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Associations between human genetic variation and clinical phenotypes have become a foundation of biomedical research. Most repositories of these data seek to be disease-agnostic and therefore lack disease-focused views. The Type 2 Diabetes Knowledge Portal (T2DKP) is a public resource of genetic datasets and genomic annotations dedicated to type 2 diabetes (T2D) and related traits. Here, we seek to make the T2DKP more accessible to prospective users and more useful to existing users. First, we evaluate the T2DKP's comprehensiveness by comparing its datasets with those of other repositories. Second, we describe how researchers unfamiliar with human genetic data can begin using and correctly interpreting them via the T2DKP. Third, we describe how existing users can extend their current workflows to use the full suite of tools offered by the T2DKP. We finally discuss the lessons offered by the T2DKP toward the goal of democratizing access to complex disease genetic results.

IntroductionPancreatic cancer is a leading cause of cancer deaths worldwide. Screening for this disease has potential to improve survival. It is not feasible, with current screening modalities, to screen the asymptomatic adult population. However, screening of individuals in high-risk groups is recommended. Our study aims to provide resources and data that will inform strategies to screen individuals with new-onset diabetes (NOD) for pancreatic cancer.Methods and analysisThe United Kingdom Early Detection Initiative (UK-EDI) for pancreatic cancer is a national, prospective, observational cohort study that aims to recruit 2500 individuals with NOD (Ethics and disseminationThe UK-EDI study has been reviewed and approved by the London-West London and GTAC Research Ethics Committee (Ref 20/LO/0058). Study results will be disseminated through presentations at national and international symposia and publication in peer-reviewed, Open Access journals.

Background Pancreatic cancer diagnosis and staging can be difficult in 10–20% of patients. Positron emission tomography (PET)/computed tomography (CT) adds precise anatomical localisation to functional data. The use of PET/CT may add further value to the diagnosis and staging of pancreatic cancer. Objective To determine the incremental diagnostic accuracy and impact of PET/CT in addition to standard diagnostic work-up in patients with suspected pancreatic cancer. Design A multicentre prospective diagnostic accuracy and clinical value study of PET/CT in suspected pancreatic malignancy. Participants Patients with suspected pancreatic malignancy. Interventions All patients to undergo PET/CT following standard diagnostic work-up. Main outcome measures The primary outcome was the incremental diagnostic value of PET/CT in addition to standard diagnostic work-up with multidetector computed tomography (MDCT). Secondary outcomes were (1) changes in patients’ diagnosis, staging and management as a result of PET/CT; (2) changes in the costs and effectiveness of patient management as a result of PET/CT; (3) the incremental diagnostic value of PET/CT in chronic pancreatitis; (4) the identification of groups of patients who would benefit most from PET/CT; and (5) the incremental diagnostic value of PET/CT in other pancreatic tumours. Results Between 2011 and 2013, 589 patients with suspected pancreatic cancer underwent MDCT and PET/CT, with 550 patients having complete data and in-range PET/CT. Sensitivity and specificity for the diagnosis of pancreatic cancer were 88.5% and 70.6%, respectively, for MDCT and 92.7% and 75.8%, respectively, for PET/CT. The maximum standardised uptake value (SUVmax.) for a pancreatic cancer diagnosis was 7.5. PET/CT demonstrated a significant improvement in relative sensitivity (p = 0.01) and specificity (p = 0.023) compared with MDCT. Incremental likelihood ratios demonstrated that PET/CT significantly improved diagnostic accuracy in all scenarios (p p = 0.001). PET/CT influenced management in 250 (45%) patients. PET/CT stopped resection in 58 (20%) patients who were due to have surgery. The benefit of PET/CT was limited in patients with chronic pancreatitis or other pancreatic tumours. PET/CT was associated with a gain in quality-adjusted life-years of 0.0157 (95% confidence interval –0.0101 to 0.0430). In the base-case model PET/CT was seen to dominate MDCT alone and is thus highly likely to be cost-effective for the UK NHS. PET/CT was seen to be most cost-effective for the subgroup of patients with suspected pancreatic cancer who were thought to be resectable. Conclusion PET/CT provided a significant incremental diagnostic benefit in the diagnosis of pancreatic cancer and significantly influenced the staging and management of patients. PET/CT had limited utility in chronic pancreatitis and other pancreatic tumours. PET/CT is likely to be cost-effective at current reimbursement rates for PET/CT to the UK NHS. This was not a randomised controlled trial and therefore we do not have any information from patients who would have undergone MDCT only for comparison. In addition, there were issues in estimating costs for PET/CT. Future work should evaluate the role of PET/CT in intraductal papillary mucinous neoplasm and prognosis and response to therapy in patients with pancreatic cancer. Study registration Current Controlled Trials ISRCTN73852054 and UKCRN 8166. Funding The National Institute for Health Research Health Technology Assessment programme.

