Genotype-Phenotype Associations of the CD-Associated Single Nucleotide Polymorphism within the Gene Locus Encoding Protein Tyrosine Phosphatase Non-Receptor Type 22 in Patients of the Swiss IBD Cohort.

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) plays an important role in immune cell function and intestinal homeostasis. The single nucleotide polymorphism (SNP) rs2476601 within the PTPN22 gene locus results in aberrant function of PTPN22 protein and protects from Crohn's disease (CD). Here, we investigated associations of PTPN22 SNP rs2476601 in inflammatory bowel disease (IBD) patients in the Swiss IBD Cohort Study (SIBDCS). 2'028 SIBDCS patients (1173 CD and 855 ulcerative colitis (UC) patients) were included. The clinical characteristics were analysed for an association with the presence of the PTPN22 SNP rs2476601 genotypes 'homozygous variant' (AA), 'heterozygous' (GA) and 'homozygous wild-type' (GG). 13 patients (0.6%) were homozygous variant (AA) for the PTPN22 polymorphism, 269 (13.3%) heterozygous variant (GA) and 1'746 (86.1%) homozygous wild-type (GG). In CD, AA and GA genotypes were associated with less use of steroids and antibiotics, and reduced prevalence of vitamin D and calcium deficiency. In UC the AA and GA genotype was associated with increased use of azathioprine and anti-TNF antibodies, but significantly less patients with the PTPN22 variant featured malabsorption syndrome (p = 0.026). Our study for the first time addressed how presence of SNP rs2476601 within the PTPN22 gene affects clinical characteristics in IBD-patients. Several factors that correlate with more severe disease were found to be less common in CD patients carrying the A-allele, pointing towards a protective role for this variant in affected CD patients. In UC patients however, we found the opposite trend, suggesting a disease-promoting effect of the A-allele

Enriching Semantic Knowledge Bases for Opinion Mining in Big Data Applications

This paper presents a novel method for contextualizing and enriching large semantic knowledge bases for opinion mining with a focus on Web intelligence platforms and other high-throughput big data applications. The method is not only applicable to traditional sentiment lexicons, but also to more comprehensive, multi-dimensional affective resources such as SenticNet. It comprises the following steps: (i) identify ambiguous sentiment terms, (ii) provide context information extracted from a domain-specific training corpus, and (iii) ground this contextual information to structured background knowledge sources such as ConceptNet and WordNet. A quantitative evaluation shows a significant improvement when using an enriched version of SenticNet for polarity classification. Crowdsourced gold standard data in conjunction with a qualitative evaluation sheds light on the strengths and weaknesses of the concept grounding, and on the quality of the enrichment process

Variational approximation for mixtures of linear mixed models

Mixtures of linear mixed models (MLMMs) are useful for clustering grouped data and can be estimated by likelihood maximization through the EM algorithm. The conventional approach to determining a suitable number of components is to compare different mixture models using penalized log-likelihood criteria such as BIC.We propose fitting MLMMs with variational methods which can perform parameter estimation and model selection simultaneously. A variational approximation is described where the variational lower bound and parameter updates are in closed form, allowing fast evaluation. A new variational greedy algorithm is developed for model selection and learning of the mixture components. This approach allows an automatic initialization of the algorithm and returns a plausible number of mixture components automatically. In cases of weak identifiability of certain model parameters, we use hierarchical centering to reparametrize the model and show empirically that there is a gain in efficiency by variational algorithms similar to that in MCMC algorithms. Related to this, we prove that the approximate rate of convergence of variational algorithms by Gaussian approximation is equal to that of the corresponding Gibbs sampler which suggests that reparametrizations can lead to improved convergence in variational algorithms as well.Comment: 36 pages, 5 figures, 2 tables, submitted to JCG

