Efficienza e sostenibilità economica dell'attività dei teatri lirici italiani

Questo lavoro propone un’analisi di efficienza di 11 teatri lirici italiani, con un approccio Data Envelopment Analysis (DEA), per il periodo 2010-2016. L’efficienza nell’attività di tali enti è un tema particolarmente rilevante, soprattutto in relazione alla cronica situazione di sofferenza economica in cui versano gli operatori del settore delle arti performative, che spesso basano la loro sopravvivenza su contributi e sussidi (Trevisan, 2017; Agid e Tarondeau, 2010). I risultati mostrano, in media, un’inefficienza di poco inferiore al 20%, identificando quindi un certo margine di miglioramento. Tuttavia le performance degli enti analizzati migliorano in modo deciso dopo la riforma introdotta dal D.L. 91/2013, finalizzata proprio al loro risanamento economico-finanziario. Successivamente, si approfondisce la relazione tra efficienza dei teatri lirici e alcune variabili di interesse, tra cui la vocazione turistica dell’area e il ricorso, più o meno intenso, a risorse produttive esterne all’ente. Efficiency and economic sustainability of the activity of Italian opera houses. This work provides an efficiency analysis of 11 Italian opera houses, adopting a Data Envelopment Analysis (DEA) approach, over the years 2010-2016. Theatres efficiency is a particularly relevant topic, especially in relation to the chronic economic difficulties faced by entities operating in the performing arts, often relying on subsidies for their survival (Trevisan, 2017; Agid and Tarondeau, 2010). Results show, on average, an inefficiency level close to 20%, thus highlighting a certain margin for improvement. However, the performance of the considered entities strongly improve after the reform started with the Decree 91/2013, aimed to foster their financial recovery. Subsequently, the analysis focuses on the relationship between opera houses efficiency and some variables of interest, including the touristic flows in the area and their (more or less evident) reliance on “external” production factors

Polish case study. Scenario based assessment of costs and benefits of adoption of comprehensive CIP standards

RT 56; The Polish case study describes results of simulations of cyber-attacks on the Polish transmission system of electricity and compares the economic and social impact of these attacks, assumed to occur in situations where the system is working in normal operation, versus situations where standards are implemented as additional security countermeasures and the same incident arises. This work analyses security measures defined in selected documents, tandardization, evaluates their effectiveness relative to attack scenarios, as well as implementation costs in comparison to weight of potential losses resulting from non-implementation. On this basis, a list of recommended safety measures, which guarantee high level of security and the highest level of return, has been prepare

In Vitro Evaluation of Antioxidant Potential of the Invasive Seagrass Halophila stipulacea

none10Marine organisms with fast growth rates and great biological adaptive capacity might have biotechnological interests, since ecological competitiveness might rely on enhanced physiological or biochemical processes’ capability promoting protection, defense, or repair intracellular damages. The invasive seagrass Halophila stipulacea, a non-indigenous species widespread in the Mediterranean Sea, belongs to this category. This is the premise to investigate the biotechnological interest of this species. In this study, we investigated the antioxidant activity in vitro, both in scavenging reactive oxygen species and in repairing damages from oxidative stress on the fibroblast human cell line WI-38. Together with the biochemical analysis, the antioxidant activity was characterized by the study of the expression of oxidative stress gene in WI-38 cells in presence or absence of the H. stipulacea extract. Concomitantly, the pigment pool of the extracts, as well as their macromolecular composition was characterized. This study was done separately on mature and young leaves. Results indicated that mature leaves exerted a great activity in scavenging reactive oxygen species and repairing damages from oxidative stress in the WI-38 cell line. This activity was paralleled to an enhanced carotenoids content in the mature leaf extracts and a higher carbohydrate contribution to organic matter. Our results suggest a potential of the old leaves of H. stipulacea as oxidative stress damage protecting or repair agents in fibroblast cell lines. This study paves the way to transmute the invasive H. stipulacea environmental threat in goods for human health.openClementina Sansone; Christian Galasso; Marco Lo Martire; Tomás Vega Fernández; Luigi Musco; Antonio Dell’Anno; Antonino Bruno; Douglas M. Noonan; Adriana Albini; Christophe BrunetSansone, Clementina; Galasso, Christian; Lo Martire, Marco; Vega Fernández, Tomás; Musco, Luigi; Dell’Anno, Antonio; Bruno, Antonino; Noonan, Douglas M.; Albini, Adriana; Brunet, Christoph

