Mapping clusters of chikungunya and dengue transmission in northern Tanzania using disease exposure and vector data

Background: Dengue and chikungunya are mosquito-borne viral diseases that are of public health importance throughout the tropical and subtropical regions of the world. Seasonal variations in transmission of these viruses have been suggested owing to the ecology of their mosquito vectors. However, little is known about the epidemiology of the diseases Tanzania. To address this gap, seasonal community-based cross-sectional surveys were undertaken to identify potential clusters of transmission in Hai district in northern Tanzania.Methods: Epidemiological and entomological data from two cross-sectional surveys were used to examine the spatial pattern of dengue and chikungunya transmission. Six villages namely, Boma Ng’ombe, Magadini, Rundugai, Nshara and Kware were involved in the study. Serological measures of dengue and chikungunya virus infections were derived using enzyme-linked immunosorbent assays, and all participants were geo-referenced to the household level using a global positioning system. Potential clusters of individual exposed to dengue and chikungunya virus , as well as clusters of Aedes mosquitoes in the wet and dry seasons were detected using SaTScan. All significant clusters (with p≤0.05) were mapped using ArcGIS.Results: A large, widely dispersed cluster of chikungunya exposed individuals was detected spanning Rundugai and parts of Magadini villages (RR = 2.58,  p= 0.01), while no significant clustering was observed in the dry season. Spatial clusters of Aedes aegypti were detected in Rundugai in both the wet and dry seasons (RR = 2.56, p< 0.001 and RR = 2.24, p=0.05, respectively). In the dry season a small cluster was also detected in Kware (RR = 2.25, p=0.05). No significant clusters of dengue were detected in both seasons.Conclusion: Clusters of chikungunya-exposed individuals and Aedes mosquitoes indicate on-going transmission of chikungunya virus in Hai district of northern Tanzania

Magnify is a universal molecular anchoring strategy for expansion microscopy

Expansion microscopy enables nanoimaging with conventional microscopes by physically and isotropically magnifying preserved biological specimens embedded in a crosslinked water-swellable hydrogel. Current expansion microscopy protocols require prior treatment with reactive anchoring chemicals to link specific labels and biomolecule classes to the gel. We describe a strategy called Magnify, which uses a mechanically sturdy gel that retains nucleic acids, proteins and lipids without the need for a separate anchoring step. Magnify expands biological specimens up to 11 times and facilitates imaging of cells and tissues with effectively around 25-nm resolution using a diffraction-limited objective lens of about 280 nm on conventional optical microscopes or with around 15 nm effective resolution if combined with super-resolution optical fluctuation imaging. We demonstrate Magnify on a broad range of biological specimens, providing insight into nanoscopic subcellular structures, including synaptic proteins from mouse brain, podocyte foot processes in formalin-fixed paraffin-embedded human kidney and defects in cilia and basal bodies in drug-treated human lung organoids

Semantic Web integration of Cheminformatics resources with the SADI framework

<p>Abstract</p> <p>Background</p> <p>The diversity and the largely independent nature of chemical research efforts over the past half century are, most likely, the major contributors to the current poor state of chemical computational resource and database interoperability. While open software for chemical format interconversion and database entry cross-linking have partially addressed database interoperability, computational resource integration is hindered by the great diversity of software interfaces, languages, access methods, and platforms, among others. This has, in turn, translated into limited reproducibility of computational experiments and the need for application-specific computational workflow construction and semi-automated enactment by human experts, especially where emerging interdisciplinary fields, such as systems chemistry, are pursued. Fortunately, the advent of the Semantic Web, and the very recent introduction of RESTful Semantic Web Services (SWS) may present an opportunity to integrate all of the existing computational and database resources in chemistry into a machine-understandable, unified system that draws on the entirety of the Semantic Web.</p> <p>Results</p> <p>We have created a prototype framework of Semantic Automated Discovery and Integration (SADI) framework SWS that exposes the QSAR descriptor functionality of the Chemistry Development Kit. Since each of these services has formal ontology-defined input and output classes, and each service consumes and produces RDF graphs, clients can automatically reason about the services and available reference information necessary to complete a given overall computational task specified through a simple SPARQL query. We demonstrate this capability by carrying out QSAR analysis backed by a simple formal ontology to determine whether a given molecule is drug-like. Further, we discuss parameter-based control over the execution of SADI SWS. Finally, we demonstrate the value of computational resource envelopment as SADI services through service reuse and ease of integration of computational functionality into formal ontologies.</p> <p>Conclusions</p> <p>The work we present here may trigger a major paradigm shift in the distribution of computational resources in chemistry. We conclude that envelopment of chemical computational resources as SADI SWS facilitates interdisciplinary research by enabling the definition of computational problems in terms of ontologies and formal logical statements instead of cumbersome and application-specific tasks and workflows.</p

