Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Faulted craters as indicators for thrust motion on Mercury

Craters cross-cut by faults are used as markers to obtain fault geometric and kinematic properties. Assuming that the shape of these craters was originally circular, it is possible to measure the horizontal and vertical components of fault displacement as well as the slip trend. By applying trigonometric relations, slip plunge, displacement magnitude, fault true dip and fault rake can be derived from the observed values. An example application of this method on craters faulted by lobate scarps on Mercury shows that most of these inferred reverse faults have moderate oblique-slip trends. Moreover, the derived dips of thrusts vary over a wide range of angles. Some preliminary results in terms of fault rake compared with fault dip, strike and latitude are presented together with a pilot study to test and discriminate global tectonic models suggested for the evolution of Mercury. The possibility of estimating quantitative fault parameters through remotely sensed data provides significant assistance in the structural characterization of faults on planetary surfaces

Planck intermediate results. XVI. Profile likelihoods for cosmological parameters

We explore the 2013 Planck likelihood function with a high-precision multi-dimensional minimizer (Minuit). This allows a refinement of the LambdaCDM best-fit solution with respect to previously-released results, and the construction of frequentist confidence intervals using profile likelihoods. The agreement with the cosmological results from the Bayesian framework is excellent, demonstrating the robustness of the Planck results to the statistical methodology. We investigate the inclusion of neutrino masses, where more significant differences may appear due to the non-Gaussian nature of the posterior mass distribution. By applying the Feldman-Cousins prescription, we again obtain results very similar to those of the Bayesian methodology. However, the profile-likelihood analysis of the cosmic microwave background (CMB) combination (Planck+WP+highL) reveals a minimum well within the unphysical negative-mass region. We show that inclusion of the Planck CMB-lensing information regularizes this issue, and provide a robust frequentist upper limit 11 mnu <= 0.26 eV (95% confidence) from the CMB+lensing+BAO data combination

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be ns = 0.9603 \ub1 0.0073, ruling out exact scale invariance at over 5sigma.Planck establishes an upper bound on the tensor-to-scalar ratio of r= 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dns/ dlnk = - 0.0134 \ub1 0.0090. We verify these conclusions through a numerical analysis, which makes no slow-roll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by Deltachi2eff 48 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the chi2eff by approximately 4 as a result of slightly lowering the theoretical prediction for the l 72 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions

Planck intermediate results. III. The relation between galaxy cluster mass and Sunyaev-Zeldovich signal

We examine the relation between the galaxy cluster mass M and Sunyaev-Zeldovich (SZ) effect signal DA2 Y500 for a sample of 19 objects for which weak lensing (WL) mass measurements obtained from Subaru Telescope data are available in the literature. Hydrostatic X-ray masses are derived from XMM-Newton archive data, and the SZ effect signal is measured from Planck all-sky survey data. We find an MWL - DA2 Y500 relation that is consistent in slope and normalisation with previous determinations using weak lensing masses; however, there is a normalisation offset with respect to previous measures based on hydrostatic X-ray mass-proxy relations. We verify that our SZ effect measurements are in excellent agreement with previous determinations from Planck data. For the present sample, the hydrostatic X-ray masses at R500 are on average ~ 20 percent larger than the corresponding weak lensing masses, which is contrary to expectations. We show that the mass discrepancy is driven by a difference in mass concentration as measured by the two methods and, for the present sample, that the mass discrepancy and difference in mass concentration are especially large for disturbed systems. The mass discrepancy is also linked to the offset in centres used by the X-ray and weak lensing analyses, which again is most important in disturbed systems. We outline several approaches that are needed to help achieve convergence in cluster mass measurement with X-ray and weak lensing observations

Abstracts from the 23rd Italian congress of Cystic Fibrosis and the 13th National congress of Cystic Fibrosis Italian Society

Cystic Fibrosis (CF) occurs most frequently in caucasian populations. Although less common, this disorder have been reported in all the ethnicities. Currently, there are more than 2000 described sequence variations in CFTR gene, uniformly distributed and including variants pathogenic and benign (CFTR1:www.genet.sickkids.on.ca/). To date,only a subset have been firmily established as variants annotated as disease-causing (CFTR2: www.cftr2.org). The spectrum and the frequency of individual CFTR variants, however, vary among specific ethnic groups and geographic areas. Genetic screening for CF with standard panels of CFTR mutations is widely used for the diagnosis of CF in newborns and symptomatic patients, and to diagnose CF carrier status. These screening panels have an high diagnostic sensitivity (around 85%) for CFTR mutations in caucasians populations but very low for non caucasians. Developed in the last decade, Next-Generation Sequencing (NGS) has been the last breakthrough technology in genetic studies with a substantial reduction in cost per sequenced base and a considerable enhancement of the sequence generation capabilities. Extended CFTR gene sequencing in NGS includes all the coding regions, the splicing sites and their flankig intronic regions, deep intronic regions where are localized known mutations,the promoter and the 5'-3' UTR regions. NGS allows the analysis of many samples concurrently in a shorter period of time compared to Sanger method . Moreover, NGS platforms are able to identify CFTR copy number variation (CNVs), not detected by Sanger sequencing. This technology has provided new and reliable approaches to molecular diagnosis of CF and CFTR-Related Disorders. It also allows to improve the diagnostic sensitivity of newborn and carrier screeningmolecular tests. In fact, bioinformatics tools suitable for all the NGS platforms can filter data generated from the gene sequencing, and analyze only mutations with well-established disease liability. This approach allows the development of targeted mutations panels with a higher number of frequent CF mutations for the target populationcompared to the standard panels and a consequent enhancement of the diagnostic sensitivity. Moreover, in the emerging challenge of diagnosing CF in non caucasians patients, the possibility of customize a NGS targeted mutations panel should increase the diagnostic sensitivity when the target population has different ethnicities

