669 research outputs found

    An aerosol challenge model of tuberculosis in Mauritian cynomolgus macaques

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    Background New interventions for tuberculosis are urgently needed. Non-human primate (NHP) models provide the most relevant pre-clinical models of human disease and play a critical role in vaccine development. Models utilising Asian cynomolgus macaque populations are well established but the restricted genetic diversity of the Mauritian cynomolgus macaques may be of added value. Methods Mauritian cynomolgus macaques were exposed to a range of doses of M. tuberculosis delivered by aerosol, and the outcome was assessed using clinical, imaging and pathology-based measures. Results All macaques developed characteristic clinical signs and disease features of tuberculosis (TB). Disease burden and the ability to control disease were dependent on exposure dose. Mauritian cynomolgus macaques showed less variation in pulmonary disease burden and total gross pathology scores within exposure dose groups than either Indian rhesus macaques or Chinese cynomolgus macaques Conclusions The genetic homogeneity of Mauritian cynomolgus macaques makes them a potentially useful model of human tuberculosis

    Anthropomorphic Measurements That Include Central Fat Distribution Are More Closely Related with Key Risk Factors than BMI in CKD Stage 3

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    Background: Body Mass Index (BMI) as a marker of obesity is an established risk factor for chronic kidney disease (CKD) and cardiovascular disease (CVD). However, BMI can overestimate obesity. Anthropomorphic measurements that include central fat deposition are emerging as a more important risk factor. We studied BMI, waist circumference (WC), waist-to-height ratio (WHtR), waist-to-hip ratio (WHR) and conicity index (CI) in a cohort of patients with CKD stage 3 and compared the associations with other known risk factors for CKD progression and CVD. Methods: 1740 patients with CKD stage 3 were recruited from primary care for the Renal Risk in Derby study. Each participant underwent clinical assessment, including anthropomorphic measurements and pulse wave velocity (PWV), as well as urine and serum biochemistry tests. Results: The mean age of the cohort was 72.969 years with 60 % females. The mean eGFR was 52.5610.4 ml/min/1.73 m 2 and 16.9 % of the cohort had diabetes. With the cohort divided into normal and increased risk of morbidity and mortality using each anthropomorphic measurement, those measurements that included increased central fat distribution were significantly associated with more risk factors for CKD progression and CVD than increased BMI. Univariable analysis demonstrated central fat distribution was correlated with more risk factors than BMI. Subgroup analyses using recognised BMI cut-offs to define obesity and quartiles of WHR and CI demonstrated that increasing central fat distribution wa

    Habitat structure: a fundamental concept and framework for urban soil ecology

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    Habitat structure is defined as the composition and arrangement of physical matter at a location. Although habitat structure is the physical template underlying ecological patterns and processes, the concept is relatively unappreciated and underdeveloped in ecology. However, it provides a fundamental concept for urban ecology because human activities in urban ecosystems are often targeted toward management of habitat structure. In addition, the concept emphasizes the fine-scale, on-the-ground perspective needed in the study of urban soil ecology. To illustrate this, urban soil ecology research is summarized from the perspective of habitat structure effects. Among the key conclusions emerging from the literature review are: (1) habitat structure provides a unifying theme for multivariate research about urban soil ecology; (2) heterogeneous urban habitat structures influence soil ecological variables in different ways; (3) more research is needed to understand relationships among sociological variables, habitat structure patterns and urban soil ecology. To stimulate urban soil ecology research, a conceptual framework is presented to show the direct and indirect relationships among habitat structure and ecological variables. Because habitat structure serves as a physical link between sociocultural and ecological systems, it can be used as a focus for interdisciplinary and applied research (e.g., pest management) about the multiple, interactive effects of urbanization on the ecology of soils

    Generalized shrinkage F-like statistics for testing an interaction term in gene expression analysis in the presence of heteroscedasticity

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    <p>Abstract</p> <p>Background</p> <p>Many analyses of gene expression data involve hypothesis tests of an interaction term between two fixed effects, typically tested using a residual variance. In expression studies, the issue of variance heteroscedasticity has received much attention, and previous work has focused on either between-gene or within-gene heteroscedasticity. However, in a single experiment, heteroscedasticity may exist both within and between genes. Here we develop flexible shrinkage error estimators considering both between-gene and within-gene heteroscedasticity and use them to construct <it>F</it>-like test statistics for testing interactions, with cutoff values obtained by permutation. These permutation tests are complicated, and several permutation tests are investigated here.</p> <p>Results</p> <p>Our proposed test statistics are compared with other existing shrinkage-type test statistics through extensive simulation studies and a real data example. The results show that the choice of permutation procedures has dramatically more influence on detection power than the choice of <it>F </it>or <it>F</it>-like test statistics. When both types of gene heteroscedasticity exist, our proposed test statistics can control preselected type-I errors and are more powerful. Raw data permutation is not valid in this setting. Whether unrestricted or restricted residual permutation should be used depends on the specific type of test statistic.</p> <p>Conclusions</p> <p>The <it>F</it>-like test statistic that uses the proposed flexible shrinkage error estimator considering both types of gene heteroscedasticity and unrestricted residual permutation can provide a statistically valid and powerful test. Therefore, we recommended that it should always applied in the analysis of real gene expression data analysis to test an interaction term.</p