Whole genome sequencing and phylogenetic analysis of strains of the agent of Lyme disease Borrelia burgdorferi from Canadian emergence zones

Lyme disease is emerging in southern Canada due to range expansion of the tick vector, followed by invasion of the agent of Lyme disease Borrelia burgdorferi sensu stricto. Strain diversity, as determined by Multi Locus Sequence Typing, occurs in this zone of emergence, and this may have its origins in adaptation to ecological niches, and have phenotypic consequences for pathogenicity and serological test performance. Sixty-four unique strains were cultured from ticks collected in southern Canada and the genomes sequenced using the Illumina MiSeq platform. A maximum likelihood phylogenetic tree of the chromosome revealed two large clades with multiple subclades. Consistent with previous studies on this species, the clades were not geographically defined, and some Canadian strains were highly divergent from previously sequenced US strains. There was evidence for recombination in the chromosome but this did not affect the phylogeny. Analysis of chromosomal genes indicated that these are under intense purifying selection. Phylogenies of the accessory genome and chromosome were congruent. Therefore strain differences identified in the phylogeny of chromosomal genes likely act as a proxy for genetic determinants of phenotypic differences amongst strains that are harboured in the accessory genome. Further studies on health implications of strain diversity are needed

Accurate prediction of clinical stroke scales and improved biomarkers of motor impairment from robotic measurements

Objective: One of the greatest challenges in clinical trial design is dealing with the subjectivity and variability introduced by human raters when measuring clinical end-points. We hypothesized that robotic measures that capture the kinematics of human movements collected longitudinally in patients after stroke would bear a significant relationship to the ordinal clinical scales and potentially lead to the development of more sensitive motor biomarkers that could improve the efficiency and cost of clinical trials. Materials and methods: We used clinical scales and a robotic assay to measure arm movement in 208 patients 7, 14, 21, 30 and 90 days after acute ischemic stroke at two separate clinical sites. The robots are low impedance and low friction interactive devices that precisely measure speed, position and force, so that even a hemiparetic patient can generate a complete measurement profile. These profiles were used to develop predictive models of the clinical assessments employing a combination of artificial ant colonies and neural network ensembles. Results: The resulting models replicated commonly used clinical scales to a cross-validated R2 of 0.73, 0.75, 0.63 and 0.60 for the Fugl-Meyer, Motor Power, NIH stroke and modified Rankin scales, respectively. Moreover, when suitably scaled and combined, the robotic measures demonstrated a significant increase in effect size from day 7 to 90 over historical data (1.47 versus 0.67). Discussion and conclusion: These results suggest that it is possible to derive surrogate biomarkers that can significantly reduce the sample size required to power future stroke clinical trials

Locally Acquired Leptospirosis in Expedition Racer, Manitoba, Canada

Leptospirosis is found worldwide, except in northern regions. We report a case associated with a backcountry adventure race in Manitoba, Canada. Initially, nonspecific symptomatology and diagnostic pitfalls contributed to a delay in identification. Careful attention needs to be paid to exposure to and risk for leptospirosis in northern and temperate climates

Suprachoroidal hemorrhage. Clinical features and results of secondary surgical management

The purposes of this study are to identify clinical features in eyes with suprachoroidal hemorrhage which portend a poor visual prognosis and to determine visual outcome in these eyes after secondary surgical management of suprachoroidal hemorrhage. This was a retrospective study of 106 patients with suprachoroidal hemorrhages occurring in association with trauma (35), cataract surgery (30), glaucoma surgery (17), penetrating keratoplasty (6), corneal perforation (5), secondary lens implantation (3), pars plana vitrectomy (3), and other causes (7). Five (10%) of 49 eyes with a suprachoroidal hemorrhage and an initial retinal detachment had a visual outcome of 20/200 or better compared with 21 (43%) of 49 eyes without a retinal detachment. The presence or absence or a retinal detachment could not be determined in eight patients and all eight of these patients had a poor visual outcome. Sixteen (20%) of 82 eyes with a 360 degrees suprachoroidal hemorrhage had a visual outcome of 20/200 or better compared with 10 (47%) of 21 for those with suprachoroidal hemorrhage limited to one or two quadrants. The extent of the hemorrhage could not be determined in three eyes. Overall, 34% (14/41) of the patients with suprachoroidal hemorrhage who had a secondary surgical procedure achieved a visual outcome of 20/200 or better. Forty-three percent (6/14) who had a suprachoroidal hemorrhage during or after cataract surgery and who were treated with secondary surgical management achieved a visual outcome of 20/200 or greater. Clinical features associated with a poorer visual outcome included initial or indeterminate retinal detachment and 360 degrees suprachoroidal hemorrhage. Limited suprachoroidal hemorrhage without initial retinal detachment usually has a good visual prognosis and does not usually require secondary surgical intervention. However, if the former complication is present, secondary surgical intervention should be considered