Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial

IMPORTANCE: Secretory phospholipase A2(sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measurewas a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95%CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95%CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246. Copyright 2014 American Medical Association. All rights reserved

ЭЛЕКТРОФИЗИЧЕСКИЕ И ДИЭЛЕКТРИЧЕСКИЕ СВОЙСТВА КОМПОЗИТОВ Pb0,85Zr0,53Ti0,47O3 - Sr2FeMoO6-δ

Ferromagnetic-ferroelectric composite materials on the base of Pb0.85Zr0.53Ti0.47O3-Sr2FeMoO6-δ (PZT-SFMO) compound have been prepared by a complex ceramic technology and the citrate-gel synthesis. It was determined that the dielectric permittivity of a sample with a content of PZT of 55 wt. % and SFMO of 45 wt. % increases with temperature due to the rise of electrical conductivity and an influence of the dielectric dispersion caused by the Maxwell-Wagner relaxation. The electrical conductivity of the sample with a content of PZT of 35 wt. % and a content of SFMO of 65 wt. % possesses a clearly expressed frequency dependence, at temperature lower than 600 K, whereas at higher temperatures the electrical conductivity almost does not depends on frequency in the range 20 Hz-1 MHz. This is concerned with a considerable decrease of critical frequency at higher temperatures. At frequencies higher than 100 kHz and temperature lower than 600 K, the electrical conductivity increases by a power law.C помощью комплексной керамической технологии и цитрат-гель синтеза изготовлены ферромагнитно-сегнетоэлектрические композиционные материалы на основе соединения Pb0,85Zr0,53Ti0,47O3-Sr2FeMoO6-δ (ЦТС-SFMO). Установлено, что диэлектрическая проницаемость образца с содержанием ЦТС - 55 вес. % и SFMO - 45 вес. % возрастает с температурой, вследствие роста электропроводности и влияния диэлектрической дисперсии, обусловленной релаксацией Максвелла - Вагнера. Электропроводность образца с содержанием ЦТС - 35 вес. % и SFMO - 65 вес. % имеет явно выраженную зависимость от частоты ниже температуры 600 K, в то время как при более высоких температурах электропроводность почти не зависит от частоты в диапазоне 20 Гц - 1 МГц. Это связано с существенным уменьшением критической частоты при более высоких температурах. При частотах выше 100 кГц и температуре ниже 600 K электропроводность возрастает по степенному закону

ОПТИМИЗАЦИЯ УСЛОВИЙ СИНТЕЗА КОМПОЗИТОВ ЦИРКОНАТА-ТИТАНАТА СВИНЦА БАРИЯ, СОДЕРЖАЩИХ АТОМЫ МЕТАЛЛОВ, И ИХ ДИЭЛЕКТРИЧЕСКИЕ СВОЙСТВА

Composition materials on the base of Pb0,75Ba0,15Zr0,53Ti0,47O3 (PBZT) with micro-inclusions of Cu and Ni are prepared by a complex ceramic technology. This technology includes metallization procedures by means of the chemical deposition method from standard solutions of nickel and copper. At determination of correlation of the structure of PBZT composites and their dielectric properties it was shown that dielectric losses increase with decreasing temperature. This is caused by the domination of the real part of the complex dielectric permittivity.C помощью комплексной керамической технологии, включающей процедуры металлизации методом химического осаждения из стандартных растворов никеля и меди, подготовлены композиционные материалы на основе соединения Pb0,75Ba0,15Zr0,53Ti0,47O3 (ЦТБС) с микро-включениями Cu и Ni. При установлении корреляций между структурой композитов ЦТБС и их диэлектрическими характеристиками показано, что при низких частотах диэлектрические потери возрастают с увеличением температуры, что обусловлено доминированием действительной части комплексной диэлектрической проницаемости

ELECTRICAL-PHYSICAL AND DIELECTRIC PROPERTIES OF Pb_0,85Zr_0,53Ti_0,47O₃ - Sr₂FeMoO_6-_δCOMPOSITES

Ferromagnetic-ferroelectric composite materials on the base of Pb0.85Zr0.53Ti0.47O3-Sr2FeMoO6-δ (PZT-SFMO) compound have been prepared by a complex ceramic technology and the citrate-gel synthesis. It was determined that the dielectric permittivity of a sample with a content of PZT of 55 wt. % and SFMO of 45 wt. % increases with temperature due to the rise of electrical conductivity and an influence of the dielectric dispersion caused by the Maxwell-Wagner relaxation. The electrical conductivity of the sample with a content of PZT of 35 wt. % and a content of SFMO of 65 wt. % possesses a clearly expressed frequency dependence, at temperature lower than 600 K, whereas at higher temperatures the electrical conductivity almost does not depends on frequency in the range 20 Hz-1 MHz. This is concerned with a considerable decrease of critical frequency at higher temperatures. At frequencies higher than 100 kHz and temperature lower than 600 K, the electrical conductivity increases by a power law

OPTIMIZATION OF SYNTHESIS CONDITIONS OF lead-barium titanate-zirconate COMPOSITES CONTAINING METAL ATOMS AND THEIR DIELECTRIC PROPERTIES

Composition materials on the base of Pb0,75Ba0,15Zr0,53Ti0,47O3 (PBZT) with micro-inclusions of Cu and Ni are prepared by a complex ceramic technology. This technology includes metallization procedures by means of the chemical deposition method from standard solutions of nickel and copper. At determination of correlation of the structure of PBZT composites and their dielectric properties it was shown that dielectric losses increase with decreasing temperature. This is caused by the domination of the real part of the complex dielectric permittivity

Nano and micro structured targets to modulate the spatial profile of laser driven proton beams

Nano and micro structured thin (μ m-scale) foils were designed, fabricated and irradiated with the high intensity laser system operating at LLC (Lund Laser Centre, Sweden) in order to systematically study and improve the main proton beam parameters. Nano-spheres deposited on the front (laser irradiated) surface of a flat Mylar foil enabled a small enhancement of the maximum energy and number of the accelerated protons. Nano-spheres on the rear side allowed to modify the proton beam spatial profile. In particular, with nanospheres deposited on the rear of the target, the proton beam spatial homogeneity was clearly enhanced. Silicon nitride thin foils having micro grating structures (with different step dimensions) on the rear surface were also used as targets to influence the divergence of the proton beam and drastically change its shape through a sort of stretching effect. The target fabrication process used for the different target types is described, and representative experimental results are shown and discussed along with supporting 3D particle-in-cell simulations. \ua9 2017 IOP Publishing Ltd and Sissa Medialab srl

Electrical-physical and dielectric properties of Pb0,85Zr0,53Ti0,47O3 – SR2FeMoO6-δ composites

Ferromagnetic-ferroelectric composite materials on the base of Pb0.85Zr0.53Ti0.47O3–Sr2FeMoO6-δ (PZT-SFMO) compound have been prepared by a complex ceramic technology and the citrate-gel synthesis. It was determined that the dielectric permittivity of a sample with a content of PZT of 55 wt. % and SFMO of 45 wt. % increases with temperature due to the rise of electrical conductivity and an influence of the dielectric dispersion caused by the Maxwell-Wagner relaxation. The electrical conductivity of the sample with a content of PZT of 35 wt. % and a content of SFMO of 65 wt. % possesses a clearly expressed frequency dependence, at temperature lower than 600 K, whereas at higher temperatures the electrical conductivity almost does not depends on frequency in the range 20 Hz–1 MHz. This is concerned with a considerable decrease of critical frequency at higher temperatures. At frequencies higher than 100 kHz and temperature lower than 600 K, the electrical conductivity increases by a power law