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L'inhalation répétée de métacholine sur la mécanique respiratoire chez la souris
No full textL’asthme est un désordre respiratoire caractérisé par une prévalence élevée dans laquelle une proportion des individus ne répondent pas bien aux traitements actuels. Afin de développer des traitements plus efficaces, il est nécessaire de mieux comprendre les mécanismes physiopathologiques de l’asthme. Le muscle lisse des voies aériennes joue un rôle central dans ce désordre respiratoire puisque son activation intense et sa contraction excessive contribuent à l’obstruction des voies aériennes donnant lieu aux symptômes de l’asthme. Les deux projets présentés dans ce mémoire étudient les effets de l’administration répétée d’un activateur du muscle lisse des voies aériennes, soit la métacholine, chez la souris. L’hypothèse du premier projet stipule que des bronchoconstrictions induites par la métacholine favoriseraient le développement de changements structuraux dans les parois aériennes des sujets exposés. Néanmoins, les résultats démontrent que des bronchoconstrictions répétées ne sont pas suffisantes pour induire plusieurs aspects du remodelage des voies aériennes, pour altérer la mécanique respiratoire et pour modifier la capacité contractile du muscle lisse trachéal. L’hypothèse du deuxième projet stipule que l’activation répétée des récepteurs muscariniques du muscle lisse des voies aériennes donne lieu à un phénomène d’adaptation des récepteurs. Ce phénomène se répercuterait en une diminution de l’effet de la métacholine sur la force générée par le muscle lisse des voies aériennes et, conséquemment, en une diminution de l’obstruction des voies respiratoires. Les résultats confirment que l’activation répétée des récepteurs muscariniques par l’administration de métacholine à des souris in vivo diminue leur réactivité bronchique à la métacholine, et ce, en diminuant la capacité contractile du muscle lisse des voies aériennes en réponse à la métacholine. De façon encore plus impressionnante, dans un modèle murin d’asthme, ce traitement permet de renverser complètement l’hyperréactivité bronchique à la métacholine. Les mécanismes moléculaires sous-jacents restent à être élucidés.Asthma is a prevalent respiratory disorder for which a proportion of patients responds poorly to actual treatment, which highlights the necessity to study the physiopathology of asthma and to develop more efficient drugs. The airway smooth muscle plays a chief role in asthma. This is because the excessive activation of airway smooth muscle that characterizes asthma, and the exaggerated contraction that ensues, leads to respiratory symptoms by obstructing the airway lumen. The two projects presented in this Master’s thesis focus on the effects of repeated inhalations of methacholine, an activator of airway smooth muscle, in mice. The hypothesis of the first project postulated that the mechanical stress the airway wall undergoes during repeated methacholine-induced constrictions leads to structural changes in the airway wall. The results demonstrated that repeated constrictions by themselves are not sufficient to induce key features of airway wall remodeling, to alter respiratory mechanics and to change the contractile capacity of airway smooth muscle. The hypothesis of the second project postulated that repeated inhalations of methacholine trigger adaptation of the muscarinic receptors, which leads to a decreased effect of muscarinic agonists over time. In turn, this would decrease the force generated by airway smooth muscle and thereby relieves airway obstruction. The results confirmed that repeated activations of the muscarinic receptors by inhaled methacholine decrease airway responsiveness to methacholine in vivo, as well as the force generated by the airway smooth muscle in response to methacholine ex vivo. Interestingly, in a murine model of asthma, repeated activations of the muscarinic receptors completely reverse airway hyperresponsiveness to methacholine. The molecular mechanisms underlying this phenomenon remain to be determined
Response and remission in asthma with tezepelumab: overlapping concepts informing on type-2 inflammatory-dependent treatment effects
Get PDFAbstract: We believe the interpretation that baseline biomarkers such as blood eosinophil count (BEC) and fractional exhaled nitric oxide (FENO ) are more predictive of response than remission may be misleading. In practice, response and remission represent a continuum: from “no response” through “response” and then “remission” [4]. Using data from their tables 1 and S1, we calculated univariable odds ratios, which suggest that both BEC and FENO predict response and remission to similar extents (figure 1). We also re-analysed their table 3 using chi-square tests for trend. These showed no significant differences in trends for BEC (p=0.26) or FENO (p=0.58) between patients achieving response versus remission, indicating comparable associations. Without access to individual-level data, we could not analyse biomarkers continuously, but the reported medians suggest minimal differences. Could the authors clarify the statistical methods behind their conclusions
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
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
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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