Genome-Wide Copy Number Analysis in Esophageal Adenocarcinoma Using High-Density Single-Nucleotide Polymorphism Arrays

We applied whole-genome single-nucleotide polymorphism arrays to define a comprehensive genetic profile of 23 esophageal adenocarcinoma (EAC) primary tumor biopsies based on loss of heterozygosity (LOH) and DNA copy number changes. Alterations were common, averaging 97 (range, 23-208) per tumor. LOH and gains averaged 33 (range, 3-83) and 31 (range, 11-73) per tumor, respectively. Copy neutral LOH events averaged 27 (range, 7-57) per EAC. We noted 126 homozygous deletions (HD) across the EAC panel (range, 0-11 in individual tumors). Frequent HDs within FHIT (17 of 23), WWOX (8 of 23), and DMD (6 of 23) suggest a role for common fragile sites or genomic instability in EAC etiology. HDs were also noted for known tumor suppressor genes (TSG), including CDKN2A, CDKN2B, SMAD4, and GALR1, and identified PDE4D and MGC48628 as potentially novel TSGs. All tumors showed LOH for most of chromosome 17p, suggesting that TSGs other than TP53 may be targeted. Frequent gains were noted around MYC (13 of 23), BCL9 (12 of 23), CTAGE1 (14 of 23), and ZNF217 (12 of 23). Thus, we have confirmed previous reports indicating frequent changes to FHIT, CDKN2A, TP53, and MYC in EAC and identified additional genes of interest. Meta-analysis of previous genome-wide EAC studies together with the data presented here highlighted consistent regions of gain on 8q, 18q, and 20q and multiple LOH regions on 4q, 5q, 17p, and 18q, suggesting that more than one gene may be targeted on each of these chromosome arms. The focal gains and deletions documented here are a step toward identifying the key genes involved in EAC development

Limitations to recording larger mammalian predators in savannah using camera traps and spoor

Traditionally, spoor (tracks, pug marks) have been used as a cost effective tool to assess the presence of larger mammals. Automated camera traps are now increasingly utilized to monitor wildlife, primarily as the cost has greatly declined and statistical approaches to data analysis have improved. While camera traps have become ubiquitous, we have little understanding of their effectiveness when compared to traditional approaches using spoor in the field. Here, we a) test the success of camera traps in recording a range of carnivore species against spoor; b) ask if simple measures of spoor size taken by amateur volunteers is likely to allow individual identification of leopards and c) for a trained tracker, ask if this approach may allow individual leopards to be followed with confidence in savannah habitat. We found that camera traps significantly under-recorded mammalian top and meso-carnivores, with camera traps more likely under-record the presence of smaller carnivores (civet 64%; genet 46%, Meller’s mongoose 45%) than larger (jackal sp. 30%, brown hyena 22%), while leopard was more likely to be recorded by camera trap (all recorded by camera trap only). We found that amateur trackers could be beneficial in regards to collecting presence data; however the large variance in measurements of spoor taken in the field by volunteers suggests that this approach is unlikely to add further data. Nevertheless, the use of simple spoor measurements in the field by a trained field researcher increases their ability to reliably follow a leopard trail in difficult terrain. This allows researchers to glean further data on leopard behaviour and habitat utilisation without the need for complex analysis

The Education of Multiple Family Members and the Life-Course Pathways to Cognitive Impairment

OBJECTIVES: This article asks how the educational attainments of multiple family members, including parents and offspring, are associated with the cognitive health of older adults in the United States. METHODS: We use panel data from the U.S. Health and Retirement Study (2000-2012) to examine how the education of an individual, their parent(s), and their offspring are associated with the prevalence of moderate/severe cognitive impairment and the onset of cognitive impairment among older adults using logistic regression and discrete-time event history analysis, respectively. RESULTS: We found that when combined, only the education of the individual is inversely associated with cognitive impairment at baseline. However, both the educational attainments of an individual and their offspring are negatively associated with the risk of becoming cognitively impaired, among individuals who were not already cognitively impaired. Conversely, parental education was not predictive of being cognitively impaired or the onset of impairment. Furthermore, we found that respondent gender did not moderate the relationship between a family member\u27s education and respondent cognitive health. DISCUSSION: This study adds to current research by asking how resources from earlier and subsequent generations matter for older adults\u27 cognitive health. Although we found little evidence that parental education matters at this life stage, results suggest that offspring education has a salient positive effect on later-life cognitive health. This finding underscores an overlooked source of health disparities-offspring resources-and highlights how a family perspective remains a powerful tool for understanding health inequalities in later life

The ENIGMA Stroke Recovery Working Group: Big data neuroimaging to study brain–behavior relationships after stroke

The goal of the Enhancing Neuroimaging Genetics through Meta‐Analysis (ENIGMA) Stroke Recovery working group is to understand brain and behavior relationships using well‐powered meta‐ and mega‐analytic approaches. ENIGMA Stroke Recovery has data from over 2,100 stroke patients collected across 39 research studies and 10 countries around the world, comprising the largest multisite retrospective stroke data collaboration to date. This article outlines the efforts taken by the ENIGMA Stroke Recovery working group to develop neuroinformatics protocols and methods to manage multisite stroke brain magnetic resonance imaging, behavioral and demographics data. Specifically, the processes for scalable data intake and preprocessing, multisite data harmonization, and large‐scale stroke lesion analysis are described, and challenges unique to this type of big data collaboration in stroke research are discussed. Finally, future directions and limitations, as well as recommendations for improved data harmonization through prospective data collection and data management, are provided

Germline TERT promoter mutations are rare in familial melanoma.

