Il tramonto della sovranità e la prospettiva cosmopolitica

Il lavoro di ricerca si propone di analizzare il ruolo dello Stato all’interno del contesto globale soffermandosi sull’analisi delle diverse proposte cosmopolite in tema di governance globale e del concetto di sovranità. La tesi è articolata in tre capitoli dedicati rispettivamente a globalizzazione e contesto globale; proposte di governance cosmopolite; Sato nazionale e Sovranità, Il primo capitolo affronta l’analisi del contesto globale prendendo avvio dal dibattito sul termine globalizzazione. In particolare, viene posta attenzione sui temi di minaccia, reale o presunta, che le trasformazioni del contesto internazionale, riassunte sotto il termine globalizzazione, attuano nei confronti dell’ordine multilaterale postbellico. Nella cornice delineata, il secondo capitolo affronta il tema del cosmopolitismo ed offre la discussione del dibattito cosmopolitico mettendo a confronto le diverse sensibilità che tendono a sottolineare gli aspetti etici-morali piuttosto che quelli politici. All’interno di questa sezione trova spazio un approfondimento dedicato alla Health governance che discute alcune proposte di governance mondiale della salute che, riprendendo i temi discussi nella sezione, si concentra sull’analisi delle specifiche proposte tra sistema di cooperazione multilivello e ruolo dell’Organizzazione Mondiale della Sanità. Il terzo capitolo approfondisce il concetto di Stato a partire dall’idea di sovranità. Nel capitolo delle conclusioni, si riassume, tenendo presente le analisi discusse nelle sezioni precedenti, un percorso filosofico che offra una lettura coerente dei cambiamenti in atto negli ambiti dell’economia, del diritto, della governance, della politica e del conflitto

Analysis and simulation of scale-up potentials in reverse electrodialysis

The Reverse Electrodialysis (RED) process has been widely accepted as a viable and promising technology to produce electric energy from salinity difference (salinity gradient power - e.g. using river water/seawater, or seawater and concentrated brines). Recent R&D efforts demonstrated how an appropriate design of the RED unit and a suitable selection of process conditions may crucially enhance the process performance. With this regard, a process simulator was developed and validated with experimental data collected on a lab-scale unit, providing a new modelling tool for process optimisation. In this work, performed within the REAPower project (www.reapower.eu), a process simulator previously proposed by the same authors has been modified in order to predict the behaviour of a cross-flow RED unit. The model was then adopted to investigate the influence of the most important variables (i.e. solution properties and stack geometry) on the overall process performance. In particular, the use of different concentrations and flow rates for the feed streams have been considered, as well as different aspect ratios in asymmetric stacks. Moreover, the influence of the scaling-up a RED unit was investigated, starting from a 22x22 cm2 100 cell pairs lab-stack, and simulating the performance of larger stacks up to a 44x88 cm2 500 cell pairs unit. Finally, different scenarios are proposed for a prototype-scale RED plant, providing useful indications for the technology scale-up towards 1 kW of power production, relevant to the installation of a real prototype plant in Trapani (Italy) being the final objective of the R&D activities of the REAPower project

Laparoscopic Pancreatoduodenectomy

In recent years, total laparoscopic pancreaticoduodenectomy (TLPD) has been introduced as a feasible alternative to open pancreaticoduodenectomy (OPD) when performed by experienced surgeons in laparoscopic and pancreatic surgery. Its application has been gradually increased, but its safety, reproducibility, and oncological outcomes are still debated due to its technical complexity and prolonged operating time. We performed a systematic analysis of the more relevant aspects of TLPD. In this chapter, we report a general overview of the different experiences present in the literature regarding indications, surgical techniques, postoperative outcomes, benefits and limitations of this approach, oncological results, learning curve, and costs. There is no standardized surgical technique for TLPD. Different techniques exist for both the demolitive stage and the reconstructive stage. We summarized the different aspects of the surgical technique based on the various experiences reported by different authors. Compared to OPD, TLPD provides the advantages of laparoscopy, i.e., reduced blood loss, decreased postoperative pain, and shorter length of hospital stay, without increasing the rate of postoperative complications or compromising oncological outcomes. An appropriate patient selection is crucial at the beginning of the learning curve. With increased experience, more challenging cases may also be approached with this technique, including those requiring major vascular resections or multi-visceral resections

Benchmarking of robotic and laparoscopic spleen-preserving distal pancreatectomy by using two different methods

