New European guidelines for the management of dyslipidaemia in cardiovascular prevention

The new guidelines from the European Atherosclerosis Society and the European Society of Cardiology include a number of updated items. In this paper, we summarize 4 of these changes that we consider to be the most pertinent. Firstly, cardiovascular risk is now stratified according to 4 (previously 2) categories: "very high risk" (patients with cardiovascular disease, patients with diabetes > 40 years old who have at least one other risk factor, patients with kidney failure, or patients in primary prevention with a SCORE value > or = 10%); "high risk" (patients in primary prevention with a SCORE value > or = 5% and or = 1% and < 5%); and "low risk" (primary prevention with SCORE < 1%). The SCORE value for patients in primary prevention is estimated using the SCORE table (calibrated for Belgium). Risk in this table may now be corrected according to HDL cholesterol level. Secondly, the therapeutic targets for each category are now more stringent: LDL cholesterol < 70 mg/dl (or reduced by at least 50%) if the risk is "very high"; < 100 mg/dl if the risk is "high"; and < 115 mg/dl if the risk is "moderate". Thirdly, for patients at "high" or "very high" risk, particularly in patients with combined dyslipidaemia, two further therapeutic targets should be considered: non-HDL cholesterol and apolipoprotein B levels. Fourthly, the follow-up of efficacy (lipid profile) and tolerance (hepatic and muscular enzymes) is described in more details so as to harmonize case management in clinical practice.Peer reviewe

Culture of per-wound bone specimens: a simplified approach for the medical management of diabetic foot osteomyelitis

AbstractSurgical percutaneous bone biopsy specimen after a 14-day antibiotic-free period represents the gold standard of care for diabetic foot osteomyelitis but may be difficult to implement in many institutions. We evaluate a simplified strategy based on the results of per-wound bone specimen culture. For that purpose, we retrospectively reviewed the charts of 80 consecutive patients with diabetic osteomyelitis and bone sample obtained via the wound after a careful debridement. The outcome was defined as favourable if there was a complete healing of the wound with no sign of infection and stable or improved bone X-ray 6 months after antibiotic therapy completion. Culture of bone specimens was positive in 96% of patients, although half of the patients did receive a course of antimicrobials within 14 days of the bone specimen being obtained. A total of 129 bacterial isolates were obtained from bone cultures with a mean of 1.6 ± 1 isolates per patient (Staphylococcus aureus: 33%; coagulase-negative staphylococci: 14%; streptococci: 9%; enterococci: 12%; corynebacteria: 4%; Gram-negative bacilli: 20%; anaerobes: 4%). Forty-six percent of cultures were monomicrobial. The mean duration of follow-up from diagnosis was 17 ± 1 months. Six months after discontinuation of antibiotics, six patients (7.5%) had died, nine were considered as therapeutic failures and 65 were considered as cured. Fifty-four of these 65 patients had follow-up data available at 1 year and remained in remission. In conclusion, a simplified procedure based on the culture of bone sample obtained via the ulcer after a careful debridement of the wound is effective in the medical management of diabetic foot osteomyelitis

On the Stability of the Satellites of Asteroid 87 Sylvia

he triple asteroidal system (87) Sylvia is composed of a 280-km primary and two small moonlets named Romulus and Remus (Marchis et al 2005). Sylvia is located in the main asteroid belt. The satellites are in nearly equatorial circular orbits around the primary. In the present work we study the stability of the satellites Romulus and Remus, in order to identify the effects and the contribution of each perturber. The results from the 3-body problem, Sylvia-Romulus-Remus, show no significant variation of their orbital elements. However, the inclinations of the satellites present a long period evolution, when the Sun is included in the system. Such amplitude is amplified when Jupiter is included. An analysis of these results show that Romulus and Remus are librating in a secular resonance and their longitude of the nodes are locked to each other. The satellites get caught in an evection resonance with Jupiter. However, the orbital evolutions of the satellites became completely stable when the oblateness of Sylvia is included in the simulations.Comment: 11 pages, 8 figures and 1 tabl

Detecting a stochastic gravitational wave background with the Laser Interferometer Space Antenna

The random superposition of many weak sources will produce a stochastic background of gravitational waves that may dominate the response of the LISA (Laser Interferometer Space Antenna) gravitational wave observatory. Unless something can be done to distinguish between a stochastic background and detector noise, the two will combine to form an effective noise floor for the detector. Two methods have been proposed to solve this problem. The first is to cross-correlate the output of two independent interferometers. The second is an ingenious scheme for monitoring the instrument noise by operating LISA as a Sagnac interferometer. Here we derive the optimal orbital alignment for cross-correlating a pair of LISA detectors, and provide the first analytic derivation of the Sagnac sensitivity curve.Comment: 9 pages, 11 figures. Significant changes to the noise estimate

