Genetic Manipulation, Gene Silencing and Biomarker Development in Multiple Experimental Models.

The thesis is set in three different parts, according to the relative experimental models. First, the domestic pig (Sus scrofa) is part of the study on reproductive biotechnologies: the transgenesis technique of Sperm Mediated Gene Transfer is widely studied starting from the quality of the semen, through the study of multiple uptakes of exogenous DNA and lastly used in the production of multi-transgenic blastocysts. Finally we managed to couple the transgenesis pipeline with sperm sorting and therefore produced transgenic embryos of predetermined sex. In the second part of the thesis the attention is on the fruit fly (Drosophila melanogaster) and on its derived cell line: the S2 cells. The in vitro and in vivo models are used to develop and validate an efficient way to knock down the myc gene. First an efficient in vitro protocol is described, than we demonstrate how the decrease in myc transcript remarkably affects the ribosome biogenesis through the study of Polysome gradients, rRNA content and qPCR. In vivo we identified two optimal drivers for the conditional silencing of myc, once the flies are fed with RU486: the first one is throughout the whole body (Tubulin), while the second is a head fat body driver (S32). With these results we present a very efficient model to study the role of myc in multiple aspects of translation. In the third and last part, the focus is on human derived lung fibroblasts (hLF-1), mouse tail fibroblasts and mouse tissues. We developed an efficient assay to quantify the total protein content of the nucleus on a single cell level via fluorescence. We coupled the protocol with classical immunofluorescence so to have at the same time general and particular information, demonstrating that during senescence nuclear proteins increase by 1.8 fold either in human cells, mouse cells and mouse tissues.

Sviluppo di un approccio congiunto fuzzy-Bayesiano per l'analisi e la modellizzazione degli ecosistemi: applicazione ad ecosistemi marini costieri.

Nell’attuale contesto di aumento degli impatti antropici e di “Global Climate Change” emerge la necessità di comprenderne i possibili effetti di questi sugli ecosistemi inquadrati come fruitori di servizi e funzioni imprescindibili sui quali si basano intere tessiture economiche e sociali. Lo studio previsionale degli ecosistemi si scontra con l’elevata complessità di questi ultimi in luogo di una altrettanto elevata scarsità di osservazioni integrate. L’approccio modellistico appare il più adatto all’analisi delle dinamiche complesse degli ecosistemi ed alla contestualizzazione complessa di risultati sperimentali ed osservazioni empiriche. L’approccio riduzionista-deterministico solitamente utilizzato nell’implementazione di modelli non si è però sin qui dimostrato in grado di raggiungere i livelli di complessità più elevati all’interno della struttura eco sistemica. La componente che meglio descrive la complessità ecosistemica è quella biotica in virtù dell’elevata dipendenza dalle altre componenti e dalle loro interazioni. In questo lavoro di tesi viene proposto un approccio modellistico stocastico basato sull’utilizzo di un compilatore naive Bayes operante in ambiente fuzzy. L’utilizzo congiunto di logica fuzzy e approccio naive Bayes è utile al processa mento del livello di complessità e conseguentemente incertezza insito negli ecosistemi. I modelli generativi ottenuti, chiamati Fuzzy Bayesian Ecological Model(FBEM) appaiono in grado di modellizare gli stati eco sistemici in funzione dell’ elevato numero di interazioni che entrano in gioco nella determinazione degli stati degli ecosistemi. Modelli FBEM sono stati utilizzati per comprendere il rischio ambientale per habitat intertidale di spiagge sabbiose in caso di eventi di flooding costiero previsti nell’arco di tempo 2010-2100. L’applicazione è stata effettuata all’interno del progetto EU “Theseus” per il quale i modelli FBEM sono stati utilizzati anche per una simulazione a lungo termine e per il calcolo dei tipping point specifici dell’habitat secondo eventi di flooding di diversa intensità.

