1,720,979 research outputs found
Multiple testing correction in a meta-analysis of all adverse events recorded in large long-term randomised trials of statin therapy
No full textBackground: Randomised trials have shown that statin therapy reduces the risk of major vascular events (ie, heart attacks, strokes and coronary revascularisation procedures) without any increase in the risk of nonvascular causes of death or of site-specific cancer, but does produce a small increase in the risk of muscle pain or weakness, diabetes and, possibly, haemorrhagic stroke. Although statins are widely prescribed, there are concerns that they might have a range of other side effects. This DPhil addresses these concerns through an individual-participant-data meta-analysis of all recorded adverse events (AEs) in all large, long-term, randomised, double-blind trials of statin therapy, taking into consideration the substantial challenges related to multiple hypotheses testing (MHT).
Methods: Double-blind randomised trials of statin therapy with at least 1,000 participants and a scheduled treatment duration of at least 2 years were included. Individual participant data on all AEs reported in 19 trials of statin vs placebo (123,940 randomised participants) and 4 trials of a more intensive versus a less intensive statin regimen (30,724 randomised participants) were analysed. A literature review identified potentially relevant MHT methods and simulation studies were done to assess their expected performance (ie, control of false positive [FP] and false negative results). Adverse event data were organised and coded according to a common medical dictionary based upon the Medical Dictionary for Regulatory Activities (MedDRA). Under the selected strategy, inverse-variance-weighted meta-analyses of the effects on all AEs were performed using time-to-event analyses for the first occurrence of each outcome among participants randomly assigned into each trial.
Results: The literature review identified 6,569 eligible papers, of which 337 were included for full text review. Five MHT methods (Holm, Hochberg, Hommel, Benjamini & Hochberg and Mehrotra & Adewale) were selected as the most appropriate based on their statistical control of type I and II error rates. Simulation analyses identified the Mehrotra & Adewale method, which controls the false discovery rate (FDR), as the most suitable as it resulted in a low expected number of FP results whilst maintaining reasonable statistical power to detect any real effects of statin therapy. Blinded (ie, using a ‘shuffled’ treatment allocation) meta-analyses of the trials of statin vs placebo were first done, which confirmed that no correction for MHT resulted in 179 (4.4%) FP findings while the Mehrotra & Adewale MHT method led to zero FPs. Unblinded analyses (ie, using the actual treatment allocation) of all non-lipid-related AEs then confirmed the already known beneficial effects of statins on major vascular events. They also showed that statin therapy was FDR-significantly associated with a reduced risk of having an arteriogram or an angiogram procedure. Subsequent analyses which ignored the already known beneficial or harmful effects of statin therapy, very rare outcomes and irrelevant overlap in tests, identified two new benefits of statin therapy: reductions in the risk of peripheral embolism and thrombosis (361 [0.6%] vs 451 [0.7%], rate ratio [RR] 0.72, 95% confidence interval [CI]: 0.61−0.83, p=0.0012), and carotid endarterectomy (47 [<0.1%] vs 83 [0.1%], RR 0.57, 95% CI: 0.40−0.80, p= 0.0013). However, statins were also FDR-significantly associated with an increased risk of hepatobiliary investigations (1,349 [2.2%] vs 1,025 [1.7%], RR 1.32, 95% CI: 1.22–1.43, p<0.0001) and the extremely rare outcome parosmia (18 vs 2, p=0.00036). The meta-analyses of the 4 trials of more vs less statin revealed that more intensive statin therapy was associated with an FDR-significantly reduced risk of coronary artery disorders (3,518 [22.9%] vs 3,779 [24.6%], RR 0.92, 95% CI: 0.88−0.96, p= 0.00025), general system disorders (5,098 [33.1%] vs 5,682 [37.1%],RR 0.87, 95% CI: 0.84−0.91, p<0.0001), any surgical and medical procedures (4,067 [26.4%] vs 4,333 [28.3%],RR 0.93, 95% CI: 0.89−0.97, p= 0.00059) and the rare AE of renal therapeutic procedures (30 [0.2%] vs 57 [0.4%], RR 0.54, 95% CI: 0.35−0.82, p= 0.0038). More intensive statin regimens were also FDR-significantly associated with an increased risk of hepatobiliary investigations (502 [3.3%] vs 253 [1.6%], RR 1.95, 95% CI: 1.69–2.25, p<0.0001) and high blood creatine phosphokinase (223 [1.4%] vs 146 [1.0%], RR 1.51, 95% CI: 1.24−1.86, p<0.0001).
Conclusion: These findings highlight the importance of using appropriate statistical methods to control for multiple testing. The results confirmed the already known benefits of statin therapy while identifying some new potential benefits and harms. However, the nature and frequency of the newly detected harms confirm that the benefits of statin therapy greatly outweigh the potential harms
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
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
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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