The medical management after surgery for advanced heart failure

The aim of the Research of this Ph D Project is to improve the medical management after surgery for advanced heart failure, both after left ventricular assist devices (LVAD) implantation, and after heart transplantation in the long-term. Regarding heart transplantation (HTx), the Research Project is focused on diagnostics, classification, prevention and treatment of cardiac allograft vasculopathy (CAV), and on treatment of post-HTx cancers; the results are presented in the first part of this Thesis. In particular, the main aspect investigated are the prognostic role of information derived from coronary angiography, coronary tomography and intravascular ultrasound, and the different sensitivity of these techniques in predicting outcomes and in diagnosing CAV. Moreover, the role of mTOR inhibitors on CAV prevention or treatment is investigated, both alone and in combination with different anti-CMV prevention strategies, as well as the impact of mTOR inhibitors on clinical outcomes in the long term. Regarding LVAD, the main focus is on the role of transthoracic echocardiography in the management of patients with a continuous-flow, centrifugal, intrapericardial pump (HVAD, Heartware); this section is reported in the second part of this Thesis. The main aspects investigated are the use of echocardiography in patients with HVAD device and its interaction with the information derived from pump curves' analysis in predicting aortic valve opening status, a surrogate of the condition of support provided by the LVAD.

Advanced data deduplication techniques and their application

Data deduplication describes a class of approaches that reduce the storage capacity needed to store data or the amount of data that has to be transferred over a network. These approaches detect coarse-grained redundancies within a data set, e.g. a file system, and remove them.rnrnOne of the most important applications of data deduplication are backup storage systems where these approaches are able to reduce the storage requirements to a small fraction of the logical backup data size.rnThis thesis introduces multiple new extensions of so-called fingerprinting-based data deduplication. It starts with the presentation of a novel system design, which allows using a cluster of servers to perform exact data deduplication with small chunks in a scalable way.rnrnAfterwards, a combination of compression approaches for an important, but often over- looked, data structure in data deduplication systems, so called block and file recipes, is introduced. Using these compression approaches that exploit unique properties of data deduplication systems, the size of these recipes can be reduced by more than 92% in all investigated data sets. As file recipes can occupy a significant fraction of the overall storage capacity of data deduplication systems, the compression enables significant savings.rnrnA technique to increase the write throughput of data deduplication systems, based on the aforementioned block and file recipes, is introduced next. The novel Block Locality Caching (BLC) uses properties of block and file recipes to overcome the chunk lookup disk bottleneck of data deduplication systems. This chunk lookup disk bottleneck either limits the scalability or the throughput of data deduplication systems. The presented BLC overcomes the disk bottleneck more efficiently than existing approaches. Furthermore, it is shown that it is less prone to aging effects.rnrnFinally, it is investigated if large HPC storage systems inhibit redundancies that can be found by fingerprinting-based data deduplication. Over 3 PB of HPC storage data from different data sets have been analyzed. In most data sets, between 20 and 30% of the data can be classified as redundant. According to these results, future work in HPC storage systems should further investigate how data deduplication can be integrated into future HPC storage systems.rnrnThis thesis presents important novel work in different area of data deduplication re- search.

Data dissemination over complex networks through gossip

This thesis offers a practical and theoretical evaluations about gossip-epidemic algorithms, comparing those most common in the literature with new proposed algorithms and analyzing their behavior. Tests have been executed using one hundred graphs that has been randomly generated by Large Unstructured NEtwork Simulator (LUNES), a simulation software provided by Parallel and Distributed Simulation Research Group (PADS), of the Department of Computer Science, Università di Bologna and simulated using Advanced RTI System (ARTÌS), based on the High Level Architecture standard. Literatures algorithms have been analyzed and taken as base for new algorithms.

Analysis of aircraft load spectrum by means of flight simulator

Damage tolerance analysis is a quite new methodology based on prescribed inspections. The load spectra used to derive results of these analysis strongly influence the final defined inspections programs that for this reason must be as much as possible representative of load acting on the considered structural component and at the same time, obtained reducing both cost and time. The principal purpose of our work is in improving the actual condition developing a complete numerical Damage Tolerance analysis, able to prescribe inspection programs on typical aircraft critical components, respecting DT regulations, starting from much more specific load spectrum then those actually used today. In particular, these more specific load spectrum to design against fatigue have been obtained through an appositively derived flight simulator developed in a Matlab/Simulink environment. This dynamic model has been designed so that it can be used to simulate typical missions performing manually (joystick inputs) or completely automatic (reference trajectory need to be provided) flights. Once these flights have been simulated, model’s outputs are used to generate load spectrum that are then processed to get information (peaks, valleys) to perform statistical and/or comparison consideration with other load spectrum. However, also much more useful information (loads amplitude) have been extracted from these generated load spectrum to perform the previously mentioned predictions (Rainflow counting method is applied for this purpose). The entire developed methodology works in a complete automatic way, so that, once some specified input parameters have been introduced and different typical flights have been simulated both, manually or automatically, it is able to relate the effects of these simulated flights with the reduction of residual strength of the considered component.

