1,721,049 research outputs found
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Pharmacokinetics and dose-concentration-effect relationship of rituximab in rheumatoid arthritis and anti-neutrophil cytoplasmic antibody-associated vasculitis
No full textLe rituximab est un anticorps monoclonal (AcMo) IgG1 chimérique qui cible le CD20, une protéine présente à la surface de la plupart des lymphocytes B. Il est indiqué dans la polyarthrite rhumatoïde (PR) et est utilisé dans les vascularites associées aux anticorps (ANCA) anti-cytoplasme des neutrophiles (AAV). Il existe une grande variabilité interindividuelle de la pharmacocinétique (PK) du rituximab et de sa relation concentration-réponse. Le rituximab se lie au CD20, et les complexes rituximab-CD20 formés sont éliminés par le système immunitaire. L’élimination médiée par la cible n'a jamais été décrite dans les maladies inflammatoires auto-immunes. Ce travail de thèse visait à étudier la PK et la relation concentration-réponse du rituximab par modélisation PK et pharmacocinétique-pharmacodynamique (PK-PD) de population. Ces travaux ont été réalisés grâce à : - 52 patients atteints de PR, suivis dans le Service de rhumatologie du CHRU de Tours, où les concentrations de rituximab, la numération CD4+ et le score d'activité de la maladie sur 28 articulations (DAS28) ont été mesurés. - 92 patients de l'essai RAVE, où les concentrations de rituximab, d'anticorps anti-protéinase 3 (PR3-ANCA) et d’anti-myéloperoxydase (MPO-ANCA) ont été mesurées. Chez les patients atteints de PR, la PK du rituximab a été décrite à l'aide d'un modèle à bicompartimental. Aucune élimination médiée par la cible n'a été détectée. Cela peut être dû à (i) une faible quantité d'antigène-cible par rapport à l’oncologie, et/ou (ii) à des données de PK peu denses. Chez les patients atteints d’AAV, une élimination non-linéaire médiée par la cible a été détectée au début du suivi. Un modèle TMDD simplifié a été utilisé, où le rituximab se fixait de façon irréversible sur le CD20, modélisé en tant que variable «latente». La variable latente peut être en partie interprétée comme la fraction de CD20 (circulante ou exprimée sur la membrane des cellules B) et disponible pour la liaison au rituximab. L'élimination médiée par la cible, négligeable, à la fin du suivi dans les AAV, peut être due aux numérations de cellules B faibles à la fin du suivi. La relation quantitative entre la déplétion des cellules B du sang, des cellules immunitaires, et la réponse clinique reste floue, aussi bien dans la PR que dans les AAV. De plus, cette relation, très variable selon les patients, n’a jamais été quantifiée à l’aide de la modélisation PK-PD. - Dans la PR, les relations entre les concentrations de rituximab et les numérations CD19+, entre les numérations CD19+ et CD4+, et entre les numérations CD4+ et le DAS28 ont respectivement été décrites à l'aide de modèles de durée de vie cellulaire « cell lifespan », de réponse indirecte et directs (Emax). Cette étude a montré que (i) l’amplitude de la déplétion CD19+ n’était pas associée à une déplétion CD4+ ou à une diminution du DAS28, et (ii) que la diminution du DAS28 était doublée en présence de déplétion des CD4+ comparé à son absence, et (iii) des concentrations plus élevées de rituximab étaient liées à une meilleure réponse clinique. - Dans les AAV, la relation entre les concentrations de rituximab et les niveaux d'ANCA a été décrite à l'aide d'un modèle de transit semi-mécanistique avec rétrocontrôle négatif. Ce modèle a montré que (i) la diminution des niveaux d'ANCA induite par le rituximab était profonde mais retardée et plus soutenue chez les patients avec MPO-ANCA que chez ceux avec PR3-ANCA, et (ii) des concentrations plus élevées de rituximab étaient associées à une diminution plus importante des niveaux d'ANCA. Des administrations répétées de rituximab seraient susceptibles d’améliorer la réponse clinique au rituximab et diminuer le risque de rechute. En conclusion, ce travail a été le premier à montrer une PK non linéaire du rituximab dans une maladie auto-immune (AAV), et à quantifier la relation complexe entre la déplétion des cellules B induite par le rituximab, la diminution des CD4+, et son efficacité cliniqueRituximab is a chimeric IgG1 monoclonal antibody (mAb) that targets CD20, a protein on the surface of most B lymphocytes. It is approved as a second line treatment in rheumatoid arthritis (RA) patients, and is used in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). There is a large interindividual variability in rituximab pharmacokinetics (PK), and its concentration–response relationship. Rituximab binds to CD20 with high affinity and specificity and form mAb-target complexes which are eliminated by immune system. This elimination is usually described using target-mediated drug disposition (TMDD) models. For rituximab, TMDD was never reported in autoimmune inflammatory diseases, as RA or AAV. This PhD work aimed at studying the variability of PK and cconcentration-response relationship of rituximab using population PK and pharmacokinetic-pharmacodynamic (PK-PD) modeling. This work was done using data from : - 52 RA patients of the rheumatology department of Tours University Hospital, where rituximab concentrations, CD4+ counts (biomarker) and disease activity score in 28 joints (DAS28, clinical