Enabling Collaborative eHealth Research using Web 2.0 Tools

In this paper, we describe two Web 2.0 based systems designed to facilitate and enhance collaborative eHealth research activities. Using a combination of Forums, Wikis and connectivity to 3rd party social networking systems, we have designed systems to support collaborative document creation (including editing, reviewing and publication), dissemination of material to relevant communities, discussion of ideas, and sharing of opinions. The ECDC Field Epidemiology Manual Wiki and Medicine Support Unit Online Forums are presented herein, including an overview to the system architectures, and user interaction models. We present our planned methods of evaluation, focusing on the ability to measure successful and sustainable community involvement

Inference of disease associations with unmeasured genetic variants by combining results from genome-wide association studies with linkage disequilibrium patterns in a reference data set

Results from whole-genome association studies of many common diseases are now available. Increasingly, these are being incorporated into meta-analyses to increase the power to detect weak associations with measured single-nucleotide polymorphisms (SNPs). Imputation of genotypes at unmeasured loci has been widely applied using patterns of linkage disequilibrium (LD) observed in the HapMap panels, but there is a need for alternative methods that can utilize the pooled effect estimates from meta-analyses and explore possible associations with SNPs and haplotypes that are not included in HapMap

Significance of sex in achieving sustained remission in the consortium of rheumatology researchers of north america cohort of rheumatoid arthritis patients

Objective To determine whether men with rheumatoid arthritis (RA) are more likely to achieve remission compared to women. Methods RA patients enrolled in the Consortium of Rheumatology Researchers of North America (CORRONA) cohort between October 2001 and January 2010 were selected for the present analyses. Detailed clinical, demographic, and drug utilization data were available at enrollment (baseline) and at subsequent followup visits. We examined the influence of sex on the Clinical Disease Activity Index remission score (≤2.8) using sustained remission or point remission as the primary outcome measure in multivariate stepwise logistic regression models. We stratified the data by RA duration at baseline (≤2 years or >2 years) to investigate whether RA duration had differential effects on remission in men and women. Results A total of 10,299 RA patients (2,406 men and 7,893 women) were available for this study. In both early and established RA, women had more severe disease at baseline with worse disease activity measures, modified Health Assessment Questionnaire disability index score, pain on a visual analog scale, and depression. Women were also more likely to have been treated with disease‐modifying antirheumatic drugs and anti–tumor necrosis factor therapy compared to men. In the regression models, male sex was associated with sustained remission in early RA (odds ratio [OR] 1.38, 95% confidence interval [95% CI] 1.07–1.78, P = 0.01), but not in established RA. However, for point remission, an inverse association was observed with male sex in established RA (OR 0.65, 95% CI 0.48–0.87, P = 0.005) and not in early RA. Conclusion Within the large real‐life CORRONA cohort of RA patients, men were more likely to achieve sustained remission compared to women in early RA, although not in established RA.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94462/1/21762_ftp.pd

A user-centred evaluation framework for the Sealife semantic web browsers

Background: Semantically-enriched browsing has enhanced the browsing experience by providing contextualised dynamically generated Web content, and quicker access to searched-for information. However, adoption of Semantic Web technologies is limited and user perception from the non-IT domain sceptical. Furthermore, little attention has been given to evaluating semantic browsers with real users to demonstrate the enhancements and obtain valuable feedback. The Sealife project investigates semantic browsing and its application to the life science domain. Sealife's main objective is to develop the notion of context-based information integration by extending three existing Semantic Web browsers (SWBs) to link the existing Web to the eScience infrastructure. / Methods: This paper describes a user-centred evaluation framework that was developed to evaluate the Sealife SWBs that elicited feedback on users' perceptions on ease of use and information findability. Three sources of data: i) web server logs; ii) user questionnaires; and iii) semi-structured interviews were analysed and comparisons made between each browser and a control system. / Results: It was found that the evaluation framework used successfully elicited users' perceptions of the three distinct SWBs. The results indicate that the browser with the most mature and polished interface was rated higher for usability, and semantic links were used by the users of all three browsers. / Conclusion: Confirmation or contradiction of our original hypotheses with relation to SWBs is detailed along with observations of implementation issues

Morphology, biological and chemical profiling of three Polyscias species, endemic to Mauritius

The aim of the study is to screen the morphological, anatomical, biological, and chemical profiles of the leave extracts of endemic Polyscias species namely P. dichroostachya (PD), P. gracilis (PG), and P. mauritiana (PM) from Mauritius. The morphology and anatomy of the leaves were studied using a microscope. Phytochemical screening of extracts using LC-MS/MS was carried out by ionization in both positive and negative modes. The leaves are pinnately compound, hypostomatic, dorsiventral, with a prominent mid vein with secretion cavities, and they can be distinguished by their midrib shape and anatomy. From the molecular mass and fragmentation data, 31 terpenoid saponins, 19 flavonoids, 17 acids, 7 terpenes, and 10 miscellaneous compounds including pyrrolidines and acetylenes in different extracts (hexane, ethanol, and aqueous) were identified. Extracts from the three species using DPPH radical scavenging activity exhibited good to moderate antioxidant activities with IC50 values in the range of 2.1-70.8 mg/ml and the ethanolic extract of PD showing the highest activity. Aqueous extracts of PG and PM potently inhibited alpha-glucosidase with IC50 values of 0.50 and 2.62 mg/ml. The different leaf extracts exhibited moderate activity against a panel of gram-positive and gram-negative bacteria. This is probably the first report on the extensive chemical profiling and morphology of these endemic Polysias spp. from Mauritius and the results indicate that these leaf extracts have beneficial health properties and are thus worth exploiting further