Design and Development of Network Monitoring Strategies in P4-enabled Programmable Switches

Network monitoring is of paramount importance for effective network management: it allows to constantly observe the network’s behavior to ensure it is working as intended and can trigger both automated and manual remediation procedures in case of failures and anomalies. The concept of SDN decouples the control logic from legacy network infrastructure to perform centralized control on multiple switches in the network, and in this context, the responsibility of switches is only to forward packets according to the flow control instructions provided by controller. However, as current SDN switches only expose simple per-port and per-flow counters, the controller has to do almost all the processing to determine the network state, which causes significant communication overhead and excessive latency for monitoring purposes. The absence of programmability in the data plane of SDN prompted the advent of programmable switches, which allow developers to customize the data-plane pipeline and implement novel programs operating directly in the switches. This means that we can offload certain monitoring tasks to programmable data planes, to perform fine-grained monitoring even at very high packet processing speeds. Given the central importance of network monitoring exploiting programmable data planes, the goal of this thesis is to enable a wide range of monitoring tasks in programmable switches, with a specific focus on the ones equipped with programmable ASICs. Indeed, most network monitoring solutions available in literature do not take computational and memory constraints of programmable switches into due account, preventing, de facto, their successful implementation in commodity switches. This claims that network monitoring tasks can be executed in programmable switches. Our evaluations show that the contributions in this thesis could be used by network administrators as well as network security engineers, to better understand the network status depending on different monitoring metrics, and thus prevent network infrastructure and service outages.

QTL mapping identifies novel major loci for ear fasciation, ear prolificacy and tillering in maize (ZEA MAYS L.)

Maize ear fasciation originates from excessive or abnormal proliferation of the ear meristem and usually manifests as multiple-tipped ear, ear flatness and/or disordered kernel arrangement. Ear prolificacy expresses as multiple ears per node. Both traits can affect grain yield. In this study, the genetic control of the two traits was analyzed using two recombinant inbred lines (RIL) populations (B73 × Lo1016 and Lo964 × Lo1016) with Lo1016 and Lo964 as donors of ear fasciation and prolificacy, respectively. Four ear fasciation-related traits (ear fasciation, kernel distribution and ear ovality indexes and ratio of ear diameters), number of kernel rows, ear prolificacy and number of tillers were phenotyped in multi-year field experiments. Ear fasciation traits and number of kernel rows showed relatively high heritability (h2 > 0.5) except ratio of ear diameters, and showed correlation. Prolificacy and tillering h2 ranged 0.41 - 0.78 and did not correlate. QTL mapping identified four QTL for ear fasciation, on chr. 1 (two QTLs), 5 and 7, the latter two overlapping with QTLs for number of kernel rows. However, the strongest effect QTL for number of kernel rows mapped on chr. 2 independently from ear fasciation. Four and five non-overlapping QTLs were mapped for ear prolificacy and tillering, respectively. Two ear fasciation QTLs from this study, qFas1.2 and qFas7, overlapped with formerly known fasciation QTLs and spanned candidate genes expressed in ear meristems namely compact plant2 and ramosa1. Our study identified novel ear fasciation, ear prolificacy and tillering loci which are unexpectedly still segregating in elite maize materials, and provides foundation for genomics-assisted breeding for yield components

Sealing practices in the Near East during the Late Bronze II period: administration and trade in the age of internationalism

This PhD research investigates sealing practices in the Near East during the Late Bronze II period (ca. 1375-1175 BCE). Sealings from archaeological contexts in the Southern Levant, North Syria, Upper and Lower Mesopotamia and South-Western Iran are taken under consideration and analyzed on multiple aspects at local, regional, and international levels. The contextual, functional, and iconographic analysis of these materials, in fact, allows to reconstruct the nature of the transactions and the agents involved in the sealing operations within local administrative systems, highlighting at the same time aspects of inter-regional interactions during the age of internationalism. Following a survey of the available evidence, a corpus consisting of 1845 records from 28 different sites across the ANE, has been filed using MS Access and MS Excel, including 740 unpublished sealing from Karkemish. Among this large evidence, the corpus of recently discovered sealings from Karkemish and the other scattered sealings from the North Syrian provinces, for instance, provide insights on the core-periphery relationships under the Hittite Empire; while the deposit from Building P at Tell Sheikh Hamad, that of the Middle Assyrian houses at Tell Fekheriye, and of the dunnu of Tell Sabi Abyad, significantly contributes to defining the administration of provinces within the Middle Assyrian state and the regional circulation of good. The less extensive evidence from South Mesopotamia under the Kassite rule and from Middle Elamite contexts in South-Western Iran somewhat contribute as well to the understanding of sealing practices in the LB II period. The South Levantine kingdoms, on the other hand, seems participates to the Egyptian regional network of exchanges and sealing practices.

