Funzionalizzazione della mandibola dopo ricostruzione con lembo libero rivascolarizzato di fibula "single strut". Al di là del deficit di verticalità.

Obiettivi: Valutare la modalità  più efficace per la riabilitazione funzionale del limbo libero di fibula "single strut", dopo ampie resezioni per patologia neoplastica maligna del cavo orale. Metodi: Da una casistica di 62 ricostruzioni microvascolari con limbo libero di fibula, 11 casi sono stati selezionati per essere riabilitati mediante protesi dentale a supporto implantare. 6 casi sono stati trattati senza ulteriori procedure chirurgiche ad eccezione dell'implantologia (gruppo 1), affrontando il deficit di verticalità  della fibula attraverso la protesi dentaria, mentre i restanti casi sono stati trattati con la distrazione osteogenetica (DO) della fibula prima della riabilitazione protesica (gruppo 2). Il deficit di verticalità  fibula/mandibola è stato misurato. I criteri di valutazione utilizzati includono la misurazione clinica e radiografica del livello osseo e dei tessuti molli peri-implantari, ed il livello di soddisfazione del paziente attraverso un questionario appositamente redatto. Risultati: Tutte le riabilitazioni protesiche sono costituite da protesi dentali avvitate su impianti. L'età  media è di 52 anni, il rapporto uomini/donne è di 6/5. Il numero medio di impianti inseriti nelle fibule è di 5. Il periodo massimo di follow-up dopo il carico masticatorio è stato di 30 mesi per il gruppo 1 e di 38.5 mesi (17-81) di media per il gruppo 2. Non abbiamo riportato complicazioni chirurgiche. Nessun impianto è stato rimosso dai pazienti del gruppo 1, la perdita media di osso peri-implantare registrata è stata di 1,5 mm. Nel gruppo 2 sono stati riportati un caso di tipping linguale del vettore di distrazione durante la fase di consolidazione e un caso di frattura della corticale basale in assenza di formazione di nuovo osso. L'incremento medio di osso in verticalità è stato di 13,6 mm (12-15). 4 impianti su 32 (12.5%) sono andati persi dopo il periodo di follow-up. Il riassorbimento medio peri-implantare, è stato di 2,5 mm. Conclusioni: Le soluzioni più utilizzate per superare il deficit di verticalità  del limbo libero di fibula consistono nell'allestimento del lembo libero di cresta iliaca, nel posizionare la fibula in posizione ideale da un punto di vista protesico a discapito del profilo osseo basale, l'utilizzo del lembo di fibula nella versione descritta come "double barrel", nella distrazione osteogenetica della fibula. La nostra esperienza concerne il lembo libero di fibula che nella patologia neoplastica maligna utilizziamo nella versione "single strut", per mantenere disponibili tutte le potenzialità  di lunghezza del peduncolo vascolare, senza necessità  di innesti di vena. Entrambe le soluzioni, la protesi dentale ortopedica e la distrazione osteogenetica seguita da protesi, entrambe avvitate su impianti, costituiscono soluzioni soddisfacenti per la riabilitazione funzionale della fibula al di là  del suo deficit di verticalità . La prima soluzione ha preso spunto dall'osservazione dei buoni risultati della protesi dentale su impianti corti, avendo un paragonabile rapporto corona/radice, la DO applicata alla fibula, sebbene sia risultata una metodica con un numero di complicazioni più elevato ed un maggior livello di riassorbimento di osso peri-implantare, costituisce in ogni caso una valida opzione riabilitativa, specialmente in caso di notevole discrepanza mandibulo/fibulare. Decisiva è la scelta del percorso terapeutico dopo una accurata valutazione di ogni singolo caso. Vengono illustrati i criteri di selezione provenienti dalla nostra esperienza.

Valutazione del danno da stress ossidativo come indicatore di effetto biologico dell'esposizione professionale a xenobiotici