    Nav1.7 is required for normal C-low threshold mechanoreceptor function in humans and mice

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    Patients with bi-allelic loss of function mutations in the voltage-gated sodium channel Nav1.7 present with congenital insensitivity to pain (CIP), whilst low threshold mechanosensation is reportedly normal. Using psychophysics (n = 6 CIP participants and n = 86 healthy controls) and facial EMG (n = 3 CIP participants and n = 8 healthy controls) we have found that these patients also have abnormalities in the encoding of affective touch which is mediated by the specialised afferents; C-low threshold mechanoreceptors (C-LTMRs). In the mouse we found that C-LTMRs express high levels of Nav1.7. Genetic loss or selective pharmacological inhibition of Nav1.7 in C-LTMRs resulted in a significant reduction in the total sodium current density, an increased mechanical threshold and reduced sensitivity to non-noxious cooling. The behavioural consequence of loss of Nav1.7 in C-LTMRs in mice was an elevation in the von Frey mechanical threshold and less sensitivity to cooling on a thermal gradient. Nav1.7 is therefore not only essential for normal pain perception but also for normal C-LTMR function, cool sensitivity and affective touch

    New Measurement of Parity Violation in Elastic Electron-Proton Scattering and Implications for Strange Form Factors

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    We have measured the parity-violating electroweak asymmetry in the elastic scattering of polarized electrons from the proton. The result is A = -15.05 +- 0.98(stat) +- 0.56(syst) ppm at the kinematic point theta_lab = 12.3 degrees and Q^2 = 0.477 (GeV/c)^2. The measurement implies that the value for the strange form factor (G_E^s + 0.392 G_M^s) = 0.025 +- 0.020 +- 0.014, where the first error is experimental and the second arises from the uncertainties in electromagnetic form factors. This measurement is the first fixed-target parity violation experiment that used either a `strained' GaAs photocathode to produce highly polarized electrons or a Compton polarimeter to continuously monitor the electron beam polarization.Comment: 8 pages, 4 figures, Tex, elsart.cls; revised version as accepted for Phys. Lett.

    High HIV Prevalence Among Men Who have Sex with Men in Soweto, South Africa: Results from the Soweto Men’s Study

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    The Soweto Men’s Study assessed HIV prevalence and associated risk factors among MSM in Soweto, South Africa. Using respondent driven sampling (RDS) recruitment methods, we recruited 378 MSM (including 15 seeds) over 30 weeks in 2008. All results were adjusted for RDS sampling design. Overall HIV prevalence was estimated at 13.2% (95% confidence interval 12.4–13.9%), with 33.9% among gay-identified men, 6.4% among bisexual-identified men, and 10.1% among straight-identified MSM. In multivariable analysis, HIV infection was associated with being older than 25 (adjusted odds ratio (AOR) 3.8, 95% CI 3.2–4.6), gay self-identification (AOR 2.3, 95% CI 1.8–3.0), monthly income less than ZAR500 (AOR 1.4, 95% CI 1.2–1.7), purchasing alcohol or drugs in exchange for sex with another man (AOR 3.9, 95% CI 3.2–4.7), reporting any URAI (AOR 4.4, 95% CI 3.5–5.7), reporting between six and nine partners in the prior 6 months (AOR 5.7, 95% CI 4.0–8.2), circumcision, (AOR 0.2, 95% CI 0.1–0.2), a regular female partner (AOR 0.2, 95% CI 0.2–0.3), smoking marijuana in the last 6 months (AOR 0.6, 95% CI 0.5–0.8), unprotected vaginal intercourse in the last 6 months (AOR 0.5, 95% CI 0.4–0.6), and STI symptoms in the last year (AOR 0.7, 95% CI 0.5–0.8). The results of the Soweto Men’s Study confirm that MSM are at high risk for HIV infection, with gay men at highest risk. HIV prevention and treatment for MSM are urgently needed

    Display of probability densities for data from a continuous distribution

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    Based on cumulative distribution functions, Fourier series expansion and Kolmogorov tests, we present a simple method to display probability densities for data drawn from a continuous distribution. It is often more efficient than using histograms.Comment: 5 pages, 4 figures, presented at Computer Simulation Studies XXIV, Athens, GA, 201
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