Mass-transport deposits on Mediterranean continental margins

Extensive mass transport deposits and multiple slide scars testify widespread and recurrent submarine sediment failures occurring during the late Quaternary on the SW-Adriatic and SE-Sicilian margins. These mass movements and their consequences contributed to shape the continental slopes and fill the basins with characteristic signatures. Geomorphological, seismo-stratigraphic, sedimentological and biostratigraphic data provide clues to: 1) define distinct failure mechanisms investigating on factors that determine dissimilar organization of coeval displaced masses, 2) reconstruct successive phases of failure stressing on the same location where slide scars crosscut and mass-transport deposits overlap, 3) analyze regional setting and indicate the most suitable place where to calculate mass wasting frequency. Discussions on the role of fluid flow, currents activity and tectonic deformation determine a wider view on the construction of the studied continental margins.

La costruzione razionale della casa. Scritti e progetti di Giuseppe Pagano

The rational construction of the house. The writings and projects of Giuseppe Pagano Description, themes and research objectives The research aims at analysing the architecture of Giuseppe Pagano, which focuses on the theme of dwelling, through the reading of 3 of his house projects. On the one hand, these projects represent “minor” works not thoroughly known by Pagano’s contemporary critics; on the other they emphasise a particular methodological approach, which serves the author to explore a theme closely linked to his theoretical thought. The house project is a key to Pagano’s research, given its ties to the socio-cultural and political conditions in which the architect was working, so that it becomes a mirror of one of his specific and theoretical path, always in a state of becoming. Pagano understands architecture as a “servant of the human being”, subject to a “utilitarian slavery” since it is a clear, essential and “modest” answer to specific human needs, free from aprioristic aesthetic and formal choices. It is a rational architecture in sensu stricto; it constitutes a perfect synthesis between cause and effect and between function and form. The house needs to accommodate these principles because it is closely intertwined with human needs and intimately linked to a specific place, climatic conditions and technical and economical possibilities. Besides, differently from his public and common masterpieces such as the Palazzo Gualino, the Istituto di Fisica and the Università Commerciale Bocconi, the house projects are representative of a precise project will, which is expressed in a more authentic way, partially freed from political influences and dogmatic preoccupations and, therefore, far from the attempt to research a specific expressive language. I believe that the house project better represents that “ingenuity”, freshness and “sincerity” that Pagano identifies with the minor architecture, thereby revealing a more authentic expression of his understanding of a project. Therefore, the thesis, by tracing the theoretical research of Pagano through the analysis of some of his designed and built works, attempts to identify a specific methodological approach to Pagano’s project, which, developed through time, achieves a certain clarity in the 1930s. In fact, this methodological approach becomes more evident in his last projects, mainly regarding the house and the urban space. These reflect the attempt to respond to the new social needs and, at the same time, they also are an expression of a freer idea of built architecture, closely linked with the place and with the human being who dwells it. The three chosen projects (Villa Colli, La Casa a struttura d’acciaio and Villa Caraccio) make Pagano facing different places, different customers and different economic and technical conditions, which, given the author’s biography, correspond to important historical and political conditions. This is the reason why the projects become apparently distant works, both linguistically and conceptually, to the point that one can define them as ”eclectic”. However, I argue that this eclecticism is actually an added value to the architectural work of Pagano, steaming from the use of a method which, having as a basis the postulate of a rational architecture as essence and logic of building, finds specific variations depending on the multiple variables to be addressed by the project. This is the methodological heritage that Pagano learns from the tradition, especially that of the rural residential architecture, defined by Pagano as a “dictionary of the building logic of man”, as an “a-stylistic background”. For Pagano this traditional architecture is a clear expression of the relationships between a theme and its development, an architectural “fact” that is resolved with purely technical and utilitarian aims and with a spontaneous development far from any aprioristic theoretical principle. Architecture, therefore, cannot be an invention for Pagano and the personal contribution of each architect has to consider his/her close relationship with the specific historical context, place and new building methods. These are basic principles in the methodological approach that drives a great deal of his research and that also permits his thought to be modern. I argue that both ongoing and new collaborations with younger protagonists of the culture and architecture of the period are significant for the development of his methodology. These encounters represent the will to spread his own understanding of the “new architecture” as well as a way of self-renewal by confronting the self with new themes and realities and by learning from his collaborators. Thesis’ outline The thesis is divided in two principal parts, each articulated in four chapters attempting to offer a new reading of the theory and work of Pagano by emphasising the central themes of the research. The first chapter is an introduction to the thesis and to the theme of the rational house, as understood and developed in its typological and technical aspects by Pagano and by other protagonists