A phase II dose-ranging study of mirabegron in patients with overactive bladder

Introduction and hypothesis Mirabegron is a potent and selective β3-adrenoceptor agonist that may represent an alternative treatment option in place of antimuscarinics for patients with overactive bladder. Methods Patients completed a single-blinded, 2-week placebo run-in period followed by 12 weeks of randomized (n=928) double-blinded treatment with mirabegron oral controlled absorption system (OCAS) 25, 50, 100, or 200 mg once-daily (QD), placebo or tolterodine extended release (ER) 4 mg QD. The primary endpoint was change from baseline to end-of-treatment in mean number of micturition episodes/24 h. Secondary endpoints included changes in mean volume voided per micturition; mean number of urinary incontinence, urgency urinary incontinence, and urgency episodes/24 h; severity of urgency; nocturia; and quality of life measures. Safety parameters included vital signs, adverse events, laboratory tests, electrocardiogram measurements and post-void residual volume. Results Mirabegron 25, 50, 100, and 200 mg resulted in dosedependent reductions (improvements) from baseline to end-oftreatment in micturition frequency of 1.9, 2.1, 2.1, and 2.2 micturitions/24 h respectively, versus 1.4 micturitions/24 h with placebo (p≤0.05 for the mirabegron 50-, 100-, and 200-mg comparisons). There was a statistically significant improvement with mirabegron compared with placebo for most secondary endpoints including quality of life variables. While there was a significant (p<0.05) increase from baseline in pulse rate in the mirabegron 100-mg and 200-mg groups, this was not associated with an increased incidence of cardiovascular adverse events. Conclusions The favorable efficacy and tolerability of mirabegron in this phase II dose-finding study has led to its successful advancement into a phase III clinical development program

A quick approach for rheological evaluation of warm asphalt binders using response surface method

This paper describes a quick approach for quantification of the effects of a chemical warm named Rediset, and its interactions with temperature and aging on the rheological properties of asphalt binders using Response Sur-face Method. The central composite method was applied to design experimental programs for three test temperature conditions, namely; very high temperature (120–180 °C), high temperature (46–82 °C), and intermediate temperature (19–31 °C). Rotational viscosity, G*/sin δ and G*sin δ were selected as parameters to assess the effects of the chemical warm additive on the rheological properties of asphalt binders for different aging conditions. Evaluation of the effects of this additive on the transformed value of G*/sin δ at high temperatures indicates that additive content has significant effect on Ln(G*/sin δ). The results for intermediate temperatures show that this additive has a positive effect on G*sin δ of asphalt binders

ПЕРИОПЕРАЦИОННАЯ ХИМИОТЕРАПИЯ ПРИ ИНВАЗИВНОМ РАКЕ МОЧЕВОГО ПУЗЫРЯ: СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ И ОБОСНОВАНИЕ НЕОБХОДИМОСТИ ПОИСКА АЛЬТЕРНАТИВНЫХ МЕТОДОВ ЛЕЧЕНИЯ. ИССЛЕДОВАНИЕ MAGNOLIA

The paper gives an overview of peri-operative chemotherapy in patients with muscle-invasive bladder cancer (MIBC) as insufficient option, demonstrates a clinical need for the development of more efficacious and safe treatment and introduces a MAGNOLIA study proposed by the European Association of Urology Research Fund in a concept of MIBC immunotherapy. The MAGNOLIA trial conducted in 56 research centers of 10 countries assesses whether adjuvant immunotherapy with recMAGE-A3+AS15 vaccine is safe and effective and improves outcome of patients with MAGE-A3 positive MIBC after cystectomy. 60 of 273 patients have been enrolled. The trial has to be continued to elaborate a general peri-operative treatment strategy for MIBC.Представлены данные II фазы рандомизированного исследования MAGNOLIA, проводившегося в 56 исследовательских центрах в 10 странах. Целью исследования MAGNOLIA является изучение эффективности и безопасности применения вакцины (recMAGEA3+ AS15) у больных инвазивным раком мочевого пузыря (ИРМП). В исследовании приняли участие 342 пациента. На основании полученных данных сделан вывод: периоперационная химиотерапия не может быть рекомендована во всех случаях выявления ИРМП и требуется продолжение исследования для выработки общей стратегии химиотерапевтического воздействия при ИРМП

Etude de la cavitation par caractérisation dynamique impulsionnelle

La cavitation ultrasonore haute fréquence est aujourd'hui de plus en plus étudiée car elle fournit un outil efficace à la synthèse chimique. Le transducteur ultrasonore étant un émetteur récepteur, il est utilisé en mode réflexion. Notre but est d'obtenir des mesures quantitatives de paramètres physiques des bulles en étudiant la propagation d'impulsions ultrasonores dans le milieu de cavitation. L'intérêt majeur de cette méthode réside dans son caractère non perturbant.As it provides a more efficient tool for some typical chemical reactions, the high frequency ultrasonic cavitation is nowadays increasingly studied. The ultrasonic transducer is a reciprocal sensor, so it is used in this work in a pulse reflection mode. Our purpose is to obtain quantitative measurements of physical parameters of the bubbles , studying the propagation of ultrasonic pulses in the cavitating medium