Systematic evaluation of clinical predictors of aggressive ulcerative colitis

Background: Studies evaluating risk factors associated with an "aggressive" disease course in ulcerative colitis (UC) are scarce. A recent definition of "aggressive" UC incorporated the following characteristics: 1) high relapse rate, 2) need for surgery, 3) development of colorectal cancer, and 4) presence of extraintestinal manifestations (EIM). The following factors for an aggressive / disabling disease course in UC have been identified so far: age < 40 years at S140 Poster presentations UC diagnosis, pancolitis, concomitant primary sclerosing cholangitis, and deep ulcerations of the colonic mucosa. We aimed to evaluate risk factors for an "aggressive" disease course in UC patients. Methods: Data from the Swiss IBD cohort study were analyzed. Patients were recruited from university centers (80%), regional hospitals (19%), and private practices (1%). We applied the following definition for "aggressive" UC: 1) patients ever treated with TNFantagonists or calcineurin inhibitors (tacrolimus / cyclosporine), and 2) need for (procto)-colectomy. Non-normal data are presented as median and interquartile range [IQR]

Uveitis manifestations in patients of the Swiss Inflammatory Bowel Disease Cohort Study.

The knowledge about risk factors for the onset of uveitis manifestations in patients with inflammatory bowel disease (IBD) is still limited. Here, we aimed to provide an overview of the clinical factors associated with the onset of uveitis in the Swiss IBD Cohort Study (SIBDCS). We included epidemiological and clinical data from 1840 patients with Crohn's disease (CD) and 1426 patients with ulcerative colitis (UC) followed up in the SIBDCS between 2006 and 2018. Associations between disease characteristics and uveitis were assessed in univariate and multivariate analyses. Overall, we identified 285 patients with uveitis. Uveitis was more frequent in patients with CD (11.1%; 205 of 1635) than UC (5.6%; 80 of 1346; odds ratio 2.11, p < 0.001). The occurrence of uveitis manifestations in patients with UC and CD was significantly associated with the onset of other extraintestinal manifestations, also in multivariate analyses. The onset of uveitis was associated with the hallmark features of severe disease in both CD and UC, including a higher clinical disease activity index and the use of immunomodulators or calcineurin inhibitors. In CD, uveitis was more frequent in females and showed a positive correlation with a positive family history of IBD. Our data demonstrate that uveitis in IBD occurs more often in CD as well as in women and is associated with a more severe disease course. This might guide physicians' awareness in at-risk patients to the presence of uveitis extraintestinal manifestations and help to improve patient care

Flight Test Evaluation of the ATD-1 Interval Management Application

Interval Management (IM) is a concept designed to be used by air traffic controllers and flight crews to more efficiently and precisely manage inter-aircraft spacing. Both government and industry have been working together to develop the IM concept and standards for both ground automation and supporting avionics. NASA contracted with Boeing, Honeywell, and United Airlines to build and flight test an avionics prototype based on NASA's spacing algorithm and conduct a flight test. The flight test investigated four different types of IM operations over the course of nineteen days, and included en route, arrival, and final approach phases of flight. This paper examines the spacing accuracy achieved during the flight test and the rate of speed commands provided to the flight crew. Many of the time-based IM operations met or exceeded the operational design goals set out in the standards for the maintain operations and a subset of the achieve operations. Those operations which did not meet the goals were due to issues that are identified and will be further analyzed

Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity

Acquisition and Relevance of Geotagged Information in Tourism

In the case of tourism applications, it is particularly evident that geography is emerging as a fundamental principle for structuring Web resources. Recent improvements in semantic and geographic Web technology, often referred to as the Geospatial Web, acknowledge the relevance of adding location metadata to existing databases and accessing the vast amounts of information stored in these databases via geospatial services. This paper outlines the acquisition of geospatial context information, describes usage scenarios and real-world applications in the tourism industry, and presents an automated software tool for annotating large collections of Web documents automatically. The quality of this tool is tested based upon Web pages from the Austrian National Tourism Organization. Initial results are encouraging and help define a roadmap for further improving the automated tagging of tourism resources