Objective US Iraq and Afghanistan Veterans with post-traumatic stress disorder (PTSD) and depression are at increased risk for obesity. Understanding the contribution of health behaviors to this relationship will enhance efforts to prevent and reduce obesity. Therefore, we examined the association of PTSD and depression symptoms with binge eating, a risk factor for obesity, among Iraq/Afghanistan Veterans. Method Iraq/Afghanistan Veterans were assessed at intake to the VA Puget Sound Healthcare System-Seattle post-deployment clinic (May 2004–January 2007). The Patient Health Questionnaire was used to measure depression and binge eating symptoms, and the PTSD Checklist-Military Version assessed PTSD symptoms. Results The majority of the sample (N = 332) was male (91.5%) and Caucasian (72.6%), with an average age of 31.1 (SD = 8.5) years; 16.3% met depression screening criteria, 37.8% met PTSD screening criteria, and 8.4% met binge eating screening criteria. In adjusted models, those meeting depression (odds ratio (OR) = 7.53; 95% CI = 2.69, 21.04; p p = .01) screening criteria were more likely to meet binge eating screening criteria. Continuous measures of PTSD and depression symptom severity were also associated with meeting binge eating screening criteria ( p s Conclusion PTSD and depression are common conditions among Iraq/Afghanistan Veterans. In the present study, PTSD and depression symptoms were associated with meeting binge eating screening criteria, identifying a possible pathway by which psychiatric conditions lead to disproportionate burden of overweight and obesity in this Veteran cohort. Tailored dietary behavior interventions may be needed for Iraq/Afghanistan Veterans with co-morbid obesity and psychiatric conditions.

Lamellar pleural thickening (LPT) is a fibrotic disease induced by exposure to Libby amphibole (LA) asbestos that causes widespread scarring around the lung, resulting in deterioration of pulmonary function. Investigating the effects of autoantibodies to mesothelial cells (MCAA) present in the study populations has been a major part of the effort to understand the mechanism of pathogenesis. It has been shown in vitro that human mesothelial cells (Met5a) exposed to MCAA increase collagen deposition into the extracellular matrix (ECM). In this study, we sought to further elucidate how MCAA drive increased collagen deposition by identifying the protein targets bound by MCAA on the cellular surface using biotinylation to label and isolate surface proteins. Isolated surface protein fractions were identified as containing MCAA targets using ELISA. The fractions that demonstrated binding by MCAA were then analyzed by tandem mass spectrometry (MS/MS) and MASCOT analysis. The most promising result from the MASCOT analysis, plasminogen (PLG), was tested for MCAA binding using purified human PLG in an ELISA. We report that serum containing MCAA bound at an optical density (OD) 3 times greater than that of controls, and LA‐exposed subjects had a high frequency of positive tests for anti‐PLG autoantibodies. This work implicates the involvement of the plasminogen/plasmin system in the mechanism of excess collagen deposition in Met5a cells exposed to MCAA. Elucidating this mechanism could contribute to the understanding of LPT.

