11 research outputs found

    Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

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    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.

    A new phylogeny for basal Trechnotheria and Cladotheria and affinities of South American endemic Late Cretaceous mammals

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    Mass Spectrometry

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    Photoionization Spectroscopy of Nucleobasesand Analogues in the Gas Phase UsingSynchrotron Radiation as Excitation LightSource

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    International audienceWe review here the photoionization and photoelectron spectroscopy ofthe gas phase nucleic acid bases adenine, thymine, uracil, cytosine, and guanine, aswell as the three base analogues 2-hydroxyisoquinoline, 2-pyridone, andδ-valerolactam in the vacuum ultraviolet (VUV) spectral regime. The chapterfocuses on experimental work performed with VUV synchrotron radiation andrelated ab initio quantum chemical calculations of higher excited states beyondthe ionization energy. After a general part, where experimental and theoreticaltechniques are described in detail, key results are presented by order of growingcomplexity in the spectra of the molecules. Here we concentrate on (1) the accuratedetermination of ionization energies of isolated gas phase NABs and investigationof the vibrational structure of involved ionic states, including their mutual vibroniccouplings, (2) the treatment of tautomerism after photoionization, in competitionwith other intramolecular processes, (3) the study of fragmentation of these molecularsystems at low and high internal energies, and (4) the study of the evolution ofthe covalent character of hydrogen bonding upon substitution, i.e., examination ofelectronic effects (acceptor, donor, etc.)

    Seven-Membered Rings

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    New synthetic methods to prepare seven-membered heterocyclic compounds containing one or more of the heteroatoms N, O, or S are covered. Aromatic systems containing at least one N atom were the focus of many reports. Research was often driven by the search for new bioactive heterocycles for use in medicinal chemistry and for the synthesis of natural products. Notable synthetic methods included transition metal-catalyzed, cycloaddition, ring-expansion, cascade-type, and C-H functionalization processes. A number of reviews in the field were also published

    Caring about microenvironments

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    Genus Gadus (Gadidae): Composition, distribution, and evolution of forms

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