Oxidative DNA damages determine the activation of cell repair processes. These processes originate repair products, including the most studied one, 8-hydroxy-2’-deoxyguanosine (8-OH-dG). Several analytical techniques have been applied to measure urinary 8-OH-dG, but a discrepancy in basal urinary 8-OH-dG levels has been noted when comparing chromatographic techniques with immunoenzymatic assays (ELISA). Our laboratory has developed a fully validated, liquid chromatography-tandem mass spectrometry method presenting high sensitivity and specificity, which has participated in an inter-laboratory validation of assays for the measurement of urinary 8-OH-dG (ESCULA project). Mass Spectrometric techniques showed more accuracy and specificity than immunoenzymatic methods. Human spot urine samples were analyzed in order to investigate the possibility to correct urinary lesion measurements for creatinine and to evaluate the intra- and inter-day variability of 8-OH-dG excretion in urine. Our results confirm the opportunity to delve into these issues. Finally, we measured urinary 8-OH-dG in workers exposed to antineoplastic drugs and in a group of unexposed subjects to evaluate the relationship between occupational exposure and oxidative damage related to the internal dose. We found higher levels of 8-OH-dG in exposed nurses, but, as compared to the non-exposed subjects, the difference was not statistically significant, probably do to the very low level of exposure. The scientific literature is rapidly developing on the topic of DNA damage and related repair capacity. Nevertheless, further studies are needed to achieve a better understanding of the sources of DNA lesions in urine and their significance, both in clinical and occupational medicine.

An optimal estimator for the correlation of CMB anisotropies with Large Scale Structures and its application to WMAP-7year and NVSS

In the thesis we present the implementation of the quadratic maximum likelihood (QML) method, ideal to estimate the angular power spectrum of the cross-correlation between cosmic microwave background (CMB) and large scale structure (LSS) maps as well as their individual auto-spectra. Such a tool is an optimal method (unbiased and with minimum variance) in pixel space and goes beyond all the previous harmonic analysis present in the literature. We describe the implementation of the QML method in the {\it BolISW} code and demonstrate its accuracy on simulated maps throughout a Monte Carlo. We apply this optimal estimator to WMAP 7-year and NRAO VLA Sky Survey (NVSS) data and explore the robustness of the angular power spectrum estimates obtained by the QML method. Taking into account the shot noise and one of the systematics (declination correction) in NVSS, we can safely use most of the information contained in this survey. On the contrary we neglect the noise in temperature since WMAP is already cosmic variance dominated on the large scales. Because of a discrepancy in the galaxy auto spectrum between the estimates and the theoretical model, we use two different galaxy distributions: the first one with a constant bias $b$ and the second one with a redshift dependent bias $b(z)$. Finally, we make use of the angular power spectrum estimates obtained by the QML method to derive constraints on the dark energy critical density in a flat $\Lambda$CDM model by different likelihood prescriptions. When using just the cross-correlation between WMAP7 and NVSS maps with 1.8° resolution, we show that $\Omega_\Lambda$ is about the 70\% of the total energy density, disfavouring an Einstein-de Sitter Universe at more than 2 $\sigma$ CL (confidence level).

Investigation on the Navigation Anomaly of Pioneer 10 and 11 probes

The present work consists of the investigation of the navigation of Pioneer 10 and 11 probes becoming known as the “Pioneer Anomaly”: the trajectories followed by the spacecrafts did not match the ones retrieved with standard navigation software. Mismatching appeared as a linear drift in the Doppler data received by the spacecrafts, which has been ascribed to a constant sunward acceleration of about 8.5×10-10 m/s2. The study presented hereafter tries to find a convincing explanation to this discrepancy. The research is based on the analysis of Doppler tracking data through the ODP (Orbit Determination Program), developed by NASA/JPL. The method can be summarized as: seek for any kind of physics affecting the dynamics of the spacecraft or the propagation of radiometric data, which may have not been properly taken into account previously, and check whether or not these might rule out the anomaly. A major effort has been put to build a thermal model of the spacecrafts for predicting the force due to anisotropic thermal radiation, since this is a model not natively included in the ODP. Tracking data encompassing more than twenty years of Pioneer 10 interplanetary cruise, plus twelve years of Pioneer 11 have been analyzed in light of the results of the thermal model. Different strategies of orbit determination have been implemented, including single arc, multi arc and stochastic filters, and their performance compared. Orbital solutions have been obtained without the needing of any acceleration other than the thermal recoil one indicating it as the responsible for the observed linear drift in the Doppler residuals. As a further support to this we checked that inclusion of additional constant acceleration as does not improve the quality of orbital solutions. All the tests performed lead to the conclusion that no anomalous acceleration is acting on Pioneers spacecrafts.

