A Meta-Analysis of Genome-Wide Association Scans Identifies IL18RAP, PTPN2, TAGAP, and PUS10 As Shared Risk Loci for Crohn's Disease and Celiac Disease

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Towards Inferring Mechanical Lock Combinations using Wrist-Wearables as a Side-Channel

Wrist-wearables such as smartwatches and fitness bands are equipped with a variety of high-precision sensors that support novel contextual and activity-based applications. The presence of a diverse set of on-board sensors, however, also expose an additional attack surface which, if not adequately protected, could be potentially exploited to leak private user information. In this paper, we investigate the feasibility of a new attack that takes advantage of a wrist-wearable's motion sensors to infer input on mechanical devices typically used to secure physical access, for example, combination locks. We outline an inference framework that attempts to infer a lock's unlock combination from the wrist motion captured by a smartwatch's gyroscope sensor, and uses a probabilistic model to produce a ranked list of likely unlock combinations. We conduct a thorough empirical evaluation of the proposed framework by employing unlocking-related motion data collected from human subject participants in a variety of controlled and realistic settings. Evaluation results from these experiments demonstrate that motion data from wrist-wearables can be effectively employed as a side-channel to significantly reduce the unlock combination search-space of commonly found combination locks, thus compromising the physical security provided by these locks

Usefulness of the organ culture system in the in vitro diagnosis of coeliac disease: A multicentre study

Objective. Diagnosis of coeliac disease is based on the presence of villous atrophy which recovers following a gluten-free diet. The presence of circulating antiendomysial antibodies as well as their disappearance after a gluten-free diet supports the diagnosis. It has also been demonstrated that antiendomysial antibodies are detectable in supernatants of cultured intestinal biopsies from patients with coeliac disease. The objective of this study was to compare the histology and antiendomysial antibodies in culture supernatants of intestinal biopsies to validate the in vitro organ culture system as a future diagnostic tool for coeliac disease. Material and methods. Seventy-five antiendomysial serum-positive patients on a gluten-containing diet were evaluated. Patients underwent endoscopy with 5 biopsy fragments: 3 for histology, 1 cultured with and the other without gliadin-peptide activator. Antiendomysial antibodies were evaluated in all culture supernatants. Results. Sixty-eight patients had evidence of villous atrophy, while 73 out of 75 were positive to the organ culture system. The agreement rate between organ culture and histology results was 94%. Conclusions. As all the centres participating in the study obtained good agreement between organ culture and histology results, the new system could be considered a reliable tool for the diagnosis of coeliac disease. Nevertheless, it is possible to highlight cases with an organ culture-positive and -negative histology. This feature could be of considerable interest because, as the sensitivity of organ culture seems to be greater than the initial histology, the new system might be useful in uncertain cases where the risk of missing the diagnosis of coeliac disease is high

Guidance on Noncorticosteroid Systemic Immunomodulatory Therapy in Noninfectious Uveitis : Fundamentals Of Care for UveitiS (FOCUS) Initiative

Supplemental material available at www.aaojournal.org. Supported by AbbVie, Inc., and the Fundamentals of Care for Uveitis Initiative National Faculty. This manuscript was developed subsequent to an AbbVie-sponsored literature review of noninfectious, nonanterior uveitis. The meeting was conducted to understand the available literature regarding the management of patients with noninfectious, nonanterior uveitis. The program involved a total of 139 experts from 28 countries, who were selected for participation by AbbVie. However, AbbVie was not involved in the development of the manuscript. The authors maintained complete control over the content and this manuscript reflects the opinions of the authors. AbbVie selected the discussion participants and reviewed the final manuscript draft for scientific accuracy, but the authors determined the final content. All authors made substantial contributions to the article or critically revised it for important intellectual content and approved the final manuscript. AbbVie provided funding to invited participants, including honoraria for their attendance at the meetings. Travel to and from the meetings was reimbursed. No payments were made to the authors for the development of this manuscript. Dhinakaran Sambandan, PhD, and Shula Sarner, PhD, of Lucid Partners, Burleighfield House, Buckinghamshire, United Kingdom, provided medical writing and editorial support to the authors in the development of this manuscript; financial support for these services was provided by AbbVie. AbbVie reviewed the manuscript, but was not involved in the methodology, data collection and analysis, or completion of this manuscript.Peer reviewedPublisher PD

Coeliac disease-associated risk variants in TNFAIP3 and REL implicate altered NF-kappaB signalling

Objective: Our previous coeliac disease genome-wide association study (GWAS) implicated risk variants in the human leucocyte antigen (HLA) region and eight novel risk regions. To identify more coeliac disease loci, we selected 458 single nucleotide polymorphisms (SNPs) that showed more modest association in the GWAS for genotyping and analysis in four independent cohorts. Design: 458 SNPs were assayed in 1682 cases and 3258 controls from three populations (UK, Irish and Dutch). We combined the results with the original GWAS cohort (767 UK cases and 1422 controls); six SNPs showed association with p Results: We identified two novel coeliac disease risk regions: 6q23.3 (OLIG3-TNFAIP3) and 2p16.1 (REL), both of which reached genome-wide significance in the combined analysis of all 2987 cases and 5273 controls (rs2327832 p= 1.3x10(-08), and rs842647 p= 5.26x10(-07)). We investigated the expression of these genes in the RNA isolated from biopsies and from whole blood RNA. We did not observe any changes in gene expression, nor in the correlation of genotype with gene expression. Conclusions: Both TNFAIP3 (A20, at the protein level) and REL are key mediators in the nuclear factor kappa B (NF-kappa B) inflammatory signalling pathway. For the first time, a role for primary heritable variation in this important biological pathway predisposing to coeliac disease has been identified. Currently, the HLA risk factors and the 10 established non-HLA risk factors explain similar to 40% of the heritability of coeliac disease

