Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

A model-based assurance case construction approach for system control software

Abstract As the massive damage caused by the failures of system control software becomes increasingly prominent, people pay more attention to the construction of assurance case to demonstrate the dependability level of system control software. In this paper, a new assurance case construction approach for system control software is proposed. Based on the metamodel of modular GSN, we give the basic procedure and tree structure deductive algorithm of the approach, and verify our work using Brake Control software used in an aircraft. The results show that the approach can develop assurance case effectively and efficiently

Orbital Angular Momentum Multiplexing in Space-Time Thermoacoustic Metasurfaces

Multiplexing technology with increased information capacity plays a crucial role in the realm of acoustic communication. Different quantities of sound waves, including time, frequency, amplitude, phase, and orbital angular momentum (OAM), have been independently introduced as the physical multiplexing approach to allow for enhanced communication densities. An acoustic metasurface is decorated with carbon nanotube patches, which when electrically pumped and set to rotate, functions as a hybrid mode-frequency-division multiplexer with synthetic dimensions. Based on this spatiotemporal modulation, a superposition of vortex beams with orthogonal OAMs and symmetric harmonics are both numerically and experimentally demonstrated. Also, flexible combinations of OAM modes with diverse frequency shifts are obtained by transforming the azimuthal phase distributions, which inspires a mode-frequency-division multiplexing approach that significantly promotes the communication capacity.This work was supported by National Basic Research Program of China (2017YFA0303702), NSFC (12074183, 11922407, 11834008, and 11874215), and the Fundamental Research Funds for the Central Universities (020414380181). J.C. acknowledges support from the European Research Council (ERC) through the Starting Grant 714577 PHONOMETA

Study on characterization of electrical contact between pantograph and catenary

Perfect sliding contact which requires appropriate contact force between pantograph and contact wire is the key point to guarantee the stability of current collection in locomotive. In order to study on characterization of electrical contact between pantograph and catenary, first, a novel test apparatus of pantograph electrical contact has been developed according to the filed application. The apparatus can simulate laterally (zigzag) movement, vertical vibration and the flexible line contact between pantograph contact strip and contact wire. Then, electrical contact experiments are carried out using this apparatus. Characteristics of static contact resistance under various contact force and traction current are analyzed. A fitted formula for contact resistance is proposed which have two independent variables of contact force and traction current. Possible mechanism for variation of contact resistance is represented in microscopic view of contact surface. It is demonstrated that the static contact resistance decreases with the contact force and traction current increasing

Identifying quasi-2D and 1D electrides in yttrium and scandium chlorides via geometrical identification

Developing and understanding electron-rich electrides offers a promising opportunity for a variety of electronic and catalytic applications. Using a geometrical identification strategy, here we identify a new class of electride material, yttrium/scandium chlorides Y(Sc)(x)Cl-y (y:x < 2). Anionic electrons are found in the metal octahedral framework topology. The diverse electronic dimensionality of these electrides is quantified explicitly by quasi-two-dimensional (2D) electrides for [YCl](+).e-and [ScCl](+).e(-) and one-dimensional (1D) electrides for [Y2Cl3](+).e(-), [Sc7Cl10](+).e(-), and [Sc5Cl8](2+). 2(e-) with divalent metal elements (Sc2+:3d(1) and Y2+:4d(1)). The localized anionic electrons were confined within the inner-layer spaces, rather than inter-layer spaces that are observed in A(2)B-type 2D electrides, e.g. Ca2N. Moreover, when hydrogen atoms are introduced into the host structures to form YClH and Y2Cl3H, the generated phases transform to conventional ionic compounds but exhibited a surprising reduction of work function, arising from the increased Fermi level energy, contrary to the conventional electrides reported so far. Y2Cl3 was experimentally confirmed to be a semiconductor with a band gap of 1.14 eV. These results may help to promote the rational design and discovery of new electride materials for further technological applications

Identifying quasi-2D and 1D electrides in yttrium and scandium chlorides via geometrical identification

Electride materials: geometrical identification Ab initio calculations identify a class of rare earth yttrium and scandium chloride electrides. A team led by Huiyang Gou at Center for High Pressure Science and Technology Advanced Research and Hideo Hosono at Tokyo Institute of Technology developed a materials screening strategy based on geometrical identification and high-throughput ab initio calculations to identify yttrium and scandium chlorides with various stoichiometries and compositions as a new class of quasi-2D and quasi-1D electrides. These materials were found to have distinctive features such as an R-Cl close-packed structure (R being Y or Sc), and an octahedral framework topology. The analyzed electrides were ferromagnetic, with the exception of Y2Cl3, which was found to be a semiconductor with an experimentally measured bandgap of 1.14 eV. When hydrogen atoms were introduced in the structures, a reduction of work function was observed in the intercalated compounds

Manipulation of nonlinear optical responses in layered ferroelectric niobium oxide dihalides

Abstract Realization of highly tunable second-order nonlinear optical responses, e.g., second-harmonic generation and bulk photovoltaic effect, is critical for developing modern optical and optoelectronic devices. Recently, the van der Waals niobium oxide dihalides are discovered to exhibit unusually large second-harmonic generation. However, the physical origin and possible tunability of nonlinear optical responses in these materials remain to be unclear. In this article, we reveal that the large second-harmonic generation in NbOX 2 (X = Cl, Br, and I) may be partially contributed by the large band nesting effect in different Brillouin zone. Interestingly, the NbOCl2 can exhibit dramatically different strain-dependent bulk photovoltaic effect under different polarized light, originating from the light-polarization-dependent orbital transitions. Importantly, we achieve a reversible ferroelectric-to-antiferroelectric phase transition in NbOCl2 and a reversible ferroelectric-to-paraelectric phase transition in NbOI2 under a certain region of external pressure, accompanied by the greatly tunable nonlinear optical responses but with different microscopic mechanisms. Our study establishes the interesting external-field tunability of NbOX 2 for nonlinear optical device applications