1,721,051 research outputs found

    Putting the taxanes to work: unanswered questions

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    The promising activity of taxanes in advanced breast cancer patients has prompted the investigators to explore their role in the adjuvant setting. Methodological issues, still unsolved pharmacokinetic and pharmacodynamic problems, and potential severe toxicities could jeopardize these attractive regimens and should be taken into account in the design and interpretation of adjuvant trials. In order to minimize the methodological drawbacks, the potential role of taxanes in the adjuvant setting should be assessed in clinical trials powered to detect an absolute survival increase of near 7% at 10 years. The use of paclitaxel in combination with anthracyclines is complicated by pharmacokinetic interactions which may be responsible for unexpected side effects and/or subadditive cytotoxicity. Moreover, possible interactions between taxanes and tamoxifen are still unclear, and therefore more data are necessary before recommending the combined use of the two drugs in the adjuvant setting. Nowadays, the majority of breast cancer patients receive conservative surgery followed by radiotherapy; when adjuvant taxanes are used, radiotherapy should be delayed because of their radiosensitization effect, with potential detrimental effects. Finally, the majority of side effects of taxane-containing regimens are short-lasting and reversible, but other potential toxicities, such as the cardiotoxicity and long-term possible sequelae of the use of high-dose steroids, need long-term evaluation

    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

    Pharmacokinetic optimisation of treatment schedules for anthracyclines and paclitaxel in patients with cancer

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    The integration of paclitaxel into chemotherapy regimens with anthracyclines offers a new opportunity for devising effective therapy for patients with breast cancer. High response rates have been obtained by combining epirubicin or doxorubicin with paclitaxel. The pharmacokinetic analysis of paclitaxel and anthracyclines, as well as the identification of relationships with their pharmacodynamics, represents a rational approach for treatment optimisation. A schedule-dependent interaction between paclitaxel and anthracyclines has been demonstrated in clinical pharmacokinetic studies. In patients given paclitaxel 125 to 200 mg/m2 as 3- to 24-hour infusions in combination with doxorubicin 48 to 60 mg/m2 as a 48-hour infusion or intravenous bolus, the peak plasma drug concentration (Cmax) of doxorubicin increased significantly and drug clearance was reduced in the sequence paclitaxel-->doxorubicin as compared with doxorubicin-->paclitaxel. The schedule paclitaxel-->doxorubicin was more toxic as compared with doxorubicin-->paclitaxel, and an incidence of 18 to 20% of congestive heart failure was observed in patients with breast cancer given doxorubicin 60 mg/m2 followed by paclitaxel 125 to 200 mg/m2. Likewise, patients given epirubicin 90 mg/m2 had a sudden rebound of epirubicinol plasma concentrations shortly after the start of infusion of paclitaxel 200 mg/m2, with a significant increase in the area under the concentration-time curve (AUC) of epirubicinol as compared with epirubicin alone (1.27 +/- 0.2 vs 0.61 +/- 0.1 mumol/L.h). Moreover, the severity of the myelosuppression induced by paclitaxel, as defined by a sigmoid maximum effect (Emax) relationship between the decrease in neutrophil count and the duration of drug plasma concentrations above the threshold value of 0.1 mumol/L, was significantly enhanced by epirubicin. Finally, chemotherapy with paclitaxel and anthracyclines may be improved by designing pharmacologically guided regimens in order to control the extent of pharmacokinetic interaction and reduce the risk of severe toxicity while maintaining the therapeutic efficacy of the combination. Future protocols should explore the activity of a prolonged paclitaxel infusion in association with an anthracycline separated from the taxane by a washout time interval in order to minimise the inhibitory effects exerted by paclitaxel on P-glycoprotein-mediated biliary clearance of anthracyclines, the most likely cause of pharmacokinetic interaction

    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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