A preliminary assessment of the Normative Framework regulating MAR schemes in Europe: the EU Directives and their Implementation in nine National Legislations

The use of MAR schemes within the European Union is not a new phenomenon, on the contrary it dates back to the beginning of the XIX century. Despite being widely adopted and currently the object of extensive studies, this tool is not soundly regulated and so far very little research has been conducted on the normative framework regulating MAR at the regional and at the national level. This paper draws upon the findings of a Report which represents one of the deliverables identified by MARSOL, a EU FP7 project launched in December 2013 that aims at demonstrating that MAR shall be regarded as a viable approach to address the predicted water shortages over the long term. Through a survey which involved a number of national experts, the researchers involved in the drafting of the Report have collected relevant data concerning the national legal frameworks of nine EU countries that adopt MAR schemes. The results of the questionnaire have been processed using a qualitative and comparative approach and have been duly included in the legal analysis, which covers the implementation at the national level of the two EU Directives relevant for MAR Schemes, i.e. the Water Framework Directive and its "daughter", the Groundwater Directive. This paper shall be considered as the outcome of a preliminary investigation which covered only a limited number of European countries, it is expected that the research will be carried out as to include a larger number of EU Member States (MSs), alongside the most relevant extra EU countries

Experimental investigation of the mooring system of a wave energy converter in operating and extreme wave conditions

A proper design of the mooring systems for Wave Energy Converters (WECs) requires an accurate investigation of both operating and extreme wave conditions. A careful analysis of these systems is required to design a mooring configuration that ensures station keeping, reliability, maintainability, and low costs, without affecting the WEC dynamics. In this context, an experimental campaign on a 1:20 scaled prototype of the ISWEC (Inertial Sea Wave Energy Converter), focusing on the influence of the mooring layout on loads in extreme wave conditions, is presented and discussed. Two mooring configurations composed of multiple slack catenaries with sub-surface buoys, with or without clump-weights, have been designed and investigated experimentally. Tests in regular, irregular, and extreme waves for a moored model of the ISWEC device have been performed at the University of Naples Federico II. The aim is to identify a mooring solution that could guarantee both correct operation of the device and load carrying in extreme sea conditions. Pitch motion and loads in the rotational joint have been considered as indicators of the device hydrodynamic behavior and mooring configuration impact on the WEC

TIME-DEPENDENT AND CRITICAL ROLE OF THE GPR17 RECEPTOR DURING OLIGODENDROCYTE DIFFERENTIATION: IMPLICATIONS FOR THE DEVELOPMENT OF NEW REMYELINATION STRATEGIES

In the adult central nervous system (CNS), neural progenitor cells expressing the proteoglycan NG2 (NG2 cells, also known as Oligodendrocyte Precursor Cells, OPCs) dispersed throughout the parenchyma serve as a primary source of myelinating cells in demyelinated lesions, such as multiple sclerosis (MS). The Gi-protein-coupled receptor GPR17, activated by both uracil nucleotides (e.g. UDP-glucose) and cysteinyl-leukotrienes (e.g. LTD4) (Ciana et al., 2006), has recently emerged as an important player in oligodendrogliogenesis (Lecca et al., 2008; Chen et al., 2009). In both brain and spinal cord, GPR17 was found on parenchymal NG2+ cells in transition from precursors to premyelinating phenotypes, whereas it is not present on mature myelinating oligodendrocytes. Previous data in cultured OPCs showed that, at early differentiation stages, GPR17 activation by endogenous ligands promotes (while inhibition by antagonists or silencing RNAs impairs) OPC differentiation (Fumagalli et al., 2011). Altogether, these data point at GPR17 as a key functional modulator of oligodendrocyte maturation. Using primary OPC cultures and OPC/DRG co-cultures, we demonstrated that: (i) GPR17 activation promotes OPC differentiation (UDP, LTD4 and LTE4) and myelination (UDP-glucose and UDP); (ii) GPR17 forced over-expression at late differentiation stages, obtained by transfecting cultured OPCs with a GFP-GPR17 fusion vector, impairs cell terminal maturation, suggesting that the receptor has a stage specific function in controlling OPC differentiation and that it needs to be down-regulated/desensitized in late immature oligodendrocytes to allow their terminal maturation; (iii) GPR17 down-regulation occurs through agonist-induced receptor phosphorylation via GRK2. Interestingly, we also demonstrated that the inhibition of the mTOR pathway by rapamycin determines a significant reduction of GRK2 levels, with parallel increases in GPR17 expression and strong impairment of OPC maturation. Globally, these data suggest that dysregulation of these pathways leading to aberrant GPR17 over-expression may prematurely block OPC maturation at a pre-immature stage. Altogether these experiments shed light on the mechanisms underlying GPR17 physiological regulation that can be exploited for the development of new pharmacological and biotechnological strategies to promote/implement the reparative potential of the OPC precursors, that are still present in the adult brain

