Build it, but will they come? A geoscience cyberinfrastructure baseline analsys

Understanding the earth as a system requires integrating many forms of data from multiple fields. Builders and funders of the cyberinfrastructure designed to enable open data sharing in the geosciences risk a key failure mode: What if geoscientists do not use the cyberinfrastructure to share, discover and reuse data? In this study, we report a baseline assessment of engagement with the NSF EarthCube initiative, an open cyberinfrastructure effort for the geosciences. We find scientists perceive the need for cross-disciplinary engagement and engage where there is organizational or institutional support. However, we also find a possibly imbalanced involvement between cyber and geoscience communities at the outset, with the former showing more interest than the latter. This analysis highlights the importance of examining fields and disciplines as stakeholders to investments in the cyberinfrastructure supporting science

Microarray analysis of Foxa2 mutant mouse embryos reveals novel gene expression and inductive roles for the gastrula organizer and its derivatives

<p>Abstract</p> <p>Background</p> <p>The Spemann/Mangold organizer is a transient tissue critical for patterning the gastrula stage vertebrate embryo and formation of the three germ layers. Despite its important role during development, there are still relatively few genes with specific expression in the organizer and its derivatives. Foxa2 is a forkhead transcription factor that is absolutely required for formation of the mammalian equivalent of the organizer, the node, the axial mesoderm and the definitive endoderm (DE). However, the targets of Foxa2 during embryogenesis, and the molecular impact of organizer loss on the gastrula embryo, have not been well defined.</p> <p>Results</p> <p>To identify genes specific to the Spemann/Mangold organizer, we performed a microarray-based screen that compared wild-type and <it>Foxa2 </it>mutant embryos at late gastrulation stage (E7.5). We could detect genes that were consistently down-regulated in replicate pools of mutant embryos versus wild-type, and these included a number of known node and DE markers. We selected 314 genes without previously published data at E7.5 and screened for expression by whole mount <it>in situ </it>hybridization. We identified 10 novel expression patterns in the node and 5 in the definitive endoderm. We also found significant reduction of markers expressed in secondary tissues that require interaction with the organizer and its derivatives, such as cardiac mesoderm, vasculature, primitive streak, and anterior neuroectoderm.</p> <p>Conclusion</p> <p>The genes identified in this screen represent novel Spemann/Mangold organizer genes as well as potential Foxa2 targets. Further investigation will be needed to define these genes as novel developmental regulatory factors involved in organizer formation and function. We have placed these genes in a Foxa2-dependent genetic regulatory network and we hypothesize how Foxa2 may regulate a molecular program of Spemann/Mangold organizer development. We have also shown how early loss of the organizer and its inductive properties in an otherwise normal embryo, impacts on the molecular profile of surrounding tissues.</p

Learning HCI Across Institutions, Disciplines and Countries: A Field Study of Cognitive Styles in Analytical and Creative Tasks

Human-computer interaction (HCI) is increasingly becoming a subject taught in universities around the world. However, little is known of the interactions of the HCI curriculum with students in different types of institutions and disciplines internationally. In order to explore these interactions, we studied the performance of HCI students in design, technology and business faculties in universities in UK, India, Namibia, Mexico and China who participated in a common set of design and evaluation tasks. We obtained participants’ cognitive style profiles based on Allinson and Hayes scale in order to gain further insights into their learning styles and explore any relation between these and performance. We found participants’ cognitive style preferences to be predominantly in the adaptive range, i.e. with combined analytical and intuitive traits, compared to normative data for software engineering, psychology and design professionals. We further identified significant relations between students’ cognitive styles and performance in analytical and creative tasks of a HCI professional individual. We discuss the findings in the context of the distinct backgrounds of the students and universities that participated in this study and the value of research that explores and promotes diversity in HCI education

Multiple Sclerosis Risk Variant HLA-DRB1*1501 Associates with High Expression of DRB1 Gene in Different Human Populations

