La violenza sull'anziano: Aspetti medico-legali di una problematica sommersa

L’abuso dell’anziano è una condizione estremamente diffusa e ha un grande costo umano e finanziario. La dimensione reale del problema del maltrattamento dell’anziano non è stata correttamente definita, in particolare i casi segnalati ufficialmente di abuso sono solo la "punta dell'iceberg". In questi anni il problema è stato riconosciuto a livello internazionale come un fenomeno comune, che viene sottostimato e degno di attenzione da parte della comunità scientifica. In Italia non ci sono molti dati, la prevalenza degli abusi e maltrattamenti può essere circa il 5% e il problema è ampiamente sottovalutato, perché sono scarse le segnalazioni di abusi. Le evidenze disponibili dimostrano che l'abuso sugli anziani in Italia costituisce una questione pubblica, tuttavia, la legislazione e le politiche per affrontare il fenomeno sono scarse, riflettendo la mancanza di una strategia nazionale coerente e globale. Il codice civile italiano non contiene alcun riferimento esplicito a persone anziane, e pochi sono anche gli articoli del codice penale che riguardano le persone anziane. Gli articoli più rilevanti interessate sono le seguenti: art. 572: "Maltrattamenti contro familiari e conviventi" e art. 643: "circonvenzione di persone incapaci". Il presente studio ha lo scopo di analizzare la situazione attuale del fenomeno nel nostro Paese, al fine di valutare la dimensione del problema e le relazioni di abuso e maltrattamenti tra vittime, caregiver e operatori sanitari alle autorità.

Staphylococcus aureus bones and joints infections: in vivo studies and host immune response

Abstract The aim of this work was the development of a murine model of septic arthrosynovitis and osteomyelitis caused by Staphylococcus aureus, which could mimic the natural disease occurring in humans and which could be suitable for testing preventive and therapeutic interventions. This model could be particularly useful since S. aureus-mediated joints and bones infections are relevant in humans, both in terms of frequency and severity. Our attention focused in tracking bacterial infiltration in joints and bones over time using different microbiological and hystopathological tools, which allowed us to have a complete overview of the situation and to evaluate the immunological actions undertaken by the host to contain or eradicate the bacterial infection. Antibodies and cytokines profiles, as well as recruitment of host immune cells at joints of immunized and infected mice were therefore monitored for a time period that allowed us to study both the acute and the chronic phases of the disease in situ. Finally the Novartis vaccine formulation proposed against S. aureus infections was tested for its capacity to protect immunized mice from joints infections, and the preventive immunization was compared to a standard antibiotic prophylaxis. The availability of powerful tools to study specific bacterial-mediated diseases is nowadays an important requirement for the scientific community to shed light on the complex interactions between host and pathogens and to test treatments for preventing or contrasting infections. We believe that our work significantly contributes to the overall knowledge in the field of S. aureus-dependent pathologies, opening the possibility for further investigations in several fields of study.

The porcine animal model goes through the 3Rs: development of in vitro and ex vivo system to study vascular biology

Since the publication of the book of Russell and Burch in 1959, scientific research has never stopped improving itself with regard to the important issue of animal experimentation. The European Directive 2010/63/EU “On the protection of animals used for scientific purposes” focuses mainly on the animal welfare, fixing the Russell and Burch’s 3Rs principles as the foundations of the document. In particular, the legislator clearly states the responsibility of the scientific community to improve the number of alternative methods to animal experimentation. The swine is considered a species of relevant interest for translational research and medicine due to its biological similarities with humans. The surgical community has, in fact, recognized the swine as an excellent model replicating the human cardiovascular system. There have been several wild-type and transgenic porcine models which were produced for biomedicine and translational research. Among these, the cardiovascular ones are the most represented. The continuous involvement of the porcine animal model in the biomedical research, as the continuous advances achieved using swine in translational medicine, support the need for alternative methods to animal experimentation involving pigs. The main purpose of the present work was to develop and characterize novel porcine alternative methods for cardiovascular translational biology/medicine. The work was mainly based on two different models: the first consisted in an ex vivo culture of porcine aortic cylinders and the second consisted in an in vitro culture of porcine aortic derived progenitor cells. Both the models were properly characterized and results indicated that they could be useful to the study of vascular biology. Nevertheless, both the models aim to reduce the use of experimental animals and to refine animal based-trials. In conclusion, the present research aims to be a small, but significant, contribution to the important and necessary field of study of alternative methods to animal experimentation.

