Update on the Diagnostic Pitfalls of Autopsy and Post-Mortem Genetic Testing in Cardiomyopathies

Inherited cardiomyopathies are frequent causes of sudden cardiac death (SCD), especially in young patients. Despite at the autopsy they usually have distinctive microscopic and/or macroscopic diagnostic features, their phenotypes may be mild or ambiguous, possibly leading to misdiagnoses or missed diagnoses. In this review, the main differential diagnoses of hypertrophic cardiomyopathy (e.g., athlete’s heart, idiopathic left ventricular hypertrophy), arrhythmogenic cardiomyopathy (e.g., adipositas cordis, myocarditis) and dilated cardiomyopathy (e.g., acquired forms of dilated cardiomyopathy, left ventricular noncompaction) are discussed. Moreover, the diagnostic issues in SCD victims affected by phenotype-negative hypertrophic cardiomyopathy and the relationship between myocardial bridging and hypertrophic cardiomyopathy are analyzed. Finally, the applications/limits of virtopsy and post-mortem genetic testing in this field are discussed, with particular attention to the issues related to the assessment of the significance of the genetic variants.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC₅₀) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC₅₀ shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development.     

Indoor body-area channel model for narrowband communications

Using wireless sensors placed on a person to continuously monitor health information is a promising new application. At the same time, new low-power wireless standards such as Bluetooth and Zigbee have been proposed for short range, low data-rate communication matching the requirements of these bio-medical applications. However, there are currently few measurements or models describing propagation around the body. To address this problem, electromagnetic waves near the torso are measured and a statistical model is derived for communication in the 915 MHz and 2.45 GHz industrial, scientific and medical bands associated with Zigbee and Bluetooth. Measurement setup and statistical analysis are described.     

Building kernels from binary strings for image matching.

In the statistical learning framework, the use of appropriate kernels may be the key for substantial improvement in solving a given problem. In essence, a kernel is a similarity measure between input points satisfying some mathematical requirements and possibly capturing the domain knowledge. In this paper, we focus on kernels for images: we represent the image information content with binary strings and discuss various bitwise manipulations obtained using logical operators and convolution with nonbinary stencils. In the theoretical contribution of our work, we show that histogram intersection is a Mercer's kernel and we determine the modifications under which a similarity measure based on the notion of Hausdorff distance is also a Mercer's kernel. In both cases, we determine explicitly the mapping from input to feature space. The presented experimental results support the relevance of our analysis for developing effective trainable systems.     

A chemical method for preparation of cobalt oxide thin films

A very simple method has been developed for the preparation of cobalt oxides, CoO(OH) and Co₃O₄, thin films on glass substrates using cobalt(II) chloride and ammonia as reacting agents. These materials were characterized by optical and electrical measurements. CoO(OH) films are insulating and have DC dielectric breakdown at about 3700 V / mm when measurements are made using silver print electrodes placed at various spacings on the film. Electrical resistivity of Co₃O₄ is 2.5 ω m. Analysis of the absorption spectra shows that CoO(OH) and CO₃O₄ have optical band gaps of 2.36 eV and 1.65 eV respectively. Spectral variation of the optical constants of these materials have also been measured.     

An on-line learning algorithm for the orthogonal weight estimation of MLP

We propose an on-line learning algorithm for Multi Layered Perceptrons (MLP) with an Orthogonal Weight Estimator (OWE) architecture. Such an architecture allows to dynamically and efficiently estimate the weights of a MLP in context dependent behaviour problems. The proposed learning algorithm attempts to solve the problem of time-consuming in the learning phase encountered to train these weight estimators.     

Second-Order optical non-linearities of {4-(dimethylamino) stilben z & e 4'-yl} dimesityl borane

Samples of {4-(dimethylamino) stilben Z & E 4'-yl} dimesityl borane (BNS) were synthesised and investigated for their non-linear optical properties. The results show that the quadratic hyperpolarisability of the Z-isomer is smaller than that of the E-isomer, the beta value found for the latter being as high as 60 × 10^?30 esu.     

Effect of Particle Size on Monometallic and Bimetallic (Au,Pd)/C on the Liquid Phase Oxidation of Glycerol

The influence of metal particle size of monometallic and bimetallic supported catalysts (Au, Pd, Au–Pd)/C was studied using as a model reaction the liquid phase oxidation of glycerol. By tuning the metal particle size from 2 to 16 nm a progressive decrease of activity and simultaneously an increase in the selectivity to sodium glycerate was observed. Moreover, the influence of the temperature was studied and it was found that by increasing the temperature, only with a large particle size the formed glycerate was retained and not over-oxidized to tartronate.