1,721,002 research outputs found
Nfatc1 As a Novel Atrial Fibrillation Susceptibility Gene
No full textposterAtrial Fibrillation (AF) is the most common type of cardiac arrhythmia. It is a progressive disease that increases the risk of stroke, heart failure, and sudden death. Familial AF, where several family members are affected by young-onset (<40) AF, has an active component of heritability. Using whole-exome sequencing, we identified a novel mutation (M527L) in the Nuclear Factor of Activated T-Cells 1 gene (nfatc1) that segregates in an autosomal dominant pattern within a family with a young-onset AF phenotype. To understand the mechanism responsible for the increased susceptibility to AF, we developed a homozygous mutant zebrafish line (delta 31) with a CRISPR/Cas9-induced 31bp deletion in exon 2 of the nfatc1 gene, predicted to cause a premature stop codon truncating the nfatc1 protein. The delta 31 zebrafish develop atrial arrhythmias at 5-9 weeks (juvenile stage). NFATc1 is a transcription factor important in heart development and pathological hypertrophy, but not previously linked to arrhythmia. We hypothesize that NFATc1 loss of function will impact atria-specific gene expression leading to increased cardiac excitability that acts as the substrate for developing AF. To test this hypothesis, we will use Quantitative Polymerase Chain Reaction (qPCR) to study changes in ion channel gene expression in juvenile delta 31 and wild-type (WT) atria and ventricle. We expect some ion channel genes will be differentially expressed in delta 31 atria compared to WT. This information will provide insight into the mechanism by which NFATc1 contributes to AF in humans and may allow for more accurate treatment for Familial AF patients using precision medicine
Cardiovascular Disease Burden, Mortality and Sudden Death Risk in Epilepsy: a UK Biobank study
No full textBackground: Sudden death is the leading cause of mortality in medically refractory epilepsy. Middle-aged persons with epilepsy (PWE) are under investigated regarding their mortality risk and burden of cardiovascular disease (CVD). Methods: Using UK Biobank, we identified 7,786 (1.6%) participants with a diagnosis of epilepsy and 6,171,803 person-years of follow-up (mean 12.30 years, SD 1.74); 566 individuals with prior history of stroke were excluded. The 7,220 PWE comprised the study cohort with the remaining 494,676 without epilepsy as the comparator group. Prevalence of CVD was determined using validated diagnostic codes. Cox proportional hazards regression were used to assess all-cause mortality and sudden death risk. Results: Hypertension, coronary artery disease, heart failure, valvular heart disease, and congenital heart disease were more prevalent in PWE. Arrhythmias including atrial fibrillation/flutter (12.2% vs 6.9%; p<0.01), bradyarrhythmias (7.7% vs 3.5%; p<0.01), conduction defects (6.1% vs 2.6%; p<0.01), and ventricular arrhythmias (2.3% vs 1.0%; p<0.01), as well as cardiac implantable electric devices (4.6% vs 2.0%; p<0.01) were more prevalent in PWE. PWE had higher adjusted all-cause mortality (HR 3.9 [95% CI, 3.01-3.39]), and sudden death-specific mortality (HR 6.65 [95% CI, 4.53-9.77]); and were almost 2 years younger at death [68.1 vs 69.8; p<0.001]. Conclusions: Middle-aged PWE have increased all-cause and sudden death specific mortality, and higher burden of CVD including arrhythmias and heart failure. Further work is required to elucidate mechanisms underlying all-cause mortality and sudden death risk in PWE of middle age, to identify prognostic biomarkers and develop preventative therapies in PWE
Congenital Long QT 3 in the Pediatric Population
No full textThere is insufficient knowledge concerning long-QT (LQT) 3 in the pediatric population to determine whether recommendations for more aggressive therapy in these patients are appropriate. An international multicenter review of 43 children with cardiac sodium channel (SCN5A) mutations and clinical manifestations of LQT syndrome without overlap of other SCN5A syndromes was undertaken to describe the clinical characteristics of LQT3 in children. Patients were aged 7.6 +/- 5.9 years at presentation and were followed for 4.7 +/- 3.9 years. There was significant intrasubject corrected QT interval (QTc) variability on serial electrocardiography. Forty-two percent presented with severe symptoms or arrhythmia and exhibited longer QTc intervals compared to asymptomatic patients. None of the 14 patients who underwent primary prevention implantable cardioverter-defibrillator (ICD) implantation received appropriate shocks in 41 patient-years of follow-up, while 2 of 6 patients who underwent secondary prevention ICD implantation received appropriate shocks in 30 patient-years of follow-up. Half of patients who underwent ICD implantation experienced inappropriate shocks or ICD-related complications. Mexiletine significantly shortened the QTc interval, and QTc shortening was greater in patients with longer pretreated QTc intervals. Two ICD patients with frequent appropriate ICD shocks showed immediate clinical improvement, with elimination of appropriate ICD shocks after mexiletine loading. In conclusion, severe symptoms are common in children with LQT3 and are associated with longer QTc intervals. ICD implantation is associated with significant morbidity. Mexiletine shortens the QTc interval, and it may be beneficial. (C) 2012 Elsevier Inc. All rights reserved. (Am J Cardiol 2012;109:1459-1465
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
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
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