Procedimento legislativo e qualita' della legislazione. Criticita' e prospettive

La tesi riprende un tema che è stato oggetto in passato di studi anche molto approfonditi; oggi sembra essere tornato alla ribalta grazie ad alcuni contributi che hanno nuovamente stimolato la dottrina a confrontarsi su aspetti così delicati anche alla luce della crisi economica. E'stato da sempre rilevato che la buona scrittura delle norme è un fattore fondamentale per il rilancio dell’economia del paese, per la semplificazione e per garantire ordine, coerenza e chiarezza all’ordinamento giuridico. La prima parte è incentrata su una ricostruzione storica e giuridica delle fonti che hanno disciplinato le “regole per la qualità delle regole”, oltre ad una panoramica della dottrina che si è occupata in passato del tema. Segue l’individuazione specifica di quali sono le regole formali e sostanziali di drafting. In particolare, una parte è dedicata alla giurisprudenza costituzionale per comprendere se esiste o meno un aggancio per la Corte Costituzionale da permetterle il sindacato sulle “regole oscure” e dichiararle illegittime. La seconda parte analizza le pressai, in particolare si è scelto di analizzare il rapporto tra Governo e Parlamento nelle problematiche principali che attengono al procedimento legislativo e alla cornice entro la quale viene esplicato in relazione alla decretazione d’urgenza, maxiemendamenti, questione di fiducia, istruttoria in commissione, gruppi di pressione. Ciò che è stato rilevato, è una scarsa aderenza ai principi e ai criteri di better regulation, peraltro difficilmente giustiziabili da parte della Corte costituzionale e sottratti al controllo di chi, al contrario, ha competenza in questo settore, ossia il Comitato per la legislazione e il DAGL. Le conclusioni, pertanto, prendono le mosse da una serie di criticità rilevate e tentano di tracciare una strada da percorrere che sia rispettosa dei canoni della “better regulation” anche alla luce delle riforme costituzionali e dei regolamenti parlamentari in corso di approvazione.

Cascading events triggering industrial accidents: quantitative assessment of NaTech and domino scenarios

The so called cascading events, which lead to high-impact low-frequency scenarios are rising concern worldwide. A chain of events result in a major industrial accident with dreadful (and often unpredicted) consequences. Cascading events can be the result of the realization of an external threat, like a terrorist attack a natural disaster or of “domino effect”. During domino events the escalation of a primary accident is driven by the propagation of the primary event to nearby units, causing an overall increment of the accident severity and an increment of the risk associated to an industrial installation. Also natural disasters, like intense flooding, hurricanes, earthquake and lightning are found capable to enhance the risk of an industrial area, triggering loss of containment of hazardous materials and in major accidents. The scientific community usually refers to those accidents as “NaTechs”: natural events triggering industrial accidents. In this document, a state of the art of available approaches to the modelling, assessment, prevention and management of domino and NaTech events is described. On the other hand, the relevant work carried out during past studies still needs to be consolidated and completed, in order to be applicable in a real industrial framework. New methodologies, developed during my research activity, aimed at the quantitative assessment of domino and NaTech accidents are presented. The tools and methods provided within this very study had the aim to assist the progress toward a consolidated and universal methodology for the assessment and prevention of cascading events, contributing to enhance safety and sustainability of the chemical and process industry.

NMR Based Foodomics to Investigate the Digestibility of Protein-Rich Food Products

Nowadays, in developed countries, the excessive food intake, in conjunction with a decreased physical activity, has led to an increase in lifestyle-related diseases, such as obesity, cardiovascular diseases, type -2 diabetes, a range of cancer types and arthritis. The socio-economic importance of such lifestyle-related diseases has encouraged countries to increase their efforts in research, and many projects have been initiated recently in research that focuses on the relationship between food and health. Thanks to these efforts and to the growing availability of technologies, the food companies are beginning to develop healthier food. The necessity of rapid and affordable methods, helping the food industries in the ingredient selection has stimulated the development of in vitro systems that simulate the physiological functions to which the food components are submitted when administrated in vivo. One of the most promising tool now available appears the in vitro digestion, which aims at predicting, in a comparative way among analogue food products, the bioaccessibility of the nutrients of interest.. The adoption of the foodomics approach has been chosen in this work to evaluate the modifications occurring during the in vitro digestion of selected protein-rich food products. The measure of the proteins breakdown was performed via NMR spectroscopy, the only techniques capable of observing, directly in the simulated gastric and duodenal fluids, the soluble oligo- and polypeptides released during the in vitro digestion process. The overall approach pioneered along this PhD work, has been discussed and promoted in a large scientific community, with specialists networked under the INFOGEST COST Action, which recently released a harmonized protocol for the in vitro digestion. NMR spectroscopy, when used in tandem with the in vitro digestion, generates a new concept, which provides an additional attribute to describe the food quality: the comparative digestibility, which measures the improvement of the nutrients bioaccessibility.