A Genome-Wide Homozygosity Association Study Identifies Runs of Homozygosity Associated with Rheumatoid Arthritis in the Human Major Histocompatibility Complex

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with a polygenic mode of inheritance. This study examined the hypothesis that runs of homozygosity (ROHs) play a recessive-acting role in the underlying RA genetic mechanism and identified RA-associated ROHs. Ours is the first genome-wide homozygosity association study for RA and characterized the ROH patterns associated with RA in the genomes of 2,000 RA patients and 3,000 normal controls of the Wellcome Trust Case Control Consortium. Genome scans consistently pinpointed two regions within the human major histocompatibility complex region containing RA-associated ROHs. The first region is from 32,451,664 bp to 32,846,093 bp (−log10(p)>22.6591). RA-susceptibility genes, such as HLA-DRB1, are contained in this region. The second region ranges from 32,933,485 bp to 33,585,118 bp (−log10(p)>8.3644) and contains other HLA-DPA1 and HLA-DPB1 genes. These two regions are physically close but are located in different blocks of linkage disequilibrium, and ∼40% of the RA patients' genomes carry these ROHs in the two regions. By analyzing homozygote intensities, an ROH that is anchored by the single nucleotide polymorphism rs2027852 and flanked by HLA-DRB6 and HLA-DRB1 was found associated with increased risk for RA. The presence of this risky ROH provides a 62% accuracy to predict RA disease status. An independent genomic dataset from 868 RA patients and 1,194 control subjects of the North American Rheumatoid Arthritis Consortium successfully validated the results obtained using the Wellcome Trust Case Control Consortium data. In conclusion, this genome-wide homozygosity association study provides an alternative to allelic association mapping for the identification of recessive variants responsible for RA. The identified RA-associated ROHs uncover recessive components and missing heritability associated with RA and other autoimmune diseases

Minor Abnormalities of Testis Development in Mice Lacking the Gene Encoding the MAPK Signalling Component, MAP3K1

In mammals, the Y chromosome is a dominant male determinant, causing the bipotential gonad to develop as a testis. Recently, cases of familial and spontaneous 46,XY disorders of sex development (DSD) have been attributed to mutations in the human gene encoding mitogen-activated protein kinase kinase kinase 1, MAP3K1, a component of the mitogen-activated protein kinase (MAPK) signal transduction pathway. In individuals harbouring heterozygous mutations in MAP3K1, dysregulation of MAPK signalling was observed in lymphoblastoid cell lines, suggesting a causal role for these mutations in disrupting XY sexual development. Mice lacking the cognate gene, Map3k1, are viable and exhibit the eyes open at birth (EOB) phenotype on a mixed genetic background, but on the C57BL/6J genetic background most mice die at around 14.5 dpc due to a failure of erythropoiesis in the fetal liver. However, no systematic examination of sexual development in Map3k1-deficient mice has been described, an omission that is especially relevant in the case of C57BL/6J, a genetic background that is sensitized to disruptions to testis determination. Here, we report that on a mixed genetic background mice lacking Map3k1 are fertile and exhibit no overt abnormalities of testis development. On C57BL/6J, significant non-viability is observed with very few animals surviving to adulthood. However, an examination of development in Map3k1-deficient XY embryos on this genetic background revealed no significant defects in testis determination, although minor abnormalities were observed, including an increase in gonadal length. Based on these observations, we conclude that MAP3K1 is not required for mouse testis determination. We discuss the significance of these data for the functional interpretation of sex-reversing MAP3K1 mutations in humans

Immune response to gut escherichia coli and susceptibility to adjuvant arthritis in the rats

We have investigated the humoral immune response to antigens of predominant gut aerobic bacterial strains (i.e. Escherichia coli) over the course of adjuvant arthritis and oil-induced arthritis in two inbred rat strains: Dark Agouti (DA) and Albino Oxford (AO). We report the presence of antibodies specific to proteins of Escherichia coli in molecular weight range between 20-30 kDa in sera of diseased DA rats, and the absence of these antibodies in the sera of AO rats. In DA rats, CFA and IFA provoked a stronger antibody response to Escherichia coli, especially of the IgG2b antibody class. Intramuscular administration of Escherichia coli preceding the adjuvant arthritis induction had no effect on the development and course of disease, as well as on the activation of T cells in the draining inguinal lymph nodes. Higher serum levels of natural and induced IgA antibodies, combined with a higher CD3(+)CD26(+) cell percentage were found in AO rats. The observed correlation between the serologic response to commensal flora and rats' genetic background as a defining factor for arthritis susceptibility may contribute to the process of creating a favorable (or less favorable) milieu for arthritis development