75 research outputs found

    Efficacy of ivermectin mass-drug administration to control scabies in asylum seekers in the Netherlands:A retrospective cohort study between January 2014 - March 2016

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    Scabies is a skin infestation with the mite Sarcoptes scabiei causing itch and rash and is a major risk factor for bacterial skin infections and severe complications. Here, we evaluated the treatment outcome of 2866 asylum seekers who received (preventive) scabies treatment before and during a scabies intervention programme (SIP) in the main reception centre in the Netherlands between January 2014 and March 2016. A SIP was introduced in the main national reception centre based on frequent observations of scabies and its complications amongst Eritrean and Ethiopian asylum seekers in the Netherlands. On arrival, all asylum seekers from Eritrea or Ethiopia were checked for clinical scabies signs and received ivermectin/permethrin either as prevention or treatment. A retrospective cohort study was conducted to compare the reinfestations and complications of scabies in asylum seekers who entered the Netherlands before and during the intervention and who received ivermectin/permethrin. In total, 2866 asylum seekers received treatment during the study period (January 2014 -March 2016) of which 1359 (47.4%) had clinical signs of scabies. During the programme, most of the asylum seekers with scabies were already diagnosed on arrival as part of the SIP screening (580 (64.7%) of the 897). Asylum seekers with more than one scabies episode reduced from 42.0% (194/462) before the programme to 27.2% (243/897) during the programme (RR = 0.64, 95% CI = 0.55-0.75). Development of scabies complications later in the asylum procedure reduced from 12.3% (57/462) to 4.6% (41/897). A scabies prevention and treatment programme at start of the asylum procedure was feasible and effective in the Netherlands; patients were diagnosed early and risk of reinfestations and complications reduced. To achieve a further decrease of scabies, implementation of the programme in multiple asylum centres may be needed

    Thyroid-stimulating hormone and free thyroxine fail to predict the severity and clinical course of hyperemesis gravidarum : A prospective cohort study

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    Funding information: This prospective cohort study was supported by a research grant from North West Hospital Group, Alkmaar, the Netherlands (Grant number: 2013T085) and by a research grant from the Amsterdam Reproduction and Development (AR&D) Research Institute, Amsterdam UMC, the Netherlands (Project number: 23346). ACKNOWLEDGMENTS We thank Dr. J.P. Bestwick (employed at Queen Mary University of London, London, UK) and Professor Dr. J.H. Lazarus (employed at Cardiff School of Medicine, Cardiff, UK) for providing TSH medians from their study in the UK. Dr. J.P. Bestwick and Professor Dr. Lazarus have nothing to disclose.Peer reviewedPublisher PD

    A genetic ensemble approach for gene-gene interaction identification

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    <p>Abstract</p> <p>Background</p> <p>It has now become clear that gene-gene interactions and gene-environment interactions are ubiquitous and fundamental mechanisms for the development of complex diseases. Though a considerable effort has been put into developing statistical models and algorithmic strategies for identifying such interactions, the accurate identification of those genetic interactions has been proven to be very challenging.</p> <p>Methods</p> <p>In this paper, we propose a new approach for identifying such gene-gene and gene-environment interactions underlying complex diseases. This is a hybrid algorithm and it combines genetic algorithm (GA) and an ensemble of classifiers (called genetic ensemble). Using this approach, the original problem of SNP interaction identification is converted into a data mining problem of combinatorial feature selection. By collecting various single nucleotide polymorphisms (SNP) subsets as well as environmental factors generated in multiple GA runs, patterns of gene-gene and gene-environment interactions can be extracted using a simple combinatorial ranking method. Also considered in this study is the idea of combining identification results obtained from multiple algorithms. A novel formula based on pairwise <it>double fault </it>is designed to quantify the degree of complementarity.</p> <p>Conclusions</p> <p>Our simulation study demonstrates that the proposed genetic ensemble algorithm has comparable identification power to Multifactor Dimensionality Reduction (MDR) and is slightly better than Polymorphism Interaction Analysis (PIA), which are the two most popular methods for gene-gene interaction identification. More importantly, the identification results generated by using our genetic ensemble algorithm are highly complementary to those obtained by PIA and MDR. Experimental results from our simulation studies and real world data application also confirm the effectiveness of the proposed genetic ensemble algorithm, as well as the potential benefits of combining identification results from different algorithms.</p

    Improved Bevirimat resistance prediction by combination of structural and sequence-based classifiers

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    <p>Abstract</p> <p>Background</p> <p>Maturation inhibitors such as Bevirimat are a new class of antiretroviral drugs that hamper the cleavage of HIV-1 proteins into their functional active forms. They bind to these preproteins and inhibit their cleavage by the HIV-1 protease, resulting in non-functional virus particles. Nevertheless, there exist mutations in this region leading to resistance against Bevirimat. Highly specific and accurate tools to predict resistance to maturation inhibitors can help to identify patients, who might benefit from the usage of these new drugs.</p> <p>Results</p> <p>We tested several methods to improve Bevirimat resistance prediction in HIV-1. It turned out that combining structural and sequence-based information in classifier ensembles led to accurate and reliable predictions. Moreover, we were able to identify the most crucial regions for Bevirimat resistance computationally, which are in line with experimental results from other studies.</p> <p>Conclusions</p> <p>Our analysis demonstrated the use of machine learning techniques to predict HIV-1 resistance against maturation inhibitors such as Bevirimat. New maturation inhibitors are already under development and might enlarge the arsenal of antiretroviral drugs in the future. Thus, accurate prediction tools are very useful to enable a personalized therapy.</p

    Bias in random forest variable importance measures: Illustrations, sources and a solution

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    BACKGROUND: Variable importance measures for random forests have been receiving increased attention as a means of variable selection in many classification tasks in bioinformatics and related scientific fields, for instance to select a subset of genetic markers relevant for the prediction of a certain disease. We show that random forest variable importance measures are a sensible means for variable selection in many applications, but are not reliable in situations where potential predictor variables vary in their scale of measurement or their number of categories. This is particularly important in genomics and computational biology, where predictors often include variables of different types, for example when predictors include both sequence data and continuous variables such as folding energy, or when amino acid sequence data show different numbers of categories. RESULTS: Simulation studies are presented illustrating that, when random forest variable importance measures are used with data of varying types, the results are misleading because suboptimal predictor variables may be artificially preferred in variable selection. The two mechanisms underlying this deficiency are biased variable selection in the individual classification trees used to build the random forest on one hand, and effects induced by bootstrap sampling with replacement on the other hand. CONCLUSION: We propose to employ an alternative implementation of random forests, that provides unbiased variable selection in the individual classification trees. When this method is applied using subsampling without replacement, the resulting variable importance measures can be used reliably for variable selection even in situations where the potential predictor variables vary in their scale of measurement or their number of categories. The usage of both random forest algorithms and their variable importance measures in the R system for statistical computing is illustrated and documented thoroughly in an application re-analyzing data from a study on RNA editing. Therefore the suggested method can be applied straightforwardly by scientists in bioinformatics research
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