Somatotroph pituitary adenoma with acromegaly and autosomal dominant polycystic kidney disease: SSTR5 polymorphism and PKD1 mutation

A 39-year-old woman with autosomal dominant polycystic kidney disease (ADPKD) presented with acromegaly and a pituitary macroadenoma. There was a family history of this renal disorder. She had undergone surgery for pituitary adenoma 6 years prior. Physical examination disclosed bitemporal hemianopsia and elevation of both basal growth hormone (GH) 106 ng/mL (normal 0-5) and insulin-like growth factor (IGF-1) 811 ng/mL (normal 48-255) blood levels. A magnetic resonance imaging scan disclosed a 3.0 cm sellar and suprasellar mass with both optic chiasm compression and left cavernous sinus invasion. Pathologic, cytogenetic, molecular and in silico analysis was undertaken. Histologic, immunohistochemical and ultrastructural studies of the lesion disclosed a sparsely granulated somatotroph adenoma. Standard chromosome analysis on the blood sample showed no abnormality. Sequence analysis of the coding regions of PKD1 and PKD2 employing DNA from both peripheral leukocytes and the tumor revealed the most common PKD1 mutation, 5014_5015delAG. Analysis of the entire SSTR5 gene disclosed the variant c.142C > A (p.L48M, rs4988483) in the heterozygous state in both blood and tumor, while no pathogenic mutations were noted in the MEN1, AIP, p27Kip1 and SSTR2 genes. To our knowledge, this is the fourth reported case of a GH-producing pituitary adenoma associated with ADPKD, but the first subjected to extensive morphological, ultrastructural, cytogenetic and molecular studies. The physical proximity of the PKD1 and SSTR5 genes on chromosome 16 suggests a causal relationship between ADPKD and somatotroph adenoma.

Pituitary tumors in patients with MEN1 syndrome

We briefly review the characteristics of pituitary tumors associated with multiple endocrine neoplasia type 1. Multiple endocrine neoplasia type 1 is an autosomal-dominant disorder most commonly characterized by tumors of the pituitary, parathyroid, endocrine-gastrointestinal tract, and pancreas. A MEDLINE search for all available publications regarding multiple endocrine neoplasia type 1 and pituitary adenomas was undertaken. The prevalence of pituitary tumors in multiple endocrine neoplasia type 1 may vary from 10% to 60% depending on the studied series, and such tumors may occur as the first clinical manifestation of multiple endocrine neoplasia type 1 in 25% of sporadic and 10% of familial cases. Patients were younger and the time between initial and subsequent multiple endocrine neoplasia type 1 endocrine lesions was significantly longer when pituitary disease was the initial manifestation of multiple endocrine neoplasia type 1. Tumors were larger and more invasive and clinical manifestations related to the size of the pituitary adenoma were significantly more frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Normalization of pituitary hypersecretion was much less frequent in patients with multiple endocrine neoplasia type 1 than in subjects with non-multiple endocrine neoplasia type 1. Pituitary tumors in patients with multiple endocrine neoplasia type 1 syndrome tend to be larger, invasive and more symptomatic, and they tend to occur in younger patients when they are the initial presentation of multiple endocrine neoplasia type 1.

A dynamical system approach to data assimilation in chaotic models

The Assimilation in the Unstable Subspace (AUS) was introduced by Trevisan and Uboldi in 2004, and developed by Trevisan, Uboldi and Carrassi, to minimize the analysis and forecast errors by exploiting the flow-dependent instabilities of the forecast-analysis cycle system, which may be thought of as a system forced by observations. In the AUS scheme the assimilation is obtained by confining the analysis increment in the unstable subspace of the forecast-analysis cycle system so that it will have the same structure of the dominant instabilities of the system. The unstable subspace is estimated by Breeding on the Data Assimilation System (BDAS). AUS- BDAS has already been tested in realistic models and observational configurations, including a Quasi-Geostrophicmodel and a high dimensional, primitive equation ocean model; the experiments include both fixed and“adaptive”observations. In these contexts, the AUS-BDAS approach greatly reduces the analysis error, with reasonable computational costs for data assimilation with respect, for example, to a prohibitive full Extended Kalman Filter. This is a follow-up study in which we revisit the AUS-BDAS approach in the more basic, highly nonlinear Lorenz 1963 convective model. We run observation system simulation experiments in a perfect model setting, and with two types of model error as well: random and systematic. In the different configurations examined, and in a perfect model setting, AUS once again shows better efficiency than other advanced data assimilation schemes. In the present study, we develop an iterative scheme that leads to a significant improvement of the overall assimilation performance with respect also to standard AUS. In particular, it boosts the efficiency of regime’s changes tracking, with a low computational cost. Other data assimilation schemes need estimates of ad hoc parameters, which have to be tuned for the specific model at hand. In Numerical Weather Prediction models, tuning of parameters — and in particular an estimate of the model error covariance matrix — may turn out to be quite difficult. Our proposed approach, instead, may be easier to implement in operational models.

