1,117 research outputs found

    Hospital-diagnosed infections before age 20 and risk of a subsequent multiple sclerosis diagnosis

    Get PDF
    The involvement of specific viral and bacterial infections as risk factors for multiple sclerosis has been studied extensively. However, whether this extends to infections in a broader sense is less clear and little is known about whether risk of a multiple sclerosis diagnosis is associated with other types and sites of infections, such as of the CNS. This study aims to assess if hospital-diagnosed infections by type and site before age 20 years are associated with risk of a subsequent multiple sclerosis diagnosis and whether this association is explained entirely by infectious mononucleosis, pneumonia, and CNS infections. Individuals born in Sweden between 1970-1994 were identified using the Swedish Total Population Register (n = 2,422,969). Multiple sclerosis diagnoses from age 20 years and hospital-diagnosed infections before age 20 years were identified using the Swedish National Patient Register. Risk of a multiple sclerosis diagnosis associated with various infections in adolescence (11-19 years) and earlier childhood (birth-10 years) was estimated using Cox regression, with adjustment for sex, parental socioeconomic position, and infection type. None of the infections by age 10 years were associated with risk of a multiple sclerosis diagnosis. Any infection in adolescence increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.33, 95% confidence interval 1.21-1.46) and remained statistically significant after exclusion of infectious mononucleosis, pneumonia, and CNS infection (hazard ratio 1.17, 95% confidence interval 1.06-1.30). CNS infection in adolescence (excluding encephalomyelitis to avoid including acute disseminated encephalitis) increased the risk of a multiple sclerosis diagnosis (hazard ratio 1.85, 95% confidence interval 1.11-3.07). The increased risk of a multiple sclerosis diagnosis associated with viral infection in adolescence was largely explained by infectious mononucleosis. Bacterial infections in adolescence increased risk of a multiple sclerosis diagnosis, but the magnitude of risk reduced after excluding infectious mononucleosis, pneumonia and CNS infection (hazard ratio 1.31, 95% confidence interval 1.13-1.51). Respiratory infection in adolescence also increased risk of a multiple sclerosis diagnosis (hazard ratio 1.51, 95% confidence interval 1.30-1.75), but was not statistically significant after excluding infectious mononucleosis and pneumonia. These findings suggest that a variety of serious infections in adolescence, including novel evidence for CNS infections, are risk factors for a subsequent multiple sclerosis diagnosis, further demonstrating adolescence is a critical period of susceptibility to environmental exposures that raise the risk of a multiple sclerosis diagnosis. Importantly, this increased risk cannot be entirely explained by infectious mononucleosis, pneumonia, or CNS infections

    Measuring health inequality among children in developing countries: does the choice of the indicator of economic status matter?

    Get PDF
    Background Currently, poor-rich inequalities in health in developing countries receive a lot of attention from both researchers and policy makers. Since measuring economic status in developing countries is often problematic, different indicators of wealth are used in different studies. Until now, there is a lack of evidence on the extent to which the use of different measures of economic status affects the observed magnitude of health inequalities. Methods This paper provides this empirical evidence for 10 developing countries, using the Demographic and Health Surveys data-set. We compared the World Bank asset index to three alternative wealth indices, all based on household assets. Under-5 mortality and measles immunisation coverage were the health outcomes studied. Poor-rich inequalities in under-5 mortality and measles immunisation coverage were measured using the Relative Index of Inequality. Results Comparing the World Bank index to the alternative indices, we found that (1) the relative position of households in the national wealth hierarchy varied to an important extent with the asset index used, (2) observed poor-rich inequalities in under-5 mortality and immunisation coverage often changed, in some cases to an important extent, and that (3) the size and direction of this change varied per country, index, and health indicator. Conclusion Researchers and policy makers should be aware that the choice of the measure of economic status influences the observed magnitude of health inequalities, and that differences in health inequalities between countries or time periods, may be an artefact of different wealth measures used

