386 research outputs found

    Using giant african pouched rats to detect human tuberculosis: a review

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    Despite its characteristically low sensitivity, sputum smear microscopy remains the standard for diagnosing tuberculosis (TB) in resource-poor countries. In an attempt to develop an alternative or adjunct to microscopy, researchers have recently examined the ability of pouched rats to detect TB-positive human sputum samples and the microbiological variables that affect their detection. Ten published studies, reviewed herein, suggest that the rats are able to detect the specific odor of Mycobacterium tuberculosis, which causes TB, and can substantially increase new-case detections when used for second-line TB screening following microscopy. Further research is needed to ascertain the rats' ability to detect TB in children and in HIV-positive patients, to detect TB when used for first-line screening, and to be useful in broad-scale applications where cost effectiveness is a major consideration

    Polio Outbreak Response in Ethiopia

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    Background: Ethiopia had been polio-free for almost four years until December 2004. However, between December 2004 and February 2006, 24 children were paralysed as a result of infection with wild poliovirus imported from the neighbouring country of Sudan. In response, the country has attempted to document the impact of various response measures on the containment of wild poliovirus transmission. Objectives: This study aims at systematic and epidemiological assessment of the extent of the outbreak, its determinants, and the lessons learned as well as the implications for future control strategies to interrupt wild poliovirus transmission. Design: A cross-sectional study design with qualitative and quantitative data collection approaches was used to conduct the epidemiologic assessment. Subjects: All confirmed wild poliovirus cases, and reported acute flaccid paralysis cases in close proximity to the confirmed polio cases were the study subjects. Child caretakers and health service providers were interviewed as part of the investigation. Results: Between December 2004 and February 2006, eight children from Tigray Regional State, nine children from Amhara Regional State and seven children from Oromia Regional State were paralysed as a result of infection with wild poliovirus type 1. Genetic sequencing demonstrated two separate importations to Ethiopia. Risk factors that may have facilitated spread of the outbreak within the country included gaps in vaccination coverage and interruption of the cold chain system, gaps in acute flaccid paralysis surveillance performance, high population mobility, poor environmental sanitation, crowded living conditions and unsafe drinking water. In response to the outbreak, Ethiopia conducted detailed outbreak investigations within two days of confirmation of the index cases. Large-scale, house-to-house vaccination campaigns were also implemented. As a result, the three regions interrupted the wild poliovirus transmission within the regions within one year of confirmation of the index case. Conclusion: Outbreak response activities were successful in interrupting the imported wild poliovirus transmission in Tigray, Amhara and Oromia Regional States of Ethiopia within a oneyear period of time. In Ethiopia, programme strategies should be intensified to contain further spread and prevent future importation of wild poliovirus. Large-scale immunisation campaigns should reach every child, including those isolated by geography, poverty and security. East African Medical Journla Vol. 85 (5) 2008: pp. 222-23

    Mutations in DNA polymerase δ subunit 1 co-segregate with CMD2-type resistance to Cassava Mosaic Geminiviruses

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    Cassava mosaic disease (CMD) suppresses cassava yields across the tropics. The dominant CMD2 locus confers resistance to cassava mosaic geminiviruses. It has been reported that CMD2-type landraces lose resistance after regeneration through de novo morphogenesis. As full genome bisulfite sequencing failed to uncover an epigenetic mechanism for this loss of resistance, whole genome sequencing and genetic variant analysis was performed and the CMD2 locus was fine-mapped to a 190 kilobase interval. Collectively, these data indicate that CMD2-type resistance is caused by a nonsynonymous, single nucleotide polymorphism in DNA polymerase δ subunit 1 (MePOLD1) located within this region. Virus-induced gene silencing of MePOLD1 in a CMD-susceptible cassava variety produced a recovery phenotype typical of CMD2-type resistance. Analysis of other CMD2-type cassava varieties identified additional candidate resistance alleles within MePOLD1. Genetic variation of MePOLD1, therefore, could represent an important genetic resource for resistance breeding and/or genome editing, and elucidating mechanisms of resistance to geminiviruses

    Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

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    SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

    Efficacy of three neuroprotective drugs in secondary progressive multiple sclerosis (MS-SMART):a phase 2b, multiarm, double-blind, randomised placebo-controlled trial

