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Role of CYP2C19 polymorphisms in short-term rabeprazole-based triple therapy- Implication of PK/PD correlation
No full text簡介子幫浦為主的三合一療法為目前幽門螺旋桿菌的標準療法之一，一般建議的療程為7~14天；縮短的三合一療法雖可以降低醫療支出、減少副作用、增進病人服藥順服性，但因為到目前為止的研究結果分歧，故仍未被建議使用於治療中。Rabeprazole是質子幫浦抑制劑中效果較強，也較不受到代謝酵素CYP2C19基因型影響的一個藥物，然而，現今已證實，rabeprazole藥動、藥效特性仍受到CYP2C19基因型的影響，因此，CYP2C19緩慢代謝者是否可因此得到較好的治療成效，與此治療優勢是否可進一步將療程縮短為7天以下值得研究。法研究收納台大醫院內證實受到幽門螺旋桿菌感染的胃炎及消化道潰瘍病人，依照受試者CYP2C19基因型隨機分為4組，其中A~C組在研究第1~7天皆服用rabeprazole 20 mg bid PO，D組則服用esomeprazole 40 mg bid，而抗生素部分，皆服用amoxicillin 1 g bid PO與clarithromycin 500 mg bid PO，A組於研究第1~4天使用，B組於第4~7天使用，C與D組於第1~7天使用，為分析藥動藥效特性，受試者於用藥第1、4、7天抽血測質子幫浦抑制劑與胃泌素濃度，所得資料使用NONMEM進行分析；而為進一步分析治療結果，受試者在治療前及治療後分別執行13碳尿素呼氣試驗。果rabeprazole藥動學部分，受試者CYP2C19基因型與體表面積兩個因子被發現可改善藥動學模型，故被納入完整藥動模型中，依照完整模型預估結果，CYP2C19緩慢代謝者在清除率與排除速率常數部分皆顯著小於快速代謝者，而單劑量與多劑量下rabeprazole藥動特性並沒有顯著差異；藥效部分，直接及間接模型皆被納入分析中，兩模型結果一致，皆由於緩慢代謝者血中rabeprazole濃度較高，故預估CYP2C19緩慢代謝者在使用rabeprazole上有較佳的酸分泌抑制效果，然而，在使用質子幫浦抑制劑的第4及7天胃泌素濃度比較上，不同CYP2C19基因型受試者並無顯著差異，可能原因應來自CYP2C19緩慢代謝者第1天起始的胃泌素濃度低於快速代謝者所造成。在esomeprazole部分，藥動學特性在單劑量及多劑量上有顯著差異，包括擬似分布體積與清除率皆在多劑量給藥下有降低現象，藥效學上，esomeprazole經模型預估後，發現使用esomeprazole受試者之藥效反應較使用rabeprazole的受試者差。臨床幽門螺旋桿菌治療成果上，不同CYP2C19基因型與不同治療方式間，治療成功率皆無顯著差異，但在CYP2C19緩慢代謝者中可觀察到較好的治療成功率。論YP2C19緩慢代謝者在使用rabeprazole為主的三合一療法時，有較好治療成效的趨勢，且在縮短療程中，CYP2C19緩慢代謝者也可達到很好的治療結果，因此，可能具有將療程縮短為4天的潛力，但因本研究樣本數較小，故無法達到統計上顯著差異，可能需進一步試驗來驗證本研究所觀察到的現象。中文摘要 ibstract iii錄 v目錄 viii目錄 ix圖目錄 x表目錄 xi1章 前言 12章 文獻探討 2.1 Helicobacter pylori (H.pylori)與消化道潰瘍 2.1.1 消化道潰瘍 2.1.2 Helicobacter pylori 2.1.3 Helicobacter pylori治療 3.2 質子幫浦抑制劑- rabeprazole (Pariet®) 6.2.1 質子幫浦 6.2.2 質子幫浦抑制劑 6.3 胃泌素 11.3.1 介紹 11.3.2 胃泌素與質子幫浦抑制劑 11.3.3 胃泌素與Helicobacter pylori 12.4 CYP2C19基因多型性 13.4.1 CYP2C19基因多型性對rabeprazole之影響 13.5 族群藥物動力學與NONMEM 15.5.1 與傳統藥物動力學比較 15.5.2 分析方式 15.5.3 NONMEM 163章 研究目的 294章 研究方法 30.1 受試者收納 30.1.1 給藥方式 30.1.2 抽血時間 30.2 實驗室分析 31.2.1 CYP2C19基因型分析 31.2.2 內視鏡、組織學、微生物學檢驗 31.2.3 13C尿素呼氣試驗 31.2.4 Rabeprazole與esomeprazole血中濃度 31.2.5 胃泌素濃度 32.3 藥動/藥效分析 33.3.1 藥動分析 33.3.2 藥效分析 33.4 統計方法 355章 結果 36.1 受試者特性 36.2 Rabeprazole藥物動力學資料與模型建立 37.2.1 血中濃度 37.2.2 Rabeprazole藥物動力學模型建構 37.3 胃泌素血中濃度與模型建立 38.3.1 血中濃度 38.3.2 藥動/藥效關係 38.4 Esomeprazole 40.4.1 Esomeprazole血中濃度與藥動模型 40.4.2 胃泌素血中濃度與藥效模型 40.5 臨床治療結果 416章 討論 66.1 CYP2C19基因型與質子幫浦抑制劑之PK/PD 66.2 質子幫浦抑制劑之PK/PD關聯性 67.3 質子幫浦抑制劑族群藥動學與其他研究比較 68.4 胃酸抑制、胃泌素與H.pylori 69.5 臨床結果 70.6 限制與未來展望 727章 結論 738章 參考資料 74錄 8
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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