Nonlinear Approaches to Attitude Control Using Magnetic and Mechanical Actuation

This thesis argues the attitude control problem of nanosatellites, which has been a challenging issue over the years for the scientific community and still constitutes an active area of research. The interest is increasing as more than 70% of future satellite launches are nanosatellites. Therefore, new challenges appear with the miniaturisation of the subsystems and improvements must be reached. In this framework, the aim of this thesis is to develop novel control approaches for three-axis stabilisation of nanosatellites equipped with magnetorquers and reaction wheels, to improve the performance of the existent control strategies and demonstrate the stability of the system. In particular, this thesis is focused on the development of non-linear control techniques to stabilise full-actuated nanosatellites, and in the case of underactuation, in which the number of control variables is less than the degrees of freedom of the system. The main contributions are, for the first control strategy proposed, to demonstrate global asymptotic stability derived from control laws that stabilise the system in a target frame, a fixed direction of the orbit frame. Simulation results show good performance, also in presence of disturbances, and a theoretical selection of the magnetic control gain is given. The second control approach presents instead, a novel stable control methodology for three-axis stabilisation in underactuated conditions. The control scheme consists of the dynamical implementation of an attitude manoeuvre planning by means of a switching control logic. A detailed numerical analysis of the control law gains and the effect on the convergence time, total integrated and maximum torque is presented demonstrating the good performance and robustness also in the presence of disturbances.

Deposition of thin films by a non-equilibrium atmospheric pressure Plasma Jet: a poly-diagnostic study

The use of atmospheric pressure plasmas for thin film deposition on thermo-sensitive materials is currently one of the main challenges of the plasma scientific community. Despite the growing interest in this field, the existing knowledge gap between gas-phase reaction mechanisms and thin film properties is still one of the most important barriers to overcome for a complete understanding of the process. In this work, thin films surface characterization techniques, combined with passive and active gas-phase diagnostic methods, were used to provide a comprehensive study of the Ar/TEOS deposition process assisted by an atmospheric pressure plasma jet. SiO2-based thin films exhibiting a well-defined chemistry, a good morphological structure and high uniformity were studied in detail by FTIR, XPS, AFM and SEM analysis. Furthermore, non-intrusive spectroscopy techniques (OES, filter imaging) and laser spectroscopic methods (Rayleigh scattering, LIF and TALIF) were employed to shed light on the complexity of gas-phase mechanisms involved in the deposition process and discuss the influence of TEOS admixture on gas temperature, electron density and spatial-temporal behaviours of active species. The poly-diagnostic approach proposed in this work opens interesting perspectives both in terms of process control and optimization of thin film performances.

Enabling Human Centric Smart Campuses via Edge Computing and Connected Objects

Early definitions of Smart Building focused almost entirely on the technology aspect and did not suggest user interaction at all. Indeed, today we would attribute it more to the concept of the automated building. In this sense, control of comfort conditions inside buildings is a problem that is being well investigated, since it has a direct effect on users’ productivity and an indirect effect on energy saving. Therefore, from the users’ perspective, a typical environment can be considered comfortable, if it’s capable of providing adequate thermal comfort, visual comfort and indoor air quality conditions and acoustic comfort. In the last years, the scientific community has dealt with many challenges, especially from a technological point of view. For instance, smart sensing devices, the internet, and communication technologies have enabled a new paradigm called Edge computing that brings computation and data storage closer to the location where it is needed, to improve response times and save bandwidth. This has allowed us to improve services, sustainability and decision making. Many solutions have been implemented such as smart classrooms, controlling the thermal condition of the building, monitoring HVAC data for energy-efficient of the campus and so forth. Though these projects provide to the realization of smart campus, a framework for smart campus is yet to be determined. These new technologies have also introduced new research challenges: within this thesis work, some of the principal open challenges will be faced, proposing a new conceptual framework, technologies and tools to move forward the actual implementation of smart campuses. Keeping in mind, several problems known in the literature have been investigated: the occupancy detection, noise monitoring for acoustic comfort, context awareness inside the building, wayfinding indoor, strategic deployment for air quality and books preserving.

