The developing juvenile talus:Radiographic identification of distinct ontogenetic phases and structural trajectories

Trabecular bone architecture in the developing skeleton is a widely researched area of bone biomechanics; however, despite its significance in weight-bearing locomotion, the developing talus has received limited examination. This study investigates the talus with the purpose of identifying ontogenetic phases and developmental patterns that contribute to the growing understanding of the developing juvenile skeleton. Colour gradient mapping and radiographic absorptiometry were utilised to investigate 62 human tali from 38 individuals, ranging in age-at-death from 28 weeks intrauterine to 20 years of age. The perinatal talus exhibited a rudimentary pattern comparable to the structural organisation observed within the late adolescent talus. This early internal organisation is hypothesised to be related to the vascular pattern of the talus. After 2 years of age, the talus demonstrated refinement, where radiographic trajectories progressively developed into patterns consistent with adult trabecular organisation, which are linked to the forces associated with the bipedal gait, suggesting a strong influence of biomechanical forces on the development of the talus.</p

Interpersonal violence in peacetime Malawi.

Background: The contribution of interpersonal violence (IPV) to trauma burden varies greatly by region. The high rates of IPV in sub-Saharan Africa are thought to relate in part to the high rates of collective violence. Malawi, a country with no history of internal collective violence, provides an excellent setting to evaluate whether collective violence drives the high rates of IPV in this region. Methods: This is a retrospective review of a prospective trauma registry from 2009 through 2016 at Kamuzu Central Hospital in Lilongwe, Malawi. Adult (\u3e16 years) victims of IPV were compared with non-intentional trauma victims. Log binomial regression determined factors associated with increased risk of mortality for victims of IPV. Results: Of 72 488 trauma patients, 25 008 (34.5%) suffered IPV. Victims of IPV were more often male (80.2% vs. 74.8%; p Discussion: Even in a sub-Saharan country that never experienced internal collective violence, IPV injury rates are high. Public health efforts to measure and address alcohol use, and studies to determine the role of mob justice, poverty, and intimate partner violence in IPV, in Malawi are needed. Level of evidence: Level III

The influence of taphonomy on histological and isotopic analyses of treated and untreated buried modern human bone

The chemical (e.g., preservation/embalming) treatment of skeletal remains can reduce overall DNA quality and quantity. The histological and stable isotope examination of treated and untreated human remains improves our understanding of how chemical preservatives impact bone diagenesis and will determine if chemical treatment adversely affects stable isotope ratio analysis of collagen. Fidelity in the application(s) of stable isotope interpretations requires that the isotope delta (δ) values have not been altered postmortem. Re-associated antimeres and refits of chemically treated and untreated rib and long bones from eight casualties [thin-sectioned human bone (n = 43) and collagen extraction/stable isotope analysis (n = 42)] from the World War II Battle of Tarawa were examined to compare skeletal elements from the same individual that had different taphonomic histories. Histological analyses included scoring upon the Oxford Histological Index (OHI) and Birefringence scale, recording microbial invasion, and general observations. The collected data were analyzed via simple descriptive statistics and paired samples t-tests. Treated remains scored higher on the OHI and for Birefringence, indicating that bone quality was good to excellent. The untreated samples scored lower on the OHI and Birefringence scales suggesting poorer preservation than the treated remains. Histology results were supported by the isotope sample preparation results: the collagen % yield was higher for treated bone than untreated bone. Additionally, chemical preservation had no meaningful impact on isotope δ values of treated and untreated remains from the same element or pair-matched elements. Overall, treated remains exhibited good preservation while untreated remains exhibit poorer preservation with significant microfocal destruction to the extent that little histological analyses can be applied. Stable isotope ratio analysis is viable for both treated and untreated remains indicating this testing modality likely can be used for most treated remains, regardless of origin

The C-Type Lectin Receptor CLECSF8/CLEC4D Is a Key Component of Anti-Mycobacterial Immunity