Mutations in KCNK4 that Affect Gating Cause a Recognizable Neurodevelopmental Syndrome

Aberrant activation or inhibition of potassium (K+) currents across the plasma membrane of cells has been causally linked to altered neurotransmission, cardiac arrhythmias, endocrine dysfunction, and (more rarely) perturbed developmental processes. The K+ channel subfamily K member 4 (KCNK4), also known as TRAAK (TWIK-related arachidonic acid-stimulated K+ channel), belongs to the mechano-gated ion channels of the TRAAK/TREK subfamily of two-pore-domain (K2P) K+ channels. While K2P channels are well known to contribute to the resting membrane potential and cellular excitability, their involvement in pathophysiological processes remains largely uncharacterized. We report that de novo missense mutations in KCNK4 cause a recognizable syndrome with a distinctive facial gestalt, for which we propose the acronym FHEIG (facial dysmorphism, hypertrichosis, epilepsy, intellectual disability/developmental delay, and gingival overgrowth). Patch-clamp analyses documented a significant gain of function of the identified KCNK4 channel mutants basally and impaired sensitivity to mechanical stimulation and arachidonic acid. Co-expression experiments indicated a dominant behavior of the disease-causing mutations. Molecular dynamics simulations consistently indicated that mutations favor sealing of the lateral intramembrane fenestration that has been proposed to negatively control K+ flow by allowing lipid access to the central cavity of the channel. Overall, our findings illustrate the pleiotropic effect of dysregulated KCNK4 function and provide support to the hypothesis of a gating mechanism based on the lateral fenestrations of K2P channels

Italian Case Study: socio-economic impact analysis of a cyber attack to a power plant in an Italian scenario. Cost and benefit estimation of CIPS standard adoptions. A reduced version

RT 55; The Italian Case study is a comprehensive report in which a possible attack scenario to a thermoelectric power plant is described in the Italian electric grid context and an assessment of social-economic impact is evaluated. A cost-benefit analysis of the adoption of comprehensive CIP standards is estimated. This is a reduced version of a full report in order to have a public deliverable purged from sensitive and confidential informatio

Flow cytometric immunobead assay for detection of BCR-ABL1 fusion proteins in chronic myleoid leukemia: Comparison with FISH and PCR techniques

Chronic Myeloid Leukemia (CML) is characterized by a balanced translocation juxtaposing the Abelson (ABL) and breakpoint cluster region (BCR) genes. The resulting BCR-ABL1 oncogene leads to increased proliferation and survival of leukemic cells. Successful treatment of CML has been accompanied by steady improvements in our capacity to accurately and sensitively monitor therapy response. Currently, measurement of BCR-ABL1 mRNA transcript levels by real-time quantitative PCR (RQ-PCR) defines critical response endpoints. An antibody-based technique for BCR-ABL1 protein recognition could be an attractive alternative to RQ-PCR. To date, there have been no studies evaluating whether flow-cytometry based assays could be of clinical utility in evaluating residual disease in CML patients. Here we describe a flow-cytometry assay that detects the presence of BCR-ABL1 fusion proteins in CML lysates to determine the applicability, reliability, and specificity of this method for both diagnosis and monitoring of CML patients for initial response to therapy. We show that: i) CML can be properly diagnosed at onset, (ii) follow-up assessments show detectable fusion protein (i.e. relative mean fluorescent intensity, rMFI%>1) when BCR-ABL1IS transcripts are between 1-10%, and (iii) rMFI% levels predict CCyR as defined by FISH analysis. Overall, the FCBA assay is a rapid technique, fully translatable to the routine management of CML patients

Benefit analysis. Assessing the cost of blackouts in case of attack. Evaluation based on Italian and Polish case studies

