1,720,953 research outputs found
Genetic determinants of response to aspirin and warfarin and development of silicon nanowire based genotyping
Get PDFPhD ThesisChronic diseases such as cardiovascular diseases and colorectal cancer are the leading
cause of mortality worldwide. Commonly used drugs such as aspirin and warfarin are shown
to effective at reducing the risk of chronic diseases but have a narrow therapeutic window and
are associated with adverse drug reactions, particularly, hemorrhage. Identification of
pharmacogenetic markers such as single nucleotide polymorphisms (SNPs) that could help
deliver personalized dose could help improve the risk-benefit ratio. Furthermore, development
of a rapid point of care genotyping device consisting of a pharmacogenetic SNP panel for
aspirin and warfarin could help implement personalized medicine in the clinical setting.
Analysis of candidate SNPs in aspirin’s pharmacokinetic and pharmacodynamic
pathways was carried out to explain variation in aspirin’s colorectal chemopreventive efficacy
using two large population based case-control datasets. Associations and interactions were
tested using logistic regression models and meta-analysis of the 2 datasets. A novel sitespecific
association for rs1799853 (OR=0.73, 95% CI=0.60-0.90, P=0.003) and rs1105879
(OR=1.16, 95% CI=1.02-1.32, P=0.03) with colon cancer risk was observed. Furthermore,
stratification by aspirin use showed increased risk of colorectal cancer in aspirin users but not
in non-users carrying variant allele of the SNPs rs4936367 and rs7112513 in PAFAH1B2
gene and rs2070959 and rs1105879 in UGT1A6 gene (Pinteraction<0.05 for all). These results
provide insight into aspirin’s differential chemopreventive efficacy and the neoplastic
transformation of cells in colon and rectum.
Utility of clinically validated pharmacogenetic dosing algorithms consisting of three
warfarin dose associated SNPs from the European population needs to tested in the Gujarati
Indians, an Indian sub-population. Dose prediction accuracy of the algorithms was compared
between Gujarati Indian and European population. Mean squared difference of both
pharmacogenetic algorithms was higher in Gujarati Indian compared to European population
(Klein et al 2009, 216.3 v/s 160.7, P=0.05; Gage et al 2008, 170.6 v/s 143.2, P=0.07). Poor
prediction accuracy could be explained by the presence of study subjects requiring dose for
target INR range 2.5-3.5 and low frequency of the VKORC1 rs9923231 variant, which is the
most important genetic determinant of warfarin dosing in Europeans. Therefore, the SNP
panel and dosing algorithms developed from European populations cannot be assumed to
have utility in the Gujarati Indian population.
Finally, to help develop a rapid, point-of care, silicon nanowire (SiNW) based SNP
genotyping device, a panel of isothermal melting probes were designed to genotype three
warfarin dose associated SNPs. Testing of hybridization and washing conditions to have
optimal hybridization kinetics between the probe and target DNA and high target sequence
specificity was carried out using custom designed microarray platform. Accurate genotype
calls for all 3 SNPs in 2 anonymised samples using empirically optimized hybridization and
washing conditions was carried out successfully. Current work highlighted associations
between probe characteristics and hybridization parameters, which would be useful in
designing and testing probes on the SiNW platform.
Identification, validation and testing of clinical utility of population specific
pharmacogenetic markers along with development and deployment of ultra-rapid point of care
genotyping technologies could help deliver personalized risk-benefit ratio for aspirin and
warfarin
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
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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