    Issues in the construction of wealth indices for the measurement of socio-economic position in low-income countries

    Get PDF
    BACKGROUND: Epidemiological studies often require measures of socio-economic position (SEP). The application of principal components analysis (PCA) to data on asset-ownership is one popular approach to household SEP measurement. Proponents suggest that the approach provides a rational method for weighting asset data in a single indicator, captures the most important aspect of SEP for health studies, and is based on data that are readily available and/or simple to collect. However, the use of PCA on asset data may not be the best approach to SEP measurement. There remains concern that this approach can obscure the meaning of the final index and is statistically inappropriate for use with discrete data. In addition, the choice of assets to include and the level of agreement between wealth indices and more conventional measures of SEP such as consumption expenditure remain unclear. We discuss these issues, illustrating our examples with data from the Malawi Integrated Household Survey 2004-5. METHODS: Wealth indices were constructed using the assets on which data are collected within Demographic and Health Surveys. Indices were constructed using five weighting methods: PCA, PCA using dichotomised versions of categorical variables, equal weights, weights equal to the inverse of the proportion of households owning the item, and Multiple Correspondence Analysis. Agreement between indices was assessed. Indices were compared with per capita consumption expenditure, and the difference in agreement assessed when different methods were used to adjust consumption expenditure for household size and composition. RESULTS: All indices demonstrated similarly modest agreement with consumption expenditure. The indices constructed using dichotomised data showed strong agreement with each other, as did the indices constructed using categorical data. Agreement was lower between indices using data coded in different ways. The level of agreement between wealth indices and consumption expenditure did not differ when different consumption equivalence scales were applied. CONCLUSION: This study questions the appropriateness of wealth indices as proxies for consumption expenditure. The choice of data included had a greater influence on the wealth index than the method used to weight the data. Despite the limitations of PCA, alternative methods also all had disadvantages

    Automated telephone follow-up after breast cancer: an acceptability and feasibility pilot study

    Get PDF
    Traditional clinical follow-up after breast cancer is inefficient at detecting relapse and is poorly suited to detecting and ameliorating psychological problems. There is interest in developing more effective and efficient methods of follow-up. We report a prospective cohort study of the acceptability and feasibility of remote, automated telephone follow-up after breast cancer. Women with a history of breast cancer were approached at their annual follow-up visit. For participants, the follow-up questionnaire was administered on paper at baseline. In place of a clinic visit following year, the women completed the same questionnaire using an automated telephone system. All patients were given mammograms. A semi-structured interview was then conducted to assess the acceptability. The potential impact on clinic usage was assessed. In all, 110 of 121 women (91%) agreed to participate. Seventy-five patients (71%) completed follow-up using the new automated system 1 year later. Seventy-one of the 75 patients found the system easy to use. Forty-nine of the 75 (65.33%) liked the system and were happy to use it as their sole method of follow-up. A further 12% were happy to use it as part of their follow-up. In only 10.66% of participants were concerns raised which led to clinic attendance. Automated questionnaire-based telephone follow-up is acceptable to women and has the potential to reduce attendance at clinic. Further studies to validate this method further are planned

    MGMR: leveraging RNA-Seq population data to optimize expression estimation

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>RNA-Seq is a technique that uses Next Generation Sequencing to identify transcripts and estimate transcription levels. When applying this technique for quantification, one must contend with reads that align to multiple positions in the genome (multireads). Previous efforts to resolve multireads have shown that RNA-Seq expression estimation can be improved using probabilistic allocation of reads to genes. These methods use a probabilistic generative model for data generation and resolve ambiguity using likelihood-based approaches. In many instances, RNA-seq experiments are performed in the context of a population. The generative models of current methods do not take into account such population information, and it is an open question whether this information can improve quantification of the individual samples</p> <p>Results</p> <p>In order to explore the contribution of population level information in RNA-seq quantification, we apply a hierarchical probabilistic generative model, which assumes that expression levels of different individuals are sampled from a Dirichlet distribution with parameters specific to the population, and reads are sampled from the distribution of expression levels. We introduce an optimization procedure for the estimation of the model parameters, and use HapMap data and simulated data to demonstrate that the model yields a significant improvement in the accuracy of expression levels of paralogous genes.</p> <p>Conclusions</p> <p>We provide a proof of principal of the benefit of drawing on population commonalities to estimate expression. The results of our experiments demonstrate this approach can be beneficial, primarily for estimation at the gene level.</p

