1,720,954 research outputs found
Causes génétiques des maladies cardiovasculaires : applications à l'hypercholestérolémie familiale et aux anévrysmes de l'aorte thoracique
No full textL'identification de nouveaux acteurs impliqués dans les maladies cardiovasculaires (MCV) permet une meilleure compréhension de leur physiopathologie. L'objectif de ces Études de thèse est de déterminer les causes génétiques des MCV et leurs facteurs de risque, en particulier de hypercholestérolémie familiale (FH) et des anévrismes de l'aorte thoracique (TAA).La première partie portait sur l’étude des causes génétiques de la FH chez des proposants français. Grâce à une approche de séquençage de l'exome, nous avons identifié les variations p.(Arg50Gln) et p.(Ala3396Thr) dans une région de líAPOB qui n'est pas généralement étudiée lors du diagnostic de la FH par le séquençage de Sanger. De plus, nous avons décrit un premier cas hétérozygote composite porteur des mutations p.(Ala3396Thr) de l'APOB et p.(Arg96Cys) de PCSK9. Des tests fonctionnels nous ont permis de montrer que la variation p.(Arg96Cys) de PCSK9 conduit à une augmentation de la dégradation du récepteur des LDL. La deuxième partie de ce travail consistait en l’étude du défaut génétique chez les patients souffrant de TAA d'origine familiale. Après exclusion des gènes connus pour être associés à la maladie, les résultats du séquençage de l'exome ont suggéré que le gène THSD4, connu aussi sous le nom d'ADAMTSL6, pourrait être un gène candidat potentiel dans les TAA. Nous avons démontré effectivement que THSD4 est un nouveau gène impliqué dans la maladie. En effet, les variations de ce gène retrouvées chez l'homme sont associées au TAA. Les études fonctionnelles que nous avons entreprises ont montré que les variations faux-sens au niveau de ce gène conduisent à une diminution des taux de THSD4 intracellulaire et affectent Également la fibrilline-1 du réseau microfibrille au niveau de la matrice extracellulaire. Les taux plasmatiques de THSD4 mesurés par ELISA suggèrent que THSD4 pourrait être un biomarqueur potentiel des anévrismes de l'aorte de différentes étiologies. Nous avons aussi étudié la FH au Liban et avons identifié des variations au niveau des gènes LDLR et LDLRAP1. Nous avons de même confirmé la forte incidence des formes hétérozygotes et homozygotes de la FH dans la population libanaise. En outre, nous avons initié les Études génétiques de la TAA afin de pouvoir Établir le spectre mutationnel de cette maladie au Liban. Ces résultats montrent l'importance des stratégies génétiques dans les Études familiales afin d'identifier de nouvelles mutations dans des gènes connus ou découvrir de nouveaux gènes responsables des maladies cardiovasculaires. Ceci permettrait l'amélioration de la compréhension de la physiopathologie des maladies complexes, un meilleur diagnostic et la mise en place de stratégies adaptées pour une prise en charge clinique optimale.The identification of new actors involved in cardiovascular diseases (CVD) allows a better understanding of their pathophysiology. The objective of our studies was to investigate the genetic causes of CVD and their risk factors with a special focus on Familial Hypercholesterolemia (FH) and Thoracic Aortic Aneurysm and Dissection (TAAD).The first part of this work consisted on studying the genetic causes of ADH in French probands. Through an exome sequencing approach, we identified the p.(Arg50Gln) and the p.(Ala3396Thr) variations in the APOB gene, which occur in a region not routinely sequenced when diagnosing FH by Sanger sequencing. In addition, we reported the first compound heterozygote with the p.(Ala3396Thr) mutation of APOB and the p.(Arg96Cys) mutation of PCSK9 and we proved by functional assays that the p.(Arg96Cys) variation of PCSK9 leads to increased LDL receptor degradation. A second part of this work consisted on studying the genetic defect in patients who suffer from familial TAAD. After exclusion of the known genes associated to the disease, exome sequencing results suggested that THSD4, also known as ADAMTSL6, might be a potential candidate gene of TAAD. We demonstrated that THSD4 is a new gene involved in the pathogenesis of the disease. Human variations in this gene are associated with TAAD. Functional studies showed that missense variants of this gene lead to a decrease in levels of intracellular THSD4 and also affect the fibrillin-1 microfibril assembly in the extracellular matrix. THSD4 levels in plasma measured by an ELISA assay suggested that THSD4 might be a potential biomarker for aortic aneurysm of different etiologies.We conducted studies on FH in Lebanon and we identified variations in the LDLR and the LDLRAP1 genes, highlighting the high incidence of heterozygous and homozygous FH in the Lebanese population. In addition, we initiated genetic studies on TAAD in order to establish the mutational spectrum of this disease in Lebanon. These results demonstrate the importance of genetic strategies applied on familial studies to discover new genes responsible of CVD, or new mutations in already known genes. This can lead to a better understanding of the pathophysiology of complex diseases, a better diagnosis, and the implementation of better strategies for adequate clinical management
Laughing in the Face of Stress: A Humour-based Group Drama Therapy Intervention to Improve Resilience for People in High-Stress Situations
Get PDFHumour has been viewed as an adaptive strength and a valuable coping mechanism. Over the past three decades researchers have studied the use of humour as an intervention for dealing with different challenges. The following research paper aims to document the reasoning behind creating a drama therapy intervention that enhances the sense of humour to improve resilience for people in high-stress situations. The theoretical intervention research is based on literature highlighting the need for resilience, especially in stressful situations, the benefits of humour, and its beneficial impact on persons living with extensive stress.
The first two steps from Fraser and Galinsky’s (2010) will be used to complete the intervention’s design. The exercises in the drama therapy intervention are inspired by the 7 Humour Habits Program (7HHP) developed by Paul McGhee (2010). The suggested intervention will focus on key humour habits and skills including establishing a playful attitude, looking for humour in everyday life, laughing more often, laughing at oneself, and, finally, finding humour amid stress
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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