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.

Constraining New Physics with Borexino Phase-II spectral data

We present a detailed analysis of the spectral data of Borexino Phase II, with the aim of exploiting its full potential to constrain scenarios beyond the Standard Model. In particular, we quantify the constraints imposed on neutrino magnetic moments, neutrino non-standard interactions, and several simplified models with light scalar, pseudoscalar or vector mediators. Our analysis shows perfect agreement with those performed by the collaboration on neutrino magnetic moments and neutrino non-standard interactions in the same restricted cases and expands beyond those, stressing the interplay between flavour oscillations and and flavour non-diagonal interaction effects for the correct evaluation of the event rates. For simplified models with light mediators we show the power of the spectral data to obtain robust limits beyond those previously estimated in the literature.Comment: 35 pages, 9 figures, 4 tables. Matches accepted versio

Global constraints on non-standard neutrino interactions with quarks and electrons

We derive new constraints on effective four-fermion neutrino non-standard interactions with both quarks and electrons. This is done through the global analysis of neutrino oscillation data and measurements of coherent elastic neutrino-nucleus scattering (CEvNS) obtained with different nuclei. In doing so, we include not only the effects of new physics on neutrino propagation but also on the detection cross section in neutrino experiments which are sensitive to the new physics. We consider both vector and axial-vector neutral-current neutrino interactions and, for each case, we include simultaneously all allowed effective operators in flavour space. To this end, we use the most general parametrization for their Wilson coefficients under the assumption that their neutrino flavour structure is independent of the charged fermion participating in the interaction. The status of the LMA-D solution is assessed for the first time in the case of new interactions taking place simultaneously with up quarks, down quarks, and electrons. One of the main results of our work are the presently allowed regions for the effective combinations of non-standard neutrino couplings, relevant for long-baseline and atmospheric neutrino oscillation experiments.Comment: 40 pages, 9 figures, 5 tables. This work updates and extends arXiv:1805.04530 and arXiv:2204.0301

Global constraints on non-standard neutrino interactions with quarks and electrons

Abstract We derive new constraints on effective four-fermion neutrino non-standard interactions with both quarks and electrons. This is done through the global analysis of neutrino oscillation data and measurements of coherent elastic neutrino-nucleus scattering (CEνNS) obtained with different nuclei. In doing so, we include not only the effects of new physics on neutrino propagation but also on the detection cross section in neutrino experiments which are sensitive to the new physics. We consider both vector and axial-vector neutral-current neutrino interactions and, for each case, we include simultaneously all allowed effective operators in flavour space. To this end, we use the most general parametrization for their Wilson coefficients under the assumption that their neutrino flavour structure is independent of the charged fermion participating in the interaction. The status of the LMA-D solution is assessed for the first time in the case of new interactions taking place simultaneously with up quarks, down quarks, and electrons. One of the main results of our work are the presently allowed regions for the effective combinations of non-standard neutrino couplings, relevant for long-baseline and atmospheric neutrino oscillation experiments

New and updated convex shape models of asteroids based on optical data from a large collaboration network

International audienc

New and updated convex shape models of asteroids based on optical data from a large collaboration network

status: publishe