response) were measured. - 92 AAV patients included in the RAVE trial (Rituximab for AAV), where rituximab concentrations, antibodies to proteinase 3 (PR3-ANCA), and antibodies to myeloperoxidase (MPO-ANCA) (biomarkers) were measured. In RA patients, rituximab PK was described using a two-compartment model with linear (endogenous) elimination. No target-elimination of rituximab or influence of B-cell count was detected. This may be due to (i) a low amount of target antigen compared to B-cell neoplasia, and/or (ii) insufficiently dense PK data. In AAV patients, nonlinear target-mediated elimination was detected at the beginning of the follow-up. A simplified TMDD model was used, where target was modeled as a latent variable, and irreversible binding to rituximab on its target was assumed. Latent variable may be partly interpreted as the fraction of CD20 (circulating or present at the B-cell membrane) available for rituximab binding. The negligible target-mediated elimination towards the end of the follow-up in RA and AAV may be due to the sustained B-cell depletion after rituximab treatment. Rituximab-induced B cell depletion was shown to alter count and function of other immune cells. However, quantitative relationship between depletion of blood B cells, immune cells, and clinical response in both RA and AAV remain unclear. In addition, this relationship, highly variable among patients, was never quantified using PK-PD modeling. In RA patients, the relationship between rituximab concentrations and CD19+ counts, between CD19+ and CD4+ counts, and between CD4+ counts and DAS28 (clinical activity score in RA) was described using cell lifespan, indirect response and direct Emax models, respectively. This study showed that (i) the amplitude of CD19+ count depletion was not associated with CD4+ decrease or DAS28, and (ii) CD4+ decrease leads to two-fold DAS28 decrease compared to no CD4+ decrease, and (iii) higher rituximab concentrations were related to a better clinical improvement. In AAV patients, the relationship between rituximab concentrations and ANCA levels was described using a semi-mechanistic transit model with negative feedback. This model showed that (i) rituximab-induced decrease of ANCA levels was deep but delayed, and more sustained in patients with MPO-ANCA than in those with PR3-ANCA, and (ii) higher rituximab concentrations were associated with deeper decrease of ANCA levels. Moreover, repeated rituximab courses may improve clinical response to rituximab, and increase the time to disease relapse. Overall, this work was the first to report nonlinear PK of rituximab in autoimmune disease (AAV), and to quantify the complex relationship between rituximab-induced B-cell depletion, CD4+ decrease, and the clinical response.
Variations on the Author
Full text link“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
Full text linkWe 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
Full text linkWe 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
Variability of response to anti-TNF alpha in inflammatory rheumatisms : contribution of biological markers and imaging
No full textIl existe une variabilité interindividuelle de la relation dose - effet chez les patients atteints de maladies inflammatoires rhumatismales traités par les inhibiteurs du Tumor Necrosis Factor-alpha (TNF-a). Dans la première partie de cette thèse, la physiopathologie du TNF-a dans le processus inflammatoire est présentée. Ensuite, le travail se concentre sur la relation concentration-effet en utilisant la modélisation pharmacocinétique-pharmacodynamique (PK-PD) modèles. À la fin, après une discussion sur les biomarqueurs d'imagerie, la thèse traite de l'utilité d'une nouvelle technique permettant de détecter la réponse précoce au traitement, à savoir la tomographie par émission de positons (TEP). En résumé, ce travail décrit la relation PK-PD dans les maladies inflammatoires rhumatismales traitées par anticorps monoclonaux en utilisant les marqueurs cliniques et biologiques, et démontre également l'influence de fortes concentrations d'anticorps monoclonaux pour la maintenance au traitement. La TEP est une technique prometteuse pour identifier la réponse précoce aux antagoistes du TNF-a.There is an interindividual variability of the dose - response relationship in patients with inflammatory rheumatic diseases treated by Tumor Necrosis Factor-alpha (TNF-a) inhibitors. In the first part of this thesis, the pathophysiology of TNF-a in inflammatory processes is presented. Then, the work focuses on the concentration-effect relationship using pharmacokinetic-pharmacodynamic (PK-PD) models. At the end, after discussion on imaging biomarkers, the thesis discusses the usefulness of a new technique to detect the early response to treatment, namely the positron emission tomography (PET). In summary, this work describes the PK-PD relationship in rheumatic inflammatory diseases treated by monoclonal antibodies using clinical and biological markers and demonstrates also the influence of high concentrations of monoclonal antibodies on maintenance to treatment. PET is a promising technique to identify early response to TNF-a antagonists
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe 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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