1,721,146 research outputs found

    The Laplace distribution

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    When studying the same object, different scientists and scientific instruments can produce widely divergent measurements. Marco Geraci and Mario Cortina Borja describe a probability distribution to model observations when heterogeneity and large errors are presen

    Distribution-free hyperrectangular tolerance regions for setting multivariate reference regions in laboratory medicine

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    Reference regions are important in laboratory medicine to interpret the test results of patients, and usually given by tolerance regions. Tolerance regions of p (>= 2) dimensions are highly desirable when the test results contains p outcome measures. Nonparametric hyperrectangular tolerance regions are attractive in real problems due to their robustness with respect to the underlying distribution of the measurements and ease of intepretation, and methods to construct them have been recently provided by Young and Mathew [1]. However, their validity is supported by a simulation study only. In this paper, nonparametric hyperrectangular tolerance regions are constructed by using Tukey's [2,3] elegant results of equivalence blocks. The validity of these new tolerance regions is proven mathematically in [2,3] under the only assumption that the underlying distribution of the measurements is continuous. The methodology is applied to analyze the kidney function problem considered in Young and Mathew [1

    Reference range: which statistical intervals to use?

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    Reference ranges, which are data-based intervals aiming to contain a pre-specified large proportion of the population values, are powerful tools to analyse observations in clinical laboratories. Their main point is to classify any future observations from the population which fall outside them as atypical and thus may warrant further investigation. As a reference range is constructed from a random sample from the population, the event ‘a reference range contains (100 P)% of the population’ is also random. Hence, all we can hope for is that such event has a large occurrence probability. In this paper we argue that some intervals, including the P prediction interval, are not suitable as reference ranges since there is a substantial probability that these intervals contain less than (100 P)% of the population, especially when the sample size is large. In contrast, a (P,γ) tolerance interval is designed to contain (100 P)% of the population with a pre-specified large confidence γ so it is eminently adequate as a reference range. An example based on real data illustrates the paper’s key points.</p

    Time to undetectable viral load after highly active antiretroviral therapy initiation among HIV-infected pregnant women

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    Background. There have been no clinical trials in resource-rich regions that have addressed the question of which highly active antiretroviral therapy (HAART) regimens are more effective for optimal viral response in antiretroviral-naive, human immunodeficiency virus (HIV)-infected pregnant women.Methods. Data on 240 HIV-1-infected women starting HAART during pregnancy who were enrolled in the prospective European Collaborative Study from 1997 through 2004 were analyzed. An interval-censored survival model was used to assess whether factors, including type of HAART regimen, race, region of birth, and baseline immunological and virological status, were associated with the duration of time necessary to suppress viral load below undetectable levels before delivery of a newborn.Results. Protease inhibitor-based HAART was initiated in 156 women (65%), 125 (80%) of whom received nelfinavir, and a nevirapine-based regimen was initiated in the remaining 84 women (35%). Undetectable viral loads were achieved by 73% of the women by the time of delivery. Relative hazards of time to achieving viral suppression were 1.54 (95% confidence interval, 1.05-2.26) for nevirapine-based HAART versus PI-based regimens and 1.90 (95% confidence interval, 1.16-3.12) for western African versus non-African women. The median duration of time from HAART initiation to achievement of an undetectable viral load was estimated to be 1.4 times greater in women receiving PI-based HAART, compared with women receiving nevirapine-based HAART. Baseline HIV RNA load was also a significant predictor of the rapidity of achieving viral suppression by delivery, but baseline immune status was not.Conclusions. In this study, nevirapine-based HAART (compared with PI [mainly nelfinavir]-based HAART), western African origin, and lower baseline viral load were associated with shorter time to achieving viral suppression

    Delayed symptom onset and increased life expectancy in Sandhoff disease mice treated with N-butyldeoxynojirimycin

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    Sandhoff disease is a neurodegenerative disorder resulting from the autosomal recessive inheritance of mutations in the HEXB gene, which encodes the β-subunit of β-hexosaminidase. G(M2) ganglioside fails to be degraded and accumulates within lysosomes in cells of the periphery and the central nervous system (CNS). There are currently no therapies for the glycosphingolipid lysosomal storage diseases that involve CNS pathology, including the G(M2) gangliosidoses. One strategy for treating this and related diseases is substrate deprivation. This would utilize an inhibitor of glycosphingolipid biosynthesis to balance synthesis with the impaired rate of catabolism, thus preventing storage. One such inhibitor is N- butyldeoxynojirimycin, which currently is in clinical trials for the potential treatment of type 1 Gaucher disease, a related disease that involves glycosphingolipid storage in peripheral tissues, but not in the CNS. In this study, we have evaluated whether this drug also could be applied to the treatment of diseases with CNS storage and pathology. We therefore have treated a mouse model of Sandhoff disease with the inhibitor N- butyldeoxynojirimycin. The treated mice have delayed symptom onset, reduced storage in the brain and peripheral tissues, and increased life expectancy. Substrate deprivation therefore offers a potentially general therapy for this family of lysosomal storage diseases, including those with CNS disease.</p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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