Detection of high levels of Survivin-immunoglobulin M immune complex in sera from hepatitis C virus infected patients with cirrhosis

The identification and surveillance of patients with liver dysfunctions and the discovering of new disease biomarkers are needed in the clinical practice. The aim of this study was to investigate on Survivin-immunoglobulin (Ig)M immune complex (IC) as a potential biomarker of chronic liver diseases.Serum levels of Survivin-IgM were measured using an enzyme-linked immunoassay that had been standardized and validated in our laboratory in 262 individuals, including healthy subjects and patients with chronic viral hepatitis, cirrhosis and hepatocellular carcinoma (HCC).Survivin-IgM IC was lower in healthy subjects (median, 99.39 AU/mL) than in patients with chronic viral hepatitis (median, 148.03 AU/mL; P = 0.002) or with cirrhosis (median, 371.00 AU/mL; P  0.001). Among patients with cirrhosis, those with hepatitis C virus (HCV) infection showed the highest level of Survivin-IgM IC (median, 633.71 AU/mL; P  0.001). The receiver-operator curve analysis revealed that Survivin-IgM accurately distinguishes HCV correlated cirrhosis from chronic viral hepatitis (area under the curve [AUC], 0.738; sensitivity, 74.5%; specificity, 70.7%). A multivariate logistic regression model, including Survivin-IgM IC, aspartate aminotransferase (AST) and AST/alanine aminotransferase (ALT) ratio increased the prediction accuracy for the identification of the cirrhotic HCV patients (AUC, 0.818; sensitivity, 87.2%; specificity, 65.9%). Conversely, Survivin-IgM IC significantly decreased in HCC patients (median, 165.72 AU/mL; P = 0.022).Our results suggest that Survivin-IgM immune complex may be used as a potential biomarker for liver damage, particularly for the identification of the HCV-related cirrhotic population

Improvement of ALT decay kinetics by all-oral HCV treatment: Role of NS5A inhibitors and differences with IFN-based regimens

Background: Intracellular HCV-RNA reduction is a proposed mechanism of action of direct-acting antivirals (DAAs), alternative to hepatocytes elimination by pegylated-interferon plus ribavirin (PR). We modeled ALT and HCV-RNA kinetics in cirrhotic patients treated with currently-used all-DAA combinations to evaluate their mode of action and cytotoxicity compared with telaprevir (TVR)+PR. Study design: Mathematical modeling of ALT and HCV-RNA kinetics was performed in 111 HCV-1 cirrhotic patients, 81 treated with all-DAA regimens and 30 with TVR+PR. Kinetic-models and Cox-analysis were used to assess determinants of ALT-decay and normalization. Results: HCV-RNA kinetics was biphasic, reflecting a mean effectiveness in blocking viral production >99.8%. The first-phase of viral-decline was faster in patients receiving NS5A-inhibitors compared to TVR+PR or sofosbuvir+simeprevir (p<0.001), reflecting higher efficacy in blocking assembly/secretion. The second-phase, noted \u3b4 and attributed to infected-cell loss, was faster in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.27 vs 0.21 d-1, respectively, p = 0.0012). In contrast the rate of ALT-normalization, noted \u3bb, was slower in patients receiving TVR+PR or sofosbuvir+simeprevir compared to NS5A-inhibitors (0.17 vs 0.27 d-1, respectively, p<0.001). There was no significant association between the second-phase of viral-decline and ALT normalization rate and, for a given level of viral reduction, ALT-normalization was more profound in patients receiving DAA, and NS5A in particular, than TVR+PR. Conclusions: Our data support a process of HCV-clearance by all-DAA regimens potentiated by NS5A-inhibitor, and less relying upon hepatocyte death than IFN-containing regimens. This may underline a process of "cell-cure" by DAAs, leading to a fast improvement of liver homeostasis

E-Learning Cooperative Environments: Simulations and Virtual Labs as the New Frontiers of Inclusiveness and Immersiveness for Organizations

Virtual environments developed thanks to the use of advanced technologies, allow students to experience in a full and total way his/her learning and knowledge, from a subjective perspective, where multisensory interaction is provided. The social context of learning can be created from the content itself. If we can create social spaces on-line than in so far as disciplines connected with the social sciences are concerned, that content can be created as an interactive learning environments with unique, though simulated, social contexts for learning. The aim of this study was to investigate students' perceptions of simulations and role plays and how these tools, if well managed, offer a variety of powerful information sharing and collaboration features. Understanding students' perceptions and usage behavior of these systems is a very important goal, because the success of them depends on several social and psychological factors. In addition, the benefits of 3D graphics for education have been explored. 3D models are very useful to familiarize students with features of different shapes and objects, and can be particularly useful in teaching activities. Some courses have been developed using 3D images that the user must interact with in order to learn a certain lesson

Online planning of optimal trajectories on assigned paths with dynamic constraints for robot manipulators

This paper addresses time-optimal path-constrained trajectory planning. Given a geometric path for a manipulator, this paper focuses on the selection of the time law along the path. This law minimizes the time required to complete the path and at the same time is consistent with constraints, both at kinematic and dynamic levels. To obtain the optimal law a decision algorithm for the acceleration along the path has been developed. Remarkably, the algorithm is amenable to online implementation, thus allowing for path replanning. An experimental validation on an ABB IRB140 robot is shown

Aeroacoustic design of aero-engine intake liners

Fan noise transmission through and radiation from realistic lined intakes is computed via the GFD method. The high accuracy of this wave-based discretization method and the use of an ”exact” radiation condition supplied by an integral formulation enable genuine 3D simulations at fan-radius Helmholtz numbers up to 22, within practical times on single processor platforms. Helmholtz numbers of 50 can be achieved on a 10-CPUs parallel platform within equivalent computational times. Both axisymmetric and negatively scarfed configurations are considered. For the scarfed case, the effect of axial and circumferential segmentations of the acoustic treatment on the sound radiation is explored at a given frequency and spinning mode order. It is shown that the presence of rigid splices reduces the attenuation effect of the acoustic treatment. Furthermore, the effect of the scarf angle on the upward/downward peak-levels observed for a rigid-wall configuration is no more evident when a segmented liner is considered