1,720,953 research outputs found

    Development and validation of a method for determination of empagliflozin in blood plasma and its adjustment for microsampling

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    Empagliflozin je peroralno zdravilo, ki se uporablja za zniževanje glukoze v krvi pri odraslih bolnikih z neustrezno urejeno sladkorno boleznijo tipa 2 in za zdravljenje bolnikov s srčnim popuščanjem. Načrtuje se farmakokinetična raziskava različnih odmerkov empagliflozina na bolnikih s srčnim popuščanjem. V okviru magistrske naloge smo zato nameravali razviti občutljivo, selektivno, točno in natančno metodo za merjenje koncentracij empagliflozina v krvni plazmi ter postaviti izhodišče za prilagoditev metode na mikrovzorčenje krvi. Preizkusili smo tekočinsko ekstrakcijo ter njeno izboljšano in novejšo različico, podprto tekočinsko ekstrakcijo. V okviru tekočinske ekstrakcije smo preizkusili različnie vrste in volumne organskih topil, pri podprti tekočinski ekstrakciji pa smo preizkusili različne kartuše. Končna metoda, ki smo jo uspešno validirali, temelji na tekočinski ekstrakciji z etil acetatom kot ekstrakcijskim topilom, ki ji sledi detekcija s tekočinsko kromatografijo, sklopljena s tandemsko masno spektrometrijo (LC-MS/MS). Razvito metodo smo ovrednotili v skladu s smernicami ICH M10. Delovno območje analizne metode smo potrdili na koncentracijskem območju med 1 ng/mL in 1000 ng/mL. Izkoristek priprave vzorca je pri nizkem in visokem kontrolnem vzorcu znašal nad 70 %. Večji vpliv ozadja in slabšo ponovljivost smo zaznali le pri najnižjem testiranem kalibracijskem vzorcu pri 0,5 ng/mL. Preverili smo relativni vpliv ozadja, pri čemer je vrednost RSD pri QCL znašala 6,98 % in pri QCH 4,17 %. Potrdili smo ustrezno točnost vseh treh nivojev kontrolnih vzorcev in LLOQ, ki je znašala med 89,2 % in 108,7 %. Prav tako smo pri vseh treh nivojih kontrolnih vzorcev in LLOQ potrdili ustrezno ponovljivost, saj so se vrednosti RSD gibale v območju med 0,45 % ter 12,6 %. Dokazali smo ustrezno dolgoročno stabilnost (vsebnost glede na t = 0 h je po 90 dneh na -20 °C na nivoju QCL znašala 88,3 %, na nivoju QCM 104,7 % in na nivoju QCH 104,6 %) in ustrezno stabilnost v času rokovanja z vzorcem za empagliflozin. Na podlagi rezultatov validacije metode lahko potrdimo, da je metoda ustrezna za določitev koncentracij empagliflozina v plazemskih vzorcih bolnikov na terapiji z empagliflozinom za npr. namen terapevtskega spremljanja koncentracij ali izvedbe farmakokinetičnih študij. Metoda je dobro izhodišče za prilagoditev na mikrovzorčenje, kar smo tudi preverili na manjši seriji posušenih krvnih madežev v območju 5-250 ng/mL.Empagliflozin is an oral medicine used to lower blood glucose in adult patients with inadequately controlled type 2 diabetes. It is also used to treat patients with heart failure. A pharmacokinetic study of different empagliflozin doses in patients with heart failure is planned. As part of the master\u27s thesis, we therefore wanted to develop a sensitive, selective, accurate and precise method for measuring empagliflozin concentrations in blood plasma, and set a starting point for adapting the method to blood microsampling. We tested two different methods of plasma sample preparation, specifically liquid–liquid extraction and its improved and newer version, supported liquid extraction. As part of the liquid–liquid extraction, we focused on testing different types and volumes of organic solvents, and in supported liquid extraction, we tested different cartridges. The final method, which we successfully validated, is based on liquid–liquid extraction with ethyl acetate as the extraction solvent, followed by detection by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The developed method was evaluated according to ICH M10 guidelines. The operating range of the analytical method was confirmed in the concentration range between 1 ng/mL and 1000 ng/mL. The sample preparation recovery was above 70% for the low and high control samples. A greater matrix effect and lower reproducibility were detected only for the lowest calibration sample tested at 0.5 ng/mL. We checked the relative matrix effect, with the RSD values being 6.98% and 4.17% for QCL and QCH, respectively. We confirmed the appropriate accuracy of all three levels of control samples and the LLOQ, which ranged between 89.2% and 108.7%. We also confirmed adequate reproducibility at all three levels of control samples and LLOQ, as RSD values ranged between 0.45% and 12.6%. Furthermore, we demonstrated adequate long-term stability and bench-top stability during sample handling for empagliflozin. Based on the method validation results, we can confirm that the method is suitable for determining empagliflozin concentrations in plasma samples of patients on empagliflozin therapy for, e.g., the purpose of therapeutic concentration monitoring or for the purpose of conducting pharmacokinetic studies. The method is a good starting point for adaptation to microsampling, which we also verified on a smaller series of dried blood spots in the range of 5–250 ng/mL

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We 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 Under Sail The Imagination of Jack London, 1893-1902

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    In 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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