1,721,120 research outputs found

    Variance decomposition in classification models for biomarker trajectories

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    L’analyse de mesures longitudinales –appelées trajectoires– est de plus en plus fréquente en recherche médicale. L’un des intérêts de cette analyse est d’identifier des groupes d’individus ayant des trajectoires similaires. La classification obtenue peut être utilisée pour mieux comprendre l’hétérogénéité des évolutions entre individus. La classification peut être déterminée à partir d’un modèle pour lequel les trajectoires des individus correspondent à la trajectoire du groupe auquel ils sont affectés. L’objectif de la thèse est de développer une extension de ce modèle de classification standard permettant une meilleure prise en compte de la variabilité au sein des groupes, (i) variabilité des valeurs du marqueur (variance résiduelle) et (ii) variabilité des profils d’évolution (variance inter-individuelle). Deux modèles de classification sont développés : 1) un premier modèle qui prend en compte une variance résiduelle au sein de chaque groupe variable d’un groupe à l’autre, et 2) un deuxième modèle qui prend en compte une variabilité des trajectoires au sein des groupes au lieu de de prédire la même trajectoire pour tous les individus d’un même groupe, variabilité qui peut être identique ou variable d’un groupe à l’autre. L’intérêt de ces deux modèles a été montré par des travaux de simulations et par des applications cliniques. Globalement, lorsque le nombre de mesures et de trajectoires est suffisant, ces modèles donnent de meilleures classifications que celles du modèle de classification standard. Par ailleurs, en dehors de plans expérimentaux très contrôlés, les deux sources de variabilité sont inhérentes à la recherche en santé. Ces modèles sont donc très pertinents d’un point de vue cliniqueThe analysis of longitudinal measures –called trajectories– is more and more frequent in clinical research. One of the interests of this analysis is to identify groups of individuals with similar trajectories. The obtained classification is used to understand and explore the heterogeneity of trajectories among subjects. The classification can be performed by a model that predicts the same trajectory for all the subjects that are classified in the same group. The objective of this thesis is to develop an extension to the standard classification model that gives greater consideration to the variability within groups, (i) the variability of marker values (residual variance), and (ii) the variability of the individual trajectories inside a group (between-individual variance). Two classification models were developed: 1) a first model that allows unequal residual variance across groups, and 2) a second model that takes into account a between-individual variance within each group instead of predicting the same trajectory for all subjects in the same group, a variance that can be equal or unequal across groups. The interest of these two models has been studied by simulations and through clinical applications. Overall, when the number of trajectories and measurements per trajectory is sufficient, these models gives better classification compared to the standard classification model. Moreover, except for highly controlled experimental designs, the two sources of variability are inherent to research in health. Therefore, these models are very relevant from a clinical point of view

    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

    Treatment selection markers in precision medicine : methodology of use and estimation of marker threshold

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    En France, la recherche contre le cancer est un enjeu majeur de santé publique. On estime notamment que le nombre de nouveaux cas de cancer a plus que doublé entre 1980 et 2012. L’hétérogénéité des caractéristiques tumorales, pour un même cancer, impose des défis complexes dans la recherche de traitements efficaces. Dans ce contexte, des espoirs importants sont placés dans la recherche de biomarqueurs prédictifs reflétant les caractéristiques des patients ainsi que de leur tumeur afin d’orienter le choix de la stratégie thérapeutique. Par exemple, pour les cancers colorectaux métastatiques, il est maintenant reconnu que l’ajout de cetuximab (un anti-EGFR) à la chimiothérapie classique (ici le FOLFOX4), n’apporte un bénéfice qu’aux patients dont le gène KRAS est non muté. Le gène KRAS est ici un biomarqueur prédictif binaire, mais de nombreux biomarqueurs sont le résultat d’une quantification ou d’un dosage. L’objectif de cette thèse est dans un premier temps, de quantifier la capacité globale d’un biomarqueur quantitatif à guider le choix du traitement. Après une revue de la littérature, une nouvelle méthode basée sur une extension des courbes ROC est proposée, et comparée aux méthodes existantes. Son principal avantage est d’être non paramétrique, et d’être indépendante de l’efficacité moyenne des traitements. Dans un second temps, lorsqu’un biomarqueur prédictif quantitatif est étudié, la définition d’un seuil de marqueur au-delà duquel la première option de traitement sera préférée, et en-deçà duquel la deuxième option de traitement sera préférée se pose. Une approche reposant sur la définition d’une fonction d’utilité est proposée permettant alors de tenir compte de l’efficacité des traitements ainsi que de leur impact sur la qualité de vie des patients. Une méthode Bayésienne d’estimation de ce seuil optimal est proposéeIn France, the cancer research is a major public health issue. The number of new cancer cases nearly doubled between 1980 and 2012. The heterogeneity of the tumor characteristics, for a given cancer, presents a great challenge in the research of new effective treatments. In this context, much hope is placed in the research of predictive (or treatment selection) biomarkers that reflect the patients’ characteristics in order to guide treatment choice. For example, in the metastatic colorectal cancer setting, it is admitted that the addition of cetuximab (an anti-EGFR) to classical chemotherapy (the FOLFOX4), only improve the outcome of patients with KRAS wild-type tumors. In that context, the KRAS gene is a binary treatment selection marker, but plenty of biomarkers result from some quantifications or dosage measurements. The first aim of this thesis is to quantify the global treatment selection ability of a biomarker. After a review of the existing litterature, a method based on an extension of ROC curves is proposed and compared to existing methods. Its main advantage is that it is non-parametric, and that it does not depend on the mean risk of event in each treatment arm. In a second time, when a quantitative treatment selection biomarker is assessed, there is a need to estimate a marker thereshold value above which one treatment is preferred, and below which the other treatment is recommended. An approach that relies on the definition of a utility function is proposed in order to take into account both efficacy and toxicity of treatments when estimating the optimal threshold. A Bayesian method for the estimation of the optimal threshold is propose

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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