Parola arcaica e costruzioni del moderno. I sentieri della scrittura in Julio Herrera y Reissig

L’obbiettivo del lavoro è quello di delimitare uno spazio critico che consenta di ripensare il concetto di modernità nelle culture ispanoamericane degli inizi del XX secolo. In questa direzione, si è deciso di focalizzare l’attenzione su un’opera letteraria, quella dell’uruguaiano Julio Herrera y Reissig, del tutto particolare se comparata al resto delle produzioni estetiche a essa più immediatamente contigue. Tornare a leggere Herrera y Reissig equivale, infatti, nella sostanza, a rimettere mano criticamente a tutta l’epoca modernista, interpretandola non in senso unitario, bensì plurale e frammentario. Spunto di partenza dell’analisi sono state le coordinate culturali comuni in cui quelle estetiche si sono determinate e sviluppate, per poi procedere verso una moltiplicazione di percorsi in grado di rendere conto della sostanziale discrepanza di mezzi e finalità che intercorre fra Julio Herrera y Reissig e gran parte del Modernismo a lui contemporaneo. Mantenendo come base metodologica i presupposti dell’archeologia culturale foucauldiana, è stato possibile rintracciare, nell’opera dell’uruguaiano, un eterogeneo ma costante movimento di riemersione e riutilizzo delle più svariate esperienze del pensiero – estetico e non – occidentale. Nelle particolarità d’uso a cui la tradizione è sottomessa nella scrittura di Herrera y Reissig si è reso così possibile tornare a ragionare sui punti focali dell’esperienza della modernità: il legame fra patrimonio culturale e attualità, la relazione fra sedimentazione tradizionale e novità, nonché, in definitiva, le modalità attraverso le quali alla letteratura è consentito di pensare e dire la propria storia – passata, presente e futura – e, in conseguenza, metabolizzarla, per tornare ad agire attivamente su di essa.

Differential expression analysis for sequence count data via mixtures of negative binomials

The recent advent of Next-generation sequencing technologies has revolutionized the way of analyzing the genome. This innovation allows to get deeper information at a lower cost and in less time, and provides data that are discrete measurements. One of the most important applications with these data is the differential analysis, that is investigating if one gene exhibit a different expression level in correspondence of two (or more) biological conditions (such as disease states, treatments received and so on). As for the statistical analysis, the final aim will be statistical testing and for modeling these data the Negative Binomial distribution is considered the most adequate one especially because it allows for "over dispersion". However, the estimation of the dispersion parameter is a very delicate issue because few information are usually available for estimating it. Many strategies have been proposed, but they often result in procedures based on plug-in estimates, and in this thesis we show that this discrepancy between the estimation and the testing framework can lead to uncontrolled first-type errors. We propose a mixture model that allows each gene to share information with other genes that exhibit similar variability. Afterwards, three consistent statistical tests are developed for differential expression analysis. We show that the proposed method improves the sensitivity of detecting differentially expressed genes with respect to the common procedures, since it is the best one in reaching the nominal value for the first-type error, while keeping elevate power. The method is finally illustrated on prostate cancer RNA-seq data.

COSMIC-LAB: Unexpected Results from High-resolution Spectra of AGB Stars in Globular Clusters

We have used high-resolution spectra, acquired with UVES@ESO-VLT, to determine the chemical abundances of different samples of AGB and RGB stars in 4 Galactic globular clusters, namely 47Tuc, NGC3201, M22 and M62. For almost all the analyzed AGB stars we found a clear discrepancy between the iron abundance measured from neutral lines and that obtained from single ionized lines, while this discrepancy is not obtained for the RGB samples observed in the same clusters and analyzed with the same procedure. Such a behavior exactly corresponds to what expected in the case of Non-Local Thermodynamical Equilibrium (NLTE) in the star atmosphere. These results have a huge impact on the proper determination of GC chemistry. In fact, one of the most intriguing consequences is that, at odds with previous claims, no iron spread is found in NGC3201 and M22 if the iron abundance is obtained from ionized lines only.

