1,721,178 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
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
Deciphering molecular and tissue mechanisms of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT)
No full textCatecholaminergic polymorphic ventricular tachycardia (CPVT) is a lethal, stressed-induced cardiac channelopathy. CPVT is characterized by ventricular arrhythmias that are triggered by catecholamines released during exercise or stress in individuals with structurally normal hearts. Cardiac calsequestrin (Casq2)-associated CPVT, termed CPVT2 is the most severe and the second most common form of CPVT. Autosomal-recessive CPVT2 is a result of a decrease in Casq2 protein levels, altering the ability of the sarcoplasmic reticulum (SR) to buffer calcium. In 2016, the first autosomal-dominant mutation, K180R, was found in CASQ2. We have found that K180R causes CPVT by decreasing the dynamic buffering capabilities of the SR without affecting Casq2 protein levels. The decreased buffering causes a decrease in calcium release refractoriness, an increase in spontaneous calcium release events, and ultimately the development of CPVT.
Even with a better understanding of the molecular mechanisms of CPVT, the anatomical origin remains unclear. Given that the arrhythmia results in the formation of ventricular tachycardia, it has been suggested that CPVT originates in the ventricular cardiomyocytes of the working myocardium or in the Purkinje cells. Currently, experimental and modeling studies suggest that the ventricular cardiomyocytes and Purkinje cells both have the potential to be responsible for arrhythmia generation, but no conclusion has been reached. Using transgenic mice with tissue specific Casq2 expression, we have found that CPVT originates in ventricular cardiomyocytes, specifically, the subendocardial cardiomyocytes juxtaposed to Purkinje cells.
Having a better understanding of the molecular and tissue mechanisms of CPVT will help develop better treatments. Currently several therapeutic options exist, but many patients still experience symptoms. New models and methods are needed to uncover treatments for CPVT. One area that has shown promise is human induced pluripotent stem cells (hiPSC). Using CRISPR/Cas9, we generated a hiPSC line where Casq2 has been ablated and have found that cardiomyocytes generated from the hiPSCs have CPVT characteristics. The hiPSC line can advance our understanding of CPVT and serve as a tool for future drug screens
Addressing Challenges to Genomic Medicine: Effects of Rare and Common Variation on Arrhythmia and Pharmacogenetic Phenotypes
No full textThe promise of genomic medicine has yet to be fully realized. In the realm of rare
disease, one of the challenges faced by genomic medicine is that of variant interpretation. A majority of variants in clinically actionable genes either lack the data needed to ascertain their pathogenicity or have conflicting clinical interpretations, and thus are called variants of uncertain significance (VUS). Furthermore, variant discovery far outpaces functional assessment, one of the strongest criteria for variant classification. Another challenge faced by genomic medicine is in the realm of common disease: precise and reliable genome markers to predict phenotypes are lacking. In fact, even the utility of such predictors is unknown for some phenotypes.
To assist with variant classification, we probed the function of variants in two cardiac ion-channel genes associated with cardiac arrhythmia disorders, SCN5A and KCNE1, using medium- and high-throughput approaches, respectively. We studied 179 SCN5A in-frame insertions/deletions and missense variants, including 94 VUS, by automated patch clamp. Functional data obtained from our studies assisted in the classification of 51/94 VUS to likely pathogenic or likely benign. We also used deep mutational scanning to assess cell surface expression of 1,886 KCNE1 variants, identifying 277 loss-of-trafficking and 183 gain-of-trafficking variants. Our data set the stage to classify hundreds of KCNE1 VUS and understand the structure/function relationship in the protein.
To assess the benefit of using polygenic predictors to predict inter-individual
variability in drug response, we calculated the heritability of 7 pharmacodynamic and 5 pharmacokinetic phenotypes across 8 different drugs using a Bayesian Hierarchical Mixed Model. We found 8/12 phenotypes to have a heritability >25%, indicating the feasibility for a polygenic predictor. Small-effect size variants had the largest contribution to phenotype heritability, indicating that current clinical approaches focusing on one, or a few, large effect alleles do not capitalize on the full potential of the genome to reduce adverse drug reactions and increase drug efficacy.
Our work highlights the role of the genome in the delivery of safe, effective and efficient healthcare for both rare and common diseases
Molecular Mechanisms in Inherited Arrhythmia Syndromes
No full textArrhythmias are abnormal heart rhythms that represent a major cause of morbidity and mortality across the world. While environmental factors such as lifestyle, diet, and other exposures may influence disease susceptibility, a substantial contribution arises from genetic variation in the form of ‘inherited arrhythmia syndromes’. Rare variants in cardiac ion channels and sarcomeric proteins may affect heart cell electrophysiology, and lead to potentially fatal arrhythmias responsible for sudden cardiac death. Despite this gene-disease link, it often remains difficult to ascertain the risk associated with specific variants in those genes. This is often because of an incomplete mechanistic view of how such variation may affect RNA transcript composition or translated protein properties. This is a challenging clinical problem, as optimal medical management is commonly thwarted by such incomplete knowledge. Indeed, a vision for human genetics is genotype-first care, where understanding variant effect can guide care for all patients who harbor such a variant. Towards this goal, I present experimental, computational, and clinical investigations into inherited arrhythmia syndromes caused by large effect, rare variants in the genes SCN5A, KCNH2, KCNQ1, and FLNC. These genes are associated with Brugada Syndrome, Long QT Syndrome, and Arrhythmogenic Cardiomyopathy. Many investigations are empowered by novel technologies that have enabled interrogation of variant effect at scale (SyncroPatch and ParSE-seq) or at high resolution (CRISPR-Cas9 and induced pluripotent stem cell-cardiomyocytes). Several of these investigations lead to the development of general methods that could be applied in many distinct disease areas. Most importantly, the studies directly help refine the path of clinical management for individuals harboring the variants in this work
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
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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