Aims
Iron deficiency (ID) is a common co‐morbidity in heart failure (HF), associated with impaired functional capacity, poor quality of life and increased morbidity and mortality. Treatment with ...intravenous (i.v.) ferric carboxymaltose (FCM) has shown improvements in functional capacity, symptoms and quality of life in stable HF patients with reduced ejection fraction. The effect of i.v. iron supplementation on morbidity and mortality in patients hospitalised for acute HF (AHF) and who have ID has yet to be established. The objective of the present article is to present the rationale and design of the AFFIRM‐AHF trial (ClinicalTrials.gov NCT02937454) which will investigate the effect of i.v. FCM (vs. placebo) on recurrent HF hospitalisations and cardiovascular (CV) mortality in iron‐deficient patients hospitalised for AHF.
Methods
AFFIRM‐AHF is a multicentre, randomised (1:1), double‐blind, placebo‐controlled trial which recruited 1100 patients hospitalised for AHF and who had iron deficiency ID defined as serum ferritin <100 ng/mL or 100–299 ng/mL if transferrin saturation <20%. Eligible patients were randomised (1:1) to either i.v. FCM or placebo and received the first dose of study treatment just prior to discharge for the index hospitalisation. Patients will be followed for 52 weeks. The primary outcome is the composite of recurrent HF hospitalisations and CV mortality. The main secondary outcomes include the composite of recurrent CV hospitalisations and CV mortality, recurrent HF hospitalisations and safety‐related outcomes.
Conclusion
The AFFIRM‐AHF trial will evaluate, compared to placebo, the effect of i.v. FCM on morbidity and mortality in iron‐deficient patients hospitalised for AHF.
Abstract
Aims
Patients with heart failure (HF) and iron deficiency experience poor health-related quality of life (HRQoL). We evaluated the impact of intravenous (IV) ferric carboxymaltose (FCM) vs. ...placebo on HRQoL for the AFFIRM-AHF population.
Methods and results
The baseline 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12), which was completed for 1058 (535 and 523) patients in the FCM and placebo groups, respectively, was administered prior to randomization and at Weeks 2, 4, 6, 12, 24, 36, and 52. The baseline KCCQ-12 overall summary score (OSS) mean ± standard error was 38.7 ± 0.9 (FCM group) and 37.1 ± 0.8 (placebo group); corresponding values for the clinical summary score (CSS) were 40.9 ± 0.9 and 40.1 ± 0.9. At Week 2, changes in OSS and CSS were similar for FCM and placebo. From Week 4 to Week 24, patients assigned to FCM had significantly greater improvements in OSS and CSS scores vs. placebo adjusted mean difference (95% confidence interval, CI) at Week 4: 2.9 (0.5–5.3, P = 0.018) for OSS and 2.8 (0.3–5.3, P = 0.029) for CSS; adjusted mean difference (95% CI) at Week 24: 3.0 (0.3–5.6, P = 0.028) for OSS and 2.9 (0.2–5.6, P = 0.035) for CSS. At Week 52, the treatment effect had attenuated but remained in favour of FCM.
Conclusion
In iron-deficient patients with HF and left ventricular ejection fraction <50% who had stabilized after an episode of acute HF, treatment with IV FCM, compared with placebo, results in clinically meaningful beneficial effects on HRQoL as early as 4 weeks after treatment initiation, lasting up to Week 24.
Graphical Abstract
Atomically smooth hexagonal boron nitride (h-BN) layers have very useful properties and thus potential applications for protective coatings, deep ultraviolet (DUV) emitters, and as a dielectric for ...nanoelectronics devices. In this paper, we report on the growth of h-BN by a low-pressure chemical vapor deposition (LPCVD) process using diborane and ammonia as the gas precursors. The use of LPCVD allows synthesis of h-BN with a controlled number of layers defined by the growth conditions, temperature, time, and gas partial pressure. Furthermore, few-layer h-BN was also grown by a sequential growth method, and insights into the growth mechanism are described, thus forming the basis of future growth of h-BN by atomic layer epitaxy.
This review summarizes the current literature regarding the involvement and the putative role(s) of galectin-3 in post-myocardial infarction cardiac remodeling.
Post-myocardial infarction remodeling ...is characterized by acute loss of myocardium, which leads to structural and biomechanical changes in order to preserve cardiac function. A hallmark herein is fibrosis formation, both in the early and late phase following acute myocardial infarction. Galectin-3, a β-galactoside-binding lectin, which is a shared factor in fibrosis formation in multiple organs, has an established role in cardiac fibrosis in the setting of pressure overload, neuro-endocrine activation and hypertension, but its role in post- myocardial infarction remodeling has received less attention. However, accumulative experimental studies have shown that myocardial galectin-3 expression is upregulated after myocardial infarction, both on mRNA and protein level. This already occurs shortly after myocardial infarction in the infarcted and border zone area, and also at a later stage in the spared myocardium, contributing to tissue repair and fibrosis. This is associated with typical aspects of fibrosis formation, such as apposition of matricellular proteins and increased factors of collagen turnover. Interestingly, myocardial fibrosis in experimental post-myocardial infarction cardiac remodeling could be attenuated by galectin-3 inhibition. In clinical studies, circulating galectin-3 levels have been shown to identify patients at risk for new-onset heart failure and atrial fibrillation. Circulating galectin-3 levels also predict progressive left ventricular dilatation after myocardial infarction.
From literature we conclude that galectin-3 is an active player in cardiac remodeling after myocardial infarction. Future studies should focus on the dynamics of galectin-3 activation after myocardial infarction, and study the possibilities to target galectin-3.
We consider a new Stefan-type problem for the classical heat equation with a latent heat and phase-change temperature depending of the variable time. We prove the equivalence of this Stefan problem ...with a class of boundary value problems for the nonlinear canonical evolution equation involving a source term with two free boundaries. This equivalence is obtained by applying a reduction to a Burgers equation and a reciprocal-type transformations. Moreover, for a particular case, we obtain a unique explicit solution for the two different problems.
The Fuente de Piedra lake is a hypersaline wetland of great extension (13.5km2) and rich in aquatic birds and other species. It became therefore the third Spanish wetland to be included in the Ramsar ...convention and has been a “nature reserve” since 1984. The lake has an endorheic basin (150km2) with variable-density flows dominated by complex hydrogeological conditions. The traditional conceptualization of endorheic basins in semiarid climates considered that the brine in this hydric system was exclusively of evaporative origin and was placed only in the lake and its surrounding discharge area in the basin. Previous geophysical and hydrochemical studies identified different types of waters and brines. In this work, natural tracers (Cl−, Br−, Na+, Mg2+) and environmental isotopes (18O, 2H, 14C, 13C and 3H) were employed to a) discriminate different types of brines according to their degree of evaporation and genesis, and b) to estimate residence times of brine waters and identify recharge areas of the different flow subsystems. A conceptual model of the hydrogeological system of the lake basin and its links to a regional karst system is proposed.
Display omitted
•The existence a deep brine related with the karstic system of Chaotic Subbetic Complex (CSC), is proposed.•The deep brine of karstic system of CSC is due to dissolution of halite.•The recharge system would mainly in carbonate blocks.
We consider an optimal control problem
governed by an elliptic quasivariational inequality with unilateral constraints. We associate to
a new optimal control problem
obtained by perturbing the state ...inequality (including the set of constraints and the nonlinear operator) and the cost functional, as well. Then, we provide sufficient conditions which guarantee the convergence of solutions of Problem
to a solution of Problem
The proofs are based on convergence results for elliptic quasivariational inequalities, obtained by using arguments of compactness, lower semicontinuity, monotonicity, penalty and various estimates. Finally, we illustrate the use of the abstract convergence results in the study of optimal control associated with two boundary value problems. The first one describes the equilibrium of an elastic body in frictional contact with an obstacle, the so-called foundation. The process is static and the contact is modeled with normal compliance and unilateral constraint, associated to a version of Coulomb's law of dry friction. The second one describes a stationary heat transfer problem with unilateral constraints. For the two problems we prove existence, uniqueness and convergence results together with the corresponding physical interpretation.
Celotno besedilo
Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
•Diffusion equation for Caputo and Riemann-Liouville derivatives in time.•Explicit solutions to two different fractional two-phase Stefan-like problems are given.•Both solutions converge to the same ...classical solution (when a classical Stefan problem is recovered when the order of derivation in the time variable is 1).•Numerical examples for the dimensionless version of the problem are presented and analyzed.
Two fractional two-phase Stefan-like problems are considered by using Riemann-Liouville and Caputo derivatives of order α ∈ (0, 1) verifying that they coincide with the same classical Stefan problem at the limit case when α=1. For both problems, explicit solutions in terms of the Wright functions are presented. Even though the similarity of the two solutions, a proof that they are different is also given. The convergence when α↗1 of the one and the other solutions to the same classical solution is also given. Numerical examples for the dimensionless version of the problem are presented and analyzed.
Context. The optical light curve of Type Ia supernovae (SNIa) is powered by thermalized gamma-rays produced by the decay of 56Ni and 56Co, the main radioactive isotopes synthesized by the ...thermonuclear explosion of a C/O white dwarf. Aims. Gamma-rays escaping the ejecta can be used as a diagnostic tool for studying the characteristics of the explosion. In particular, it is expected that the analysis of the early gamma emission, near the maximum of the optical light curve, could provide information about the distribution of the radioactive elements in the debris. Methods. The gamma data obtained from SN2014J in M 82 by the instruments on board INTEGRAL were analysed paying special attention to the effect that the detailed spectral response has on the measurements of the intensity of the lines. Results. The 158 keV emission of 56Ni has been detected in SN2014J at ~5σ at low energy with both ISGRI and SPI around the maximum of the optical light curve. After correcting the spectral response of the detector, the fluxes in the lines suggest that, in addition to the bulk of radioactive elements buried in the central layers of the debris, there is a plume of 56Ni, with a significance of ~3σ, moving at high velocity and receding from the observer. The mass of the plume is in the range of ~0.03−0.08 M⊙. Conclusions. No SNIa explosion model has ever predicted the mass and geometrical distribution of 56Ni suggested here. According to its optical properties, SN2014J looks like a normal SNIa, so it is extremely important to discern whether it is also representative in the gamma-ray band.
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