62 research outputs found

    Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

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    Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≄3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≄100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≄3 years, if baseline LDL-C is ≄100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

    Structural, Morphological, Optical, and Room Temperature Magnetic Characterization on Pure and Sm-Doped ZnO Nanoparticles

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    Nano crystalline Zn1-xSmxO, (0.00 ≀ x ≀ 0.10), were prepared by wet chemical coprecipitation method. The effect of samarium doping on the structural, morphological, optical, and magnetic properties of ZnO nanoparticles was examined by X-ray powder diffraction (XRD), Transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR), Ultraviolet-visible spectroscopy (UV) and M-H magnetic hysteresis. XRD analysis showed the hexagonal wurtzite structure of ZnO. The absence of Sm2O3 as separate phase may be attributed to the complete dissolving of samarium in ZnO lattice. The lattice parameters (a and c) of Zn1-xSmxO were calculated and they fluctuated with the increase of Sm doping which indicated that the structure of ZnO was perturbed by the doping of Sm. The crystallite size was computed for all the samples using Debye-Scherrer’s method. The crystallite size decreased with the increase of Sm doping. TEM micrographs revealed that the size and the shape of the ZnO nanocomposites were changed by modifying the doping level of samarium. FTIR analysis spectrum confirmed the formation of ZnO phase and revealed a peak shift between pure and Sm-doped ZnO. The band gap energy and Urbach energy were calculated for Zn1-xSmxO, (0.00 ≀ x ≀ 0.10). The band energy gaps of pure and Sm doped ZnO samples are in the range 2.6–2.98 eV. M-H hysteresis inspection, at room temperature, showed that the pure ZnO exhibited a ferromagnetic behavior incorporated with diamagnetic and paramagnetic contributions. Ferromagnetic behavior was reduced for the doped samples with x=0.01 and x=0.04. The samples with x=0.02 and 0.06 ≀ x ≀ 0.10 tend to be superparamagnetic. The saturation magnetization (Ms), the coercivity (Hc), and the retentivity (Mr) were recorded for Zn1-xSmxO, (0.00 ≀ x ≀ 0.10)

    Fractional-Order PID Controller Based on Immune Feedback Mechanism for Time-Delay Systems

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    The control of processes with time delays is crucial in process industries such as petrochemical, hydraulic, and manufacturing. It is a challenging task for automation engineers, as it may affect both phase and gain margins. In this case, a robust control system is preferred. This article presents a novel controller structure combining computational intelligence (CI) and fractional-order control. A fractional-order PID (FOPID) controller based on a bio-inspired immune feedback mechanism (IFM) is developed for controlling processes described as first-order plus time-delay systems (FOPTD). A genetic algorithm (GA) is used to optimize the controller parameters. Fractional-order control has been used to give extra flexibilities and an immune feedback mechanism for its self-adaptability. Numerical simulations are presented to validate the proposed control strategy in terms of reference tracking and disturbance rejection. Comparative simulation results with an immune integer-order PID controller are also included to demonstrate the efficiency of the proposed fractional-order method

    Are chitin synthases targets for antimicrobial compounds and sources of MAMPs in oomycetes?

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    National audienceChitin is a crystalline N-Acetyl-Glucosamine (GlcNAc) polymer that is essential to cell wall function in Fungi, and chitooligosaccharides derived from it are Microbe-Associated Molecular Patterns recognized by LysM-containing receptors. Whereas GlcNAc is usually a minor component in the cell wall of most oomycetes, large scale sequencing shows the presence of chitin synthase (CHS) genes in their genomes. We are interested in determining the biological role of oomycete, and their involvement in the generation of signals perceived by the plant cell. Our microbial models are Aphanomyces euteiches, a legume root parasite, and a Phytophthora parasitica strain pathogenic to tobacco. Whereas chitin has never been detected in P. parasitica, our data suggest that its CHS gene(s) play(s) an essential role. In A. euteiches, we recently showed that amorphous GlcNAc polymers (chitosaccharides) are involved in cell wall function (Badreddine et al 2008). We are now engaged in characterizing these chitosaccharides in order to determine their links to the other cell wall polymers, and to understand how the host plant Medicago truncatula distinguishes chitosaccharide-derived fragments from other microbial signals such as symbiotic Nod factors. Our approaches include 13C-NMR studies of the cell wall polysaccharides, purification of the chitosaccharides after sequential chemical and enzymatic hydrolyses, elicitation bioassays involving the measurement of reactive oxygen species and expression of defense-related genes, and genetic studies targeting candidate genes of the LysM-containing putative receptors family. Last data obtained on both the microbe and plant sides will be presented

    Physiological Impairment and Biochemical Modifications Induced by Triclosan in Mediterranean Mussels

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    The effects of pharmaceutical under aquatic biota are still not well established. In this investigation, we assessed the results of a common pharmaceutical’s, triclosan (TCS), treatment on physiological and biochemical status of the Mediterranean mussels. Filtration and respiration rates were statistically reduced after treatment with highest considered concentration TCS2 = 100 ”g·L−1. However, no modification (p > 0.05) was detected after treatment with TCS1 = 50 ”g·L−1. For biochemical responses, oxidative stress parameters including H2O2 level and antioxidant enzymes were enhanced following concentration in considered organs. In parallel, Malondialdheyde content was measured in mussels after TCS treatment and lipid peroxidation occurred at high TCS concentration. Neurotoxicity evaluated by acetylcholinesterase (AChE) activity was induced in gills and digestive glands after exposure to TCS2. Overall, physiological impairment, oxidative stress, lipid peroxidation and neurotoxicity could be induced by triclosan in mussels. The association of physiological and biochemical biomarkers constitute a useful tool to measure the impact of pharmaceuticals in marine organism

    Regional Variation across Canadian Centers in Radioiodine Administration for Thyroid Remnant Ablation in Well-Differentiated Thyroid Cancer Diagnosed in 2000–2010

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    Background. Use of radioactive iodine (RAI) ablation has been reported to vary significantly between studies. We explored variation in RAI ablation care patterns between seven thyroid cancer treatment centers in Canada. Methods. The Canadian Collaborative Network for Cancer of the Thyroid (CANNECT) is a collaborative registry to describe and analyze patterns of care for thyroid cancer. We analyzed data from seven participating centers on RAI ablation in patients diagnosed with well-differentiated (papillary and follicular) thyroid cancer between 2000 and 2010. We compared RAI ablation protocols including indications (based on TNM staging), preparation protocols, and administered dose. We excluded patients with known distant metastases at time of RAI ablation. Results. We included 3072 patients. There were no significant differences in TNM stage over time. RAI use increased in earlier years and then declined. The fraction of patients receiving RAI varied significantly between centers, ranging between 20–85% for T1, 44–100% for T2, 58–100% for T3, and 59–100% for T4. There were significant differences in the RAI doses between centers. Finally, there was major variation in the use of thyroid hormone withdrawal or rhTSH for preparation of RAI ablation. Conclusion. Our study identified significant variation in use of RAI for ablation in patients with well-differentiated thyroid cancer both between Canadian centers and over time
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