of the Italian rationalism of the 1930s. Here the attention is on two different aspects defining, according to Pagano, the house project: on the one hand, the typological renewal, aimed at defining a “standard form” as a clear and essential answer to certain needs and variables of the project leading to different formal expressions. On the other, it focuses on the building, understood as a technique to “produce” architecture, where new technologies and new materials are not merely tools but also essential elements of the architectural work. In this way the villa becomes different from the theme of the common house or from that of the minimalist house, by using rules in the choice of material and in the techniques that are every time different depending on the theme under exploration and on the contingency of place. It is also visible the rigorous rationalism that distinguishes the author's appropriation of certain themes of rural architecture. The pages of “Casabella” and the events of the contemporary Triennali form the preliminary material for the writing of this chapter given that they are primary sources to individuate projects and writings produced by Pagano and contemporary architects on this theme. These writings and projects, when compared, reconstruct the evolution of the idea of the rational house and, specifically, of the personal research of Pagano. The second part regards the reading of three of Pagano’s projects of houses as a built verification of his theories. This section constitutes the central part of the thesis since it is aimed at detecting a specific methodological approach showing a theoretical and ideological evolution expressed in the vast edited literature. The three projects that have been chosen explore the theme of the house, looking at various research themes that the author proposes and that find continuity in the affirmation of a specific rationalism, focussed on concepts such as essentiality, utility, functionality and building honesty. These concepts guide the thought and the activities of Pagano, also reflecting a social and cultural period. The projects span from the theme of the villa moderna, Villa Colli, which, inspired by the architecture of North Europe, anticipates a specific rationalism of Pagano based on rigour, simplicity and essentiality, to the theme of the common house, Casa a struttura d’acciaio, la casa del domani, which ponders on the definition of new living spaces and, moreover, on new concepts of standardisation, economical efficiency and new materials responding to the changing needs of the modern society. Finally, the third project returns to the theme of the, Villa Caraccio, revisiting it with new perspectives. These perspectives find in the solution of the open plant, in the openness to nature and landscape and in the revisiting of materials and local building systems that idea of the freed house, which express clearly a new theoretical thought. Methodology It needs to be noted that due to the lack of an official Archive of Pagano’s work, the analysis of his work has been difficult and this explains the necessity to read the articles and the drawings published in the pages of «Casabella» and «Domus». As for the projects of Villa Colli and Casa a struttura d’acciaio, parts of the original drawings have been consulted. These drawings are not published and are kept in private archives of the collaborators of Pagano. The consultation of these documents has permitted the analysis of the cited works, which have been subject to a more complete reading following the different proposed solutions, which have permitted to understand the project path. The projects are analysed thought the method of comparison and critical reading which, specifically, means graphical elaborations and analytical schemes, mostly reconstructed on the basis of original projects but, where possible, also on a photographic investigation. The focus is on the project theme which, beginning with a specific living (dwelling) typology, finds variations because of the historico-political context in which Pagano is embedded and which partially shapes his research and theoretical thought, then translated in the built work. The analysis of the work follows, beginning, where possible, from a reconstruction of the evolution of the project as elaborated on the basis of the original documents and ending on an analysis of the constructive principles and composition. This second phase employs a methodology proposed by Pagano in his article Piante di ville, which, as expected, focuses on the plant as essential tool to identify the “true practical and poetic qualities of the construction”(Pagano, «Costruzioni-Casabella», 1940, p. 2). The reading of the project is integrated with the constructive analyses related to the technical aspects of the house which, in the case of Casa a struttura d’acciaio, play an important role in the project, while in Villa Colli and in Villa Caraccio are principally linked to the choice of materials for the construction of the different architectural elements. These are nonetheless key factors in the composition of the work. Future work could extend this reading to other house projects to deepen the research that could be completed with the consultation of Archival materials, which are missing at present. Finally, in the appendix I present a critical selection of the Pagano’s writings, which recall the themes discussed and embodied by the three projects. The texts have been selected among the articles published in Casabella and in other journals, completing the reading of the project work which cannot be detached from his theoretical thought. Moving from theory to project, we follow a path that brings us to define and deepen the central theme of the thesis: rational building as the principal feature of the architectural research of Pagano, which is paraphrased in multiple ways in his designed and built works.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Valutazione dei disturbi cognitivi nei pazienti sottoposti a Rivascolarizzazione Carotidea (Endoarterectomia vs Stenting) mediante dosaggio di marker di danno neuronale, Mini Mental State Examination e Risonanza Magnetica