    Evidence of a Conserved Molecular Response to Selection for Increased Brain Size in Primates

    Get PDF
    The adaptive significance of human brain evolution has been frequently studied through comparisons with other primates. However, the evolution of increased brain size is not restricted to the human lineage but is a general characteristic of primate evolution. Whether or not these independent episodes of increased brain size share a common genetic basis is unclear. We sequenced and de novo assembled the transcriptome from the neocortical tissue of the most highly encephalized nonhuman primate, the tufted capuchin monkey (Cebus apella\textit{Cebus apella}). Using this novel data set, we conducted a genome-wide analysis of orthologous brain-expressed protein coding genes to identify evidence of conserved gene-phenotype associations and species-specific adaptations during three independent episodes of brain size increase. We identify a greater number of genes associated with either total brain mass or relative brain size across these six species than show species-specific accelerated rates of evolution in individual large-brained lineages. We test the robustness of these associations in an expanded data set of 13 species, through permutation tests and by analyzing how genome-wide patterns of substitution co-vary with brain size. Many of the genes targeted by selection during brain expansion have glutamatergic functions or roles in cell cycle dynamics. We also identify accelerated evolution in a number of individual capuchin genes whose human orthologs are associated with human neuropsychiatric disorders. These findings demonstrate the value of phenotypically informed genome analyses, and suggest at least some aspects of human brain evolution have occurred through conserved gene-phenotype associations. Understanding these commonalities is essential for distinguishing human-specific selection events from general trends in brain evolution.This work was supported by the National Science Foundation, grant award numbers BCS-0751508, BCS-0827546, and BCS-1061370 for AMB and DEW. Professor Chet Sherwood (The George Washington University) provided useful guidance in the initial stages of this project. S.H.M. is grateful for support from a BBSRC doctoral training grant and a Research Fellowship from the Royal Commission for the Exhibition of 1851. N.I.M. is grateful for support from the Leverhulme Trust and Murray Edwards College, Cambridge

    Genome-wide association studies and genetic architecture of common human diseases

    Get PDF
    Genome-wide association scans provide the first successful method to identify genetic variation contributing to risk for common complex disease. Progress in identifying genes associated with melanoma show complex relationships between genes for pigmentation and the development of melanoma. Novel risk loci account for only a small fraction of the genetic variation contributing to this and many other diseases. Large meta-analyses find additional variants, but there is current debate about the contribution of common polymorphisms, rare polymorphisms or mutations to disease risk

    GPs' decisions on drug treatment for patients with high cholesterol values: A think-aloud study

    Get PDF
    BACKGROUND: The purpose was to examine how General Practitioners (GPs) use clinical information and rules from guidelines in their decisions on drug treatment for high cholesterol values. METHODS: Twenty GPs were presented with six case vignettes and were instructed to think aloud while successively more information about a case was presented, and finally to decide if a drug should be prescribed or not. The statements were coded for the clinical information to which they referred and for favouring or not favouring prescription. RESULTS: The evaluation of clinical information was compatible with decision-making as a search for reasons or arguments. Lifestyle-related information like smoking and overweight seemed to be evaluated from different perspectives. A patient's smoking favoured treatment for some GPs and disfavoured treatment for others. CONCLUSIONS: The method promised to be useful for understanding why doctors differ in their decisions on the same patient descriptions and why rules from the guidelines are not followed strictly
    corecore