1,720,959 research outputs found
Studio di associazione tra fattori genetici e livelli plasmatici in pazienti trattati con NAO: Dabigatran, Rivaroxaban e Apixaban
Full text linkIntroduzione: gli anticoagulanti orali svolgono un importante ruolo nel ridurre complicanze e mortalità associate ai disturbi tromboembolici. Il Warfarin, un antagonista della vitamina K (AVK), ha rappresentato per 50 anni l’unico farmaco disponibile ed efficace per la profilassi di eventi tromboembolici, i cui limiti sono dati da un monitoraggio dell’INR, da interazioni alimentari e farmacologiche. Tali limiti sono stati superati con i nuovi anticoagulanti orali (NAO), che si somministrano in dosi fisse, non necessitano di monitoraggio continuo, hanno una rapida insorgenza d’azione, un buon profilo di sicurezza, una farmacodinamica ed una farmacocinetica prevedibile, poche interazioni con cibo e farmaci, e sono utilizzati nella terapia anticoagulante orale di quei pazienti con patologie come fibrillazione atriale, cardiopatie dilatative, valvulopatie, malattie tromboemboliche e protesi valvolari cardiache. Si tratta del Dabigatran, inibitore diretto della trombina (fattore IIa), e del Rivaroxaban e Apixaban, inibitori del fattore Xa. È stata riportata una variabilità inter-individuale nelle concentrazioni di farmaco ritrovate nel sangue; in particolare i geni ABCB1 e CES1 esercitano un effetto importante nel metabolismo degli anticoagulanti e varianti alleliche in questi due loci giocano un ruolo determinante sulla suscettibilità del farmaco.
Obiettivi: analizzare i polimorfismi su geni coinvolti nel processo metabolico del Dabigatran, Rivaroxaban e Apixaban, in particolare sul gene ABCB1 che codifica per un trasportatore della glicoproteina P (pompa di efflusso ATP-dipendente) per tutti e tre i farmaci e sul gene CES1 che è un enzima metabolizzante carbossilesterasi 1, che interviene nella trasformazione del dabigatran etexilato in forma attiva. Inoltre, determinazione della concentrazione plasmatica dei 3 farmaci prima e dopo assunzione dello stesso.
Materiali e Metodi: In una coorte di 92 pazienti in terapia con i dabigatran, 51 con rivaroxaban e71 con apixaban, abbiamo esaminato, attraverso sequenziamento diretto, le varianti geniche del gene ABCB1(rs4148738) per tutti i farmaci e le varianti geniche del gene CES1 (rs8192935 e rs2244613) per i pazienti in dabigatran e determinato la concentrazione plasmatica di valle e di picco dei farmaci stessi, attraverso la tecnica combinata HPLC-spettrometria di massa.
Risultati e Conclusioni: Tra i 92 pazienti che assumono dabigatran (età media: 72.0 anni) analizzati, nessuna variabile clinico o genotipo è stata associata con una differenza significativa nelle concentrazioni di picco di dabigatran. Per quanto riguarda le concentrazioni di valle, oltre alla clearance della creatinina, e il sesso è stata rilevata una significativa associazione con i rs8192935 CES1 SNP (p = 0,023). I livelli plasmatici medi aggiustati erano più elevati tra i pazienti con il genotipo CC (86,3 ng / dl) rispetto a quelli che portano l’allele T (62,1 ng / dl). Nessun effetto significativo è stato rilevato per i rs4148738 ABCB1 SNP. Nel caso del Rivaroxaban per entrambe le dosi, non è stato trovato nessun effetto dello SNP ABCB1 sui livelli plasmatici. Per l’Apixaban, invece, è stata rilevata un’associazione con la dose di 10 mg, in particolare una significativa associazione con lo SPN di ABCB1 (p=0,048).
Abstract in English Background: the oral anticoagulants play an important role in reducing complications and mortality associated with thromboembolic disorders. Warfarin, a vitamin K antagonist (VKA), represented for 50 years the only drug available and effective for the prophylaxis of thromboembolic events, but it presents the limits, in particular it needs a monitoring of INR, interaction of food and drug. These limits have been exceeded with the new oral anticoagulants (NAO), which are administered in fixed doses, do not require continuous monitoring, they have a rapid onset of action, a good safety profile, pharmacodynamics and pharmacokinetics predictable, few interactions with food and drugs, and are used in the oral anticoagulation therapy for patients with diseases such as atrial fibrillation, dilated heart disease, valvular disease, thromboembolic disease and heart valve prostheses. They are the Dabigatran, direct inhibitor of thrombin (factor IIa), and the rivaroxaban and apixaban, factor Xa inhibitors. It was found an inter-individual variability in drug concentrations found in the blood; especially the ABCB1 and CES1 genes exert an important effect in the metabolism of anticoagulants and allelic variants in these two loci play a decisive role on the susceptibility of the drug.
Objectives: to analyze the polymorphisms of genes involved in the metabolic process of dabigatran, rivaroxaban and apixaban, in particular on the ABCB1 gene encoding a transporter P-glycoprotein (ATP-dependent efflux pump) for all three drugs and CES1 gene that is an enzyme carboxylesterase 1, which is involved in the transformation of dabigatran etexilate in active form. Furthermore, we have determined the plasma concentration of 3 drugs before and after intake of the same.
Patients/Methods: In a cohort of 92 patients treated with dabigatran, 51 with rivaroxaban and 71 with apixaban, we have examined by direct sequencing, gene variants of the ABCB1 (rs4148738 gene) for all drugs and genetic variants of CES1 gene (rs8192935 and rs2244613) for patients on dabigatran and we have determined the plasma concentration of trough and peak of the drugs, by the combined technique HPLC-mass spectrometry .
Results and Conclusion: Among the 92 patients treated with dabigatran (mean age: 72.0 years) analyzed, no clinical variable or genotype was associated with a significant difference in peak concentrations of dabigatran. As for trough concentrations, in addition to creatinine clearance and sex it is found a significant association with rs8192935 SNP CES1 (p=0.023) . The adjusted average plasma levels were higher among patients with the CC genotype (86.3 ng/dl) than those who carry the T allele (62.1 ng/dl). No significant effect was observed for the ABCB1 SNP rs4148738. In the case of rivaroxaban for both doses, it was not found any of the ABCB1 SNP effect on plasma levels. For the apixaban, instead, an association has been detected with the dose of 10 mg, in particular a significant association with the SPN of the ABCB1 (p = 0.048)
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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
Full text link“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
Full text linkWe 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
Full text linkWe 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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