Scopo del nostro studio è quello di valutare i disturbi cognitivi in relazione al tasso di microembolia cerebrale in due gruppi di pazienti trattati per lesione carotidea asintomatica con endoarterectomia (CEA) o stenting (CAS). Comparando le due metodiche mediante l’utilizzo di risonanza magnetica in diffusione (DW-MRI), neuromarkers (NSE e S100β) e test neuropsicometrici. MATERIALE E METODI: 60 pazienti sono stati sottoposti a rivascolarizzazione carotidea (CEA n=32 e CAS n=28). Sono stati tutti valutati con DW-MRI e Mini-Mental State Examination (MMSE) test nel preoperatorio, a 24 ore, a 6 ed a 12 mesi dall’intervento. In tutti sono stati dosati i livelli sierici di NSE e S100β mediante 5 prelievi seriati nel tempo, quello basale nel preoperatorio, l’ultimo a 24 ore. L’ananlisi statistica è stata effettuata con test t di Student per confronti multipli per valori continui e con test χ2 quadro e Fisher per le variabili categoriche. Significatività P <0,05. RISULTATI: Non vi è stato alcun decesso. Un paziente del gruppo CAS ha presentato un ictus ischemico. In 6 pazienti CAS ed in 1 paziente CEA si sono osservate nuove lesioni subcliniche alla RMN-DWI post-operatoria (21,4% vs 3% p=0,03). Nel gruppo CAS le nuove lesioni presenti alla RMN sono risultate significativamente associate ad un declino del punteggio del MMSE (p=0,001). L’analisi dei livelli di NSE e S100β ha mostrato un significativo aumento a 24 ore nei pazienti CAS (P = .02). A 12 mesi i pazienti che avevano presentato nuove lesioni ischemiche nel post-operatorio hanno mostrato minor punteggio al MMSE, non statisticamente significativo. CONCLUSIONI: I neuromarkers in combinazione con MMSE e RMN-DWI possono essere utilizzati nella valutazione del declino cognitivo correlato a lesioni silenti nell’immediato postoperatorio di rivascolarizzazione carotidea. Quest’ultime dovrebbero essere valutate quindi non solo rispetto al tasso di mortalità e ictus, ma anche rispetto al tasso di microembolia.

Riabilitazione e valutazione di pazienti con deficit neurologici mediante l'utilizzo di realtà virtuale, feedback aumentati, sensori inerziali e tecnologie video a basso costo.