Memoria 1980

El día 23 de julio de 1980 tomó posesión de su cargo el nuevo Presidente del C.S.I.C. D. Alejandro Nieto. Después de un breve acto en la Sala de Juntas del Ministerio de Universidades e Investigación -en el que, con asistencia de los altos cargos del Departamento y numerosos miembros del C.S.I.C, intervinieron el Ministro, D. Luis Gonzalez Seara, y el Presidente saliente, D. Carlos Sánchez del Reo-, se traslado el Sr. Nieto a la Sala de Juntas del Consejo, donde estaban convocados los componentes de la Junta de Gobierno y de las Comisiones Científica y Económica del C.S.I.C. Ante ellos expuso un programa de actuación, del que aquí se entresacan las líneas más relevantes.N

Planck 2013 results. XX. Cosmology from Sunyaev-Zeldovich cluster counts

We present constraints on cosmological parameters using number counts as a function of redshift for a sub-sample of 189 galaxy clusters from the Planck SZ (PSZ) catalogue. The PSZ is selected through the signature of the Sunyaev-Zeldovich (SZ) effect, and the sub-sample used here has a signal-to-noise threshold of seven, with each object confirmed as a cluster and all but one with a redshift estimate. We discuss the completeness of the sample and our construction of a likelihood analysis. Using a relation between mass M and SZ signal Y calibrated to X-ray measurements, we derive constraints on the power spectrum amplitude sigma8 and matter density parameter Omega_m in a flat Lambda CDM model. We test the robustness of our estimates and find that possible biases in the Y-M relation and the halo mass function are larger than the statistical uncertainties from the cluster sample. Assuming the X-ray determined mass to be biased low relative to the true mass by between zero and 30%, motivated by comparison of the observed mass scaling relations to those from a set of numerical simulations, we find that sigma8 = 0.75 \ub1 0.03, Omega_m = 0.29 \ub1 0.02, and sigma8(Omegam/ 0.27)0.3 = 0.764 \ub1 0.025. The value of sigma8 is degenerate with the mass bias; if the latter is fixed to a value of 20% (the central value from numerical simulations) we find sigma8(Omega_m/0.27)0.3 = 0.78 \ub1 0.01 and a tighter one-dimensional range sigma8 = 0.77 \ub1 0.02. We find that the larger values of sigma8 and Omegam preferred by Planck's measurements of the primary CMB anisotropies can be accommodated by a mass bias of about 40%. Alternatively, consistency with the primary CMB constraints can be achieved by inclusion of processes that suppress power on small scales relative to the LambdaCDM model, such as a component of massive neutrinos. We place our results in the context of other determinations of cosmological parameters, and discuss issues that need to be resolved in order to make further progress in this field

Planck intermediate results IV. The XMM-Newton validation programme for new Planck galaxy clusters

We present the final results from the XMM-Newton validation follow-up of new Planck galaxy cluster candidates. We observed 15 new candidates, detected with signal-to-noise ratios between 4.0 and 6.1 in the 15.5-month nominal Planck survey. The candidates were selected using ancillary data flags derived from the ROSAT All Sky Survey (RASS) and Digitized Sky Survey all-sky maps, with the aim of pushing into the low SZ flux, high-z regime and testing RASS flags as indicators of candidate reliability. Fourteen new clusters were detected by XMM-Newton, ten single clusters and two double systems. Redshifts from X-ray spectroscopy lie in the range 0.2 to 0.9, with six clusters at z > 0.5. Estimated masses (M-500) range from 2.5 x 10(14) to 8 x 10(14) M-circle dot. We discuss our results in the context of the full XMM-Newton validation programme, in which 51 new clusters have been detected. This includes four double and two triple systems, some of which are chance projections on the sky of clusters at different redshifts. We find that association with a source from the RASS-Bright Source Catalogue is a robust indicator of the reliability of a candidate, whereas association with a source from the RASS-Faint Source Catalogue does not guarantee that the SZ candidate is a bona fide cluster. Nevertheless, most Planck clusters appear in RASS maps, with a significance greater than 2 sigma being a good indication that the candidate is a real cluster. Candidate validation from association with SDSS galaxy overdensity at z > 0.5 is also discussed. The full sample gives a Planck sensitivity threshold of Y-500 similar to 4 x 10(-4) arcmin(2), with indication for Malmquist bias in the YX-Y500 relation below this threshold. The corresponding mass threshold depends on redshift. Systems with M-500 > 5 x 10(14) M-circle dot at z > 0.5 are easily detectable with Planck. The newly-detected clusters follow the Y-X-Y-500 relation derived from X-ray selected samples. Compared to X-ray selected clusters, the new SZ clusters have a lower X-ray luminosity on average for their mass. There is no indication of departure from standard self-similar evolution in the X-ray versus SZ scaling properties. In particular, there is no significant evolution of the Y-X/Y-500 ratio