ABSTRACT
Objective:
Diagnostic criteria for coeliac disease (CD) from the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN) were published in 1990. Since then, the ...autoantigen in CD, tissue transglutaminase, has been identified; the perception of CD has changed from that of a rather uncommon enteropathy to a common multiorgan disease strongly dependent on the haplotypes human leukocyte antigen (HLA)‐DQ2 and HLA‐DQ8; and CD‐specific antibody tests have improved.
Methods:
A panel of 17 experts defined CD and developed new diagnostic criteria based on the Delphi process. Two groups of patients were defined with different diagnostic approaches to diagnose CD: children with symptoms suggestive of CD (group 1) and asymptomatic children at increased risk for CD (group 2). The 2004 National Institutes of Health/Agency for Healthcare Research and Quality report and a systematic literature search on antibody tests for CD in paediatric patients covering the years 2004 to 2009 was the basis for the evidence‐based recommendations on CD‐specific antibody testing.
Results:
In group 1, the diagnosis of CD is based on symptoms, positive serology, and histology that is consistent with CD. If immunoglobulin A anti‐tissue transglutaminase type 2 antibody titers are high (>10 times the upper limit of normal), then the option is to diagnose CD without duodenal biopsies by applying a strict protocol with further laboratory tests. In group 2, the diagnosis of CD is based on positive serology and histology. HLA‐DQ2 and HLA‐DQ8 testing is valuable because CD is unlikely if both haplotypes are negative.
Conclusions:
The aim of the new guidelines was to achieve a high diagnostic accuracy and to reduce the burden for patients and their families. The performance of these guidelines in clinical practice should be evaluated prospectively.
Recently, activating mutations in the TERT promoter were identified in cutaneous melanoma. We tested a cohort of ocular melanoma samples for similar mutations.
The TERT promoter region was analysed ...by Sanger sequencing in 47 uveal (ciliary body or choroidal) melanomas and 38 conjunctival melanomas.
Mutations of the TERT promoter were not identified in uveal melanomas, but were detected in 12 (32%) conjunctival melanomas. Mutations had a UV signature and were identical to those found in cutaneous melanoma.
Mutations of TERT promoter with UV signatures are frequent in conjunctival melanomas and favour a pathogenetic kinship with cutaneous melanomas. Absence of these mutations in uveal melanomas emphasises their genetic distinction from cutaneous and conjunctival melanomas.
We use oxDNA, a coarse-grained model of DNA at the nucleotide level, to simulate large nanoprisms that are composed of multi-arm star tiles, in which the size of bulge loops that have been ...incorporated into the tile design is used to control the flexibility of the tiles. The oxDNA model predicts equilibrium structures for several different nanoprism designs that are in excellent agreement with the experimental structures as measured by cryoTEM. In particular we reproduce the chiral twisting of the top and bottom faces of the nanoprisms, as the bulge sizes in these structures are varied due to the greater flexibility of larger bulges. We are also able to follow how the properties of the star tiles evolve as the prisms are assembled. Individual star tiles are very flexible, but their structures become increasingly well-defined and rigid as they are incorporated into larger assemblies. oxDNA also finds that the experimentally observed prisms are more stable than their inverted counterparts, but interestingly this preference for the arms of the tiles to bend in a given direction only emerges after they are part of larger assemblies. These results show the potential for oxDNA to provide detailed structural insight as well as to predict the properties of DNA nanostructures and hence to aid rational design in DNA nanotechnology.
Standard for diagnosis of inflammatory bowel disease (IBD) is the endoscopy of the stomach and the intestine. Aim of this study was to determine the value of 18F-fluorodeoxyglucose positron emission ...tomography (FDG-PET) in pediatric patients with mild to moderate IBD.We included 23 children and adolescents between 8 and 17 years (median 15 years, 13 boys, 10 girls) in this retrospective study in a routine clinical setting. Diagnoses were Crohn's disease in 19 and ulcerative colitis in 4 cases.3 children had a conventional FDG-PET, 20 patients a combined FDG-PET-computed tomography exam. All children had upper and lower intestinal endoscopy with biopsy and a Hydro-MRI exam to assess the jejunum and proximal ileum. The gastrointestinal tract was divided in 7 segments: Stomach plus duodenum, jejunum and proximal ileum, terminal ileum, cecum plus ascending colon, transverse colon, descending colon, and rectosigmoid.Superficial gastric lesions were missed, gastric ulcerations were detected. For the stomach, the sensitivity was 0.25, the specificity was 1.00, the positive predictive value was 1.00, for the lower intestine (terminal ileum and colon) the values were 0.74, 0.88, and 0.96; for the terminal ileum 0.89, 0.75 and 0.94, respectively.The sensitivity and specificity for of ileal and colonic lesions is high. FDG-PET has to be discussed as a tool for the determination of extent and degree of inflammation, especially in those parts of the small bowel that are not accessible to endoscopy. This has to be weighed against the additional radiation exposure administrated.
