Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

The microstructure of Cu In,Ga S2 solar cell absorber films prepared using three stage and two stage evaporation

The microstructure of three stage Cu poor Cu In,Ga S2 solar cell absorbers has been compared with that of two stage Cu rich absorbers using high resolution Transmission Electron Microscopy. It was found that the grains from three stage evaporation have more stacking faults, and most of the grain boundaries are irregular, such as sawtooth shaped. The grains from two stage evaporation have less defects, and the grain boundaries are straight. The difference of growth mechanisms between three stage and two stage evaporation are discussed and compared to the case of Cu In,Ga Se

Instantaneous preparation of CuIn S 1 x , Se x 2 films by means of sparks using microwave irradiation

CuIn S1 amp; 8722;x,Sex 2 CISSe films aimed at flexible solar cells were directly prepared on Ti foils from elemental In, Cu, S, and Se particle precursor using microwave irradiation. The formation of the CISSe phase was deduced from X ray diffraction XRD patterns. The 112 peaks of CISSe were well defined and the lattice con stants increased in direct proportion to the S S Se ratio almost satisfying Vegard s law. In particular, CuInSe2 was formed in the desired chalcopyrite lattice as indicated by the presence of 101 , 103 and 211 peaks in the XRD pattern. Porous surfaces and formation of by products were avoided by employing an evaporated In and Cu films instead of In and Cu particle

Direct synthesis of CuIn Sex, S1 x 2 films from elemental In, Cu, Se, S particle precursor films and its dependence on energy

CuIn Sex, S1 amp; 8722; x 2 films were prepared by means of non vacuum, instantaneous, direct synthesis from elemental In, Cu, Se and S particle precursor films by passing an electrical current with precise control through the metal substrate. For a constant reaction period of 1 s, unreacted elemental particles remained in the films for powers below 1 kV A, whereas the reaction to CuIn Sex, S1 amp; 8722; x 2 x 1 appeared to be complete at higher power. Chalcopyrite structure was observed in the range from 1.08 kV A to 1.24 kV A, the sphalerite structure appeared over 1.35 kV A. X ray diffraction shows single 112 peaks of CuIn Sex, S1 amp; 8722; x 2 and the peak position agreed with the nominal composition of the precursors

Electric properties of Cu poor and Cu rich Cu In,Ga S2 films after O2 annealing

We compare the fundamental electric properties of Cu poor and Cu rich Cu In,Ga S2 films before and after annealing, respectively. It has been found that the hole density of Cu poor films increases after annealing in a O2 S combined atmosphere, whereas annealing in S only does not produce a significant effect. We conclude that the oxygen is effective for the passivation of donor type defects in the Cu poor Cu In,Ga S2 films. In the case of Cu rich films, the hole density also increases with O2 S annealing. However, annealing in sulphur atmosphere no oxygen gas in this case has comparable consequences. These observations suggest fundamental differences in the incorporation mechanisms of oxygen and sulphur in both types of the film. A tentative model is presented, taking into account results from micro structural characterization of the film

Wide band gap Cu In,Ga S2 solar cells with the junction prepared on the rear surface of the three stage Cu deficient absorber films

Cu In,Ga S 2 CIGS solar cells were prepared from Cu deficient absorber films using a lift off process and then compared with CIGS solar cells prepared without using the lift off process. The lift off was achieved through sacrificial molybdenum layers and optimized by different modifications of the latter. We report on the properties of the detached surfaces in terms of their dependence on the composition of the films and compare them to those of the original upper surfaces. This comparison suggests the advantageous properties of the detached surfaces in terms of composition, absence of Cu deficient phases, and effective dopin

Rapid direct preparation of Cu2ZnSn S1 x,Sex 4 films using microwave irradiation

Cu2ZnSn S1 amp; 8722;x,Sex 4 CZTSSe solid solution films were prepared on Ti foils by means of non vacuum, instantaneous, direct synthesis from elemental Cu, Zn, Sn, S, and Se precursor films using microwave irradiation. XRD patterns and Raman scattering spectra show that the resulting films consist of CZTSe crystals. The lattice constants of CZTSSe decreased in direct proportion to the S S Se ratio almost satisfying Vegard s law. Resulting films were relatively compact and continuous in the inner par

Direct preparation of Cu2ZnSnSe4 films by microwave irradiation and its dependence on the Sn Sn Zn ratio

Cu2ZnSnSe4 CZTSe films with various Sn Sn Zn ratios were directly prepared on metallic Ti foils by microwave irradiation and their properties were investigated. The Sn Sn Zn ratio and Cu Sn Zn ratio of the precursor could be preserved by using a sealed container filled with 0.15 atm of Ar. Single phase CZTSe crystals with a kesterite stannite structure and without by products were observed with Sn Sn Zn ratios between 0.4 and 0.6. The hole densities of the Cu Zn Sn Se films are minimal lt;10 17 cm3 with Sn Sn Zn ratios ranging from 0.5 to 0.

The effect of sulphur pressure on the depth distribution of elements in Cu In,Ga S2 films

We have studied the deposition of Cu In,Ga S2 films for thin film solar cells. In this study, Cu In,Ga S2 films have been prepared with varied sulphur pressure. A sequential multi source evaporation process has been employed. Deposition of an In Ga S precursor layer was followed by the diffusion of Cu and S into the precursor layer. The depth profiles of the impurities O and C, and constituent elements In and Ga were investigated by secondary ion mass spectroscopy SIMS . Coevaporated films were measured for comparison and the concentrations of O, C, In, and Ga were almost constant throughout the film. In case of our sequential process, a higher Ga concentration inside the Cu In,Ga S2 layer and a lower one towards the surface has been confirmed. X ray diffraction XRD data also confirm the existence of two Cu In,Ga S2 layers with different Ga content. It has been found that the O concentration was constant in the bulk and maximum at the interface between Ga rich bottom layers and In rich surface layers with a decreased concentration next to the surface. On the other hand, C was also nearly constant in the bulk, but tended to increase in a layer close to the surface. A model of the incorporation of impurities will be proposed. The changes of concentrations of O, C, In, and Ga become less pronounced with increasing S pressure. This indicates that higher S partial pressure may promote the diffusion of the constituent elements and impurities in the film. A solar cell made from one of our Cu In,Ga S2 films showed an efficiency of 9.3 total area, no antireflection coating, effective band gapg1.52 e

Three stage evaporation of Cu In,Ga S2 solar cell absorber films without KCN treatment and Na control

Cu poor Cu In,Ga S2 films have been prepared by three stage sequential evaporation In,Ga S Cu S In,Ga S on Mo covered soda lime glass without Na control. The depth profiles of O and Na in the grown films were investigated by secondary ion mass spectroscopy SIMS . It has been found that the O concentration was constant in the bulk, and decreased close to the surface comparable to the case of the two stage process. The observed depth profile of Na resembles that of O. The correlation of the depth profiles between O and Na is again indicated. The efficiencies of solar cells from the O2 annealed Cu rich Cu In,Ga S2 films did not increase, but the efficiencies of some solar cells prepared from Cu poor Cu In,Ga S2 films increased when the absorber was annealed in oxygen. The best efficiency of a solar cell from our O2 annealed Cu poor Cu In,Ga S2 films was 9.3 no antireflection coating without KCN treatment and Na contro