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.

Measurement of the Mass of the Z-Boson and the Energy Calibration of Lep

Contains fulltext : 26847___.PDF (publisher's version ) (Open Access

Moral, direitos humanos e participação social Morality, human rights and social participation

Este artigo verifica a representação que universitários têm do seu envolvimento e do envolvimento do governo com os Direitos Humanos (DH), analisa a relação entre essa representação e variáveis psicossociais e compara alguns valores morais veiculados pela Rede Globo de Televisão à representação dos universitários. Para verificar as representações dos estudantes sobre os DH, foi realizado, baseado na teoria psicossociológica das representações sociais, um estudo com 93 universitários da UFPB e da UEPB. Os resultados revelaram que a representação do envolvimento possui quatro dimensões - pessoal-abstrato, pessoal-concreto, governamental-abstrato e governamental-concreto; o compromisso dos estudantes é maior com direitos individuais do que com direitos societais; a representação do envolvimento com os DH está ancorada, sobretudo, na identificação partidária e na participação desses estudantes em atividades sócio-políticas; e que existe uma similitude entre valores morais predominantes nos programas analisados e o tipo de artigo da Declaração Universal dos Direitos Humanos mais valorizado pelos estudantes.<br>This article analyzes the representation university students make of their own involvement and the involvement of the government with Human Rights (HR); it also analyzes the relationship between this representation and the psychosocial variables and compares some moral values transmitted by Rede Globo de Televisão (the most influential TV channel in Brazil) to the university students' representation. A study based on the psychosocial theory of the social representations was carried out with 93 university students from UFPB and UEPB in order to check the students' representation about HR. The results revealed that the representation of the involvement has four dimensions - the abstract-personal, the concrete-personal, the abstract-governmental and the concrete-governmental. It was found that the students' commitment with individual rights is stronger than with societal rights; the representation of the involvement with HR is mainly grounded on party affiliations and on the participation of these students in socio-political activities. There is also a similarity between the prevailing moral values of the TV programs under examination and the type of article of the Universal Declaration of Human Rights the students support more strongly

CIRCADIAN CLOCK-ASSOCIATED 1 regulates ROS homeostasis and oxidative stress responses

Organisms have evolved endogenous biological clocks as internal timekeepers to coordinate metabolic processes with the external environment. Here, we seek to understand the mechanism of synchrony between the oscillator and products of metabolism known as Reactive Oxygen Species (ROS) in Arabidopsis thaliana. ROS-responsive genes exhibit a time-of-day–specific phase of expression under diurnal and circadian conditions, implying a role of the circadian clock in transcriptional regulation of these genes. Hydrogen peroxide production and scavenging also display time-of-day phases. Mutations in the core-clock regulator, CIRCADIAN CLOCK ASSOCIATED 1 (CCA1), affect the transcriptional regulation of ROS-responsive genes, ROS homeostasis, and tolerance to oxidative stress. Mis-expression of EARLY FLOWERING 3, LUX ARRHYTHMO, and TIMING OF CAB EXPRESSION 1 affect ROS production and transcription, indicating a global effect of the clock on the ROS network. We propose CCA1 as a master regulator of ROS homeostasis through association with the Evening Element in promoters of ROS genes in vivo to coordinate time-dependent responses to oxidative stress. We also find that ROS functions as an input signal that affects the transcriptional output of the clock, revealing an important link between ROS signaling and circadian output. Temporal coordination of ROS signaling by CCA1 and the reciprocal control of circadian output by ROS reveal a mechanistic link that allows plants to master oxidative stress responses