Benchmarking; PancreatectomyBenchmarking; PancreatectomiaBenchmarking; PancreatectomíaBackground Benchmarking is an important tool for quality comparison and improvement. However, no benchmark values are available for minimally invasive spleen-preserving distal pancreatectomy, either laparoscopically or robotically assisted. The aim of this study was to establish benchmarks for these techniques using two different methods. Methods Data from patients undergoing laparoscopically or robotically assisted spleen-preserving distal pancreatectomy were extracted from a multicentre database (2006–2019). Benchmarks for 10 outcomes were calculated using the Achievable Benchmark of Care (ABC) and best-patient-in-best-centre methods. Results Overall, 951 laparoscopically assisted (77.3 per cent) and 279 robotically assisted (22.7 per cent) procedures were included. Using the ABC method, the benchmarks for laparoscopically assisted and robotically assisted spleen-preserving distal pancreatectomy respectively were: 150 and 207 min for duration of operation, 55 and 100 ml for blood loss, 3.5 and 1.7 per cent for conversion, 0 and 1.7 per cent for failure to preserve the spleen, 27.3 and 34.0 per cent for overall morbidity, 5.1 and 3.3 per cent for major morbidity, 3.6 and 7.1 per cent for pancreatic fistula grade B/C, 5 and 6 days for duration of hospital stay, 2.9 and 5.4 per cent for readmissions, and 0 and 0 per cent for 90-day mortality. Best-patient-in-best-centre methodology revealed milder benchmark cut-offs for laparoscopically and robotically assisted procedures, with operating times of 254 and 262.5 min, blood loss of 150 and 195 ml, conversion rates of 5.8 and 8.2 per cent, rates of failure to salvage spleen of 29.9 and 27.3 per cent, overall morbidity rates of 62.7 and 55.7 per cent, major morbidity rates of 20.4 and 14 per cent, POPF B/C rates of 23.8 and 24.2 per cent, duration of hospital stay of 8 and 8 days, readmission rates of 20 and 15.1 per cent, and 90-day mortality rates of 0 and 0 per cent respectively. Conclusion Two benchmark methods for minimally invasive distal pancreatectomy produced different values, and should be interpreted and applied differently

Failure analysis of boron steel components for automotive applications

The automotive industry is continuously looking for an innovative mix of new steels and manufacturing techniques in order to improve process chain efficiency and cost reduction. To this aim, boron steels are becoming increasingly popular thanks to their high hardenability and machinability. Due to their reduced finishing steps, boron steels are commonly processed using fine blanking technologies. The success of fine blanking on boron steel components is due to heat treatments which must be carefully designed to avoid precipitation of boron-rich compounds that would lower steel hardenability. At high temperature, boron is very reactive with oxygen and nitrogen. The main focus of this paper is to show some drawbacks that can occur during heat treatments of automotive components. An experimental campaign was performed on two different boron steels, namely EN 34MnB5 and EN 22MnB5. The steel samples were previously spheroidized annealed in a neutral environment (hydrogen/nitrogen atmosphere), and then fine blanked to obtain specific automotive components which were subsequently quenched and tempered. Experimental tests revealed precipitation of nanometric compounds, causing strong grain refinement and localized decrease of steel hardenability. Hardenability problems were brought back to nitrogen pick-up during initial spheroidize annealing treatments

Minimum standards for safe nursing care for users of alcoholic beverages

Objective: to develop minimum standards for nursing care for people intoxicated by alcohol and treated in the emergency units. Method: documental research, built upon the experience of the authors as members of the nursing care team of a center of toxicological assistance, based on literature review. Results: we presented the results in two units. Firstly, through a brief literature review on patient safety and alcohol users attended in emergency department, and secondly through a description of minimum standards for initial nursing care necessary for the safety of users of alcohol in three aspects: clinical/biological, psycho-emotional and social. Conclusion: The presented standardization, besides regulating nursing practice, improves the execution of assistance programs in the toxicology centers

Growth hormone-releasing hormone attenuates cardiac hypertrophy and improves heart function in pressure overload-induced heart failure

