Crackling Noise

Crackling noise arises when a system responds to changing external conditions through discrete, impulsive events spanning a broad range of sizes. A wide variety of physical systems exhibiting crackling noise have been studied, from earthquakes on faults to paper crumpling. Because these systems exhibit regular behavior over many decades of sizes, their behavior is likely independent of microscopic and macroscopic details, and progress can be made by the use of very simple models. The fact that simple models and real systems can share the same behavior on a wide range of scales is called universality. We illustrate these ideas using results for our model of crackling noise in magnets, explaining the use of the renormalization group and scaling collapses. This field is still developing: we describe a number of continuing challenges

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.

Evacetrapib and Cardiovascular Outcomes in High-Risk Vascular Disease

BACKGROUND: The cholesteryl ester transfer protein inhibitor evacetrapib substantially raises the high-density lipoprotein (HDL) cholesterol level, reduces the low-density lipoprotein (LDL) cholesterol level, and enhances cellular cholesterol efflux capacity. We sought to determine the effect of evacetrapib on major adverse cardiovascular outcomes in patients with high-risk vascular disease. METHODS: In a multicenter, randomized, double-blind, placebo-controlled phase 3 trial, we enrolled 12,092 patients who had at least one of the following conditions: an acute coronary syndrome within the previous 30 to 365 days, cerebrovascular atherosclerotic disease, peripheral vascular arterial disease, or diabetes mellitus with coronary artery disease. Patients were randomly assigned to receive either evacetrapib at a dose of 130 mg or matching placebo, administered daily, in addition to standard medical therapy. The primary efficacy end point was the first occurrence of any component of the composite of death from cardiovascular causes, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina. RESULTS: At 3 months, a 31.1% decrease in the mean LDL cholesterol level was observed with evacetrapib versus a 6.0% increase with placebo, and a 133.2% increase in the mean HDL cholesterol level was seen with evacetrapib versus a 1.6% increase with placebo. After 1363 of the planned 1670 primary end-point events had occurred, the data and safety monitoring board recommended that the trial be terminated early because of a lack of efficacy. After a median of 26 months of evacetrapib or placebo, a primary end-point event occurred in 12.9% of the patients in the evacetrapib group and in 12.8% of those in the placebo group (hazard ratio, 1.01; 95% confidence interval, 0.91 to 1.11; P=0.91). CONCLUSIONS: Although the cholesteryl ester transfer protein inhibitor evacetrapib had favorable effects on established lipid biomarkers, treatment with evacetrapib did not result in a lower rate of cardiovascular events than placebo among patients with high-risk vascular disease. (Funded by Eli Lilly; ACCELERATE ClinicalTrials.gov number, NCT01687998 .)

Multicenter pilot study of a serpentine balloon-expandable stent (beStent(TM)): Acute angiographic and clinical results

The beStent is a new stainless steel, balloon-expandable mesh stent which has a unique serpentine design. Rotation of the unique low stress junctions upon expansion leads to orthogonal locking of the wires, maximizing radial strength and assuring zero shortening. The stent has delineating gold markers which assure precise positioning. We aim to present the initial acute results in a pilot registry for stent evaluation. Two hundred eighty-four stents were used in a total of 217 patients (age 57.9 ± 3.10 years; 178 males; 39 females) in seven centers, for variable indications. Stents of 15-, 25-, and 35-mm length were used. The arteries treated were the left anterior descending (n = 112, 42%), circumflex (n = 54, 20.2%), right coronary (n = 95, 35.5%), left main (n = 1, 0.4%), and vein graft (n = 5, 1.9%). Lesion types were: A in 42 patients (16.5%); B1 in 53 patients (20.7%); B2 in 81 patients (31.8%); and C in 79 patients (31%). One hundred fifty-nine patients required one stent, 40 patients required two stents, and 18 patients required three or more stents. Anticoagulation protocol included procedural heparin with aspirin with/without ticlopidine. Smooth angiographie results were obtained in all cases with no plaque herniation. Acute angiographic success was obtained in 97% of the patients, and acute clinical success in 95% of the patients. Complications within 30 days were: 3 deaths (1.4%) (2 noncardiac); 2 (0.9%) myocardial infarctions; and 2 (0.9%) stent thromboses. Therefore, the beStent is useful in treatment of complex lesions of variable length and complexity, providing excellent acute results with a low complication rate, in spite of unfavorable basic clinical and angiographie characteristics

The Well London program--a cluster randomized trial of community engagement for improving health behaviors and mental wellbeing: baseline survey results.

BACKGROUND: The Well London program used community engagement, complemented by changes to the physical and social neighborhood environment, to improve physical activity levels, healthy eating, and mental wellbeing in the most deprived communities in London. The effectiveness of Well London is being evaluated in a pair-matched cluster randomized trial (CRT). The baseline survey data are reported here. METHODS: The CRT involved 20 matched pairs of intervention and control communities (defined as UK census lower super output areas (LSOAs); ranked in the 11% most deprived LSOAs in London by the English Indices of Multiple Deprivation) across 20 London boroughs. The primary trial outcomes, sociodemographic information, and environmental neighbourhood characteristics were assessed in three quantitative components within the Well London CRT at baseline: a cross-sectional, interviewer-administered adult household survey; a self-completed, school-based adolescent questionnaire; a fieldworker completed neighborhood environmental audit. Baseline data collection occurred in 2008. Physical activity, healthy eating, and mental wellbeing were assessed using standardized, validated questionnaire tools. Multiple imputation was used to account for missing data in the outcomes and other variables in the adult and adolescent surveys. RESULTS: There were 4,107 adults and 1,214 adolescent respondents in the baseline surveys. The intervention and control areas were broadly comparable with respect to the primary outcomes and key sociodemographic characteristics. The environmental characteristics of the intervention and control neighborhoods were broadly similar. There was greater between-cluster variation in the primary outcomes in the adult population compared to the adolescent population. Levels of healthy eating, smoking, and self-reported anxiety/depression were similar in the Well London adult population and the national Health Survey for England. Levels of physical activity were higher in the Well London adult population but this is likely to be due to the different measurement tools used in the two surveys. CONCLUSIONS: Randomization of social interventions such as Well London is acceptable and feasible and in this study the intervention and control arms are well-balanced with respect to the primary outcomes and key sociodemographic characteristics. The matched design has improved the statistical efficiency of the study amongst adults but less so amongst adolescents. Follow-up data collection will be completed 2012