Medicine (RMH) - Research Publications
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ItemNo Preview AvailableIndustry Viable Electrochemical DNA Detection Sensor Architecture via a Stem-Loop Methylene Blue Redox Reporter and Rapid In Situ Probe Immobilization Method for Pharmacogenetic Biomarker Testing Application(ELECTROCHEMICAL SOC INC, 2022-01-01)Identification of biomarkers in clinical applications for diagnostics at the point-of-care (POC) setting requires the development of industry viable biosensing platform. Herein, we report such development of biosensor architecture for the detection of pharmacogenetic biomarker HLA-B*15:02 gene. The biosensor architecture comprises of an oligonucleotide stem-loop probe modified with a methylene blue redox (MB) reporter, immobilized via a rapid “printing” method on the commercially available disposable screen-printed electrodes (SPE). The square wave voltammetric measurements on the DNA sensor showed a clear peak difference of ∼80 nA with a significant difference in peak height values of the faradaic current generated for the MB redox moiety between the positive control (biotin-modified 19 based oligonucleotides with the sequence mimicking the specific region of the HLA-B*15:02 allele and complementary to the probe sequence) and negative control samples (biotin-modified 19 based oligonucleotides with the sequence unrelated to the probe sequence and the HLA-B*15:02 allele). These initial proof of concept results provide support for the possibility of using this signal-off biosensor architecture in the intended pharmacogenetic biomarker testing.
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ItemEosinophilic and Noneosinophilic Asthma: An Expert Consensus Framework to Characterize Phenotypes in a Global Real-Life Severe Asthma Cohort.(Elsevier BV, 2021-09)BACKGROUND: Phenotypic characteristics of patients with eosinophilic and noneosinophilic asthma are not well characterized in global, real-life severe asthma cohorts. RESEARCH QUESTION: What is the prevalence of eosinophilic and noneosinophilic phenotypes in the population with severe asthma, and can these phenotypes be differentiated by clinical and biomarker variables? STUDY DESIGN AND METHODS: This was an historical registry study. Adult patients with severe asthma and available blood eosinophil count (BEC) from 11 countries enrolled in the International Severe Asthma Registry (January 1, 2015-September 30, 2019) were categorized according to likelihood of eosinophilic phenotype using a predefined gradient eosinophilic algorithm based on highest BEC, long-term oral corticosteroid use, elevated fractional exhaled nitric oxide, nasal polyps, and adult-onset asthma. Demographic and clinical characteristics were defined at baseline (ie, 1 year before or closest to date of BEC). RESULTS: One thousand seven hundred sixteen patients with prospective data were included; 83.8% were identified as most likely (grade 3), 8.3% were identified as likely (grade 2), and 6.3% identified as least likely (grade 1) to have an eosinophilic phenotype, and 1.6% of patients showed a noneosinophilic phenotype (grade 0). Eosinophilic phenotype patients (ie, grades 2 or 3) showed later asthma onset (29.1 years vs 6.7 years; P < .001) and worse lung function (postbronchodilator % predicted FEV1, 76.1% vs 89.3%; P = .027) than those with a noneosinophilic phenotype. Patients with noneosinophilic phenotypes were more likely to be women (81.5% vs 62.9%; P = .047), to have eczema (20.8% vs 8.5%; P = .003), and to use anti-IgE (32.1% vs 13.4%; P = .004) and leukotriene receptor antagonists (50.0% vs 28.0%; P = .011) add-on therapy. INTERPRETATION: According to this multicomponent, consensus-driven, and evidence-based eosinophil gradient algorithm (using variables readily accessible in real life), the severe asthma eosinophilic phenotype was more prevalent than previously identified and was phenotypically distinct. This pragmatic gradient algorithm uses variables readily accessible in primary and specialist care, addressing inherent issues of phenotype heterogeneity and phenotype instability. Identification of treatable traits across phenotypes should improve therapeutic precision.
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Item1 Carer perspectives of trust and authority during COVID-19(British Medical Journal Publishing Group, 2021-03)
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ItemHydropluviometric variability in non-Sahelian West Africa: Case of the Koliba/Corubal River Basin (Guinea and Guinea-Bissau)(Copernicus GmbH, 2020-09-15)Abstract. The Koliba/Corubal River watershed is poorly documented due to the hydrometric measurements shutdown and gaps in the very short hydropluviometric timeseries. The purpose of this study is to analyze the variability of rainfall in the Basin, by simulating flows using the GR2M rain-flow model and extending the discharge timeseries. From the regional vector method, the rainfall timeseries were homogenized, and the gaps filled by the estimated values. The rank correlation and Pettitt test on annual rainfall amounts (1924–2015) indicate breaks in 1958, 1967 and 1969, leading to rainfall deficits ranging from 9.7 % to 20.2 %. For some stations, the segmentation method shows a recovery of rainfall towards the end of the 1980s (Gaoual, Mali) and the early 2000s (Gabu). The analysis of the temporal distribution of the Monthly Rainfall Coefficients shows an improvement of the contributions of a few months during the period after rupture. From a hydrological point of view, the correlation between the mean annual rainfall and the runoff has allowed to extend the flow timeseries. The mean monthly rainfall calculated using the inverse square of distance method, the Potential Evapotranspiration, and the flow rates were used to calibrate and validate the model to determine the parameters that better transform rainfall in flow. The values of the Nash criteria close to 100 have made it possible to extend the monthly flow data from Koliba/Corubal to Gaoual, Cade and Tche-Tche until 2015.
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