Design and Synthesis of Novel Kinase Inhibitors for the Treatment of Chronic Respiratory Diseases

In 2017, Chronic Respiratory Diseases accounted for almost four million deaths worldwide. Unfortunately, current treatments are not definitive for such diseases. This unmet medical need forces the scientific community to increase efforts in the identification of new therapeutic solutions. PI3K delta plays a key role in mechanisms that promote airway chronic inflammation underlying Asthma and COPD. The first part of this project was dedicated to the identification of novel PI3K delta inhibitors. A first SAR expansion of a Hit, previously identified by a HTS campaign, was carried out. A library of 43 analogues was synthesised taking advantage of an efficient synthetic approach. This allowed the identification of an improved Hit of nanomolar enzymatic potency and moderate selectivity for PI3K delta over other PI3K isoforms. However, this compound exhibited low potency in cell-based assays. Low cellular potency was related to sub optimal phys-chem and ADME properties. The analysis of the X-ray crystal structure of this compound in human PI3K delta guided a second tailored SAR expansion that led to improved cellular potency and solubility. The second part of the thesis was focused on the rational design and synthesis of new macrocyclic Rho-associated protein kinases (ROCKs) inhibitors. Inhibition of these kinases has been associated with vasodilating effects. Therefore, ROCKs could represent attractive targets for the treatment of pulmonary arterial hypertension (PAH). Known ROCK inhibitors suffer from low selectivity across the kinome. The design of macrocyclic inhibitors was considered a promising strategy to obtain improved selectivity. Known inhibitors from literature were evaluated for opportunities of macrocyclization using a knowledge-based approach supported by Computer Aided Drug Design (CADD). The identification of a macrocyclic ROCK inhibitor with enzymatic activity in the low micro molar range against ROCK II represented a promising result that validated this innovative approach in the design of new ROCKs inhibitors.

Analytical instrumental approaches and strategies to support the sensory assessment of virgin olive oils

At the beginning, this Ph.D. project led to an overview of the most common and emerging types of fraud and possible countermeasures in the olive oil sector. Furthermore, possible weaknesses in the current conformity check system for olive oil were highlighted. Among those, despite the organoleptic assessment is a fundamental tool for establishing the virgin olive oils (VOOs) quality grade, the scientific community has evidenced some drawbacks in it. In particular, the application of instrumental screening methods to support the panel test could reduce the work of sensory panels and the cost of this analysis (e.g. for industries, distributors, public and private control laboratories), permitting the increase in the number and the efficiency of the controls. On this basis, a research line called “Quantitative Panel Test” is one of the main expected outcomes of the OLEUM project that is also partially discussed in this doctoral dissertation. In this framework, analytical activities were carried out, within this PhD project, aimed to develop and validate analytical protocols for the study of the profiles in volatile compounds (VOCs) of the VOOs headspace. Specifically, two chromatographic approaches, one targeted and one semi-targeted, to determine VOCs were investigated in this doctoral thesis. The obtained results, will allow the possible establishment of concentration limits and ranges of selected volatile markers, as related to fruitiness and defects, with the aim to support the panel test in the commercial categorization of VOOs. In parallel, a rapid instrumental screening method based on the analysis of VOCs has been investigated to assist the panel test through a fast pre-classification of VOOs samples based on a known level of probability, thus increasing the efficiency of quality control.

Efficacia del Tocilizumab nel trattamaneto del rigetto umorale cronico attivo nel paziente trapiantato di rene

In the last decades significant improvements has been reached in short term graft survival, conversely long-term graft survival in still an open challenge for the scientific community. One of the major causes of long term graft loss is represented by chronic- active antibody mediated rejection (cAMR), a recently identified entity whose diagnosis is based on laboratoristic and histologic elements: the presence of DSA associated to specific morphological lesions as inflammation and microvascular damage associated or not to C4d deposition. Treatment of cAMR is an open field of debate. Tocilizumab, an anti-IL6 monoclonal antibody has been recently proposed as a first line treatment for cAMR, showing encouranging results. We describe our monocentric experience using Tocilizumab as first-line therapy for cAMR. Graft function (eGFR), proteinuria and DSA have been evaluated every 6 month for 24 months; histology have been performed after 12 months of treatment. No adverse events have been observed during study period. 12 patients completed the study with a follow-up of 24 months. Kidney function showed a worsening during follow-up that reaches statistical significance at 12 and 24 months (eGFR from 32.2±13.9 ml/min to 26.9±13 ml/min), but far less than expected for these kind of patients. 4 patients (30%) reached ESRD during follow-up, 3 requiring renal replacement therapy. We did not observed any statically significant variation in proteinuria and in DSA MFI levels. From a histological point of view, we observed a significant improvement in active cAMR lesions (C4d deposition and Acute tissue injury (MTA, g>0/ptc>0, v>0) and no progression among chronic lesions (Transplant glomerulopathy, PTC multilayering and aterial intimal fibrosis) Tocilizumab shown good results, with a stabilization of graft function, a reduction in kidney inflammation and active lesions in kidney biopsy and not allowing progression of chronic lesions.

