BE and FE approaches in both artificial and realistic three layer head models, showing that all approaches lead to high numerical accuracies. Furthermore, we give an impression of the significant influence of modeling the CSF compartment as disregarding this compartment leads to model errors that lie clearly above the observed numerical errors

Multihospital surveillance of nosocomial methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococcus, and Clostridium difficile: analysis of a 4-year data-sharing project, 1999-2002.

BACKGROUND: This study sought to establish a benchmark of resistant organism rates among a cohort of regional hospitals. METHODS: The Centers for Disease Control and Prevention (CDC) definitions were used to standardize the methodology for obtaining rates per 1000 patient days of nosocomial infection and colonization with methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococcus (VRE), and nosocomial infection with Clostridium difficile (CDIF). Only newly acquired nosocomial cases were counted. Data were reported as individual hospital control charts and as cohorted aggregate data. VHA East Coast Infection Control Professionals from 32 hospitals in New Jersey and Pennsylvania were involved. RESULTS: Benchmarks were established with pooled mean rates for each cohort. During the observational period, a statistically significant downward trend was observed for VRE and MRSA (P = .02 and .0007, respectively), and an upward trend was observed for CDIF (P = .0256). CONCLUSION: Benchmarks were established to compare nosocomial MRSA, VRE, and CDIF rates. Although significant changes in rates were observed, no attempt was made to establish a causal relationship between infection control practices and observed rates. However, a secondary gain was achieved through sharing best practices