Energy-maximising model predictive control for a multi degree-of-freedom pendulum-based wave energy system

Renewable energy sources can be a solution for the recent pollution increasing scenario and the need for diversification of the energy market. Among such alternative sources,wave energy represents a viable solution, due to the its high power density and accessibility.Nonetheless, wave energy is still in phase of development, and a key stepping stone towards commercialisation is strongly linked to the availability of optimal control strategies for maximum energy harvesting. With its ability to handle system constraints and optimise power absorption directly, model predictive control (MPC) has gained popularity within the WEC community as a potential solution for the corresponding energy-maximising problem. In this study, an MPC strategy is developed for real-time control of the so-called PeWEC energy harvesting system,providing also a solution for the wave excitation estimation and forecasting problem, inherently required by the MPC controller to achieve optimal performance. Improved computational requirements are obtained via definition of a reduced control-oriented model, describing the dynamics of the system in a compact form. The performance of the proposed strategy is illustrated via a comprehensive numerical appraisal

Integrating formal methods into medical software development : the ASM approach

Medical devices are safety-critical systems since their malfunctions can seriously compromise human safety. Correct operation of a medical device depends upon the controlling software, whose development should adhere to certification standards. However, these standards provide general descriptions of common software engineering activities without any indication regarding particular methods and techniques to assure safety and reliability. This paper discusses how to integrate the use of a formal approach into the current normative for the medical software development. The rigorous process is based on the Abstract State Machine (ASM) formal method, its refinement principle, and model analysis approaches the method supports. The hemodialysis machine case study is used to show how the ASM-based design process covers most of the engineering activities required by the related standards, and provides rigorous approaches for medical software validation and verification

H2 reformation in post-shock regions

H2 formation is an important process in post-shock regions, since H2 is an active participant in the cooling and shielding of the environment. The onset of H2 formation therefore has a strong effect on the temperature and chemical evolution in the post shock regions. We recently developed a model for H2 formation on a graphite surface in warm conditions. The graphite surface acts as a model system for grains containing large areas of polycyclic aromatic hydrocarbon structures. Here this model is used to obtain a new description of the H2 formation rate as a function of gas temperature that can be implemented in molecular shock models. The H2 formation rate is substantially higher at high gas temperatures as compared to the original implementation of this rate in shock models, because of the introduction of H atoms which are chemically bonded to the grain (chemisorption). Since H2 plays such a key role in the cooling, the increased rate is found to have a substantial effect on the predicted line fluxes of an important coolant in dissociative shocks [O I] at 63.2 and 145.5 micron. With the new model a better agreement between model and observations is obtained. Since one of the goals of Herschel/PACS will be to observe these lines with higher spatial resolution and sensitivity than the former observations by ISO-LWS, this more accurate model is very timely to help with the interpretation of these future results.Comment: 12 pages, 3 figures, 1 table, accepted in MNRAS Letter

A kinetic Monte Carlo study of desorption of H2 from graphite (0001)

The formation of H2 in the interstellar medium proceeds on the surfaces of silicate or carbonaceous particles. To get a deeper insight of its formation on the latter substrate, this letter focuses on H2 desorption from graphite (0001) in Temperature-Programmed-Desorption Monte-Carlo simulations. The results are compared to experimental results which show two main peaks and an intermediate shoulder for high initial coverage. The simulation program includes barriers obtained by ab-initio methods and is further optimised to match two independent experimental observations. The simulations reproduce the two experimental observed desorption peaks. Additionally, a possible origin of the intermediate peak is given.Comment: 9 pages, 5 figures, Chem. Phys. Lett. in pres

Pressure ulcers management: an economic evaluation

Introduction. Pressure ulcer management represents a growing problem for medical and social health care systems all over the world, particularly in European Union countries where the incidence of pressure ulcers in older persons (> 60 years of age) is predicted to rise. Objectives. The aim of this study was to provide evidence for the lower impact on economic resources of using advanced dressings for the treatment of pressure ulcers with respect to conventional simple dressings. Methods. Two different models of analysis, derived from Activity Based Costing and Health Technology Assessment, were used to measure, over a 30-day period, the direct costs incurred by pressure ulcer treatment for community-residing patients receiving integrated home care. Results. Although the mean cost per home care visit was higher in the advanced dressings patient group than in the simple dressings patient one (? 22.31 versus ? 16.03), analysis of the data revealed that the cost of using advanced dressings was lower due to fewer home care visits (22 versus 11). Conclusion. The results underline the fact that decision-makers need to improve their understanding of the advantages of taking a long-term view with regards to the purchase and use of materials. This could produce considerable savings of resources in addition to improving treatment efficacy for the benefit of patients and the health care system

Eating and oral hygiene habits in a population of young adults: An observational study

