A Smart Grid for the city of Rome: A Cost Benefit Analysis

In this work, the JRC applies its Smart Grid CBA methodology to a full-scale project rather than only to a small-size demonstrative one. To this end, the JRC and ACEA - one of Italy’s biggest Distribution System Operators (DSOs), in charge of managing the distribution system of Rome - teamed up to study the merits of deploying Smart Grid technologies (preliminarily tested in a pilot project) in a big city like the Italian capital, hosting several million electricity users. The ACEA Smart Grid Pilot Project (named "Malagrotta" after the area where pilot solutions were first realised) is the starting point for this study, as it displays many of the characteristics of emerging Smart Grids projects and interconnects several diversified generation facilities (like biogas, waste-to-electricity and PV plants) and consumption centres. This study illustrates the outcome of the application of the JRC Cost Benefit Analysis (CBA) to a) the ACEA Smart Grids pilot project; and b) the planned deployment of Smart Grid technologies (tested in the ACEA Smart Grids pilot project) to the whole of the city of Rome. The CBA is conducted from both the private investor’s and the societal perspective, in order to assess whether scaling up the Smart Grid pilot project benefits the distribution operator and the citizens. Finally, this report shows how the JRC's CBA methodology can be effectively used to assess the financial and economic viability of real Smart Grids projects and help the investment decisions of DSOs.JRC.F.3-Energy Security, Systems and Marke

Matrix metalloproteinase-9 might affect adaptive immunity in non-ST segment elevation acute coronary syndromes by increasing CD31 cleavage on CD4+ T-cells

Aims In patients with acute coronary syndrome (ACS), the higher activity of effector T-cells suggests that mechanisms involving adaptive immunity dysregulation might play a role in coronary instability. The shedding of the functional CD31 domain 1-5 leads to uncontrolled lymphocyte activation. In experimental models, matrix metalloproteinase-9 (MMP-9) has been implicated in endothelial CD31 cleavage. Interestingly, higher serum levels of MMP-9 have been observed in ACS. We aim to investigate the mechanisms underlying CD31 dysregulation in ACS. Methods and results To assess CD31 cleavage on CD4+ T-cells, we analysed by flow cytometry CD4+ T-cells of 30 ACS, 25 stable angina (SA) patients, and 28 controls (CTRL) using two different CD31 antibodies that specifically recognize domain 1-5 or the non-functional membrane-proximal domain 6. The ratio between the domains was significantly lower in ACS than in SA and CTRL (P = 0.002 ACS vs. SA; P = 0.002 ACS vs. CTRL). After stimulation with anti-CD3/CD28, the 1-5/6 domain ratio was significantly lower in ACS than in SA (P = 0.005). ELISA of supernatants obtained from T-cell receptor-stimulated CD4+ T-cells showed higher production of MMP-9 in ACS than in SA (P < 0.001). CD31 domain 1-5 expression in activated CD4+ T-cells from ACS patients increased after treatment with a specific MMP-9 inhibitor (P = 0.042). Conclusion Our study suggest that enhanced MMP-9 release plays a key role in determining the cleavage and shedding of the functional CD31 domain 1-5 in CD4+ T-cells of ACS patients. This mechanism might represent an important therapeutic target to modulate T-cell dysregulation in ACS

Alterations of Hyaluronan Metabolism in Acute Coronary Syndrome: Implications for Plaque Erosion

Background: Superficial erosion currently causes at least one-third of acute coronary syndromes (ACS), and its incidence is increasing. Yet, the underlying mechanisms in humans are still largely unknown. Objectives: The authors sought to assess the role of hyaluronan (HA) metabolism in ACS. Methods: Peripheral blood mononuclear cells were collected from ACS (n = 66), stable angina (SA) (n = 55), and control (CTRL) patients (n = 45). The authors evaluated: 1) gene expression of hyaluronidase 2 (HYAL2) (enzyme degrading high-molecular-weight HA to its proinflammatory 20-kDa isoform) and of CD44v1, CD44v4, and CD44v6 splicing variants of HA receptor; and 2) HYAL2 and CD44 protein expression. Moreover, they compared HYAL2 and CD44 gene expression in ACS patients with plaque erosion (intact fibrous cap and thrombus) and in ACS patients with plaque rupture, identified by optical coherence tomography analysis. Results: Gene expression of HYAL2, CD44v1, and CD44v6 were significantly higher in ACS as compared with SA (p = 0.003, p < 0.001, and p = 0.033, respectively) and CTRL subjects (p < 0.001, p < 0.001, and p = 0.009, respectively). HYAL2 protein expression was significantly higher in ACS than in SA (p = 0.017) and CTRL (p = 0.032), whereas no differences were found in CD44 protein expression. HYAL2 and CD44v6 gene expression was significantly higher in patients with plaque erosion than in those with plaque rupture (p = 0.015 and p = 0.029, respectively). Conclusions: HYAL2 and CD44v6 splicing variants seem to play an important role in ACS, in particular when associated with plaque erosion. After further validation, HYAL2 might represent a potentially useful biomarker for the noninvasive identification of this mechanism of coronary instability

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982

Adaptive Immunity Dysregulation in Acute Coronary Syndromes: From Cellular and Molecular Basis to Clinical Implications

Although the early outcome of acute coronary syndrome (ACS) has considerably improved in the last decade, cardiovascular diseases still represent the main cause of morbidity and mortality worldwide. This is mainly because recurrence of ACS eventually leads to the pandemics of heart failure and sudden cardiac death, thus calling for a reappraisal of the mechanisms responsible for coronary instability. This review discusses recent advances in our understanding of how adaptive immunity contributes to the pathogenesis of ACS and the clinical implications that arise from these new pathogenic concepts

Allergic Inflammation Is Associated With Coronary Instability and a Worse Clinical Outcome After Acute Myocardial Infarction

The role of allergic inflammation in acute coronary syndromes (ACS) has not been clearly defined to date. Aim of this study was to assess eosinophil and basophil activation in ACS and the prognostic role of eosinophil cationic protein in ST-segment-elevation myocardial infarction