Heart failure gene therapy: the path to clinical practice

Gene therapy, aimed at the correction of key pathologies being out of reach for conventional drugs, bears the potential to alter the treatment of cardiovascular diseases radically and thereby of heart failure. Heart failure gene therapy refers to a therapeutic system of targeted drug delivery to the heart that uses formulations of DNA and RNA, whose products determine the therapeutic classification through their biological actions. Among resident cardiac cells, cardiomyocytes have been the therapeutic target of numerous attempts to regenerate systolic and diastolic performance, to reverse remodeling and restore electric stability and metabolism. Although the concept to intervene directly within the genetic and molecular foundation of cardiac cells is simple and elegant, the path to clinical reality has been arduous because of the challenge on delivery technologies and vectors, expression regulation, and complex mechanisms of action of therapeutic gene products. Nonetheless, since the first demonstration of in vivo gene transfer into myocardium, there have been a series of advancements that have driven the evolution of heart failure gene therapy from an experimental tool to the threshold of becoming a viable clinical option. The objective of this review is to discuss the current state of the art in the field and point out inevitable innovations on which the future evolution of heart failure gene therapy into an effective and safe clinical treatment relies.

QoE-aware Multiple Path Video Transmission for Wireless Multimedia Sensor Networks

Wireless Multimedia Sensor Networks (WMSNs) promise a wide scope of emerging potential applications in both civilian and military areas, which require visual and audio information to enhance the level of collected information. The transmission of multimedia content requires a minimal video quality level from the user’s perspective. However, links in WMSN communi- cations are typically unreliable, as they often experience fluctuations in quality and weak connectivity, and thus, the routing protocol must evaluate the routes by using end-to-end link quality information to increase the packet delivery ratio. Moreover, the use multiple paths together with key video metrics can enhance the video quality level. In this paper, we propose a video-aware multiple path hierarchical routing protocol for efficient multimedia transmission over WMSN, called video-aware MMtransmission. This protocol finds node-disjoint multiple paths, and implements an end-to-end link quality estimation with minimal over- head to score the paths. Thus, our protocol assures multimedia transmission with Quality of Experience (QoE) and energy-efficiency support. The simula- tion results show the benefits of video-aware MMtransmission for disseminating video content by means of energy-efficiency and QoE analysis.

The Law of the WTO and the Communications Law of the EC : On a Path of Harmony or Discord?

This paper presents an overview of the law of the World Trade Organization (WTO) relevant to telecommunications services and correlates this body of law with the current regulatory framework for electronic communications networks and services in the European Community. The latter has been adapted to meet the challenges of technological and market developments in communications, epitomized by the processes of digitization, enhanced transport networks and convergence. The novel solutions embodied in the EC electronic communications regime, notably, a new design of the Significant Market Power mechanism, a projected withdrawal of sector specific regulation and an affirmation of the principle of technological neutrality, pose interesting questions as to the conformity of this reformed EC communications law with the WTO rules on telecommunications services and the obligations of the European Communities and their Member States. Looking beyond the WTO legal compatibility test, essential questions regarding the need for evolution of the WTO telecommunications rules are raised. The present paper contributes to the ongoing debate in that context in light of the EC experience.

Early adolescents' enjoyment experienced in learning situations and its relation to student achievement

While many studies confirm that positive emotions, including enjoyment, lead to better student achievement, less empirical evidence exists about possible mediator variables that link achievement to enjoyment. It is proposed that achievement and enjoyment form a circular dependency; enjoyment in learning leads to higher achievement but a degree of achievement is required to enjoy learning. This study provides insight into the reverse of the much studied enjoyment to achievement link and provides practical recommendations on how to use these findings. Founded in Control-value theory, which suggests that control and value cognitions are important variables that mediate the connection between enjoyment and achievement, this study explores the reciprocal achievement-cognition-enjoyment link. The reciprocal link was investigated by applying a one year longitudinal design to students of grade 6 and 7 (N = 356). This age group was chosen because early adolescence represents a critical period during which a strong decrease in positive learning emotions is observed. Part of the work involved identifying factors that might be responsible for this negative development. Results of cross-lagged path analysis identified reciprocal effects between student achievement and enjoyment with control and value cognitions functioning as partial mediators. High achievement goes with high control and value cognitions, which in turn positively affect enjoyment. However, cross-lagged correlations could only be partly confirmed. The results are discussed in terms of theoretical and practical implications.

Age dependency of safety and outcome of endovascular therapy for acute stroke

Elderly patients generally experience less favorable outcomes and higher mortality after acute stroke than younger patients. The aim of this study was to analyze the influence of age on outcome and safety after endovascular therapy in a large cohort of patients aged between 20 and 90 years. We prospectively acquired data of 1,000 stroke patients treated with endovascular therapy at a single center. Logistic regression analysis was performed to determine predictors of outcome and linear regression analysis to evaluate the association of age and outcome after 3 months. Younger age was an independent predictor of favorable outcome (OR 0.954, p < 0.001) and survival (OR 0.947, p < 0.001) in multivariate regression analysis. There was a linear relationship between age and outcome. Ever increase in 26 years of age was associated with an increase in the modified Rankin Scale of 1 point (p < 0.001). However, increasing age was not a risk factor for symptomatic (p = 0.086) or asymptomatic (p = 0.674) intracerebral hemorrhage and did not influence recanalization success (p = 0.674). Advancing age was associated with a decline of favorable outcomes and survival after endovascular therapy. This decline was linear from age 20 to 90 years, but was not related to lower recanalization rates or higher bleeding risk in the elderly. The efficacy of endovascular stroke therapy seems to be preserved also in the elderly and other factors than efficacy of endovascular therapy such as decreased plasticity are likely to explain the worse outcome with advancing age.