Design and implementation of a novel multi-constellation FPGA-based dual frequency GNSS receiver for space applications

The PhD activity described in the document is part of the Microsatellite and Microsystem Laboratory of the II Faculty of Engineering, University of Bologna. The main objective is the design and development of a GNSS receiver for the orbit determination of microsatellites in low earth orbit. The development starts from the electronic design and goes up to the implementation of the navigation algorithms, covering all the aspects that are involved in this type of applications. The use of GPS receivers for orbit determination is a consolidated application used in many space missions, but the development of the new GNSS system within few years, such as the European Galileo, the Chinese COMPASS and the Russian modernized GLONASS, proposes new challenges and offers new opportunities to increase the orbit determination performances. The evaluation of improvements coming from the new systems together with the implementation of a receiver that is compatible with at least one of the new systems, are the main activities of the PhD. The activities can be divided in three section: receiver requirements definition and prototype implementation, design and analysis of the GNSS signal tracking algorithms, and design and analysis of the navigation algorithms. The receiver prototype is based on a Virtex FPGA by Xilinx, and includes a PowerPC processor. The architecture follows the software defined radio paradigm, so most of signal processing is performed in software while only what is strictly necessary is done in hardware. The tracking algorithms are implemented as a combination of Phase Locked Loop and Frequency Locked Loop for the carrier, and Delay Locked Loop with variable bandwidth for the code. The navigation algorithm is based on the extended Kalman filter and includes an accurate LEO orbit model.

Assessment of Daily Life Mobility Levels using Wearable Inertial Sensors and Minimun Measured Input Models

Tracking activities during daily life and assessing movement parameters is essential for complementing the information gathered in confined environments such as clinical and physical activity laboratories for the assessment of mobility. Inertial measurement units (IMUs) are used as to monitor the motion of human movement for prolonged periods of time and without space limitations. The focus in this study was to provide a robust, low-cost and an unobtrusive solution for evaluating human motion using a single IMU. First part of the study focused on monitoring and classification of the daily life activities. A simple method that analyses the variations in signal was developed to distinguish two types of activity intervals: active and inactive. Neural classifier was used to classify active intervals; the angle with respect to gravity was used to classify inactive intervals. Second part of the study focused on extraction of gait parameters using a single inertial measurement unit (IMU) attached to the pelvis. Two complementary methods were proposed for gait parameters estimation. First method was a wavelet based method developed for the estimation of gait events. Second method was developed for estimating step and stride length during level walking using the estimations of the previous method. A special integration algorithm was extended to operate on each gait cycle using a specially designed Kalman filter. The developed methods were also applied on various scenarios. Activity monitoring method was used in a PRIN’07 project to assess the mobility levels of individuals living in a urban area. The same method was applied on volleyball players to analyze the fitness levels of them by monitoring their daily life activities. The methods proposed in these studies provided a simple, unobtrusive and low-cost solution for monitoring and assessing activities outside of controlled environments.

