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.

Water temperature affects aggressive interactions in a Neotropical cichlid fish

<div><p>ABSTRACT Changes in water temperature may affect the aggressive behavior of aquatic organisms, such as fish, either by changing some physiological mechanisms or by increasing the probability of encounters between individuals as a result of variation in their swimming activity. In our study, we evaluated the influence of increasing and decreasing temperature on the aggressive behavior of the Neotropical cichlid fish Cichlasoma paranaense. Firstly, we tested the critical thermal maximum (CTMax) tolerated by this species. Then, we tested the effect of decreasing or increasing the water temperature in 6o C (starting at 27° C) on the aggressive interactions of fish under isolation or housed in groups. We found a CTMax value of 39° C for C. paranaense. We also observe that a 6° C decrease in water temperature lowers swimming activity and aggressive interactions in both isolated and group-housed fish, as expected. On the other hand, the increase in temperature had no effect on the fish’s aggressive behavior, neither for isolated nor for grouped fish. We concluded that C. paranaense shows high tolerance to elevated temperatures and, in turn, it does not affect aggressive behavior. Nevertheless, we cannot dismiss possible effects of elevated temperatures on aggressive interactions over longer periods.</p></div

Combined Analysis of Neutrino and Antineutrino Oscillations at T2K

T2K reports its first results in the search for CP violation in neutrino oscillations using appearance and disappearance channels for neutrino- and antineutrino-mode beams. The data include all runs from January 2010 to May 2016 and comprise 7.482 ×10^(20) protons on target in neutrino mode, which yielded in the far detector 32 e-like and 135 μ-like events, and 7.471 × 10^(20) protons on target in antineutrino mode, which yielded 4 e-like and 66 μ-like events. Reactor measurements of sin(2)2θ(13) have been used as an additional constraint. The one-dimensional confidence interval at 90% for the phase δCP spans the range (−3.13, −0.39) for normal mass ordering. The CP conservation hypothesis (δCP = 0, π) is excluded at 90% C.L.ISSN:0031-9007ISSN:1079-711

1st Workshop on CP Studies and Non-standard Higgs Physics

There are many possibilities for new physics beyond the Standard Model that feature non-standard Higgs sectors. These may introduce new sources of CP violation, and there may be mixing between multiple Higgs bosons or other new scalar bosons. Alternatively, the Higgs may be a composite state, or there may even be no Higgs at all. These non-standard Higgs scenarios have important implications for collider physics as well as for cosmology, and understanding their phenomenology is essential for a full comprehension of electroweak symmetry breaking. This report discusses the most relevant theories which go beyond the Standard Model and its minimal, CP-conserving supersymmetric extension: two-Higgs-doublet models and minimal supersymmetric models with CP violation, supersymmetric models with an extra singlet, models with extra gauge groups or Higgs triplets, Little Higgs models, models in extra dimensions, and models with technicolour or other new strong dynamics. For each of these scenarios, this report presents an introduction to the phenomenology, followed by contributions on more detailed theoretical aspects and studies of possible experimental signatures at the LHC and other colliders.There are many possibilities for new physics beyond the Standard Model that feature non-standard Higgs sectors. These may introduce new sources of CP violation, and there may be mixing between multiple Higgs bosons or other new scalar bosons. Alternatively, the Higgs may be a composite state, or there may even be no Higgs at all. These non-standard Higgs scenarios have important implications for collider physics as well as for cosmology, and understanding their phenomenology is essential for a full comprehension of electroweak symmetry breaking. This report discusses the most relevant theories which go beyond the Standard Model and its minimal, CP-conserving supersymmetric extension: two-Higgs-doublet models and minimal supersymmetric models with CP violation, supersymmetric models with an extra singlet, models with extra gauge groups or Higgs triplets, Little Higgs models, models in extra dimensions, and models with technicolour or other new strong dynamics. For each of these scenarios, this report presents an introduction to the phenomenology, followed by contributions on more detailed theoretical aspects and studies of possible experimental signatures at the LHC and other colliders

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. Copyright © 2017 Massachusetts Medical Society