Comparative Analysis of Genus Bifidobacterium: Insight into its Host Adaptation

Bifidobacteria is amongst one of the health promoting bacteria. The role of this important probiotic genera can be elucidated by understanding its genome. Comparative analysis of the whole genus of these bacteria can reveal their adaptation to a diverse host range. This study comprises of four research projects. In the first study, a reference library for genus Bifidobacterium was prepared. The core genes in each genus were selected based on a newly proposed statistical definition of core genome. Comparative analysis of Bifidobacterium with another probiotic genus Lactobacillus revealed the metabolic characteristics of genus Bifidobacterium. The second study investigated the immunomodulatory role of a B. bifidum strain TMC3115. The analysis of TMC3115 provided insights into its extracellular structures which might have their role in host interaction and immunomodulation. The study highlighted the variability among these genomes just not on species level but also on strain level in terms of host interaction. The last two studies aim to inspect the relationship between bifidobacteria and its host diet. Bifidobacteria, are both host- and niche-specific. Such adaptation of bifidobacterial species is considered relevant to the intestinal microecosystem and hosts’ oligosaccharides. Many species should have co-evolved with their hosts, but the phylogeny of Bifidobacterium is dissimilar to that of host animals. The discrepancy could be linked to the niche-specific evolution due to hosts’ dietary carbohydrates. The distribution of carbohydrate-active enzymes, in particular glycoside hydrolases (GHs) that metabolize unique oligosaccharides was examined. When bifidobacterial species were classified by their distribution of GH genes, five groups arose according to their hosts’ feeding behaviour. The distribution of GH genes was only weakly associated with the phylogeny of the host animals or with genomic features such as genome size. Thus, the hosts’ dietary pattern is the key determinant of the distribution and evolution of GH genes.

Measurement of CP violation with $B^0_{(s)} \to h^+ h^{\prime-}$ decays, $|V_{cb}|$ with $B^0_{s}\to D^{(*)-}_s \mu^+ \nu_\mu$ decays, and simulation and characterisation of the LHCb Upgrade II ECAL

The time-dependent CP asymmetries of the $B^0\to\pi^+\pi^-$ and $B^0_s\toK^+K^-$ decays and the time-integrated CP asymmetries of the $B^0\toK^+\pi^-$ and $B^0_s\to\pi^+K^-$ decays are measured, using the $p-p$ collision data collected with the LHCb detector and corresponding to the full Run2. The results are compatible with previous determinations of these quantities from LHCb, except for the CP-violation parameters of the $B^0_s\to K^+K^-$ decays, that show a discrepancy exceeding 3 standard deviations between different data-taking periods. The investigations being conducted to understand the discrepancy are documented. The measurement of the CKM matrix element $|V_{cb}|$ using $B^0_{s}\to D^{(*)-}_s\mu^+ \nu_\mu$ is also reported, using the $p-p$ collision data collected with the LHCb detector and corresponding to the full Run1. The measurement leads to $|V_{cb}| = (41.4\pm0.6\pm0.9\pm1.2)\times 10^{-3}$, where the first uncertainty is statistical, the second is systematic, and the third is due to external inputs. This measurement is compatible with the world averages and constitutes the first measurement of $|V_{cb}|$ at a hadron collider and the absolute first one with decays of the $B^0_s$ meson. The analysis also provides the very first measurements of the branching ratio and form factors parameters of the signal decay modes. The study of the characteristics ruling the response of an electromagnetic calorimeter (ECAL) to profitably operate in the high luminosity regime foreseen for the Upgrade2 of LHCb is reported in the final part of this Thesis. A fast and flexible simulation framework is developed to this purpose. Physics performance of different configurations of the ECAL are evaluated using samples of fully simulated $B^0\to \pi^+\pi^-\pi^0$ and $B^0\to K^{*0}e^+e^-$ decays. The results are used to guide the development of the future ECAL and are reported in the Framework Technical Design Report of the LHCb Upgrade2 detector.

Nanostructured smart materials as functional components of medical devices

The field of medical devices has experienced, more than others, technological advances, developments and innovations, thanks to the rapidly expanding scientific knowledge and collaboration between different disciplines such as biology, engineering and materials science. The design of functional components can be achieved by exploiting composite materials based on nanostructured smart materials, that due to the inherent characteristics of single constituents develop unique properties that make them suitable for different applications preserving excellent mechanical proprieties. For instance, recent developments have focused on the fabrication of piezoelectric devices with multiple biomedical functions, as actuation and sensing functions in one component for monitoring pressure signals. The present Ph.D. Thesis aims at investigating nanostructured smart materials embedded into a polymeric matrix to obtain a composite material that can be used as a functional component for medical devices. (i) Nanostructured piezoelectric material with self-sensing capability was successfully manufactured by using ceramic (i.e. lead zirconate titanate (PZT)) and (ii) polymeric (i.e. poly(vinylidene fluoride-trifluoro ethylene (PVDF-TRFE)) piezoelectric materials. PZT nanofibers were obtained by sol-gel electrospinning starting from synthetized PZT precursor solution. Synthesis, sol-gel electrospinning process, and thermal treatment were accurately controlled to obtain PZT nanofibers dimensionally stable with densely packed grains in the perovskite phase. To guarantee the impact resistance of the laminate, the morphology and size of the hosting filler were accurately designed by increasing the surface area to volume ratio. Moreover, to solve the issue relative to the mechanical discrepancy between rigid electronic materials/soft human tissues/different material of the device (iii) a nanostructured flexible composite material based on a network of Poly-L-lactic acid (PLLA) made of curled nanofibers that present a tuneable mechanical response as a function of the applied stress was successful fabricated.

