Onchocerciasis transmission in Ghana: biting and parous rates of host-seeking sibling species of the Simulium damnosum complex

Background: Ghana is renowned for its sibling species diversity of the Simulium damnosum complex, vectors of Onchocerca volvulus. Detailed entomological knowledge becomes a priority as onchocerciasis control policy has shifted from morbidity reduction to elimination of infection. To date, understanding of transmission dynamics of O. volvulus has been mainly based on S. damnosum sensu stricto (s.s.) data. We aim to elucidate bionomic features of vector species of importance for onchocerciasis elimination efforts. Methods: We collected S. damnosum sensu lato from seven villages in four Ghanaian regions between 2009 and 2011, using standard vector collection, and human- and cattle-baited tents. Taxa were identified using morphological and molecular techniques. Monthly biting rates (MBR), parous rates and monthly parous biting rates (MPBR) are reported by locality, season, trapping method and hour of collection for each species. Results: S. damnosum s.s./S. sirbanum were collected at Asubende and Agborlekame, both savannah villages. A range of species was caught in the Volta region (forest-savannah mosaic) and Gyankobaa (forest), with S. squamosum or S. sanctipauli being the predominant species, respectively. In Bosomase (southern forest region) only S. sanctipauli was collected in the 2009 wet season, but in the 2010 dry season S. yahense was also caught. MBRs ranged from 714 bites/person/month at Agborlekame (100% S. damnosum s.s./S. sirbanum) to 8,586 bites/person/month at Pillar 83/Djodji (98.5% S. squamosum). MBRs were higher in the wet season. In contrast, parous rates were higher in the dry season (41.8% vs. 18.4%), resulting in higher MPBRs in the dry season. Daily host-seeking activity of S. damnosum s.s./S. sirbanum was bimodal, whilst S. squamosum and S. sanctipauli had unimodal afternoon peaks. Conclusions: The bionomic differences between sibling species of the S. damnosum complex need to be taken into account when designing entomological monitoring protocols for interventions and parameterising mathematical models for onchocerciasis control and elimination

Studies in the Treatment of Malaria: XXIII. Oral Administration of Quinine Sulphate Grains 30 on Each of Two Consecutive Days Weekly, Over a Period of Five Weeks, in Malignant Tertian Malaria

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Uncovering the molecular signature of feline diffuse iris melanoma through transcriptomic analysis of disease severity

Feline diffuse iris melanoma (FDIM) is the most common primary ocular tumour in cats, with metastatic disease occurring in 19-63% of patients. Greater intraocular invasion correlates with increased mortality. No effective therapeutics exist for metastatic FDIM, partly due to a lack of known molecular targets associated with aggressive tumour behaviour. Here, we define the transcriptomic landscape of FDIM in treatment-naïve cats using bulk RNA sequencing on laser capture microdissection and core biopsy specimens from formalin-fixed paraffin-embedded tissue. Samples included 'iris melanosis' (dysplastic melanocytes confined to the anterior iris; n = 7), 'early FDIM' (neoplastic melanocytes confined to the iris stroma; n = 13), and 'late FDIM' (neoplastic infiltration into the ciliary body and sclera; n = 13). Iris melanosis exhibited genetic overlap with early FDIM, supporting its reclassification as 'melanoma in situ'. Early FDIM showed upregulation of genes linked to tumour initiation, immune recruitment, and motility (e.g., STOX1, PEG3, XIAP, MCAM, VIM). Late FDIM exhibited immune microenvironment remodelling, immune evasion, and apoptosis inhibition (e.g., BIRC2, BIRC5, CCL2, HAVCR2), with downregulation of FOX1, FOXC2, and SOX11. These results provide critical biomarkers of disease severity, which may aid in the development of more accurate prognostic tests and more effective targeted therapies for FDIM.</p

Studies in the Treatment of Malaria: XIII.—Oral Administration of Quinine Sulphate Grains 90 on Two Consecutive Days Only, in Simple Tertian Malaria[Second Series]

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Stochastic virtual tests for fiber composites

