1,721,366 research outputs found

    Sviluppo di un metodo per il dosaggio plasmatico del busulfan mediante HPLC-ESI-MS/MS in studi di farmacocinetica su pazienti talassemici

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    L'ottimizzazione del dosaggio busulfan in pazienti sottoposti a trapianto di midollo osseo si raccomanda al fine di ridurre gli effetti tossici associati all’elevata esposizione al farmaco. Una variabilità dell'area sotto la curva di concentrazione / tempo (AUC) comporta il rischio di sovra o sotto dosaggio con il conseguente aumento del rischio di tossicità o di recidiva. E’ stato sviluppato un metodo di analisi rapido, sensibile e specifico per il rilevamento del busulfan nel plasma umano. Il test si basa su una estrazione liquido-liquido con acetato di etile e di rilevamento mediante cromatografia liquida, con ionizzazione electrospray e spettrometria tandem massa (HPLC-ESI-MS/MS). Il busulfan deuterato è stato utilizzato come standard interno. Il metodo è lineare nel range 39-2500 ng / mL, con r2> 0,99 e una durata della corsa cromatografica di soli 5 minuti (con un tempo di ritenzione del busulfan di 1,62 minuti). La precisione inter-day and intra-day è nel range di 1,01 - 3,72% e di 0,35-4,32%, rispettivamente. Il recupero è > 70%. Il limite di rivelabilità e di quantificazione sono di 6 e 10 ng/mL, rispettivamente. Il metodo di analisi riportato, richiede soltanto 200 μL di plasma per l'analisi. Il metodo convalidato è stato applicato con successo per l’analisi di campioni di plasma ottenuti da bambini talassemici sottoposti a un regime di condizionamento con busulfan e sottoposti a trapianto di midollo osseo. Questo metodo permette la correzione della dose consentendo un dosaggio adeguato al fine di ottenere la concentrazione ottimale di busulfan. Questo metodo è attualmente utilizzato per analizzare le concentrazioni plasmatiche di busulfan dopo somministrazione per via endovenosa ed è applicato nel monitoraggio terapeutico dei farmaci.Optimisation of busulfan dosage in patients undergoing bone marrow transplantation is recommended in order to reduce toxic effects associated with high drug exposure. Variation in the area under the concentration /time curve (AUC) results in risk of over or under treatment with excess risk of toxicity or relapse. A rapid, sensitive and specific assay for detection of busulfan in human plasma was developed. The assay is based on a liquid-liquid extraction with ethyl acetate and detection by high performance liquid chromatography with electrospray ionization and tandem mass spectrometry (HPLC-ESI-MS/MS). Deuterated busulfan was used as internal standard. The method was linear over the range 39-2500 ng/mL, with r2 > 0.99 and a run time of only 5 minutes (busulfan retention time of 1.62 minutes). The inter-day and intra-day precision were in the range 1,01- 3,72 % and 0,35-4,32 %, respectively. The recovery was >70%. The limits of detection and quantification were 6 and 10 ng/mL, respectively. The reported assay required only 200 µL of plasma for the analysis. The validated method was successfully applied to analyze plasma samples from children with thalassemia undergoing a conditioning regimen with busulfan and submitted to bone marrow transplantation. This method permits dose correction allowing a better dosing adjustment towards the target level of busulfan. This method is currently used to analyze the plasma concentrations of busulfan after intravenous administration and it is applied in therapeutic drug monitoring

    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
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