Development of a web-based insulin decision aid for the elderly: usability barriers and guidelines

In recent years, researchers have attempted to shift patient decision aids (PDAs) from paper-based to web-based to increase its accessibility. Insulin decision aids help diabetes patients, most of whom are elderly to make an informed decision to start insulin. However, the lack of usability guidelines applicable for such target group causes developers to struggle to answer the challenging question ‘How can such web service be made usable, and, ultimately, acceptable and accessible for elderly patients?’. Hence, the purpose of this study is to identify the common usability requirements that may facilitate good practices to empower elderly diabetes patients in utilizing a web-based insulin decision aid for their benefit. We set out an approach to use prototyping and retrospective think-aloud techniques to explore web usability barriers that elderly patients may encounter when using an insulin decision aid web site and use the feedback for improving the prototype. Usability requirements were captured iteratively through scoping, brainstorming, prototype, testing and evaluating. The study suggests that the insights from experts and users are equally important to assure the validity of the identified usability guidelines; they reflect the accessibility needs of the aging community while complementing the key requirements of an insulin decision aid. The study contributes to recommend web usability guidelines backed by a series of expert and user evaluations which could be a proactive resource to improve usability, acceptability and accessibility of online insulin decision aids for elderly with diabetes

Melanesian mtDNA Complexity

Melanesian populations are known for their diversity, but it has been hard to grasp the pattern of the variation or its underlying dynamic. Using 1,223 mitochondrial DNA (mtDNA) sequences from hypervariable regions 1 and 2 (HVR1 and HVR2) from 32 populations, we found the among-group variation is structured by island, island size, and also by language affiliation. The more isolated inland Papuan-speaking groups on the largest islands have the greatest distinctions, while shore dwelling populations are considerably less diverse (at the same time, within-group haplotype diversity is less in the most isolated groups). Persistent differences between shore and inland groups in effective population sizes and marital migration rates probably cause these differences. We also add 16 whole sequences to the Melanesian mtDNA phylogenies. We identify the likely origins of a number of the haplogroups and ancient branches in specific islands, point to some ancient mtDNA connections between Near Oceania and Australia, and show additional Holocene connections between Island Southeast Asia/Taiwan and Island Melanesia with branches of haplogroup E. Coalescence estimates based on synonymous transitions in the coding region suggest an initial settlement and expansion in the region at ∼30–50,000 years before present (YBP), and a second important expansion from Island Southeast Asia/Taiwan during the interval ∼3,500–8,000 YBP. However, there are some important variance components in molecular dating that have been overlooked, and the specific nature of ancestral (maternal) Austronesian influence in this region remains unresolved

Acidosis Activation of the Proton-Sensing GPR4 Receptor Stimulates Vascular Endothelial Cell Inflammatory Responses Revealed by Transcriptome Analysis

Acidic tissue microenvironment commonly exists in inflammatory diseases, tumors, ischemic organs, sickle cell disease, and many other pathological conditions due to hypoxia, glycolytic cell metabolism and deficient blood perfusion. However, the molecular mechanisms by which cells sense and respond to the acidic microenvironment are not well understood. GPR4 is a proton-sensing receptor expressed in endothelial cells and other cell types. The receptor is fully activated by acidic extracellular pH but exhibits lesser activity at the physiological pH 7.4 and minimal activity at more alkaline pH. To delineate the function and signaling pathways of GPR4 activation by acidosis in endothelial cells, we compared the global gene expression of the acidosis response in primary human umbilical vein endothelial cells (HUVEC) with varying level of GPR4. The results demonstrated that acidosis activation of GPR4 in HUVEC substantially increased the expression of a number of inflammatory genes such as chemokines, cytokines, adhesion molecules, NF-κB pathway genes, and prostaglandin-endoperoxidase synthase 2 (PTGS2 or COX-2) and stress response genes such as ATF3 and DDIT3 (CHOP). Similar GPR4-mediated acidosis induction of the inflammatory genes was also noted in other types of endothelial cells including human lung microvascular endothelial cells and pulmonary artery endothelial cells. Further analyses indicated that the NF-κB pathway was important for the acidosis/GPR4-induced inflammatory gene expression. Moreover, acidosis activation of GPR4 increased the adhesion of HUVEC to U937 monocytic cells under a flow condition. Importantly, treatment with a recently identified GPR4 antagonist significantly reduced the acidosis/GPR4-mediated endothelial cell inflammatory response. Taken together, these results show that activation of GPR4 by acidosis stimulates the expression of a wide range of inflammatory genes in endothelial cells. Such inflammatory response can be suppressed by GPR4 small molecule inhibitors and hold potential therapeutic value

Implicit sequence learning is preserved in dyslexic children

This study investigates the implicit sequence learning abilities of dyslexic children using an artificial grammar learning task with an extended exposure period. Twenty children with developmental dyslexia participated in the study and were matched with two control groups-one matched for age and other for reading skills. During 3 days, all participants performed an acquisition task, where they were exposed to colored geometrical forms sequences with an underlying grammatical structure. On the last day, after the acquisition task, participants were tested in a grammaticality classification task. Implicit sequence learning was present in dyslexic children, as well as in both control groups, and no differences between groups were observed. These results suggest that implicit learning deficits per se cannot explain the characteristic reading difficulties of the dyslexics.info:eu-repo/semantics/publishedVersio