The human leukocyte antigen (HLA) DRB1*1501 has been consistently associated with multiple sclerosis (MS) in nearly all populations tested. This points to a specific antigen presentation as the pathogenic mechanism though this does not fully explain the disease association. The identification of expression quantitative trait loci (eQTL) for genes in the HLA locus poses the question of the role of gene expression in MS susceptibility. We analyzed the eQTLs in the HLA region with respect to MS-associated HLA-variants obtained from genome-wide association studies (GWAS). We found that the Tag of DRB1*1501, rs3135388 A allele, correlated with high expression of DRB1, DRB5 and DQB1 genes in a Caucasian population. In quantitative terms, the MS-risk AA genotype carriers of rs3135388 were associated with 15.7-, 5.2- and 8.3-fold higher expression of DQB1, DRB5 and DRB1, respectively, than the non-risk GG carriers. The haplotype analysis of expression-associated variants in a Spanish MS cohort revealed that high expression of DRB1 and DQB1 alone did not contribute to the disease. However, in Caucasian, Asian and African American populations, the DRB1*1501 allele was always highly expressed. In other immune related diseases such as type 1 diabetes, inflammatory bowel disease, ulcerative colitis, asthma and IgA deficiency, the best GWAS-associated HLA SNPs were also eQTLs for different HLA Class II genes. Our data suggest that the DR/DQ expression levels, together with specific structural properties of alleles, seem to be the causal effect in MS and in other immunopathologies rather than specific antigen presentation alone

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD

How equitable is bed net ownership and utilisation in Tanzania? A practical application of the principles of horizontal and vertical equity

BACKGROUND: Studies show that the burden of malaria remains huge particularly in low-income settings. Although effective malaria control measures such as insecticide-treated nets (ITNs) have been promoted, relatively little is known about their equity dimension. Understanding variations in their use in low-income settings is important for scaling up malaria control programmes particularly ITNs. The objective of this paper is to measure the extent and causes of inequalities in the ownership and utilisation of bed nets across socioeconomic groups (SEGs) and age groups in Tanga District, north-eastern Tanzania. METHODS: A questionnaire was administered to heads of 1,603 households from rural and urban areas. Households were categorized into SEGs using both an asset-based wealth index and education level of the household head. Concentration indices and regression-based measures of inequality were computed to analyse both vertical and horizontal inequalities in ownership and utilisation of bed nets. Focus Group Discussions (FGDs) were used to explore community perspectives on the causes of inequalities. RESULTS: Use of ITNs remained appallingly low compared to the RBM target of 80% coverage. Inequalities in ownership of ITNs and all nets combined were significantly pro-rich and were much more pronounced in rural areas. FGDs revealed that lack of money was the key factor for not using ITNs followed by negative perceptions about the effect of insecticides on the health of users. Household SES, living within the urban areas and being under-five were positively associated with bed net ownership and/or utilisation. CONCLUSION: The results highlight the need for mass distribution of ITN; a community-wide programme to treat all untreated nets and to promote the use of Long-Lasting Insecticidal nets (LLINs) or longer-lasting treatment of nets. The rural population and under-fives should be targeted through highly subsidized schemes and mass distribution of free nets. Public campaigns are also needed to encourage people to use treated nets and mitigate negative perceptions about insecticides

Correlates of Out-of-Pocket and Catastrophic Health Expenditures in Tanzania: Results from a National Household Survey.

Inequality in health services access and utilization are influenced by out-of-pocket health expenditures in many low and middle-income countries (LMICs). Various antecedents such as social factors, poor health and economic factors are proposed to direct the choice of health care service use and incurring out-of-pocket payments. We investigated the association of these factors with out-of-pocket health expenditures among the adult and older population in the United Republic of Tanzania. We also investigated the prevalence and associated determinants contributing to household catastrophic health expenditures. We accessed the data of a multistage stratified random sample of 7279 adult participants, aged between 18 and 59 years, as well as 1018 participants aged above 60 years, from the first round of the Tanzania National Panel survey. We employed multiple generalized linear and logistic regression models to evaluate the correlates of out-of-pocket as well as catastrophic health expenditures, accounting for the complex sample design effects. Increasing age, female gender, obesity and functional disability increased the adults' out-of-pocket health expenditures significantly, while functional disability and visits to traditional healers increased the out-of-pocket health expenditures in older participants. Adult participants, who lacked formal education or worked as manual laborers earned significantly less (p < 0.001) and spent less on health (p < 0.001), despite having higher levels of disability. Large household size, household head's occupation as a manual laborer, household member with chronic illness, domestic violence against women and traditional healer's visits were significantly associated with high catastrophic health expenditures. We observed that the prevalence of inequalities in socioeconomic factors played a significant role in determining the nature of both out-of-pocket and catastrophic health expenditures. We propose that investment in social welfare programs and strengthening the social security mechanisms could reduce the financial burden in United Republic of Tanzania