Design and implementation of the ESEO spacecraft simulator

The thesis work is developed under the European Student Earth Orbiter (ESEO) project supported by the European Space Agency (ESA) in order to help prepare a well-qualified space-engineering workforce for Europe's future. In the following chapters we are going to analyse how to simulate some ESEO subsystem. First of all, the Thermal Subsystem that evaluates the temperature evolution of on-board instruments. For this purpose, simulating also the orbital and attitude dynamics of the spacecraft, it is necessary in order to evaluate external environmental fluxes. The Power Subsystem will be the following step and it models the ability of a spacecraft to produce and store electrical energy. Finally, we will integrate in our software a block capable of simulating the communication link between the satellite and the Ground Station (GS). This last step is designed and validated during the thesis preparation.

Design, implementation and performance evaluation of an anonymous distributed simulator

La simulazione è definita come la rappresentazione del comportamento di un sistema o di un processo per mezzo del funzionamento di un altro o, alternativamente, dall'etimologia del verbo “simulare”, come la riproduzione di qualcosa di fittizio, irreale, come se in realtà, lo fosse. La simulazione ci permette di modellare la realtà ed esplorare soluzioni differenti e valutare sistemi che non possono essere realizzati per varie ragioni e, inoltre, effettuare differenti valutazioni, dinamiche per quanto concerne la variabilità delle condizioni. I modelli di simulazione possono raggiungere un grado di espressività estremamente elevato, difficilmente un solo calcolatore potrà soddisfare in tempi accettabili i risultati attesi. Una possibile soluzione, viste le tendenze tecnologiche dei nostri giorni, è incrementare la capacità computazionale tramite un’architettura distribuita (sfruttando, ad esempio, le possibilità offerte dal cloud computing). Questa tesi si concentrerà su questo ambito, correlandolo ad un altro argomento che sta guadagnando, giorno dopo giorno, sempre più rilevanza: l’anonimato online. I recenti fatti di cronaca hanno dimostrato quanto una rete pubblica, intrinsecamente insicura come l’attuale Internet, non sia adatta a mantenere il rispetto di confidenzialità, integrità ed, in alcuni, disponibilità degli asset da noi utilizzati: nell’ambito della distribuzione di risorse computazionali interagenti tra loro, non possiamo ignorare i concreti e molteplici rischi; in alcuni sensibili contesti di simulazione (e.g., simulazione militare, ricerca scientifica, etc.) non possiamo permetterci la diffusione non controllata dei nostri dati o, ancor peggio, la possibilità di subire un attacco alla disponibilità delle risorse coinvolte. Essere anonimi implica un aspetto estremamente rilevante: essere meno attaccabili, in quanto non identificabili.

Oxidative stress and inflammation response after nanoparticle exposure: differences between human lung cell monocultures and an advanced three-dimensional model of the human epithelial airways

Combustion-derived and manufactured nanoparticles (NPs) are known to provoke oxidative stress and inflammatory responses in human lung cells; therefore, they play an important role during the development of adverse health effects. As the lungs are composed of more than 40 different cell types, it is of particular interest to perform toxicological studies with co-cultures systems, rather than with monocultures of only one cell type, to gain a better understanding of complex cellular reactions upon exposure to toxic substances. Monocultures of A549 human epithelial lung cells, human monocyte-derived macrophages and monocyte-derived dendritic cells (MDDCs) as well as triple cell co-cultures consisting of all three cell types were exposed to combustion-derived NPs (diesel exhaust particles) and to manufactured NPs (titanium dioxide and single-walled carbon nanotubes). The penetration of particles into cells was analysed by transmission electron microscopy. The amount of intracellular reactive oxygen species (ROS), the total antioxidant capacity (TAC) and the production of tumour necrosis factor (TNF)-alpha and interleukin (IL)-8 were quantified. The results of the monocultures were summed with an adjustment for the number of each single cell type in the triple cell co-culture. All three particle types were found in all cell and culture types. The production of ROS was induced by all particle types in all cell cultures except in monocultures of MDDCs. The TAC and the (pro-)inflammatory reactions were not statistically significantly increased by particle exposure in any of the cell cultures. Interestingly, in the triple cell co-cultures, the TAC and IL-8 concentrations were lower and the TNF-alpha concentrations were higher than the expected values calculated from the monocultures. The interplay of different lung cell types seems to substantially modulate the oxidative stress and the inflammatory responses after NP exposure.

Biomechanical model of tumor growth: application to the European ContraCancrum project

This abstract presents the biomechanical model that is used in the European ContraCancrum project, aiming at simulating tumor evolution in the brain and lung. The construction of the finite element model as well as a simulation of tumor growth are shown. The construction of the mesh is fully automatic and is therefore compatible with a clinical application. This biomechanical model will be later combined to a cellular level simulator also developed in the project.

Plasma copeptin levels before and during exogenous arginine vasopressin infusion in patients with advanced vasodilatory shock

Plasma copeptin levels before and during exogenous arginine vasopressin infusion (AVP) were evaluated, and the value of copeptin levels before AVP therapy to predict complications during AVP therapy and outcome in vasodilatory shock patients was determined.

Concomitant Cisplatin and Hyperfractionated Radiotherapy in Locally Advanced Head and Neck Cancer: 10-Year Follow-up of a Randomized Phase III Trial (SAKK 10/94)

To compare the long-term outcome of treatment with concomitant cisplatin and hyperfractionated radiotherapy versus treatment with hyperfractionated radiotherapy alone in patients with locally advanced head and neck cancer.