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    Neurodegeneration is the pathological substrate that causes major disability in secondary progressive multiple sclerosis. A synthesis of preclinical and clinical research identified three neuroprotective drugs acting on different axonal pathobiologies. We aimed to test the efficacy of these drugs in an efficient manner with respect to time, cost, and patient resource. Methods: We did a phase 2b, multiarm, parallel group, double-blind, randomised placebo-controlled trial at 13 clinical neuroscience centres in the UK. We recruited patients (aged 25-65 years) with secondary progressive multiple sclerosis who were not on disease-modifying treatment and who had an Expanded Disability Status Scale (EDSS) score of 4·0-6·5. Participants were randomly assigned (1:1:1:1) at baseline, by a research nurse using a centralised web-based service, to receive twice-daily oral treatment of either amiloride 5 mg, fluoxetine 20 mg, riluzole 50 mg, or placebo for 96 weeks. The randomisation procedure included minimisation based on sex, age, EDSS score at randomisation, and trial site. Capsules were identical in appearance to achieve masking. Patients, investigators, and MRI readers were unaware of treatment allocation. The primary outcome measure was volumetric MRI percentage brain volume change (PBVC) from baseline to 96 weeks, analysed using multiple regression, adjusting for baseline normalised brain volume and minimisation criteria. The primary analysis was a complete-case analysis based on the intention-to-treat population (all patients with data at week 96). This trial is registered with ClinicalTrials.gov, NCT01910259

    Cross-sectional validation of the Aging Perceptions Questionnaire: a multidimensional instrument for assessing self-perceptions of aging

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    <p>Abstract</p> <p>Background</p> <p>Self-perceptions of aging have been implicated as independent predictors of functional disability and mortality in older adults. In spite of this, research on self-perceptions of aging is limited. One reason for this is the absence of adequate measures. Specifically, there is a need to develop a measure that is theoretically-derived, has good psychometric properties, and is multidimensional in nature. The present research seeks to address this need by adopting the Self-Regulation Model as a framework and using it to develop a comprehensive, multi-dimensional instrument for assessing self-perceptions of aging. This study describes the validation of this newly-developed instrument, the Aging Perceptions Questionnaire (APQ).</p> <p>Methods</p> <p>Participants were 2,033 randomly selected community-dwelling older (+65 yrs) Irish adults who completed the APQ alongside measures of physical and psychological health. The APQ assesses self-perceptions of aging along eight distinct domains or subscales; seven of these examine views about own aging, these are: timeline chronic, timeline cyclical, consequences positive, consequences negative, control positive, control negative, and emotional representations; the eighth domain is the identity domain and this examines the experience of health-related changes.</p> <p>Results</p> <p>Mokken scale analysis showed that the majority of items within the views about aging subscales were strongly scalable. Confirmatory factor analysis also indicated that the model provided a good fit for the data. Overall, subscales had good internal reliabilities. Hierarchical linear regression was conducted to investigate the independent contribution of APQ subscales to physical and psychological health and in doing so determine the construct validity of the APQ. Results showed that self-perceptions of aging were independently related to physical and psychological health. Mediation testing also supported a role for self-perceptions of aging as partial mediators in the relationship between indices of physical functioning and physical and psychological health outcomes.</p> <p>Conclusion</p> <p>Findings support the complex and multifaceted nature of the aging experience. The good internal reliability and construct validity of the subscales suggests that the APQ is a promising instrument that can enable a theoretically informed, multidimensional assessment of self-perceptions of aging. The potential role of self-perceptions of aging in facilitating physical and psychological health in later life is also highlighted.</p

    Feasibility studies for imaging e+^{+}e^{-} annihilation with modular multi-strip detectors

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    Studies based on imaging the annihilation of the electron (e^{-}) and its antiparticle positron (e+^{+}) open up several interesting applications in nuclear medicine and fundamental research. The annihilation process involves both the direct conversion of e+^{+}e^{-} into photons and the formation of their atomically bound state, the positronium atom (Ps), which can be used as a probe for fundamental studies. With the ability to produce large quantities of Ps, manipulate them in long-lived Ps states, and image their annihilations after a free fall or after passing through atomic interferometers, this purely leptonic antimatter system can be used to perform inertial sensing studies in view of a direct test of Einstein equivalence principle. It is envisioned that modular multistrip detectors can be exploited as potential detection units for this kind of studies. In this work, we report the results of the first feasibility study performed on a e+^{+} beamline using two detection modules to evaluate their reconstruction performance and spatial resolution for imaging e+^{+}e^{-} annihilations and thus their applicability for gravitational studies of Ps
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