Aim: Eating Disorders (ED) are a group of psychological disorders affecting patients’ relationship with food and their own body. In particular, they have an impact on teeth and oral mucosa and may cause dental caries, erosions, xerostomia, salivary glands modifications and perioral tissue metabolic impairment. The aim of this paper is to investigate the risk factors associated with ED in a population of young adults by considering the impact such disorders have on oral health, particularly in view of the increased rate of tooth erosion recorded in recent years. Materials and methods: An observational study was conducted by submitting, to a population of young adults in the Brescia area, an anonymous questionnaire (39 questions) to reveal their behaviours regarding their eating habits and lifestyles. The areas investigated were oral hygiene and eating habits. Results: A total of 212 young people were interviewed (M/F 18-25 in Brescia and its province) and the sample is at risk of developing ED in general owing to their eating habits and lifestyles: 65% of the respondents think diligently about food, and 57% of them worry about putting on weight, both these characteristics are typical to all EDs; 14% of the sample stated not eating in the company of family and friends in the way they would like out of embarrassment and shame. After eating, 8% of them “nearly always” feel remorse, and 41% “only on some occasions”. After having ‘transgressed’, 22% will fast or go on a diet to compensate for their excesses. Conclusions: EDs are a continually growing and evolving pathological problem. Informing and training healthcare professionals and citizens about the damage caused by EDs to the entire body could help to understand the importance of making a multidisciplinary evaluation from the outset of the problem and right from the first contact with the patient. To this end, dentists and dental hygienists are in the delicate situation of being among the first health professionals able to see early signs and symptoms of ED in the mouth and elsewhere

Spider venom administration impairs glioblastoma growth and modulates immune response in a non-clinical model.

Molecules from animal venoms are promising candidates for the development of new drugs. Previous in vitro studies have shown that the venom of the spider Phoneutria nigriventer (PnV) is a potential source of antineoplastic components with activity in glioblastoma (GB) cell lines. In the present work, the effects of PnV on tumor development were established in vivo using a xenogeneic model. Human GB (NG97, the most responsive line in the previous study) cells were inoculated (s.c.) on the back of RAG-/- mice. PnV (100 µg/Kg) was administrated every 48 h (i.p.) for 14 days and several endpoints were evaluated: tumor growth and metabolism (by microPET/CT, using 18F-FDG), tumor weight and volume, histopathology, blood analysis, percentage and profile of macrophages, neutrophils and NK cells isolated from the spleen (by flow cytometry) and the presence of macrophages (Iba-1 positive) within/surrounding the tumor. The effect of venom was also evaluated on macrophages in vitro. Tumors from PnV-treated animals were smaller and did not uptake detectable amounts of 18F-FDG, compared to control (untreated). PnV-tumor was necrotic, lacking the histopathological characteristics typical of GB. Since in classic chemotherapies it is observed a decrease in immune response, methotrexate (MTX) was used only to compare the PnV effects on innate immune cells with a highly immunosuppressive antineoplastic drug. The venom increased monocytes, neutrophils and NK cells, and this effect was the opposite of that observed in the animals treated with MTX. PnV increased the number of macrophages in the tumor, while did not increase in the spleen, suggesting that PnV-activated macrophages were led preferentially to the tumor. Macrophages were activated in vitro by the venom, becoming more phagocytic; these results confirm that this cell is a target of PnV components. Spleen and in vitro PnV-activated macrophages were different of M1, since they did not produce pro- and anti-inflammatory cytokines. Studies in progress are selecting the venom molecules with antitumor and immunomodulatory effects and trying to better understand their mechanisms. The identification, optimization and synthesis of antineoplastic drugs from PnV molecules may lead to a new multitarget chemotherapy. Glioblastoma is associated with high morbidity and mortality; therefore, research to develop new treatments has great social relevance. Natural products and their derivatives represent over one-third of all new molecular entities approved by FDA. However, arthropod venoms are underexploited, although they are a rich source of new molecules. A recent in vitro screening of the Phoneutria nigriventer spider venom (PnV) antitumor effects by our group has shown that the venom significantly affected glioblastoma cell lines. Therefore, it would be relevant to establish the effects of PnV on tumor development in vivo, considering the complex neoplastic microenvironment. The venom was effective at impairing tumor development in murine xenogeneic model, activating the innate immune response and increasing tumor infiltrating macrophages. In addition, PnV activated macrophages in vitro for a different profile of M1. These activated PnV-macrophages have potential to fight the tumor without promoting tumorigenesis. Studies in progress are selecting the venom molecules with antitumor and immunomodulatory effects and trying to better understand their mechanisms. We aim to synthesize and carry out a formulation with these antineoplastic molecules for clinical trials. Spider venom biomolecules induced smaller and necrotic xenogeneic GB; spider venom activated the innate immune system; venom increased blood monocytes and the migration of macrophages to the tumor; activated PnV-macrophages have a profile different of M1 and have a potential to fight the tumor without promote tumorigenesis