1,720,955 research outputs found
The development of HPLC methods for the determination of methotrexate and doxorubicin metabolites and their application to clinical studies
Get PDFThis thesis describes the development of specific assays for two important anti-cancer agents which have been available for some time, methotrexate (MTX) introduced in 1 949 and doxorubicin (ADR) introduced in 1969. Both of these drugs undergo significant Phase I metabolism and since such metabolites may be of pharmacological or toxicological significance the assays developed had to be capable of estimating these as well as the parent drugs. High performance liquid chromatography (HPLC) is an ideal technique for this purpose. The assay developed for MTX and its metabolites employed a liquid/solid extraction which gave reproducibly high recoveries of MTX, its deglutamated metabolites and their 7-hydroxylated derivatives, followed by an HPLC procedure using an anionic ion- pairing agent in the eluant which gave excellent chromatographic efficiency and resolution. This resulted in a highly sensitive and specific assay for all the above components. The assay was applicable to serum and urine and a modified method applicable to in vitro studies was also developed and used for analyses of cells both bacterial and human, and the culture media in which they were grown. Studies using clinical samples showed that the assay was sufficiently sensitive to measure MTX and its metabolites in plasma from patients treated with low-dose oral MTX for psoriasis. High-dose studies were carried out during following IV infusions of MTX in cancer patients. The results obtained gave rise to some new findings concerning MTX handling. In low-dose, intra-individual MTX clearance was highly reproducible, but there was substantial intersubject variation in this and other pharmacokinetic parameters. In particular MTX bioavailability varied between 17 and 120%. The implications of this and the other variations in disposition are considered. In the high-dose studies the kinetics were markedly different from the low-dose studies, most probably due to the presence of other drugs and the possibility of third spaces. Sequential high-dose studies showed that changes in the renal component of clearance was a major factor in accumulation of 7-hydroxy methotrexate (7-OHMTX). Clearances were calculated from both urinary data and plasma data and the results were found to be comparable. A second potential metabolite DAMPA, which had been reported in plasma by Donehower (1979) was detected in some plasma samples following high-dose MTX therapy. The kinetics indicate that the most likely source of this is as an impurity in the infusion fluid rather than as a result of metabolism in man by hepatic bacterial deglutamation. This product was not detected in vitro following incubation of either bacterial or human cell lines with MTX. A third potential metabolite of MTX, 7-OHDAMPA, not previously described in man, was synthesised and characterised in vitro and some evidence obtained as to its presence in urine from patients with DAMPA present in plasma. An HPLC assay for doxorubicin (ADR) was developed which was highly sensitive for ADR and its main Phase I metabolites. The HPLC assay employed a novel separation mechanism which was fully investigated and an explanation proposed. The assay proved suitable for the examination of clinical samples. The effects of gastrointestinal bacteria and human cell lines were investigated and metabolism of these drugs in some cells was found, although the relevance of these findings to cell resistance remains to be ascertained. Similar studies with ADR showed that bacterial cells metabolised the drug but not to any of the known metabolites. These studies indicate that the use of specific methods for measuring metabolites of anti-cancer drugs as well as the parent drug can lead to more information as regards the metabolism and disposition of these drugs than the non-specific tracer methods employed in many reference studies. It is suggested that the application of these and similar methods to clinical studies in patients treated with chemotherapeutic agents may lead to more rational individual dosage regimes giving rise to increased efficiency and reduced toxicity
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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