1,033 research outputs found

    Context-aware support for assistive systems and services

    Get PDF

    Duodenal ulcer is a multifactorial disorder the role of pepsinogen I

    Get PDF
    Serum pepsinogen I (PGI) levels were measured in 231 duodenal ulcer (DU) patients and 100 sex and age-comparable healthy controls. Significantly higher mean serum PGI levels were found in DU patients than in controls (124,7 ± 3,4 ng/ml v. 92,9 ± 2,3 ng/ml; P < 0,001) (mean ± SE). These levels were higher in male DU patients than in female DU patients (128,5 ± 3,9 ng/IDl v. 107,4 ± 6,4 ng/ml; P < 0,05). Smoking was associated with elevated serum PGI levels in DU patients (145,3 ± 5,1 ng/ml v. 109,0 ± 4,2 ngl/ml; P < 0,001). Healed DUs were associated with lower mean serum PGI levels than active ulcers (110,9 ± 7,6 ng/ml v. 129,4 ± 3,8 ng/ml, P < 0,05). Whether patients were positive or negative for Helicobacter pylori, infection did not affect mean serum PGI levels. All the risk factors for DU may not affect serum PGI levels and DU may therefore be considered a multifactorial disease

    The application of componentised modelling techniques to catastrophe model generation

    Get PDF
    In this paper we show that integrated environmental modelling (IEM) techniques can be used to generate a catastrophe model for groundwater flooding. Catastrophe models are probabilistic models based upon sets of events representing the hazard and weights their likelihood with the impact of such an event happening which is then used to estimate future financial losses. These probabilistic loss estimates often underpin re-insurance transactions. Modelled loss estimates can vary significantly, because of the assumptions used within the models. A rudimentary insurance-style catastrophe model for groundwater flooding has been created by linking seven individual components together. Each component is linked to the next using an open modelling framework (i.e. an implementation of OpenMI). Finally, we discuss how a flexible model integration methodology, such as described in this paper, facilitates a better understanding of the assumptions used within the catastrophe model by enabling the interchange of model components created using different, yet appropriate, assumptions

    Molecular and clinical characterization of a claudin-low subtype of gastric cancer

    Get PDF
    Purpose Claudin-low molecular subtypes have been identified in breast and bladder cancers and are characterized by low expression of claudins, enrichment for epithelial-to-mesenchymal transition (EMT), and tumor-initiating cell (TIC) features. We evaluated whether the claudin-low subtype also exists in gastric cancer. Materials and Methods Four hundred fifteen tumors from The Cancer Genome Atlas (TCGA) gastric cancer mRNA data set were clustered on the claudin, EMT, and TIC gene sets to identify claudin-low tumors. We derived a 24-gene predictor that classifies gastric cancer into claudin-low and non-claudin-low subtypes. This predictor was validated with the Asian Cancer Research Group(ACRG)data set. We characterized molecular and clinical features of claudin-low tumors. Results We identified 46 tumors that had consensus enrichment for claudin-low features in TCGA data set. Claudin-low tumors were most commonly diffuse histologic type (82%) and originally classified as TCGA genomically stable(GS)subtype (78%). Compared with GS subtype, claudin-low subtype had significant activation in Rho family of GTPases signaling, which appears to play a key role in its EMT and TIC properties. In the ACRG data set, 28 of 300 samples were classified as claudin-low tumors by the 24-gene predictor and were phenotypically similar to the initially derived claudin-low tumors. Clinically, claudin-low subtype had the worst overall survival. Of note, the hazard ratios that compared claudin-low versus GS subtype were 2.10 (95% CI, 1.07 to 4.11) in TCGA and 2.32 (95% CI, 1.18 to 4.55) in the ACRG cohorts, with adjustment for age and pathologic stage. Conclusion We identified a gastric claudin-low subtype that carries a poor prognosis likely related to therapeutic resistance as a result of its EMT and TIC phenotypes

    Genetic liability for depression, social factors and their interaction effect in depressive symptoms and depression over time in older adults

    Get PDF
    Objectives The objectives of this study were to investigate the effect of genetic and social factors on depressive symptoms and depression over time and to test whether social factors moderate the relationship between depressive symptoms and its underlying genetics in later life. Methods The study included 2,279 participants with a mean follow-up of 15 years from the Longitudinal Aging Study Amsterdam with genotyping data. The personal genetic loading for depression was estimated for each participant by calculating a polygenic risk scores (PRS-D), based on 23,032 single nucleotide polymorphisms associated with major depression in a large genome-wide association study. Partner status, network size, received and given emotional support were assessed via questionnaires and depressive symptoms were assessed using the CES-D Scale. A CES-D Scale of 16 and higher was considered as clinically relevant depression. Results Higher PRS-D was associated with more depressive symptoms whereas having a partner and having a larger network size were independently associated with less depressive symptoms. After extra adjustment for education, cognitive function and functional limitations, giving more emotional support was also associated with less depressive symptoms. No evidence for gene-environment interaction between PRS-D and social factors was found. Similar results were found for clinically relevant depression. Conclusion Genetic and social factors are independently associated with depressive symptoms over time in older adults. Strategies that boost social functioning should be encouraged in the general population of older adults regardless of the genetic liability for depression

    Probable Secondary Infections in Households of SARS Patients in Hong Kong

    Get PDF
    Although severe acute respiratory syndrome (SARS) is highly infectious in clinical settings, SARS has not been well examined in household settings. The household and household member attack rates were calculated for 1,214 SARS case-patients and their household members, stratified by two phases of the epidemic. A case-control analysis identified risk factors for secondary infection. Secondary infection occurred in 14.9% (22.1% versus 11% in earlier and later phases) of all households and 8% (11.7% versus 5.9% in the earlier and later phases) of all household members. Healthcare workers’ households were less likely to be affected. Risk factors from the multivariate analysis included at-home duration before hospitalization, hospital visitation to the SARS patient (and mask use during the visit), and frequency of close contact. SARS transmission at the household level was not negligible in Hong Kong. Transmission rates may be greatly reduced with precautionary measures taken by household members of SARS patients

    Thermotolerance Requires Refolding of Aggregated Proteins by Substrate Translocation through the Central Pore of ClpB

    Get PDF
    AbstractCell survival under severe thermal stress requires the activity of the ClpB (Hsp104) AAA+ chaperone that solubilizes and reactivates aggregated proteins in concert with the DnaK (Hsp70) chaperone system. How protein disaggregation is achieved and whether survival is solely dependent on ClpB-mediated elimination of aggregates or also on reactivation of aggregated proteins has been unclear. We engineered a ClpB variant, BAP, which associates with the ClpP peptidase and thereby is converted into a degrading disaggregase. BAP translocates substrates through its central pore directly into ClpP for degradation. ClpB-dependent translocation is demonstrated to be an integral part of the disaggregation mechanism. Protein disaggregation by the BAP/ClpP complex remains dependent on DnaK, defining a role for DnaK at early stages of the disaggregation reaction. The activity switch of BAP to a degrading disaggregase does not support thermotolerance development, demonstrating that cell survival during severe thermal stress requires reactivation of aggregated proteins
    corecore