Adenosine A2A receptors: localization and function

Adenosine is an endogenous purine nucleoside present in all mammalian tissues, that originates from the breakdown of ATP. By binding to its four receptor subtypes (A1, A2A, A2B, and A3), adenosine regulates several important physiological functions at both the central and peripheral levels. Therefore, ligands for the different adenosine receptors are attracting increasing attention as new potential drugs to be used in the treatment of several diseases. This chapter is aimed at providing an overview of adenosine metabolism, adenosine receptors localization and their signal transduction pathways. Particular attention will be paid to the biochemistry and pharmacology of A2A receptors, since antagonists of these receptors have emerged as promising new drugs for the treatment of Parkinson's disease. The interactions of A2A receptors with other nonadenosinergic receptors, and the effects of the pharmacological manipulation of A2A receptors on different body organs will be discussed, together with the usefulness of A2A receptor antagonists for the treatment of Parkinson's disease and the potential adverse effects of these drugs

Five insights from the Global Burden of Disease Study 2019

The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a rules-based synthesis of the available evidence on levels and trends in health outcomes, a diverse set of risk factors, and health system responses. GBD 2019 covered 204 countries and territories, as well as first administrative level disaggregations for 22 countries, from 1990 to 2019. Because GBD is highly standardised and comprehensive, spanning both fatal and non-fatal outcomes, and uses a mutually exclusive and collectively exhaustive list of hierarchical disease and injury causes, the study provides a powerful basis for detailed and broad insights on global health trends and emerging challenges. GBD 2019 incorporates data from 281 586 sources and provides more than 3.5 billion estimates of health outcome and health system measures of interest for global, national, and subnational policy dialogue. All GBD estimates are publicly available and adhere to the Guidelines on Accurate and Transparent Health Estimate Reporting. From this vast amount of information, five key insights that are important for health, social, and economic development strategies have been distilled. These insights are subject to the many limitations outlined in each of the component GBD capstone papers.Peer reviewe

Improving the involvement of digital volunteers in disaster management

Volunteered geographic information (VGI) has been seen as useful information in times of disasters. Several authors have shown that VGI is useful for coping with preparedness and response phases of disaster management. However, because it is still a young technology, the use of VGI remains uncertain, due to its lack of strong reliability and validity. It is our assumption that to improve reliability and validity the promotion of citizen engagement (CE) is needed. CE is not new topic, but in the digital humanitarian context, it involves important factors that are not yet considered by disaster managers, such as communication processes, motivation of volunteers, different media for production of information, etc. To fill this gap, we identified a set of preliminary factors which should be considered to promote the involvement of volunteers in disaster management. These factors were derived from critical review of CE literature and from an analysis of lessons learned from an experiment on interaction with citizens carried out in context of the EU-project “DRIVER – Driving Innovation in Crisis Management for European Resilience”

Stimuli-SoS: a model-based approach to derive stimuli generators for simulations of systems-of-systems software architectures

Abstract Background Systems-of-systems (SoS) are alliances of independent and interoperable software-intensive systems. SoS often support critical domains, being required to exhibit a reliable operation, specially because people’s safety relies on their services. In this direction, simulations enable the validation of different operational scenarios in a controlled environment, allowing a benchmarking of its response as well as revealing possible breaches that could lead to failures. However, simulations are traditionally manual, demanding a high level of human intervention, being costly and error-prone. A stimuli generator could aid in by continuously providing data to trigger a SoS simulation and maintaining its operation. Methods We established a model-based approach termed Stimuli-SoS to support the creation of stimuli generators to be used in SoS simulations. Stimuli-SoS uses software architecture descriptions for automating the creation of such generators. Specifically, this approach transforms SoSADL, a formal architectural description language for SoS, into dynamic models expressed in DEVS, a simulation formalism. We carried out a case study in which Stimuli-SoS was used to automatically produce stimuli generators for a simulation of a flood monitoring SoS. Results We run simulations of a SoS architectural configuration with 69 constituent systems, i.e., 42 sensors, 9 crowdsourcing systems, and 18 drones. Stimuli generators were automatically generated for each type of constituent. These stimuli generators were capable of receiving the input data from the database and generating the expected stimuli for the constituents, allowing to simulate constituent systems interoperations into the flood monitoring SoS. Using Stimuli-SoS, we simulated 38 days of flood monitoring in little more than 6 h. Stimuli generators correctly forwarded data to the simulation, which was able to reproduce 29 flood alerts triggered by the SoS during a flooding event. In particular, Stimuli-SoS is almost 65 times more productive than a manual approach to producing data for the same type of simulation. Conclusions Our approach succeeded in automatically deriving a functional stimuli generator that can reproduce environmental conditions for simulating a SoS. In particular, we presented new contributions regarding productivity and automation for the use of a model-based approach in SoS engineering