RT 52; This report provides an economic quantification of the benefits of implementing security standards, expressed in terms of avoided costs of blackouts. The evaluation considers specifically the blackouts described in the Italian and Polish trials, employing a mixed methodology relying on the “production function” approach for the non-household sector, while an econometric method based on survey data (stated preferences) is used for household consumers. With reference to non-households, a separate evaluation is carried on for the electricity industry. The results show that the costs of blackout are substantial, either for household and non-household consumers, and largely exceed the damage suffered by the utilities ue to lost sales. Finally, since for non-households only losses in production are considered, we provide, in a separate section, three case studies demonstrating that some industries can suffer relevant additional blackout cost

A Solve-RD ClinVar-based reanalysis of 1522 index cases from ERN-ITHACA reveals common pitfalls and misinterpretations in exome sequencing

Purpose: Within the Solve-RD project (https://solve-rd.eu/), the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies aimed to investigate whether a reanalysis of exomes from unsolved cases based on ClinVar annotations could establish additional diagnoses. We present the results of the "ClinVar low-hanging fruit" reanalysis, reasons for the failure of previous analyses, and lessons learned. Methods: Data from the first 3576 exomes (1522 probands and 2054 relatives) collected from European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies was reanalyzed by the Solve-RD consortium by evaluating for the presence of single-nucleotide variant, and small insertions and deletions already reported as (likely) pathogenic in ClinVar. Variants were filtered according to frequency, genotype, and mode of inheritance and reinterpreted. Results: We identified causal variants in 59 cases (3.9%), 50 of them also raised by other approaches and 9 leading to new diagnoses, highlighting interpretation challenges: variants in genes not known to be involved in human disease at the time of the first analysis, misleading genotypes, or variants undetected by local pipelines (variants in off-target regions, low quality filters, low allelic balance, or high frequency). Conclusion: The "ClinVar low-hanging fruit" analysis represents an effective, fast, and easy approach to recover causal variants from exome sequencing data, herewith contributing to the reduction of the diagnostic deadlock.The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 779257. Data were analyzed using the RD-Connect Genome-Phenome Analysis Platform, which received funding from the EU projects RD-Connect, Solve-RD, and European Joint Programme on Rare Diseases (grant numbers FP7 305444, H2020 779257, H2020 825575), Instituto de Salud Carlos III (grant numbers PT13/0001/0044, PT17/0009/0019; Instituto Nacional de Bioinformática), and ELIXIR Implementation Studies. The collaborations in this study were facilitated by the European Reference Network for Intellectual disability, TeleHealth, Autism and Congenital Anomalies, one of the 24 European Reference Networks approved by the European Reference Network Board of Member States, cofunded by the European Commission. This project was supported by the Czech Ministry of Health (number 00064203) and by the Czech Ministry of Education, Youth and Sports (number - LM2018132) to M.M.S

A MT-TL1 variant identified by whole exome sequencing in an individual with intellectual disability, epilepsy, and spastic tetraparesis

Funder: The Solve-RD project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 779257Abstract: The genetic etiology of intellectual disability remains elusive in almost half of all affected individuals. Within the Solve-RD consortium, systematic re-analysis of whole exome sequencing (WES) data from unresolved cases with (syndromic) intellectual disability (n = 1,472 probands) was performed. This re-analysis included variant calling of mitochondrial DNA (mtDNA) variants, although mtDNA is not specifically targeted in WES. We identified a functionally relevant mtDNA variant in MT-TL1 (NC_012920.1:m.3291T > C; NC_012920.1:n.62T > C), at a heteroplasmy level of 22% in whole blood, in a 23-year-old male with severe intellectual disability, epilepsy, episodic headaches with emesis, spastic tetraparesis, brain abnormalities, and feeding difficulties. Targeted validation in blood and urine supported pathogenicity, with heteroplasmy levels of 23% and 58% in index, and 4% and 17% in mother, respectively. Interestingly, not all phenotypic features observed in the index have been previously linked to this MT-TL1 variant, suggesting either broadening of the m.3291T > C-associated phenotype, or presence of a co-occurring disorder. Hence, our case highlights the importance of underappreciated mtDNA variants identifiable from WES data, especially for cases with atypical mitochondrial phenotypes and their relatives in the maternal line