We will describe a Virtual Test system for continuous fiber composites. The virtual test draws from a new wave of advanced experiments and theory that address physical, mathematical, and engineering aspects of material definition and failure prediction. The methods go far beyond currently standard tests and conventional FEM analysis to challenge our conception of what can constitute a practicable engineering approach. Emphasis will be given to high temperature ceramic matrix composites with textile reinforcement, which have been the subject material of the National Hypersonic Science Center, Materials and Structures, a joint AFOSR/NASA program. However, thematic topics also address generic fiber composites. Development has been organized as a “pipeline” that links the separate disciplinary efforts of groups housed in seven institutions spread across the United States. The main research steps are: high resolution three-dimensional (3D) imaging of the microstructure, statistical characterization of the microstructure, formulation of a probabilistic generator for creating virtual specimens that replicate the measured statistics, creation of a computational model for a virtual specimen that allows general representation of discrete damage events, calibration of the model using room and high temperature tests, simulation of failure, and model validation. Key new experiments include digital surface image correlation and µm-resolution 3D computed tomography imaging of the microstructure and evolving damage, both executed at temperatures exceeding 1500°C. Conceptual advances include using both geometry and topology to characterize stochastic microstructures. Computational methods include new probabilistic algorithms for generating stochastic virtual specimens and a new Augmented Finite Element Method that yields extreme efficiency in dealing with arbitrary cracking in heterogeneous materials. The challenge of relating variance in engineering properties to stochastic microstructure in a computationally tractable manner, while retaining necessary physical details in models, will be discussed

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Design and development of the Australian and New Zealand (ANZ) myeloma and related diseases registry

© 2016 The Author(s). Background: Plasma cell dyscrasias (PCD) are a spectrum of disorders resulting from the clonal expansion of plasma cells, ranging from the pre-malignant condition monoclonal gammopathy of undetermined significance (MGUS) to multiple myeloma (MM). MM generates a significant burden of disease on the community and it is predicted that it will increase in both incidence and prevalence owing to an ageing population and longer survival secondary to new therapeutic options. Robust and comprehensive clinical data are currently lacking but are required to define current diagnostic, investigational and management patterns in Australia and New Zealand (ANZ) for comparison to both local and international guidelines for standards of care. A clinical registry can provide this information and subsequently support development of strategies to address any differences, including providing a platform for clinical trials. The Myeloma and Related Diseases Registry (MRDR) was developed to monitor and explore variations in practices, processes and outcomes in ANZ and provide benchmark outcomes nationally and internationally for PCD. This paper describes the MRDR aims, development and implementation and discusses challenges encountered in the process. Methods: The MRDR was established in 2012 as an online database for a multi-centre collaboration across ANZ, collecting prospective data on patients with a diagnosis of MGUS, MM, solitary plasmacytoma or plasma cell leukaemia. Development of the MRDR required multi-disciplinary team participation, IT and biostatistical support as well as financial resources. Results: More than 1250 patients have been enrolled at 23 sites to date. Here we describe how database development, data entry and securing ethics approval have been major challenges for participating sites and the coordinating centre, and our approaches to resolving them. Now established, the MRDR will provide clinically relevant and credible monitoring, therapy and 'real world' outcome data, to support the conduction of high quality studies. In addition, the Myeloma 1000 sub-study is establishing a repository of paired peripheral blood specimens from registry patients to study mechanisms underlying disease progression. Conclusion: Establishment of the MRDR has been challenging, but it is a valuable investment that will provide a platform for coordinated national and international collaboration for clinical research in PCD in ANZ

Superconductivity at 1 K in Cd2Re2O7

We report the first pyrochlore oxide superconductor Cd2Re2O7. Resistivity,magnetic susceptibility,and specific heat measurements on single crystals evidence a bulk superconductivity at 1 K. Another phase transition found at 200 K suggests that a peculiar electronic structure lies behind the superconductivity.Comment: 4 pages, 4 figures, PRL, in pres

SoTL Lab: Undergraduate student-faculty collaborative research in teaching and learning in CSD

The University of Wisconsin-Eau Claire Communication Sciences and Disorders SoTL Lab was designed to provide hands-on research experiences to undergraduate students on a large scale. Student reflections on experiences within the SoTL Lab identify the value of collaboration, development of confidence, and exposure to the entire research process as key outcomes. These experiences foster development of research skills and may lead students to consider academic careers