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.     

Software assurance practices for mobile applications

Mobile software applications have to cope with a particular environment that involves small size, limited resources, high autonomy requirements, competitive business models and many other challenges. To provide development guidelines that respond to these needs, several practices have been introduced; however, it is not clear how these guidelines may contribute to solve the issues present in the mobile domain. Furthermore, the rapid evolution of the mobile ecosystem challenges many of the premises upon which the proposed practices were designed. In this paper, we present a survey of the literature on software assurance practices for mobile applications, with the objective of describing them and assessing their contribution and success. We identified, organized and reviewed a body of research that spans in three levels: software development processes, software product assurance practices, and software implementation practices. By carrying out this literature survey, we reviewed the different approaches that researchers on Software Engineering have provided to address the needs that raise in the mobile software development arena. Moreover, we review the evolution of these practices, identifying how the constant changes and modernization of the mobile execution environment has impacted the methods proposed in the literature. Finally, we introduced discussion on the application of these practices in a real productive setting, opening an area for further research that may determine if practitioners have followed the proposed assurance paradigms.     

Intrinsic CFRP-metal-hybrids with rubber interface for the improvement of the damping behaviour

This paper presents an integrated passive damping approach in hybrid metal-CFRP parts for structural applications. In this concept a viscoelastic material is embedded in the joint zone of the hybrid component. To examine the connection strength single-lap-joint specimens were produced and tested and the influence of the used material combinations, different surface structures, and different process parameters i.e. the moment of cross-linking were evaluated. Afterwards, the metal-CFRP hybrids were tested in quasi-static tests to assess their connection strength and failure behaviour. Dynamic cyclic tensile tests with step-wise increased loading conditions were performed to determine the specimens damping behaviour and to estimate their fatigue performance. Finally, these results are compared to a state of the art metal-CFRP hybrid with rivets connecting both materials.     

On stochastic comparisons of finite mixtures for some semiparametric families of distributions

In this paper, we consider the classical finite mixture model, which is an effective tool for modeling lifetime distributions for random samples from heterogeneous populations. We discuss new results on stochastic comparison for two finite mixtures when each of them is drawn from one of the following semiparametric families, i.e., proportional hazards, accelerated lifetime and proportional reversed hazards.     

Is the List of Incomplete Open Cubes Complete?

Variations of Incomplete Open Cubes is the major project by the twentieth-century conceptual artist Sol LeWitt. In this paper we interpret the enumerative component of the project as embeddings of graphs. This formulation permits use of an algorithm to check the completeness of the list of the structures produced by the artist. Our conclusion is that the artist found the correct number of structures (that is, 122), but that his list contains a mistake in the presentation of a pair of incomplete cubes, a discovery that appears not to have been noted before.     

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.