1,721,020 research outputs found
Pharmacokinetics, safety and inducible cytokine responses during a Phase 1 trial of the histone deacetylase inhibitor ITF2357 (GIVINOSTAT)
Full text linkInhibitors of histone deacetylases (HDAC) are used widely in medicine. ITF2357 is a hydroxamic acid-containing, orally active HDAC inhibitor with anti-inflammatory properties. In endotoxin-stimulated human PBMC, ITF2357 at 50 to 125 nM inhibited the release of TNFalpha and IL-1β by more than 70%, respectively. The induction of IFNgamma by the combination of IL 18 plus IL 12 was also reduced by ITF2357. We report here a Phase I safety and pharmacokinetic trial. After an oral dose of 50 mg, the maximal plasma concentration was 104 nM at 2 hours post dosing with a half-life of 6.9 hours. For the 100 mg dose, the Cmax was 199 nM at 2.1 hours and a half life of 6.0 hours. For a dose of 200 mg, the Cmax was 470 nM after 2.1 hours and a half-life of 6.0 hours. Repeat daily doses of ITF2357 for 7 consecutive days of 50, 100 or 200 mg resulted in nearly the same Cmax and half-life each day as was observed following a single dose. Side effects were limited to reductions in platelets (10-25% of baseline) within the first week after 7 days of treatment, reached a nadir point after 2 to 3 weeks and resolved fully within 2 to 3 weeks. Whole blood was cultured with endotoxin (10 ng/mL). Production of TNFα progressively decreased reaching a nadir 4 hours after oral dosing (45 and 52% of the pre-drug level for 50 and 100 mg, respectively). Similar decreases were observed after 4 hours for IL 1 beta, IL 6 and interferon gamma but not for IL 8. The IL 1 receptor antagonist did not decrease in the same samples. After 24 hours, the levels had returned to base line measurements. In a one week-long multiple dosing schedule, the fall in cytokine production in blood cultures observed on day 7 was nearly the same as that of the first day. We conclude that ITF2357 is a safe and effective therapy for reducing cytokine production following oral dosing.Gli inibitori delle istone deacetilasi (HDAC) sono stati recentemente introdotti nella terapia medica oncologica. ITF2357 (Givinostat) è un inibitore delle HDAC, attivo per via orale e con proprietà anti-infiammatorie. In colture di PBMC umani stimolati con LPS, ITF2357 alle concentrazioni da 50 a 125 nM ha dimostrato efficacia nell’inibire il rilascio di TNFα ed IL-1β. Anche l'induzione di IFNγ mediante la combinazione di IL-18 ed IL-12 è ridotta in vitro. Il seguente rappresenta uno studio di Fase I relativo alla sicurezza e alla farmacocinetica di ITF2357 in volontari sani. Dopo una dose orale di 50 mg, la concentrazione plasmatica massima è stata di 104 nM a 2 ore dalla somministrazione, con una emivita di 6,9 ore. Per la dose di 100 mg, la Cmax è stata di 199 nM a 2,1 ore e con un’emivita di 6,0 ore. Per la dose di 200 mg, la Cmax è stata di 470 nM dopo 2,1 ore e una t1/2 di 6,0 ore. Ripetute dosi giornaliere di ITF2357 per 7 giorni consecutivi (50, 100 o 200 mg) hanno generato la stessa Cmax ed emivita osservate dopo una singola dose. Gli effetti collaterali si sono limitati ad una riduzione delle piastrine (10-25% del basale) entro la prima settimana di assunzione con un nadir al settimo giorno ed un ripristino completo dopo 3 settimane. Il sangue intero dei soggetti in studio è stato incubato con lipolisaccaride (10 ng/mL). La produzione di TNFα è risultata ridotta raggiungendo un nadir a 4 ore dall’assunzione orale (-45 e -52% comparati con i livelli pre-assunzione per i dosaggi di 50 e 100 mg, rispettivamente). diminuzioni simili sono state osservate dopo 4 ore per IL-1beta, IL-6 ed IFNgamma ma non per IL-8 ed IL-1Ra. Nei campioni di sangue prelevati a 24 ore dall’assunzione, i livelli citochinici sono tornati comparabili al basale. Nello studio con dosi multiple, l’effetto anti-citochinico osservato al settimo giorno è stato sovrapponibile a quello del primo. In conclusione ITF2357 è una terapia sicura ed efficace nel ridurre la produzione di citochine in un modello ex-vivo
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
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