Il testo esposto. Forme iconotestuali ed ecfrastiche nella letteratura italiana contemporanea (1988-2021)

A partire dal dibattito teorico proposto dalla comunità scientifica, che afferma che negli iconotesti le immagini non illustrano il testo e i testi non descrivono le immagini, e che tra i due linguaggi esiste un rapporto di insubordinazione e conflitto, l’obiettivo principale della mia tesi è quello di individuare come tale rapporto prenda forma in un corpus composto da autori italiani (Daniele Del Giudice, Umberto Eco, Michele Mari, Giorgio Agamben, Tommaso Pincio, Filippo Tuena, Emanuele Trevi, Antonella Anedda) e stranieri (John Berger, Sophie Calle, W. G. Sebald, Julio Cortázar, Orhan Pamuk, Jorge Luis Borges). Dopo aver tracciato la storia dell'iconotesto, la tesi si propone di definire una nuova categoria di iconotesto, in cui immagini e testi sono esposti all'interno di altre immagini. Può trattarsi di fotografie scattate dagli autori o da altri fotografi, oppure di immagini d'archivio. L’obiettivo è quello di mostrare le influenze formali del "Bilderatlas Mnemosyne" di Aby Warburg nel corpus selezionato e di verificare come questa tipologia sia sempre più diffusa nella letteratura contemporanea, come proiezione di una tendenza all'ipertestualità: ricorrono alcuni elementi come il montaggio, la mise en abyme, la ripetizione e il dettaglio, e una particolare forma di ekphrasis-didascalia, secondo cui la presenza dell'immagine implica una metamorfosi della concezione tradizionale del testo che descrive un'immagine, attraverso il passaggio dalla descrizione alla mostrazione.

CO2 utilization and alternative solvents: effective tools for sustainable applications

The growing concentration of CO2 in the atmosphere and its harmful consequences has led the scientific community to direct its efforts towards sustainable processes. Among the possible approaches, the use of CO2 and alternative solvents are two strategies that are having widespread diffusion. In this work the reuse of CO2 is expressed by using it as a reaction reagent and as trigger to change the physical properties of a catalyst thus facilitating its recovery. As regards the CO2 use as reagent, two catalytic systems have been developed for the conversion of CO2 and epoxides into cyclic carbonates, used in the synthesis of polymers and as aprotic solvents. Homogeneous catalysts made by choline-based eutectic mixtures and heterogeneous catalysts made from biopolymers and waste pyrolysis have been synthesized and tested on this reaction. The carbonate interchange reaction (CIR) of a diol with a linear carbonate (as dimethyl carbonate) is an interesting alternative, for the synthesis of cyclic carbonates; as the second application of CO2 as polarity trigger, it was used for catalyst recovery. In fact DBU, here used as catalyst, is part of the so called “switchable solvents”: they can pass from a less-polar to a more-polar form (and from being soluble to non-soluble in the reaction mixture) when reacting with CO2 in presence of water or alcohols. Also in this case, heterogeneous catalysts made from biopolymers and waste pyrolysis have been synthesized and tested on CIR. As for the use of alternative solvents, this work focuses on the use of Deep Eutectic Solvents (DESs). They are a new generation of solvents composed by a mixture of two or more substances, liquid at room temperature, and non-volatile. New and biobased DESs were here used: i) as reaction media to carry out chemoenzymatic epoxidation; ii) in the extraction of astaxanthin from microalgae culture.

Sustainability in buildings and waste sector: metrics, challanges, and opportunities

Nowadays, the scientific community has devoted a consistent effort to the sustainable development of the waste management sector and resource efficiency in building infrastructures. Waste is the fourth largest source sector of emissions and the municipal solid waste management system is considered as the most complex system to manage, due to its diverse composition and fragmentation of producers and responsibilities. Nevertheless, given the deep complexity that characterize the waste management sector, sustainability is still a challenging task. Interestingly, open issues arise when dealing with the sustainability of the waste sector. In this thesis, some recent advances in the waste management sector have been presented. Specifically, through the analysis of four author publications this thesis attempted to fill the gap in the following open issues: (i) the waste collection and generation of waste considering the pillars of sustainability; (ii) the environmental and social analysis in designing building infrastructures; (iv) the role of the waste collection in boosting sustainable systems of waste management; (v) the ergonomics impacts of waste collection. For this purpose, four author publications in international peer – reviewed journals were selected among the wholly author's contributions (i.e., final publication stage).