La neuroriabilitazione è un processo attraverso cui individui affetti da patologie neurologiche mirano al conseguimento di un recupero completo o alla realizzazione del loro potenziale ottimale benessere fisico, mentale e sociale. Elementi essenziali per una riabilitazione efficace sono: una valutazione clinica da parte di un team multidisciplinare, un programma riabilitativo mirato e la valutazione dei risultati conseguiti mediante misure scientifiche e clinicamente appropriate. Obiettivo principale di questa tesi è stato sviluppare metodi e strumenti quantitativi per il trattamento e la valutazione motoria di pazienti neurologici. I trattamenti riabilitativi convenzionali richiedono a pazienti neurologici l’esecuzione di esercizi ripetitivi, diminuendo la loro motivazione. La realtà virtuale e i feedback sono in grado di coinvolgerli nel trattamento, permettendo ripetibilità e standardizzazione dei protocolli. È stato sviluppato e valutato uno strumento basato su feedback aumentati per il controllo del tronco. Inoltre, la realtà virtuale permette l’individualizzare il trattamento in base alle esigenze del paziente. Un’applicazione virtuale per la riabilitazione del cammino è stata sviluppata e testata durante un training su pazienti di sclerosi multipla, valutandone fattibilità e accettazione e dimostrando l'efficacia del trattamento. La valutazione quantitativa delle capacità motorie dei pazienti viene effettuata utilizzando sistemi di motion capture. Essendo il loro uso nella pratica clinica limitato, una metodologia per valutare l’oscillazione delle braccia in soggetti parkinsoniani basata su sensori inerziali è stata proposta. Questi sono piccoli, accurati e flessibili ma accumulano errori durante lunghe misurazioni. È stato affrontato questo problema e i risultati suggeriscono che, se il sensore è sul piede e le accelerazioni sono integrate iniziando dalla fase di mid stance, l’errore e le sue conseguenze nella determinazione dei parametri spaziali sono contenuti. Infine, è stata presentata una validazione del Kinect per il tracking del cammino in ambiente virtuale. Risultati preliminari consentono di definire il campo di utilizzo del sensore in riabilitazione.

What are the components that contribute to variability in echocardiographic measurements in aortic stenosis?

INTRODUCTION Echocardiography is the standard clinical approach for quantification of the severity of aortic stenosis (AS). A comprehensive examination of its overall reproducibility and the simultaneous estimation of its variance components by multiple operators, readers, probe applications, and beats have not been undertaken. METHOD AND RESULTS Twenty-seven subjects with AS were scanned over 7 months in the echo-department by a median of 3 different operators. From each patient and each operator multiple runs of beats from multiple probe positions were stored for later analysis by multiple readers. The coefficient of variation was 13.3%, 15.9%, 17.6%, and 20.2% for the aortic peak velocity (Vmax), and velocity time integral (VTI), and left ventricular outflow tract (LVOT) Vmax and VTI respectively. The largest individual contributors to the overall variability were the beat-to-beat variability (9.0%, 9.3%, 9.5%, 9.4% respectively) and that of inability of an individual operator to precisely apply the probe to the same position twice (8.3%, 9.4%, 12.9%, 10.7% respectively). The tracing (inter-reader) and reader (inter-reader), and operator (inter-operator) contribution were less important. CONCLUSIONS Reproducibility of measurements in AS is poorer than often reported in the literature. The source of this variability does not appear, as traditionally believed, to result from a lack of training or operator and reader specific factors. Rather the unavoidable beat-to-beat biological variability, and the inherent impossibility of applying the ultrasound probe in exactly the same position each time are the largest contributors. Consequently, guidelines suggesting greater standardisation of procedures and further training for sonographers are unlikely to result in an improvement in precision. Clinicians themselves should be wary of relying on even three-beat averages as their expected coefficient of variance is 10.3% for the peak velocity at the aortic valve.

"Ho cominciato a perdere le scarpe". La ridefinizione del mondo nelle narrazioni di pazienti affetti da sclerosi multipla

Il lavoro di tesi analizza da un punto di vista metodologico e concettuale le narrazioni di malattia delle persone affette da sclerosi multipla. Lo scopo della ricerca è duplice: da un lato quello di indagare quali siano le trame narrative di coloro che raccontano la diagnosi della loro malattia, e dall’altro di analizzare i vissuti di malattia attraverso le categorie della sociologia della salute e della medicina e dell’antropologia medica.

Fattori eziologici della Sindrome del Tunnel Carpale: una revisione sistematica con meta-analisi degli studi analitici

