1,721,232 research outputs found
Calcium, Its Regulatory Hormones, and Their Causal Role on Blood Pressure : A Two-Sample Mendelian Randomization Study
No full textCONTEXT: Vitamin D (Vit-D), parathyroid hormone (PTH), and fibroblast growth factor 23 (FGF23) are the major calciotropic hormones involved in the regulation of blood calcium levels from the intestine, kidney, and bone through a tight endocrine feedback loop system. Altered levels of calcium itself or through the effect of its regulatory hormones could affect blood pressure (BP), but the exact mechanisms remain unclear. OBJECTIVE: To evaluate whether a causal relationship exists between serum calcium level and/or the regulatory hormones involved in its homeostasis with BP, we performed a two-sample Mendelian randomization (MR) study. METHODS: From 4 large genome-wide association studies (GWAS) we obtained independent (r2 < 0.001) single nucleotide polymorphisms (SNPs) associated with serum calcium (119 SNPs), Vit-D (78 SNPs), PTH (5 SNPs), and FGF23 (5 SNPs), to investigate through MR their association with systolic BP (SBP) and diastolic BP (DBP) in a Swedish urban-based study, the Malmö Diet and Cancer study (n = 29 298). Causality was evaluated by the inverse variance weighted method (IVW) and weighted median, while MR Egger and MR-PRESSO were used as sensitivity analyses. RESULTS: Genetically predicted serum calcium level was found to be associated with DBP (IVW: beta = 0.10, SE = 0.04, P = 0.007) and SBP (IVW: beta = 0.07, SE = 0.04, P = 0.04). Genetically predicted Vit-D and PTH showed no association with the traits, while FGF23 was inversely associated with SBP (IVW: beta = -0.11, SE = 0.04, P = 0.01), although this association lost statistical significance in sensitivity analysis. CONCLUSION: Our study shows a direct association between genetically predicted calcium level and DBP, and a weaker association with SBP. No such clear association was found for genetically predicted calciotropic hormone levels. It is of interest to detect which target genes involved in calcium homeostasis mediate the effect of calcium on BP, particularly for improving personalized intervention strategies
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
Genetic evidence for repurposing of glucagon-like peptide-1 receptor agonists to prevent heart failure
No full textBackground: To investigate the genetic evidence for repurposing of glucagon-like peptide-1 receptor (GLP1R) agonists to prevent heart failure (HF) and whether the potential benefit exceeds the benefit conferred by more general glycemic control. Methods and Results: We applied two-sample Mendelian randomization of genetically proxied GLP1R agonism on HF as the main outcome and left ventricular ejection fraction (LVEF) as the secondary outcome. The associations were compared to those of general glycemic control on the same outcomes. Genetic associations were obtained from genome-wide association study summary statistics of type 2 diabetes (228,499 cases and 1,178,783 controls), glycated hemoglobin (n=344,182), HF (47,309 cases and 930,014 controls), and LVEF (n=16,923). Genetic proxies for GLP1R agonism associated with reduced risk of HF (odds ratio per 1mmol/mol decrease in glycated hemoglobin 0.75, 95% confidence interval 0.64-0.87, P=1.69x10-4), and higher LVEF (standard deviation change in LVEF per 1mmol/mol decrease in glycated hemoglobin 0.22, 95% confidence interval 0.03-0.42, P=0.03). The magnitude of these benefits exceeded those expected from improved glycemic control more generally. The results were similar in sensitivity analyses, and we did not find evidence to suggest that these associations were mediated by reduced coronary artery disease risk. Conclusions: This genetic evidence supports the re-purposing of GLP1R agonists for preventing HF
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
Applications of genetic data to identify cardiovascular disease mechanisms and therapeutic opportunities
Full text linkRecent years have offered a wealth of genetic association data, with a concurrent explosion in the availability of methods for exploring causal effects through randomly allocated genetic variants that serve as proxies for traits of interest. This thesis investigates the state of this field within the remit of cardiovascular disease. Following an introduction into cardiovascular disease and Mendelian randomization (MR), the research focuses on dietary, social and pharmacological exposures as demonstrative examples for highlighting the breadth of techniques that can be harnessed towards understanding underlying mechanisms and therapeutic opportunities. Both two-sample and one-sample MR analyses are performed, using genetic summary data from large-scale consortia and the UK Biobank. Sample sizes for individual analyses typically exceed tens of thousands of participants. A diverse array of MR methods are employed, appropriate to the setting and objective of each analysis. Considering systemic iron status as a diet-related trait, genetic instruments are identified with consequent MR analyses supporting a protective effect on risk of cardiovascular outcomes related to atherosclerosis but a detrimental effect on outcomes related to thrombosis arising from stasis of blood. Phenome-wide association study further highlights effects of systemic iron status outside the remit of cardiovascular disease. In the investigation of social factors, MR mediation analysis techniques are applied to identify the pathways by which education affects cardiovascular disease risk, with multivariable MR further used to disentangle the direct effects of education and intelligence respectively. In the investigation of pharmacological exposures, genetic instruments for antihypertensive drugs are identified and validated by comparing against corresponding estimates from clinical trials. Phenome-wide association study is used to identify possible side-effects and repurposing opportunities, with a potential detrimental effect of calcium channel blockers identified on risk of diverticulosis. The final section provides an overview of the current state of applied MR, as well as future perspectives.Open Acces
Causal Effect of Adiposity Measures on Blood Pressure Traits in 2 Urban Swedish Cohorts: A Mendelian Randomization Study.
Full text linkBackground Different adiposity traits may be causally related to hypertension in different ways. By using genetic variants as randomly allocated proxies for studying the effect of modifying adiposity traits, the Mendelian randomization approach can be used to investigate this. Methods and Results In this study, we used 4 different genetic risk scores (GRS; GRS-BMI565, GRS-WHR324, GRS-VAT208, GRS-BF81) including hundreds of single nucleotide polymorphisms associated with body mass index, waist-to-hip ratio, visceral adipose tissue, and body fat, respectively. These were applied as instrumental variables in Mendelian randomization analyses. Two Swedish urban-based cohort studies, the Malmö Diet and Cancer, and the Malmö Preventive 795Projects were used to obtain genetic association estimates with blood pressure (BP). In both the Malmö Preventive Projects and Malmö Diet and Cancer studies, except for that for body fat, all of the genetic risk scores were significantly associated with systolic BP and diastolic BP, but with different magnitudes. In particular, in both cohorts, each standard deviation increase in the genetic risk score made up by the 324 single nucleotide polymorphisms associated with waist-to-hip ratio was associated with doubling of the likelihood of hypertension prevalence at baseline. However, only the genetic risk score made up by the 565 SNPs associated with body mass index was significantly associated with hypertension incidence during 23.6±4.3 years of follow-up in the Malmö Preventive Project. Conclusions We support a causal link between genetically mediated adiposity, especially waist-to-hip ratio and body mass index, and BP traits including hypertension prevalence and, for the first time to our knowledge, hypertension incidence. The differences in magnitude between these associations might suggest different mechanisms by which different adiposity affects BP/hypertension and consequently may indicate that tailored interventions are needed to reduce cardiovascular risk
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