Germline CDKN2A mutations occur in 40 % of 3-or-more case melanoma families while mutations of CDK4, BAP1, and genes involved in telomere function (ACD, TERF2IP, POT1), have also been implicated in melanomagenesis. Mutation of the promoter of the telomerase reverse transcriptase (TERT) gene (c.-57 T>G variant) has been reported in one family. We tested for the TERT promoter variant in 675 multicase families wild-type for the known high penetrance familial melanoma genes, 1863 UK population-based melanoma cases and 529 controls. Germline lymphocyte telomere length was estimated in carriers. The c.-57 T>G TERT promoter variant was identified in one 7-case family with multiple primaries and early age of onset (earliest, 15 years) but not among population cases or controls. One family member had multiple primary melanomas, basal cell carcinomas and a bladder tumour. The blood leukocyte telomere length of a carrier was similar to wild-type cases. We provide evidence confirming that a rare promoter variant of TERT (c.-57 T>G) is associated with high penetrance, early onset melanoma and potentially other cancers, and explains <1 % of UK melanoma multicase families. The identification of POT1 and TERT germline mutations highlights the importance of telomere integrity in melanoma biology.The authors would like to thank the families for their willingness to participate; and Rajiv Kumar for the provision of mutation positive samples. The collection of samples in the UK population-ascertained sample set was funded by Cancer Research UK (awards C588/A19167 and C8216/A6129) and by the NIH (CA83115). The work of N.A.G. and R.v.D was supported by the Dutch Cancer Society (UL 2012-5489). D.J.A and C.D.R.E are supported by Cancer Research UK, ERC Combat Cancer and the Wellcome Trust. N.K.H is supported by a fellowship from the National Health and Medical Research Council of Australia. A.M.D. and K.A.P. were supported by CRUK grant (C8197/A16565) and The Isaac Newton Trust. K.M.B. is supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics; National Cancer Institute; National Institutes of Health.This is the final version of the article. It first appeared from Springer via http://dx.doi.org/10.1007/s10689-015-9841-

Prelacteal feeding practices in Pakistan: A mixed-methods study

Background: Prelacteal feeding, the feeding a newborn substances or liquids before breastfeeding, is a common cultural practice in Pakistan, but is associated with neonatal morbidity and mortality because it delays early initiation of breastfeeding. In this study, we sought to examine the social and cultural factors associated with prelacteal feeding in Pakistan.Methods: This mixed-method study used data from the Pakistan Demographic and Health Survey (PDHS) 2012-13. Findings from the survey were complemented by qualitative interviews with mothers and healthcare providers. In a subset of PDHS dyads (n = 1361) with children (0-23 months), descriptive statistics and bivariate and multivariable logistic regression analysis examined factors associated with prelacteal feeding. The qualitative study included in-depth interviews with six mothers and six health care providers, which were analyzed using NVivo software version 10.Results: In PDHS, a majority of children (64.7%) received prelacteal feeding. The most common prelacteal food was milk other than breast milk (24.5%), while over a fifth (21.8%) of mothers reported giving honey and sugar water. Factors associated with prelacteal feeding included: birth at public health facilities (AOR 0.46, 95% CI 0.02, 0.95), maternal primary education (AOR 2.28, 95% CI 1.35, 3.85), and delayed breastfeeding initiation (AOR 0.03, 95% CI 0.01, 0.61). In our qualitative study, the major themes found associated with prelacteal feedings included: easy access to prelacteal substances at health facilities, deliveries in private health facilities, prelacteals as a family tradition for socialization, insufficient breast milk, Sunna of Holy Prophet, and myths about colostrum.Conclusions: These data indicate that prelacteal feeding is a well-established practice and social norm in Pakistan. Policies and interventions aimed at promoting breastfeeding need to take these customs into consideration to achieve the desired behavioral changes

Early-Life Origins of the Race Gap in Men's Mortality

Using a life course framework, we examine the early life origins of the race gap in men’s all-cause mortality. Using the National Longitudinal Survey of Older Men (1966–1990), we evaluate major social pathways by which early life conditions differentiate the mortality experiences of blacks and whites. Our findings indicate that early life socioeconomic conditions, particularly parental occupation and family structure, explain part of the race gap in mortality. Black men’s higher rates of death are associated with lower socioeconomic standing in early life and living in homes lacking both biological parents. However, these effects operate indirectly through adult socioeconomic achievement processes, as education, family income, wealth, and occupational complexity statistically account for the race gap in men’s mortality. Our findings suggest that policy interventions to eliminate race disparities in mortality and health should address both childhood and adult socioeconomic conditions

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts