Fabry Disease and the Heart: A Comprehensive Review

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene that result in a deficiency of the enzymatic activity of α-galactosidase A and consequent accumulation of glycosphingolipids in body fluids and lysosomes of the cells throughout the body. GB3 accumulation occurs in virtually all cardiac cells (cardiomyocytes, conduction system cells, fibroblasts, and endothelial and smooth muscle vascular cells), ultimately leading to ventricular hypertrophy and fibrosis, heart failure, valve disease, angina, dysrhythmias, cardiac conduction abnormalities, and sudden death. Despite available therapies and supportive treatment, cardiac involvement carries a major prognostic impact, representing the main cause of death in FD. In the last years, knowledge has substantially evolved on the pathophysiological mechanisms leading to cardiac damage, the natural history of cardiac manifestations, the late-onset phenotypes with predominant cardiac involvement, the early markers of cardiac damage, the role of multimodality cardiac imaging on the diagnosis, management and follow-up of Fabry patients, and the cardiac efficacy of available therapies. Herein, we provide a comprehensive and integrated review on the cardiac involvement of FD, at the pathophysiological, anatomopathological, laboratory, imaging, and clinical levels, as well as on the diagnosis and management of cardiac manifestations, their supportive treatment, and the cardiac efficacy of specific therapies, such as enzyme replacement therapy and migalastat.     

The Contribution of Small Vessel Disease to Neurodegeneration: Focus on Alzheimer’s Disease,Parkinson’s Disease and Multiple Sclerosis

Brain small vessel disease (SVD) refers to a variety of structural and functional changes affecting small arteries and micro vessels, and manifesting as white matter changes, microbleeds and lacunar infarcts. Growing evidence indicates that SVD might play a significant role in the neurobiology of central nervous system (CNS) neurodegenerative disorders, namely Alzheimer’s disease (AD) and Parkinson’s disease (PD), and neuroinflammatory diseases, such as multiple sclerosis (MS). These disorders share different pathophysiological pathways and molecular mechanisms (i.e., protein misfolding, derangement of cellular clearance systems, mitochondrial impairment and immune system activation) having neurodegeneration as biological outcome. In these diseases, the actual contribution of SVD to the clinical picture, and its impact on response to pharmacological treatments, is not known yet. Due to the high frequency of SVD in adult-aged patients, it is important to address this issue. In this review, we report preclinical and clinical data on the impact of SVD in AD, PD and MS, with the main aim of clarifying the predictability of SVD on clinical manifestations and treatment response.     

Detection of water ingress in composite sandwich structures: a magnetic resonance approach

Water ingress inside honeycomb sandwich panels during service has been linked to in-flight failure in some aircraft. There is an ongoing effort to develop nondestructive testing methods to detect the presence of water within the panels. Magnetic resonance (MR) represents an attractive approach in that it is sensitive to moisture. Using a unilateral MR sensor, testing can be applied directly to the surface of the panel. The viability of MR is demonstrated through laboratory imaging of both water within sandwich panels, as well as the adhesive itself. The detection of water using a one-sided handheld MR sensor is presented. It is shown that simple detection, as well as spatial localization of water within sandwich panels is possible.     

Comparison of a contactor catalytic membrane reactor with a conventional reactor: example of wet air oxidation

A wet air oxidation reaction was carried out in a gas/liquid catalytic membrane reactor of the contactor type. The oxidation of formic acid was used as a model reaction. The mesoporous top-layer of a ceramic tubular membrane was used as catalyst (Pt) support, and was placed at the interface of the gas (air) and liquid (HCOOH solution) phases.

A similar reaction was carried out in a conventional batch reactor, using a steering rate high enough to avoid gas-diffusion limitations, and exactly identical conditions than for the CMR (amount of catalyst, pressure, etc.). At room temperature, the CMR showed an initial activity three to six times higher than the conventional reactor. This activity increase was attributed to an easier oxygen access to the catalytic sites. Nevertheless, the catalytic membrane gradually deactivated after a few hours of operation. Different deactivation mechanisms are presented.     