LabKey Server: An open source platform for scientific data integration, analysis and collaboration

<p>Abstract</p> <p>Background</p> <p>Broad-based collaborations are becoming increasingly common among disease researchers. For example, the Global HIV Enterprise has united cross-disciplinary consortia to speed progress towards HIV vaccines through coordinated research across the boundaries of institutions, continents and specialties. New, end-to-end software tools for data and specimen management are necessary to achieve the ambitious goals of such alliances. These tools must enable researchers to organize and integrate heterogeneous data early in the discovery process, standardize processes, gain new insights into pooled data and collaborate securely.</p> <p>Results</p> <p>To meet these needs, we enhanced the LabKey Server platform, formerly known as CPAS. This freely available, open source software is maintained by professional engineers who use commercially proven practices for software development and maintenance. Recent enhancements support: (i) Submitting specimens requests across collaborating organizations (ii) Graphically defining new experimental data types, metadata and wizards for data collection (iii) Transitioning experimental results from a multiplicity of spreadsheets to custom tables in a shared database (iv) Securely organizing, integrating, analyzing, visualizing and sharing diverse data types, from clinical records to specimens to complex assays (v) Interacting dynamically with external data sources (vi) Tracking study participants and cohorts over time (vii) Developing custom interfaces using client libraries (viii) Authoring custom visualizations in a built-in R scripting environment.</p> <p>Diverse research organizations have adopted and adapted LabKey Server, including consortia within the Global HIV Enterprise. Atlas is an installation of LabKey Server that has been tailored to serve these consortia. It is in production use and demonstrates the core capabilities of LabKey Server. Atlas now has over 2,800 active user accounts originating from approximately 36 countries and 350 organizations. It tracks roughly 27,000 assay runs, 860,000 specimen vials and 1,300,000 vial transfers.</p> <p>Conclusions</p> <p>Sharing data, analysis tools and infrastructure can speed the efforts of large research consortia by enhancing efficiency and enabling new insights. The Atlas installation of LabKey Server demonstrates the utility of the LabKey platform for collaborative research. Stable, supported builds of LabKey Server are freely available for download at <url>http://www.labkey.org</url>. Documentation and source code are available under the Apache License 2.0.</p

High Resolution Genomic Scans Reveal Genetic Architecture Controlling Alcohol Preference in Bidirectionally Selected Rat Model

Investigations on the influence of nature vs. nurture on Alcoholism (Alcohol Use Disorder) in human have yet to provide a clear view on potential genomic etiologies. To address this issue, we sequenced a replicated animal model system bidirectionally-selected for alcohol preference (AP). This model is uniquely suited to map genetic effects with high reproducibility, and resolution. The origin of the rat lines (an 8-way cross) resulted in small haplotype blocks (HB) with a corresponding high level of resolution. We sequenced DNAs from 40 samples (10 per line of each replicate) to determine allele frequencies and HB. We achieved ~46X coverage per line and replicate. Excessive differentiation in the genomic architecture between lines, across replicates, termed signatures of selection (SS), were classified according to gene and region. We identified SS in 930 genes associated with AP. The majority (50%) of the SS were confined to single gene regions, the greatest numbers of which were in promoters (284) and intronic regions (169) with the least in exon\u27s (4), suggesting that differences in AP were primarily due to alterations in regulatory regions. We confirmed previously identified genes and found many new genes associated with AP. Of those newly identified genes, several demonstrated neuronal function involved in synaptic memory and reward behavior, e.g. ion channels (Kcnf1, Kcnn3, Scn5a), excitatory receptors (Grin2a, Gria3, Grip1), neurotransmitters (Pomc), and synapses (Snap29). This study not only reveals the polygenic architecture of AP, but also emphasizes the importance of regulatory elements, consistent with other complex traits

Chemical–Genetic Profiling of Imidazo[1,2-a]pyridines and -Pyrimidines Reveals Target Pathways Conserved between Yeast and Human Cells

Small molecules have been shown to be potent and selective probes to understand cell physiology. Here, we show that imidazo[1,2-a]pyridines and imidazo[1,2-a]pyrimidines compose a class of compounds that target essential, conserved cellular processes. Using validated chemogenomic assays in Saccharomyces cerevisiae, we discovered that two closely related compounds, an imidazo[1,2-a]pyridine and -pyrimidine that differ by a single atom, have distinctly different mechanisms of action in vivo. 2-phenyl-3-nitroso-imidazo[1,2-a]pyridine was toxic to yeast strains with defects in electron transport and mitochondrial functions and caused mitochondrial fragmentation, suggesting that compound 13 acts by disrupting mitochondria. By contrast, 2-phenyl-3-nitroso-imidazo[1,2-a]pyrimidine acted as a DNA poison, causing damage to the nuclear DNA and inducing mutagenesis. We compared compound 15 to known chemotherapeutics and found resistance required intact DNA repair pathways. Thus, subtle changes in the structure of imidazo-pyridines and -pyrimidines dramatically alter both the intracellular targeting of these compounds and their effects in vivo. Of particular interest, these different modes of action were evident in experiments on human cells, suggesting that chemical–genetic profiles obtained in yeast are recapitulated in cultured cells, indicating that our observations in yeast can: (1) be leveraged to determine mechanism of action in mammalian cells and (2) suggest novel structure–activity relationships