It has been shown that growth hormone-releasing hormone (GHRH) reduces cardiomyocyte (CM) apoptosis, prevents ischemia/reperfusion injury, and improves cardiac function in ischemic rat hearts. However, it is still not known whether GHRH would be beneficial for life-threatening pathological conditions, like cardiac hypertrophy and heart failure (HF). Thus, we tested the myocardial therapeutic potential of GHRH stimulation in vitro and in vivo, using GHRH or its agonistic analog MR-409. We show that in vitro, GHRH(1-44)NH2attenuates phenylephrine-induced hypertrophy in H9c2 cardiac cells, adult rat ventricular myocytes, and human induced pluripotent stem cell-derived CMs, decreasing expression of hypertrophic genes and regulating hypertrophic pathways. Underlying mechanisms included blockade of Gq signaling and its downstream components phospholipase Cβ, protein kinase Ce, calcineurin, and phospholamban. The receptor-dependent effects of GHRH also involved activation of Gαsand cAMP/PKA, and inhibition of increase in exchange protein directly activated by cAMP1 (Epac1). In vivo, MR-409 mitigated cardiac hypertrophy in mice subjected to transverse aortic constriction and improved cardiac function. Moreover, CMs isolated from transverse aortic constriction mice treated with MR-409 showed improved contractility and reversal of sarcolemmal structure. Overall, these results identify GHRH as an antihypertrophic regulator, underlying its therapeutic potential for HF, and suggest possible beneficial use of its analogs for treatment of pathological cardiac hypertrophy

Inhibition of chloride intracellular channel 1 (CLIC1) as biguanide class-effect to impair human glioblastoma stem cell viability

The antidiabetic biguanide metformin exerts antiproliferative effects in different solid tumors. However, during preclinical studies, metformin concentrations required to induce cell growth arrest were invariably within the mM range, thus difficult to translate in a clinical setting. Consequently, the search for more potent metformin derivatives is a current goal for new drug development. Although several cell-specific intracellular mechanisms contribute to the anti-tumor activity of metformin, the inhibition of the chloride intracellular channel 1 activity (CLIC1) at G1/S transition is a key events in metformin antiproliferative effect in glioblastoma stem cells (GSCs). Here we tested several known biguanide-related drugs for the ability to affect glioblastoma (but not normal) stem cell viability, and in particular: phenformin, a withdrawn antidiabetic drug; moroxydine, a former antiviral agent; and proguanil, an antimalarial compound, all of them possessing a linear biguanide structure as metformin; moreover, we evaluated cycloguanil, the active form of proguanil, characterized by a cyclized biguanide moiety. All these drugs caused a significant impairment of GSC proliferation, invasiveness, and self-renewal reaching IC50values significantly lower than metformin, (range 0.054-0.53 mM vs. 9.4 mM of metformin). All biguanides inhibited CLIC1-mediated ion current, showing the same potency observed in the antiproliferative effects, with the exception of proguanil which was ineffective. These effects were specific for GSCs, since no (or little) cytotoxicity was observed in normal umbilical cord mesenchymal stem cells, whose viability was not affected by metformin and moroxydine, while cycloguanil and phenformin induced toxicity only at much higher concentrations than required to reduce GSC proliferation or invasiveness. Conversely, proguanil was highly cytotoxic also for normal mesenchymal stem cells. In conclusion, the inhibition of CLIC1 activity represents a biguanide class-effect to impair GSC viability, invasiveness, and self-renewal, although dissimilarities among different drugs were observed as far as potency, efficacy and selectivity as CLIC1 inhibitors. Being CLIC1 constitutively active in GSCs, this feature is relevant to grant the molecules with high specificity toward GSCs while sparing normal cells. These results could represent the basis for the development of novel biguanidestructured molecules, characterized by high antitumor efficacy and safe toxicological profile

WldS protein requires Nmnat activity and a short N-terminal sequence to protect axons in mice

The slow Wallerian degeneration (WldS) protein protects injured axons from degeneration. This unusual chimeric protein fuses a 70–amino acid N-terminal sequence from the Ube4b multiubiquitination factor with the nicotinamide adenine dinucleotide–synthesizing enzyme nicotinamide mononucleotide adenylyl transferase 1. The requirement for these components and the mechanism of WldS-mediated neuroprotection remain highly controversial. The Ube4b domain is necessary for the protective phenotype in mice, but precisely which sequence is essential and why are unclear. Binding to the AAA adenosine triphosphatase valosin-containing protein (VCP)/p97 is the only known biochemical property of the Ube4b domain. Using an in vivo approach, we show that removing the VCP-binding sequence abolishes axon protection. Replacing the WldS VCP-binding domain with an alternative ataxin-3–derived VCP-binding sequence restores its protective function. Enzyme-dead WldS is unable to delay Wallerian degeneration in mice. Thus, neither domain is effective without the function of the other. WldS requires both of its components to protect axons from degeneration