The three Global Ozone Monitoring Experiment-2 instruments will provide unique and long data sets for atmospheric research and applications. The complete time period will be 2007–2022, including the ...period of ozone depletion as well as the beginning of ozone layer recovery. Besides ozone chemistry, the GOME-2 (Global Ozone Monitoring Experiment-2) products are important e.g. for air quality studies, climate modelling, policy monitoring and hazard warnings. The heritage for GOME-2 is in the ERS/GOME and Envisat/SCIAMACHY instruments. The current Level 2 (L2) data cover a wide range of products such as ozone and minor trace gas columns (NO2, BrO, HCHO, H2O, SO2), vertical ozone profiles in high and low spatial resolution, absorbing aerosol indices, surface Lambertian-equivalent reflectivity database, clear-sky and cloud-corrected UV indices and surface UV fields with different weightings and photolysis rates. The Satellite Application Facility on Ozone and Atmospheric Chemistry Monitoring (O3M SAF) processes and disseminates data 24/7. Data quality is guaranteed by the detailed review processes for the algorithms, validation of the products as well as by a continuous quality monitoring of the products and processing. This paper provides an overview of the O3M SAF project background, current status and future plans for the utilisation of the GOME-2 data. An important focus is the provision of summaries of the GOME-2 products including product principles and validation examples together with sample images. Furthermore, this paper collects references to the detailed product algorithm and validation papers.
Focused Energy is a new startup company with the goal of developing laser-driven inertial fusion energy for electrical power production. The company combines the results from decades of fundamental ...research in inertial confinement fusion at universities and national laboratories with the flexibility and the speed of a startup company. Focused Energy has chosen the direct-drive, proton fast ignition approach to reach ignition, burn and high gain as the most promising approach. Located in Austin/US and Darmstadt/Germany, supported by the science community and private investment Focused Energy is paving the way to inertial fusion energy combining the best skill set and state-of-the-art technology from both sides of the Atlantic Ocean. In this paper we discuss the details and reasoning for the approach and the technical directions we have chosen. We will outline our roadmap for getting to a fusion pilot plant in the mid to late 2030s.
Beginning in the early stages of Alzheimer’s disease (AD), the hippocampus reduces its functional connections to other cortical regions due to synaptic depletion. However, little is known regarding ...connectivity abnormalities within the hippocampus. Here, we describe rostral-caudal hippocampal convergence (rcHC), a metric of the overlap between the rostral and caudal hippocampal functional networks, across the clinical spectrum of AD. We predicted a decline in rostral-caudal hippocampal convergence in the early stages of the disease. Using fMRI, we generated resting-state hippocampal functional networks across 56 controls, 48 early MCI (EMCI), 35 late MCI (LMCI), and 31 AD patients from the Alzheimer’s Disease Neuroimaging Initiative cohort. For each diagnostic group, we performed a conjunction analysis and compared the rostral and caudal hippocampal network changes using a mixed effects linear model to estimate the convergence and differences between these networks, respectively. The conjunction analysis showed a reduction of rostral-caudal hippocampal convergence strength from early MCI to AD, independent of hippocampal atrophy. Our results demonstrate a parallel between the functional convergence within the hippocampus and disease stage, which is independent of brain atrophy. These findings support the concept that network convergence might contribute as a biomarker for connectivity dysfunction in early stages of AD.
BACKGROUND AND OBJECTIVES:A revision of criteria for diagnosing coeliac disease (CD) is being conducted by The European Society for Pediatric Gastroenterology, Hepatology, and Nutrition (ESPGHAN). In ...parallel, we have performed a survey aimed to evaluate present practices for CD among paediatric gastroenterologists and to learn their views on the need for modification of present criteria for CD diagnosis.
PATIENTS AND METHODS:Questionnaires were distributed to experienced paediatric gastroenterologists (ESPGHAN members) via the Internet.
RESULTS:Overall, 95 valid questionnaires were available for analysis, pertaining to 28 different countries, with the majority of responders treating patients with CD for >15 years. Only about 12% of the responders comply with present criteria, noncompliance being related mainly to the challenge policy. Approximately 90% request a revision and modification of the present criteria. Forty-four percent want to omit the small bowel biopsy in symptomatic children with positive anti-tissue transglutaminase immunoglobulin (Ig) A or endomysial IgA antibodies, especially if they are DQ2/DQ8 positive. For silent cases detected by screening with convincingly positive anti-tissue transglutaminase IgA or EMA IgA, about 30% consider that no small bowel biopsy should be required in selected cases. Adding human leukocyte antigen typing in the diagnostic workup was asked for by 42% of the responders. As for gluten challenge, a new policy is advocated restricting its obligation to cases whenever the diagnosis is doubtful or unclear.
CONCLUSIONS:Based on these opinions, revision of the ESPGHAN criteria for diagnosing CD is urgently needed.
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