Open Access funded by Wellcome Trust: Under a Creative Commons license Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved. Acknowledgments We would like to thank S. Hardison, P. Redelinghuys, J. Taylor, C. Wallace, A. Richmond, S. Hadebe, A. Plato, F. Abbass, L. Fick, N. Allie, R. Wilkinson, K. Wilkinson, S. Cooper, D. Lang, and V. Kumar for reagents and assistance, and the animal facility staff for the care of our animals. This work was supported by the MRC (UK) and Wellcome Trust (G.D.B.); MRC (South Africa) and Sydney Brenner Fellowship (M.J.M.); Vici (M.G.N.), Vidi (R.v.C.), and Veni grants (T.S.P.) from the Netherlands Organization for Scientific Research; the Royal Netherlands Academy of Arts and Sciences (T.H.M.O.); EC FP7 projects (NEWTBVAC, ADITEC; T.H.M.O.); Carnegie Corporation and CIDRI (J.C.H.); and the University of Aberdeen (B.K.).Peer reviewedPublisher PD

MICL controls inflammation in rheumatoid arthritis

Acknowledgments We thank G Milne, D MacCallum, S Hardison, G Wilson, C Wallace, S Hadebe and A Richmond for assistance; H. El-Gabalawy for tissues and the animal facility staff for the care of our animals. Flow cytometry was undertaken in the Iain Fraser Cytometry Centre, University of Aberdeen. Funding: GDB was funded by the Wellcome Trust and MRC (UK). AA and CDB are supported by the Arthritis Research UK Tissue Engineering Centre (grant 19429). This study makes use of data generated by the Wellcome Trust Case Control Consortium. A full list of the investigators who contributed to the generation of the data is available from http://www.wtccc.org.uk, and was funded by the Wellcome Trust (076113). MJGF was funded by The Arthritis Society and the Canadian Arthritis Network and J-ML by a scholarship from the Canadian Arthritis Network.Peer reviewedPublisher PD

Evaluation of a Heat Vulnerability Index on Abnormally Hot Days: An Environmental Public Health Tracking Study

Background: Extreme hot weather conditions have been associated with increased morbidity and mortality, but risks are not evenly distributed throughout the population. Previously, a heat vulnerability index (HVI) was created to geographically locate populations with increased vulnerability to heat in metropolitan areas throughout the United States

MiRNA-Related SNPs and Risk of Esophageal Adenocarcinoma and Barrett's Esophagus: Post Genome-Wide Association Analysis in the BEACON Consortium.

Incidence of esophageal adenocarcinoma (EA) has increased substantially in recent decades. Multiple risk factors have been identified for EA and its precursor, Barrett's esophagus (BE), such as reflux, European ancestry, male sex, obesity, and tobacco smoking, and several germline genetic variants were recently associated with disease risk. Using data from the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON) genome-wide association study (GWAS) of 2,515 EA cases, 3,295 BE cases, and 3,207 controls, we examined single nucleotide polymorphisms (SNPs) that potentially affect the biogenesis or biological activity of microRNAs (miRNAs), small non-coding RNAs implicated in post-transcriptional gene regulation, and deregulated in many cancers, including EA. Polymorphisms in three classes of genes were examined for association with risk of EA or BE: miRNA biogenesis genes (157 SNPs, 21 genes); miRNA gene loci (234 SNPs, 210 genes); and miRNA-targeted mRNAs (177 SNPs, 158 genes). Nominal associations (P0.50), and we did not find evidence for interactions between variants analyzed and two risk factors for EA/BE (smoking and obesity). This analysis provides the most extensive assessment to date of miRNA-related SNPs in relation to risk of EA and BE. While common genetic variants within components of the miRNA biogenesis core pathway appear unlikely to modulate susceptibility to EA or BE, further studies may be warranted to examine potential associations between unassessed variants in miRNA genes and targets with disease risk.This work was supported by the National Institutes of Health [R01CA136725 to T.L.V. and D.C.W, T32CA009168 to T.L.V, and K05CA124911 to T.L.V.]. Additional funding sources for individual studies included in the BEACON GWAS, and for BEACON investigators, have been acknowledged previously (16).This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.012861

Polymorphisms in Genes of Relevance for Oestrogen and Oxytocin Pathways and Risk of Barrett's Oesophagus and Oesophageal Adenocarcinoma: A Pooled Analysis from the BEACON Consortium.

