Gamma rays from microquasars Cygnus X-1 and Cygnus X-3

Gamma-ray observations of microquasars at high and very-high energies can provide valuable information of the acceleration processes inside the jets, the jet-environment interaction and the disk-jet coupling. Two high-mass microquasars have been deeply studied to shed light on these aspects: Cygnus X-1 and Cygnus X-3. Both systems display the canonical hard and soft X-ray spectral states of black hole transients, where the radiation is dominated by non-thermal emission from the corona and jets and by thermal emission from the disk, respectively. Here, we report on the detection of Cygnus X-1 above 60 MeV using 7.5 yr of Pass8 Fermi-LAT data, correlated with the hard X-ray state. A hint of orbital flux modulation was also found, as the source is only detected in phases around the compact object superior conjunction. We conclude that the high-energy gamma-ray emission from Cygnus X-1 is most likely associated with jets and its detection allow us to constrain the production site. Moreover, we include in the discussion the final results of a MAGIC long-term campaign on Cygnus X-1 that reaches almost 100 hr of observations at different X-ray states. On the other hand, during summer 2016, Cygnus X-3 underwent a flaring activity period in radio and high-energy gamma rays, similar to the one that led to its detection in the high-energy regime in 2009. MAGIC performed comprehensive follow-up observations for a total of about 70 hr. We discuss our results in a multi-wavelength context.Comment: Proceedings of the 35th International Cosmic Ray Conference (ICRC 2017), Bexco, Busan, Korea (arXiv:1708.05153

Effectiveness of Statins as Primary Prevention in People With Different Cardiovascular Risk: A Population-Based Cohort Study

The purpose was to analyze statin effectiveness in a general population with differing levels of coronary heart disease (CHD) risk. Patients (35-74 years) without previous cardiovascular disease were included and stratified according to 10-year CHD risk ( < 5%, 5-7.4%, 7.5-9.9%, and 10-19.9%). New users were categorized according to their medical possession ratio (MPR). The main outcome was atherosclerotic cardiovascular disease (ASCVD) (myocardial infarction and ischemic stroke). In adherent patients (MPR 70%), statin treatment decreased ASCVD risk across the range of coronary risk (from 16-30%). The 5-year number needed to treat (NNT) was 470 and 204 in the risk categories < 5% and 5-7.4%, respectively, and 75 and 62 in the 7.5-9.9% category than in the 10-19.9% category, respectively. Statin therapy should remain a priority in patients at high 10-year CHD risk (10-19.9%). Most patients with intermediate risk could benefit from statin treatment, but the treatment decision should focus on the net benefit, safety, and patient preference, given the higher NNT

A population pharmacokinetic model to predict the individual starting dose of tacrolimus in adult renal transplant recipients

Aims: The aims of this study were to describe the pharmacokinetics of tacrolimus immediately after kidney transplantation, and to develop a clinical tool for selecting the best starting dose for each patient. Methods: Data on tacrolimus exposure were collected for the first 3 months following renal transplantation. A population pharmacokinetic analysis was conducted using nonlinear mixed-effects modelling. Demographic, clinical and genetic parameters were evaluated as covariates. Results: A total of 4527 tacrolimus blood samples collected from 337 kidney transplant recipients were available. Data were best described using a two-compartment model. The mean absorption rate was 3.6 h-1 , clearance was 23.0 l h-1 (39% interindividual variability, IIV), central volume of distribution was 692 l (49% IIV) and the peripheral volume of distribution 5340 l (53% IIV). Interoccasion variability was added to clearance (14%). Higher body surface area (BSA), lower serum creatinine, younger age, higher albumin and lower haematocrit levels were identified as covariates enhancing tacrolimus clearance. Cytochrome P450 (CYP) 3A5 expressers had a significantly higher tacrolimus clearance (160%), whereas CYP3A4*22 carriers had a significantly lower clearance (80%). From these significant covariates, age, BSA, CYP3A4 and CYP3A5 genotype were incorporated in a second model to individualize the tacrolimus starting dose: [Formula: see text] Both models were successfully internally and externally validated. A clinical trial was simulated to demonstrate the added value of the starting dose model. Conclusions: For a good prediction of tacrolimus pharmacokinetics, age, BSA, CYP3A4 and CYP3A5 genotype are important covariates. These covariates explained 30% of the variability in CL/F. The model proved effective in calculating the optimal tacrolimus dose based on these parameters and can be used to individualize the tacrolimus dose in the early period after transplantation

Autonomic nervous system assessment in critically ill patients undergoing a cognitive rehabilitation therapy

Recent clinical and electrophysiological studies reveal a high incidence of autonomic nervous system (ANS) dysfunction in patients treated in Intensive Care Units (ICUs). Cognitive rehabilitation (CR) is a behavioral therapy that has proven to be effective improving cognitive deficits in clinical populations with abnormalities in brain activation patterns. A total of 17 critically ill patients received CR aimed to improve the ANS status, which was quantified in terms of HRV. The CR included cognitive exercises aimed to improve prefrontal activation. HRV was obtained during pre-CR, CR and post-CR. Power in the low (PLF) and high (PHF) frequency bands related to sympathetic and parasympathetic systems was computed. PHF was obtained within a band centered at respiratory rate. Comparing with baseline values, 7 patients showed an increased PHF in post-CR, suggesting an increase of parasympathetic activity