OBIETTIVO: sintetizzare le evidenze disponibili sulla relazione tra i fattori di rischio (personali e lavorativi) e l’insorgenza della Sindrome del Tunnel Carpale (STC). METODI: è stata condotta una revisione sistematica della letteratura su database elettronici considerando gli studi caso-controllo e di coorte. Abbiamo valutato la qualità del reporting degli studi con la checklist STROBE. Le stime studio-specifiche sono state espresse come OR (IC95%) e combinate con una meta-analisi condotta con un modello a effetti casuali. La presenza di eventuali bias di pubblicazione è stata valutata osservando l’asimmetria del funnel plot e con il test di Egger. RISULTATI: Sono stati selezionati 29 studi di cui 19 inseriti nella meta-analisi: 13 studi caso-controllo e 6 di coorte. La meta-analisi ha mostrato un aumento significativo di casi di STC tra i soggetti obesi sia negli studi caso-controllo [OR 2,4 (1,9-3,1); I(2)=70,7%] che in quelli di coorte [OR 2,0 (1,6-2,7); I(2)=0%]. L'eterogeneità totale era significativa (I(2)=59,6%). Risultati simili si sono ottenuti per i diabetici e soggetti affetti da malattie della tiroide. L’esposizione al fumo non era associata alla STC sia negli studi caso-controllo [OR 0,7 (0,4-1,1); I(2)=83,2%] che di coorte [OR 0,8 (0,6-1,2); I(2)=45,8%]. A causa delle molteplici modalità di valutazione non è stato possibile calcolare una stima combinata delle esposizioni professionali con tecniche meta-analitiche. Dalla revisione, è risultato che STC è associata con: esposizione a vibrazioni, movimenti ripetitivi e posture incongrue di mano-polso. CONCLUSIONI: I risultati della revisione sistematica confermano le evidenze dell'esistenza di un'associazione tra fattori di rischio personali e STC. Nonostante la diversa qualità dei dati sull'esposizione e le differenze degli effetti dei disegni di studio, i nostri risultati indicano elementi di prova sufficienti di un legame tra fattori di rischio professionali e STC. La misurazione dell'esposizione soprattutto per i fattori di rischio professionali, è un obiettivo necessario per studi futuri.

From Radio Channel Modeling to a System Level Perspective in Body-Centric Communications

Body-centric communications are emerging as a new paradigm in the panorama of personal communications. Being concerned with human behaviour, they are suitable for a wide variety of applications. The advances in the miniaturization of portable devices to be placed on or around the body, foster the diffusion of these systems, where the human body is the key element defining communication characteristics. This thesis investigates the human impact on body-centric communications under its distinctive aspects. First of all, the unique propagation environment defined by the body is described through a scenario-based channel modeling approach, according to the communication scenario considered, i.e., on- or on- to off-body. The novelty introduced pertains to the description of radio channel features accounting for multiple sources of variability at the same time. Secondly, the importance of a proper channel characterisation is shown integrating the on-body channel model in a system level simulator, allowing a more realistic comparison of different Physical and Medium Access Control layer solutions. Finally, the structure of a comprehensive simulation framework for system performance evaluation is proposed. It aims at merging in one tool, mobility and social features typical of the human being, together with the propagation aspects, in a scenario where multiple users interact sharing space and resources.

La governance del sociosanitario in Emilia Romagna: Esperienze e prospettive

In un contesto dominato da invecchiamento della popolazione, prevalenza della cronicità e presenza crescente di pazienti multiproblematici e non autosufficienti è indispensabile spostare il baricentro delle cure dall'acuzie alla cronicità, e quindi assicurare la continuità e la coerenza fra i diversi setting di cura, sia sanitari che socio-sanitari (ospedale, servizi sanitari territoriali, domicilio, strutture residenziali di Long term care). Dall'analisi della letteratura emerge che il maggiore ostacolo a realizzare questa continuità è rappresentato dalla presenza, caratteristica del sistema di welfare italiano, di molteplici attori e strutture con competenze, obiettivi e funzioni diverse e separate, e la raccomandazione di lavorare per l'integrazione contemporaneamente su più livelli: - normativo-istituzionale - programmatorio - professionale e gestionale Il sistema della "governance" realizzato in Emilia-Romagna per l'integrazione socio-sanitaria è stato valutato alla luce di queste raccomandazioni, seguendo il modello della Realist evaluation per i Social complex interventions: enucleando le "teorie" alla base dell'intervento ed analizzando i diversi step della sua implementazione. Alla luce di questa valutazione, il modello della "governance" è risultato coerente con le indicazioni delle linee guida, ed effettivamente capace di produrre risultati al fine della continuità e della coerenza fra cure sanitarie e assistenza sociale e sanitaria complessa. Resta da realizzare una valutazione complessiva dell'impatto su efficacia, costi e soddisfazione dei pazienti.