A unified method for optimal arbitrary pole placement

We consider the classic problem of pole placement by state feedback. We offer an eigenstructure assignment algorithm to obtain a novel parametric form for the pole-placing feedback matrix that can deliver any set of desired closed-loop eigenvalues, with any desired multiplicities. This parametric formula is then exploited to introduce an unconstrained nonlinear optimisation algorithm to obtain a feedback matrix that delivers the desired pole placement with optimal robustness and minimum gain. Lastly we compare the performance of our method against several others from the recent literature.     

Cable-direct-driven-robot (CDDR) with a 3-link passive serial support

Cable-direct-driven-robots (CDDRs) provided with a passive serial support represent an interesting and rising evolution of planar cable robots. The paper is devoted to present and analyze a novel CDDR robot. The robot consists in a fully actuated CDDR supported against loading normal to the motion plane with a 3-link passive planar serial manipulator. This hybrid structure combines positive features of both parallel and serial architectures, and prevents out-of-plane movements without the necessity for the robot to be supported on the motion plane. The adoption of a 3-link serial manipulator ensures a greater workspace area compared with similar structures that adopt a smaller number of links, and improves specific characteristics of their dynamics. Nevertheless undesired oscillations may occur since the serial manipulator is underconstrained. For this reason damping elements are inserted in the structure. Simulation examples are presented to demonstrate the novel CDDR concept and its dynamics. In addition, a strategy to select proper values of damping coefficients is presented.     

A molecular level mechanism ofn-butane oxidation to maleic anhydride over vanadyl pyrophosphate

A molecular level mechanism is proposed for the highly selective 14-e^– oxidative transformation ofn-butane to maleic anhydride on the surface of vanadyl pyrophosphate. The mechanism suggests that the dimeric active sites assume at any given time, one of four possible interconvertible states which differ from each other in the number of available oxygen atoms and the formal oxidation states of the individual vanadium atoms. The relative ratios of active sites in each of the four possible states are dictated by the reaction conditions, the redox properties of the reacting gases and the structure of the vanadyl pyrophosphate active surface. A crucial feature of the mechanism is a pseudo-ozonide surface species formed by the interaction of a chemisorbed dioxygen molecule and an adjacent metal-oxo group. This unusual species is responsible for the initial activation of then-butane, which occurs when the chemisorbed dioxygen abstracts an H-atom from the alkane and the adjacent metal-oxo group reacts with the incipient alkyl radical to form an alkoxy group. The proposed mechanism is entirely consistent with literature reports describing the behaviour of (VO)₂P₂O₇ in flow, pulse and TAP reactors.     

Activation of Pozzolanic Reaction of Hydrated Portland Cement Fly Ash Pastes in Sulfate Solution

The activation of the pozzolanic reaction of fly ash in portland cement paste immersed in sulfate solution has been studied. Mixtures of two Spanish fly ashes (ASTM class F) with 0%, 15%, and 35% replacement of portland cement by fly ash were immersed in Na₂SO₄ solution, of 2880 ppm SO₄²⁻ concentration, for a period of 90 days. The resistance of the different mixtures to the sulfate attack was evaluated using the Koch-Steinegger test. The results showed that all of the mixtures were sulfate resistant, despite the high Al₂O₃ content of the fly ash. The diffusion of SO₄²⁻ and Na⁺ ions through the pore solution activated the pozzolanic reactivity of the fly ashes, causing microstructural changes, which were characterized by X-ray diffraction (XRD), mercury intrusion porosimetry (MIP), and scanning electron microscopy (SEM). As a result, the flexural strength of the mixtures increased, principally for the fly ash of a lower particle size and 35% of addition.     

Twin-image suppression in digital in-line holography based on wave-front filtering

Pattern Analysis and Applications - Digital holography is an imaging process able to recreate three-dimensional representations of objects from recording pattern interference among distinct waves....