Adalimumab in Patients with Active Noninfectious Uveitis

BACKGROUND: Patients with noninfectious uveitis are at risk for long-term complications of uncontrolled inflammation, as well as for the adverse effects of long-term glucocorticoid therapy. We conducted a trial to assess the efficacy and safety of adalimumab as a glucocorticoid-sparing agent for the treatment of noninfectious uveitis. METHODS: This multinational phase 3 trial involved adults who had active noninfectious intermediate uveitis, posterior uveitis, or panuveitis despite having received prednisone treatment for 2 or more weeks. Investigators and patients were unaware of the study-group assignments. Patients were randomly assigned in a 1:1 ratio to receive adalimumab (a loading dose of 80 mg followed by a dose of 40 mg every 2 weeks) or matched placebo. All patients received a mandatory prednisone burst followed by tapering of prednisone over the course of 15 weeks. The primary efficacy end point was the time to treatment failure occurring at or after week 6. Treatment failure was a multicomponent outcome that was based on assessment of new inflammatory lesions, best corrected visual acuity, anterior chamber cell grade, and vitreous haze grade. Nine ranked secondary efficacy end points were assessed, and adverse events were reported. RESULTS: The median time to treatment failure was 24 weeks in the adalimumab group and 13 weeks in the placebo group. Among the 217 patients in the intention-to-treat population, those receiving adalimumab were less likely than those in the placebo group to have treatment failure (hazard ratio, 0.50; 95% confidence interval, 0.36 to 0.70; P<0.001). Outcomes with regard to three secondary end points (change in anterior chamber cell grade, change in vitreous haze grade, and change in best corrected visual acuity) were significantly better in the adalimumab group than in the placebo group. Adverse events and serious adverse events were reported more frequently among patients who received adalimumab (1052.4 vs. 971.7 adverse events and 28.8 vs. 13.6 serious adverse events per 100 person-years). CONCLUSIONS: In our trial, adalimumab was found to be associated with a lower risk of uveitic flare or visual impairment and with more adverse events and serious adverse events than was placebo

Gliadin, through the activation of innate immunity, triggers lncrna neat1 expression in celiac disease duodenal mucosa

Celiac disease (CD) is an autoimmune enteropathy arising in genetically predisposed subjects exposed to gluten, which activates both innate and adaptive immunity. Although the pathogenesis is common to all patients, the clinical spectrum is quite variable, and differences could be explained by gene expression variations. Among the factors able to affect gene expression, there are lncRNAs. We evaluated the expression profile of 87 lncRNAs in CD vs. healthy control (HC) intestinal biopsies by RT-qPCR array. Nuclear enriched abundant transcript 1 (NEAT1) and taurine upregulated gene 1 (TUG1) were detected as downregulated in CD patients at diagnosis, but their expression increased in biopsies of patients on a gluten-free diet (GFD) exposed to gluten. The increase in NEAT1 expression after gluten exposure was mediated by IL-15 and STAT3 activation and binding to the NEAT1 promoter, as demonstrated by gel shift assay. NEAT1 is localized in the nucleus and can regulate gene expression by sequestering transcription factors, and it has been implicated in immune regulation and control of cell proliferation. The demonstration of its regulation by gluten thus also supports the role of lncRNAs in CD and prompts further research on these RNAs as gene expression regulators

Guidance on noncorticosteroid systemic immunomodulatory therapy in noninfectious uveitis: fundamentals of care for uveitis (focus) initiative

Topic: An international, expert-led consensus initiative to develop systematic, evidence-based recommendations for the treatment of noninfectious uveitis in the era of biologics. Clinical Relevance: The availability of biologic agents for the treatment of human eye disease has altered practice patterns for the management of noninfectious uveitis. Current guidelines are insufficient to assure optimal use of noncorticosteroid systemic immunomodulatory agents. Methods: An international expert steering committee comprising 9 uveitis specialists (including both ophthalmologists and rheumatologists) identified clinical questions and, together with 6 bibliographic fellows trained in uveitis, conducted a Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol systematic reviewof the literature (English language studies from January 1996 through June 2016; Medline [OVID], the Central Cochrane library, EMBASE,CINAHL,SCOPUS,BIOSIS, andWeb of Science). Publications included randomized controlled trials, prospective and retrospective studies with sufficient follow-up, case series with 15 cases or more, peer-reviewed articles, and hand-searched conference abstracts from key conferences. The proposed statements were circulated among 130 international uveitis experts for review.Atotal of 44 globally representativegroupmembersmet in late 2016 to refine these guidelines using a modified Delphi technique and assigned Oxford levels of evidence. Results: In total, 10 questions were addressed resulting in 21 evidence-based guidance statements covering the following topics: when to start noncorticosteroid immunomodulatory therapy, including both biologic and nonbiologic agents; what data to collect before treatment; when to modify or withdraw treatment; how to select agents based on individual efficacy and safety profiles; and evidence in specific uveitic conditions. Shared decision-making, communication among providers and safety monitoring also were addressed as part of the recommendations. Pharmacoeconomic considerations were not addressed. Conclusions: Consensus guidelines were developed based on published literature, expert opinion, and practical experience to bridge the gap between clinical needs and medical evidence to support the treatment of patients with noninfectious uveitis with noncorticosteroid immunomodulatory agents