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The increased power and voltage ratings of semiconductors fosters the use in medium voltage components, such as ac–dc converters. With a bipolar medium frequent rectangular (MF RECT) voltage, the converter size can be reduced and the efficiency increased. Possible insulating materials for medium voltage transformers are oil and insulation paper. The breakdown voltage of insulation materials is depending on the frequency and the shape of the voltage curve. Until today, only a few investigations of the breakdown voltage of insulating materials at sinusoidal and RECT voltages up to a few tens of kilohertz have been published. To design and optimize MF transformers at RECT voltages, further investigations are necessary. Therefore, a test bench for measuring the breakdown voltage at RECT voltages in the frequency range between one and ten kilohertz up to several tens of kilovolts is developed. The test bench is inspired by a Marx generator, which is a high voltage source for impulse voltages. By substituting resistances and spark gaps by IGBTs and adding galvanically insulated power sources, a medium frequent bipolar voltage can be generated. The test bench is characterized with respect to slew rate, input power, frequency, and voltage amplitude. Its usability is shown in first breakdown voltage measurements of insulation papers, used for transformer insulation. [ABSTRACT FROM AUTHOR]

Aims The transthyretin (TTR) stabilizer, tafamidis, has demonstrated efficacy and safety in the treatment of TTR familial amyloid polyneuropathy (20 mg day−1). Tafamidis use in TTR cardiomyopathy led to the study of the potential effect of tafamidis on the QTc interval in healthy subjects. Methods This randomized, three treatment, three period, six sequence crossover study with placebo, a positive control (moxifloxacin 400 mg) and tafamidis (400 mg, to achieve a supra-therapeutic Cmax of ~20 µg ml−1) was conducted in healthy volunteers at three clinical research units. Oral dosing in each of the three treatment periods was separated by a washout period of ≥ 14 days. Serial triplicate 12-lead electrocardiograms were performed. QTc intervals were derived using the Fridericia correction method. Safety and tolerability were assessed by physical examination, vital signs measurement, laboratory analyses and monitoring of adverse events (AEs). Results A total of 42 subjects completed the study. The upper limit of the two-sided 90% confidence intervals (CIs) for the difference in baseline-adjusted QTcF between tafamidis 400 mg and placebo was <10 ms (non-inferiority criterion) for all time points. The lower limit of the two-sided 90% CI between moxifloxacin 400 mg and placebo exceeded 5 ms at the pre-specified moxifloxacin tmax of 3 h post-dose, confirming assay sensitivity. Cmax and AUC(0,24 h) for tafamidis were 20.36 µg ml−1 and 305.4 µg ml−1 h, respectively. There were no serious/severe AEs or treatment discontinuations due to AEs. Conclusions This thorough QTc study suggests that a supra-therapeutic single 400 mg oral dose of tafamidis does not prolong the QTc interval and is well-tolerated in healthy volunteers. [ABSTRACT FROM AUTHOR]

This planned analysis of the GEMINI-AALA study evaluated the utility of single-pill amlodipine/atorvastatin for the attainment of blood pressure (BP) and lipid goals in diabetic patients of diverse ethnicity with hypertension (HTN) and dyslipidemia (DYS). GEMINI-AALA was a 14-week, multicenter, open-label study in patients with HTN/DYS from 27 countries across 5 continents. Eight dosages of single-pill amlodipine/atorvastatin (5/10-10/80 mg) were administered and electively titrated at Weeks 6, 10 (titration optional), and 12. The percentage of patients who attained JNC 7 and NCEP ATP III goals for BP (<130/80 mm Hg) and low-density lipoprotein cholesterol (LDL-C) (< 100 mg/dL) at Week 14 was assessed. Changes from baseline in BP and LDLC were also measured. Of the 1638 patients included in the intent-to-treat (ITT) population, 605 patients had type 2 diabetes. For diabetic patients, the mean dose of amlodipine/atorvastatin during the study was 6.2 mg/18.3 mg. Mean BP and LDL-C at baseline were 145.0/86.2 mmHg and 120.6 mg/dL, respectively. After 14 weeks treatment, 41.3% of diabetic patients reached both BP and LDL-C goals (0.0% at baseline), 46.3% reached BP goal (0.2% at baseline), and 84.6% reached LDL-C goal (30.6% at baseline). Mean BP reduction was 18.1/10.2 mmHg, and mean decrease in LDL-C was 40.5 mg/dL (27.5%). Attainment of both goals for the Middle East/Africa, Asia-Pacific, and Central/Southern America was 33.7%, 45.1%, and 40.6%, respectively. Among diabetic patients, 4.3% discontinued due to adverse events. Amlodipine/atorvastatin single-pill therapy was an effective and safe intervention that helped diabetic patients of diverse ethnicity with combined HTN/DYS to achieve BP and LDL-C goals. [ABSTRACT FROM AUTHOR]