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.

A multivariate analysis of risk factors influencing the cesarean section rate in two university hospitals in Leiden (the Netherlands) and Bandung (Indonesia)

[no abstract available

Impression de biomolécules par lithographie douce, applications pour les biopuces, de l échelle micrométrique à nanométrique

L objectif des travaux est de démontrer que la lithographie douce, quelquefois baptisée Micro-Contcat Printing ( CP) , constitue une méthode de dépôt de biomolécules présentant de nombreux avantages pour des applications de type Biopuces. Pour la fabrication de puces à ADN, nous démontrons que le CP est une technique compétitive par rapport au dépôt robotisé de gouttes traditionnellement utilisé. Le coût est inférieur, la densité des puces est augmentée et la qualité et la définition des motifs biomoléculaires sont supérieures. Une étude complète des mécanismes d encrage des timbres élastomères d impression ainsi que des mécanismes de transfert par contact des molécules vers le substrat est présentée. Le rôle prépondérant des fragments de polymère non réticulés présents à la surface des timbres est mis en évidence. Dans un second volet nous étudions la possibilité de générer par la même méthode des puces à biomolécules uniques. Nous montrons comment le CP peut être poussé jusqu à une résolution sub-micrométrique proche de 50 nm. Une voie technologique originale impliquant la lithographie douce est proposée : peigner individuellement en des sites organisés précisément sur la surface des longs brins d ADN pour des études de génétiqueThe main purpose of this research work is the demonstration that soft-lithography, very often called Micro-Contact Printing ( CP) is an efficient patterning technique for arranging biomolecules on a surface in the perspective of biochip applications. For DNA Micro-arrays applications, we demonstrate that CP is a competitive method compared to the conventional spotting technology, commonly used today. The cost of the technology is much lower, the surface density of the chip is drastically increased and the quality and definition of the biopatterns are greatly improved. A systematic study of the inking mechanisms of the elastomeric stamps is provided together with the study and comprehension of transfer mechanisms of molecules from the surface of the stamp to the substrate. The crucial role played by the free fragments of polymers not cross-linked during the polymerisation of the stamp is highlighted. In a second section we investigate the possibility of using CP for generating single biomolecule biochips. We show how this printing technique can be optimized for reaching sub-micrometric scale down to 50 nanometers features. A technological process involving soft-lithography is proposed: combing long DNA molecules on spatially organized and registered positions for genetic applicationsINIST-CNRS (INIST), under shelf-number: RP 17272 / SudocSudocFranceF

Transpiration of a mixed forest stand: field measurements and simulation using SVAT models

Transpiration of a mixed spruce-aspen-birch forest at the Valday Hills in Russia was determined using sap flow measurements and two different SVAT (Soil–Vegetation–Atmosphere-Transfer) models. The more sophisticated Mixed Forest multi-layer SVAT model (MF-SVAT) considers water uptake and transpiration of each tree species individually, and the simple Multi-Layer (ML-SVAT) describes the forest stand using averaged effective parameters of canopy structure and tree physiology. Comparisons of modelled and measured transpiration rates under sufficient soil moisture conditions did not show any significant differences between two models. Under limited soil moisture conditions MF-SVAT described forest transpiration still realistically whereas ML-SVAT overestimated it by up to 50%. Drought in the upper soil layers reduced transpiration of spruces more than of deciduous trees due to differences in physiological properties and vertical root distribution. Individual regulation of the transpiration of different tree species is typical for mixed forests and cannot be accurately described with averaged parameterisation such as used in ML-SVAT