1,721,121 research outputs found

    Lacosamide: a new approach to target voltage-gated sodium currents in epileptic disorders

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    The mechanism of action of several antiepileptic drugs (AEDs) rests on their ability tomodulate the activity of voltage-gated sodium currents that are responsible for fast action potentialgeneration. Recent data indicate that lacosamide - a compound with analgesic and anticonvulsanteffects in animal models - shares a similar mechanism. When compared with other AEDs, lacosamidehas the unique ability to interact with sodium channel slow inactivation without affecting fastinactivation. This article reviews these findings and discusses their relevance within the context ofneuronal activity seen during epileptiform discharges generated by limbic neuronal networks in thepresence of chemical convulsants. These seizure-like events are characterized by sustained dischargesof sodium-dependent action potentials supported by robust depolarizations thus providingsynchronization within neuronal networks. Generally, AEDs such as phenytoin, carbamazepine andlamotrigine block sodium channels when activated. By contrasts, lacosamide facilitates slowinactivation of sodium channels both in term of kinetics and voltage-dependency. This effect may berelatively selective for repeatedly depolarized neurons such as those participating in seizure activity inwhich the persistence of sodium currents is more pronounced and promotes neuronal excitation. Theclinical effectiveness of lacosamide has been demonstrated in randomized placebo-controlled doubleblindparallel-group, adjunctive-therapy trials in patients with refractory partial seizures. Furtherstudies should determine whether lacosamide effects in animal models and in clinical settings are fullyexplained by its selective action on sodium current slow inactivation or whether other effects (e.g.,interactions with the collapsin-response mediator protein 2) play a contributory role

    Quantitative comparison of barbiturates in essential hand and head tremor

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    The tremorolytic effects of primidone and phenobarbital in essential tremor of hands and head were compared in a double-blind, placebo-controlled trial. Quantitative measurements of tremor were obtained in 15 patients by means of an accelerometric method. Only primidone proved to be superior to placebo in reducing hand tremor, suggesting that its tremorolytic effectiveness is largely dependent on the parent drug rather than its metabolite phenobarbital. Head tremor tended to improve only in three out of six patients with both primidone and phenobarbital, but, likely due to the small number of affected patients, the effect failed to reach statistical significance

    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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