In light of past research being targeted to find specific particles which may be similar to gunshot residue (GSR), this project was formulated to detect any possible particulate by random particle fallout onto substrates at firework displays and to assess the impact this may have on GSR evidence. Firework residue was collected at a display site, from amongst spectators as well as from the author's hair 90min after the display. SEM-EDX analysis has detected such particulate in all three scenarios, with the firework particle population at large providing a solid ground for discrimination from GSR. Wind dispersal was found to decrease the particle population and subsequently, the latter's discriminatory power. Some particles, if treated individually were found to be indistinguishable from GSR. Findings also include residues which may mimic strontium based GSR as well as GSR which may be mixed with that from previous firings. The continuous changes made to primer and propellant compositions by manufacturers also call for greater consideration when classifying particles as originating from pyrotechnic devices. Furthermore, authorities such as police forces should be made more aware about the incidence of such particle transfer in firework related periods.

A study was conducted to determine the prevalence of Campylobacter with antimicrobial resistance from chickens, pigs, dairy cows, healthy farm workers, and children hospitalized with diarrhea in northern Thailand. Resistance was highest in pig samples and lowest in healthy farm workers. Resistance to fluoroquinolones and tetracycline was high in all study populations. The increased prevalence of resistant isolates from meat samples collected at markets, compared to isolates collected from animals on the farm or the slaughterhouse, suggests that contamination after carcasses leave the slaughterhouse is an important factor in the spread of resistant bacteria into the human food chain.

A cross-sectional pilot study was conducted in Chiang Mai, Thailand, to determine the prevalence of Salmonella and Escherichia coli in swine, broiler chickens and human workers from farms and abattoirs in northern Thailand, and compare their antimicrobial resistance profiles. Fecal samples and cloacal swabs were collected from 150 swine and 150 chickens at the farm. Fecal samples from swine, cloacal swabs from chickens, and carcass swabs from both animals were collected from 100 swine and 100 chickens at the abattoir. Stool samples were collected from 15 swine farm workers and seven chicken farm workers. Primary isolation and identification of Salmonella and E. coli were conducted using standard methods. In vitro susceptibility testing of Salmonella and E. coli was conducted using the broth microdilution method, based on the United States National Committee for Clinical Laboratory Standards (NCCLS) guidelines. The prevalence of Salmonella from swine and chicken samples ranged from 2% to 25%. The prevalence of E. coli in chickens and swine ranged from 36.8% to 47.6%. In humans, the prevalence of Salmonella was 15%, and the prevalence of E. coli ranged from 51% to 53%. Resistance in Salmonella was found for tetracycline (84.7%), nalidixic acid (27.1%), florfenicol (18.6%), ampicillin (13.6%), and ceftiofur (3.4%), and in E. coli for tetracycline (91.5%), nalidixic acid (67.4%), ampicillin (61.6%), florfenicol (51.8%), enrofloxacin (28.7%), ciprofloxacin (12.5%), ceftiofur (4.9%) and ceftriaxone (1.5%).

An 82-year-old woman who had immigrated to Canada 40 years previously, after escaping Nazi persecution in the Second World War and living in the Netherlands for 20 years, was admitted to our General Internal Medicine ward with aspiration pneumonitis. Her medical history was significant for

Catabolic states, e.g., injury or surgical trauma, are associated with hyperglycemia, elevated blood concentrations of gluconeogenic precursors, and hyperketonemia. 1 In these conditions, circulating insulin concentrations are low, but secretion of the catabolic hormones, cortisol, glucagon, and catecholamines is increased. Uncontrolled diabetes mellitus is a catabolic state also, and when insulin-dependent diabetics are deprived of insulin, there is a significant correlation between the rise in ketone body levels and plasma glucagon concentration. 2 Plasma cortisol levels also rise in insulin-deprived diabetics although this is delayed in comparison with glucagon. In this study we have investigated the metabolic effects of cortisol and glucagon at pathophysiologic concentrations in normal man and during deficiency induced by somatostatin infusion.