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.

Innovative approach to identity management solution development for e-government at EU level

This paper presents the main aspects of research, analysis and design of the open identity management architecture for e-government development within GUIDE, a project financed by the 6FP of the EC. The most important identity management issues strongly influencing the European e-government development are briefly discussed. An emphasis is placed on the innovative interdisciplinary approach used in GUIDE, aimed at covering the whole range of technical, process, policy, legal and social identity management issues, and seeking to overcome the existing fragmentation of identity management initiatives. GUIDE brings together the European industrial, financial and technical market leaders in e-government solutions, as well as leading academic institutes of the relevant scientific disciplines. Through its scientific, technological and socio-economic goals GUIDE will contribute towards initiatives that will ultimately deliver multiple benefits to governments, citizens and businesses

Time of arrival estimation in pulsar-based navigation systems

This paper focuses on the Time of Arrival (TOA) estimation problem related to new application of pulsar signals for airplane-based navigation. The aim of the paper is to propose and evaluate a possible algorithm for TOA estimation that consists of epoch folding, filtering, CFAR detection, crosscorrelation and TOA calculation. The TOA estimation algorithm proposed is verified using real experimental data obtained from the Westerbork radio observatory in The Netherlands. The performance of the proposed TOA algorithm is evaluated in terms of SNR at the cross-correlator input and the TOA accuracy

Comparison of two Algorithms for signal detection in pulsar-based FSR

Two detection algorithms (heuristic and CFAR) for target detection in pulsar FSR are analyzed using the simulation approach. The simulation results are verified by processing of the experimental data obtained by the radio observatory Dwingeloo in the Netherlands. The simulation and experimental results proved that the CFAR detection algorithm is more effective than the heuristic algorithm and can be successfully used in a pulsar FSR system for protection of air space from unwanted air objects

Separation of Pulsar signals in FSR System

In this paper, one possible algorithm for target detection and velocity estimation in a pulsar FSR system is proposed. In this processing algorithm, two approaches for extraction of the target signal from the input mixture “direct pulsar signal + reradiated target signal” are studied and compared. The signal processing algorithm is evaluated by computer simulation