Cross-sensors analysis of multispectral Earth observation data for environmental monitoring

Time Series Analysis of multispectral satellite data offers an innovative way to extract valuable information of our changing planet. This is now a real option for scientists thanks to data availability as well as innovative cloud-computing platforms, such as Google Earth Engine. The integration of different missions would mitigate known issues in multispectral time series construction, such as gaps due to clouds or other atmospheric effects. With this purpose, harmonization among Landsat-like missions is possible through statistical analysis. This research offers an overview of the different instruments from Landsat and Sentinel missions (TM, ETM, OLI, OLI-2 and MSI sensors) and products levels (Collection-2 Level-1 and Surface Reflectance for Landsat and Level-1C and Level-2A for Sentinel-2). Moreover, a cross-sensors comparison was performed to assess the interoperability of the sensors on-board Landsat and Sentinel-2 constellations, having in mind a possible combined use for time series analysis. Firstly, more than 20,000 pairs of images almost simultaneously acquired all over Europe were selected over a period of several years. The study performed a cross-comparison analysis on these data, and provided an assessment of the calibration coefficients that can be used to minimize differences in the combined use. Four of the most popular vegetation indexes were selected for the study: NDVI, EVI, SAVI and NDMI. As a result, it is possible to reconstruct a longer and denser harmonized time series since 1984, useful for vegetation monitoring purposes. Secondly, the spectral characteristics of the recent Landsat-9 mission were assessed for a combined use with Landsat-8 and Sentinel-2. A cross-sensor analysis of common bands of more than 3,000 almost simultaneous acquisitions verified a high consistency between datasets. The most relevant discrepancy has been observed in the blue and SWIRS bands, often used in vegetation and water related studies. This analysis was supported with spectroradiometer ground measurements.

Valutazione non invasiva dell'epatopatia Fontan indotta

Introduzione: L’intervento di Fontan comporta un aumento istantaneo della pressione venosa centrale che causa, nel medio-lungo termine, una forma di epatopatia specifica detta FALD. Il monitoraggio della FALD è complesso ma potrebbe consentire di bloccarne o rallentarne l’insorgenza. Lo studio ha valutato l’efficacia delle modalità di monitoraggio non invasivo. Materiale e metodi: Sei pazienti (età media 24 anni) operati presso l’IRCCS Azienda Ospedaliero Universitaria di Bologna sono stati sottoposti a RMN 4D-Flow e ad Ecodoppler epatico. Sono stati raccolti i dati anagrafici, morfologici, anamnestici e i markers sierologici per il calcolo degli scores MELD-XI, APRI, FIB4, i valori di Shear Stress assiale e circonferenziale e gli indici di pulsatilità e resistenza delle arterie epatica e renale. Risultati: Il tempo trascorso tra la Fontan e lo studio è stato di 17,8 anni. Età media alla Fontan 6,8 anni. Tutti i pazienti avevano un quadro compatibile con epatopatia. I markers sierologici e gli scores MELD-XI,APRI e FIB4 si sono dimostrati di scarsa utilità. All’ecografia tutti i pazienti avevano ecostruttura irregolare, splenomegalia e valori elevati di pulsatilità e resistenza dell’arteria epatica e splenica. La rigidità epatica media è stata di 12,4 Kpa. Alla RMN 4DF lo Shear stress assiale è stato massimo a livello del condotto (0,16 Pa) e minimo a livello delle vene sovra epatiche (0,05 Pa). Lo Shear Stress si è mostrato massimo nei pazienti con emodinamica sfavorevole e peggior quadro ecografico addominale, evidenziando aree di inefficienza energetica. Conclusioni: La combinazione delle diagnostiche di imaging non invasive potrebbe rivelarsi adeguata per il monitoraggio della FALD. In particolare, la RMN 4D Flow potrebbe rivelare aree di inefficienza energetica predisponenti alla FALD. Questo potrebbe indirizzare in modo specifico la terapia dei pazienti operati o addirittura indurre la modifica del disegno della Fontan verso forme più efficienti.