BACKGROUND: The strong male predominance in oesophageal adenocarcinoma (OAC) and Barrett's oesophagus (BO) continues to puzzle. Hormonal influence, e.g. oestrogen or oxytocin, might contribute. METHODS: This genetic-epidemiological study pooled 14 studies from three continents, Australia, Europe, and North America. Polymorphisms in 3 key genes coding for the oestrogen pathway (receptor alpha (ESR1), receptor beta (ESR2), and aromatase (CYP19A1)), and 3 key genes of the oxytocin pathway (the oxytocin receptor (OXTR), oxytocin protein (OXT), and cyclic ADP ribose hydrolase glycoprotein (CD38)), were analysed using a gene-based approach, versatile gene-based test association study (VEGAS). RESULTS: Among 1508 OAC patients, 2383 BO patients, and 2170 controls, genetic variants within ESR1 were associated with BO in males (p = 0.0058) and an increased risk of OAC and BO combined in males (p = 0.0023). Genetic variants within OXTR were associated with an increased risk of BO in both sexes combined (p = 0.0035) and in males (p = 0.0012). We followed up these suggestive findings in a further smaller data set, but found no replication. There were no significant associations between the other 4 genes studied and risk of OAC, BO, separately on in combination, in males and females combined or in males only. CONCLUSION: Genetic variants in the oestrogen receptor alpha and the oxytocin receptor may be associated with an increased risk of BO or OAC, but replication in other large samples are needed

Updating requirements for Endangered, Threatened and Protected species MSC Fisheries Standard v3.0 to operationalise best practices

Bycatch in fisheries is a key threat to non-target marine species, particularly for those species that have life histories with low productivity or poor conservation status. In this paper, the requirements of the new Marine Stewardship Council (MSC) Fisheries Standard (hereafter “the Standard”) are summarised relevant to Endangered, Threatened and Protected (ETP) species. This covers both how species are designated as ETP, and how performance of management is assessed with respect to ETP species, when scoring fisheries against the Standard. The process used to select these requirements is described, including a review of the requirements for earlier versions of the Standard and the scoring of these requirements in assessment reports for a selection of fisheries that have achieved MSC certification. The review identified a lack of consistency in the implementation of scoring guidelines, which was in part due to a lack of clarity in the requirements of the Standard. The revised Standard has been designed to achieve more consistent implementation of the requirements with respect to management of impacts on ETP species, and to align the requirements more closely with global best practice. The requirements may be used as a template for fisheries managers seeking to prioritise bycatch species for improved management and setting more specific and measurable objectives in relation to population status and minimising mortalities

Interactions Between Genetic Variants and Environmental Factors Affect Risk of Esophageal Adenocarcinoma and Barrett's Esophagus.

BACKGROUND & AIMS: Genome-wide association studies (GWAS) have identified more than 20 susceptibility loci for esophageal adenocarcinoma (EA) and Barrett's esophagus (BE). However, variants in these loci account for a small fraction of cases of EA and BE. Genetic factors might interact with environmental factors to affect risk of EA and BE. We aimed to identify single nucleotide polymorphisms (SNPs) that may modify the associations of body mass index (BMI), smoking, and gastroesophageal reflux disease (GERD), with risks of EA and BE. METHODS: We collected data on single BMI measurements, smoking status, and symptoms of GERD from 2284 patients with EA, 3104 patients with BE, and 2182 healthy individuals (controls) participating in the Barrett's and Esophageal Adenocarcinoma Consortium GWAS, the UK Barrett's Esophagus Gene Study, and the UK Stomach and Oesophageal Cancer Study. We analyzed 993,501 SNPs in DNA samples of all study subjects. We used standard case-control logistic regression to test for gene-environment interactions. RESULTS: For EA, rs13429103 at chromosome 2p25.1, near the RNF144A-LOC339788 gene, showed a borderline significant interaction with smoking status (P = 2.18×10-7). Ever smoking was associated with an almost 12-fold increase in risk of EA among individuals with rs13429103-AA genotype (odds ratio=11.82; 95% CI, 4.03-34.67). Three SNPs (rs12465911, rs2341926, rs13396805) at chromosome 2q23.3, near the RND3-RBM43 gene, interacted with GERD symptoms (P = 1.70×10-7, P = 1.83×10-7, and P = 3.58×10-7, respectively) to affect risk of EA. For BE, rs491603 at chromosome 1p34.3, near the EIF2C3 gene, and rs11631094 at chromosome 15q14, at the SLC12A6 gene, interacted with BMI (P = 4.44×10-7) and pack-years of smoking history (P = 2.82×10-7), respectively. CONCLUSION: The associations of BMI, smoking, and GERD symptoms with risks of EA and BE appear to vary with SNPs at chromosomes 1, 2, and 15. Validation of these suggestive interactions is warranted.UK funding from MRC and Cancer Research U