Evolocumab in pediatric heterozygous familial hypercholesterolemia

BACKGROUND Evolocumab, a fully human monoclonal antibody directed against proprotein convertase subtilisin–kexin type 9, is widely used in adult patients to lower low-density lipoprotein (LDL) cholesterol levels. Its effects in pediatric patients with heterozygous familial hypercholesterolemia are not known. METHODS We conducted a 24-week, randomized, double-blind, placebo-controlled trial to evaluate the efficacy and safety of evolocumab in pediatric patients with heterozygous familial hypercholesterolemia. Patients 10 to 17 years of age who had received stable lipid-lowering treatment for at least 4 weeks before screening and who had an LDL cholesterol level of 130 mg per deciliter (3.4 mmol per liter) or more and a triglyceride level of 400 mg per deciliter (4.5 mmol per liter) or less were randomly assigned in a 2:1 ratio to receive monthly subcutaneous injections of evolocumab (420 mg) or placebo. The primary end point was the percent change in LDL cholesterol level from baseline to week 24; key secondary end points were the mean percent change in LDL cholesterol level from baseline to weeks 22 and 24 and the absolute change in LDL cholesterol level from baseline to week 24. RESULTS A total of 157 patients underwent randomization and received evolocumab (104 patients) or placebo (53 patients). At week 24, the mean percent change from baseline in LDL cholesterol level was −44.5% in the evolocumab group and −6.2% in the placebo group, for a difference of −38.3 percentage points (P&lt;0.001). The absolute change in the LDL cholesterol level was −77.5 mg per deciliter (−2.0 mmol per liter) in the evolocumab group and −9.0 mg per deciliter (−0.2 mmol per liter) in the placebo group, for a difference of −68.6 mg per deciliter (−1.8 mmol per liter) (P&lt;0.001). Results for all secondary lipid variables were significantly better with evolocumab than with placebo. The incidence of adverse events that occurred during the treatment period was similar in the evolocumab and placebo groups. CONCLUSIONS In this trial involving pediatric patients with familial hypercholesterolemia, evolocumab reduced the LDL cholesterol level and other lipid variables

Multi-center evaluation of the hepatitis B surface antigen (HBsAg) assay and HbsAg confirmatory assay for the family of Access immunoassay systems

BACKGROUND: Accurate detection of Hepatitis B Surface Antigen (HBsAg) is an important aid in the diagnosis of patients infected with the hepatitis B virus (HBV). A multi-center study was conducted to characterize the performance of the HBsAg assay on the family of Access immunoassay systems from Beckman Coulter. METHODS: The Access HBsAg assay was characterized in a multi-center study and compared to the Abbott AxSYM* and PRISM* HBsAg assays. The bioMérieux VIDAS* assay was used to resolve discrepant results. Reproducibility studies (intra-assay, inter-assay and inter-lot) were performed with pooled serum samples (negative sample, close to cut off, low, medium and high positive samples). Analytical sensitivity, subtype and genotype detection were studied with various commercial panels (SFTS panel, WHO 80/549, WHO 00/588, Teragenix HBV Genotype panel). A panel of recombinant HBsAg mutant proteins was tested to investigate reactivity towards genetic mutations. Clinical sensitivity was verified with seroconversion panels and samples from subjects with known HBV infection. Analytical specificity was studied with samples from patients with potential cross-reactive infections. Clinical specificity was validated among blood donors and a hospitalized population. RESULTS: The imprecision was &lt; 10%. Analytical sensitivity was &lt; or = 0.1 ng/mL (SFTS panel), 0.020 PEI Units/mL (ad panel), 0.024 PEI Units/mL (ay panel), 0.092 IU/mL with WHO 80/549 and 0.056 IU/mL with WHO 00/588. All genotype samples and HBsAg mutants were reactive with the Access HBsAg assay. Seroconversion panels tested showed no significant difference with the reference method. Sensitivity for subjects with known HBV infection was 100%. No interference with potentially cross-reactive infections was observed after confirmatory testing. Specificity was 99.96% (100% after confirmatory testing) in a blood donor population and 99.5% (100% after confirmatory testing) in a hospitalized population. Excellent separation of positive and negative populations was observed. CONCLUSIONS: The Access HBsAg and HBsAg Confirmatory assays meet all clinical and analytical performance requirements of assays for the detection of HBsAg

Calibration and Characterization of the IceCube Photomultiplier Tube

Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube neutrino observatory. Many are placed deep in the ice to detect Cherenkov light emitted by the products of high-energy neutrino interactions, and others are frozen into tanks on the surface to detect particles from atmospheric cosmic ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu Photonics. This paper describes the laboratory characterization and calibration of these PMTs before deployment. PMTs were illuminated with pulses ranging from single photons to saturation level. Parameterizations are given for the single photoelectron charge spectrum and the saturation behavior. Time resolution, late pulses and afterpulses are characterized. Because the PMTs are relatively large, the cathode sensitivity uniformity was measured. The absolute photon detection efficiency was calibrated using Rayleigh-scattered photons from a nitrogen laser. Measured characteristics are discussed in the context of their relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure

Lateral Distribution of Muons in IceCube Cosmic Ray Events

In cosmic ray air showers, the muon lateral separation from the center of the shower is a measure of the transverse momentum that the muon parent acquired in the cosmic ray interaction. IceCube has observed cosmic ray interactions that produce muons laterally separated by up to 400 m from the shower core, a factor of 6 larger distance than previous measurements. These muons originate in high pT (> 2 GeV/c) interactions from the incident cosmic ray, or high-energy secondary interactions. The separation distribution shows a transition to a power law at large values, indicating the presence of a hard pT component that can be described by perturbative quantum chromodynamics. However, the rates and the zenith angle distributions of these events are not well reproduced with the cosmic ray models tested here, even those that include charm interactions. This discrepancy may be explained by a larger fraction of kaons and charmed particles than is currently incorporated in the simulations

Search for Relativistic Magnetic Monopoles with IceCube

We present the first results in the search for relativistic magnetic monopoles with the IceCube detector, a subsurface neutrino telescope located in the South Polar ice cap containing a volume of 1 km$^{3}$. This analysis searches data taken on the partially completed detector during 2007 when roughly 0.2 km$^{3}$ of ice was instrumented. The lack of candidate events leads to an upper limit on the flux of relativistic magnetic monopoles of \Phi_{\mathrm{90%C.L.}}\sim 3\e{-18}\fluxunits for $\beta\geq0.8$. This is a factor of 4 improvement over the previous best experimental flux limits up to a Lorentz boost $\gamma$ below $10^{7}$. This result is then interpreted for a wide range of mass and kinetic energy values.Comment: 11 pages, 11 figures. v2 is minor text edits, no changes to resul