Gait analysis using a single wearable inertial measurement unit

Procedures for quantitative walking analysis include the assessment of body segment movements within defined gait cycles. Recently, methods to track human body motion using inertial measurement units have been suggested. It is not known if these techniques can be readily transferred to clinical measurement situations. This work investigates the aspects necessary for one inertial measurement unit mounted on the lower back to track orientation, and determine spatio-temporal features of gait outside the confines of a conventional gait laboratory. Apparent limitations of different inertial sensors can be overcome by fusing data using methods such as a Kalman filter. The benefits of optimizing such a filter for the type of motion are unknown. 3D accelerations and 3D angular velocities were collected for 18 healthy subjects while treadmill walking. Optimization of Kalman filter parameters improved pitch and roll angle estimates when compared to angles derived using stereophotogrammetry. A Weighted Fourier Linear Combiner method for estimating 3D orientation angles by constructing an analytical representation of angular velocities and allowing drift free integration is also presented. When tested this method provided accurate estimates of 3D orientation when compared to stereophotogrammetry. Methods to determine spatio-temporal features from lower trunk accelerations generally require knowledge of sensor alignment. A method was developed to estimate the instants of initial and final ground contact from accelerations measured by a waist mounted inertial device without rigorous alignment. A continuous wavelet transform method was used to filter and differentiate the signal and derive estimates of initial and final contact times. The technique was tested with data recorded for both healthy and pathologic (hemiplegia and Parkinson’s disease) subjects and validated using an instrumented mat. The results show that a single inertial measurement unit can assist whole body gait assessment however further investigation is required to understand altered gait timing in some pathological subjects.

Stima dell'assetto di un UAV

Lo scopo del lavoro è simulare il comportamento di un sistema di misura dell'assetto detto ARS (Attitude Reference System), dove sostanzialmente le misure fornite da giroscopi ed accelerometri, quindi accelerazioni e velocità angolari, vengono elaborate da un filtro osservatore dello stato che permette di ricavare la stima dell'angolo di elevazione Q e dell'angolo di inclinazione f, non misurabili direttamente, e quindi dell'orientamento del sistema rispetto al piano orizzontale.

Modellazione e controllo avanzato di un velivolo multirotore : presso il Laboratorio di meccanica del volo

Grazie alla loro versatilità, i velivoli multirotore hanno ricevuto sempre più interesse durante gli ultimi anni, in ambito accademico e di recente anche industriale. Il lavoro presentato è volto a studiare e confrontare le moderne tecniche di navigazione e di controllo di questo tipo di velivoli. Difatti, spesso, gli algoritmi utilizzati sono stati limitati dalla capacità di calcolo del processore imbarcato e dalla qualità dei sensori utilizzati. Negli ultimi anni, però, lo sviluppo della microelettronica ha ricevuto un forte impulso (dovuto principalmente alla ricerca nell’ambito della telefonia), che ha portato all’abbattimento dei costi e alla nascita di progetti opensource, tra i quali le famose schede Arduino prodotte da Olivetti, attorno alle quali si sono sviluppati molti progetti di velivoli opensource. L’importanza di ciò, in ambito accademico, è rilevante, poiché consente l’utilizzo di algoritmi e di configurazioni hardware comprovati, lasciando spazio a modifiche e migliorie. Nel nostro caso, in particolare, si vuole osservare come complessi algoritmi di navigazione, resi possibili da un processore più potente, possano migliorare le prestazioni del noto progetto opensource ArduPilot [3]. Tali miglioramenti possono essere rilevanti in applicazioni per le quali sia richiesta una certa precisione nel posizionamento, come ad esempio lo studio di formazioni o la navigazione in ambienti angusti.

Target Tracking in UWB Multistatic Radars

Detection, localization and tracking of non-collaborative objects moving inside an area is of great interest to many surveillance applications. An ultra- wideband (UWB) multistatic radar is considered as a good infrastructure for such anti-intruder systems, due to the high range resolution provided by the UWB impulse-radio and the spatial diversity achieved with a multistatic configuration. Detection of targets, which are typically human beings, is a challenging task due to reflections from unwanted objects in the area, shadowing, antenna cross-talks, low transmit power, and the blind zones arised from intrinsic peculiarities of UWB multistatic radars. Hence, we propose more effective detection, localization, as well as clutter removal techniques for these systems. However, the majority of the thesis effort is devoted to the tracking phase, which is an essential part for improving the localization accuracy, predicting the target position and filling out the missed detections. Since UWB radars are not linear Gaussian systems, the widely used tracking filters, such as the Kalman filter, are not expected to provide a satisfactory performance. Thus, we propose the Bayesian filter as an appropriate candidate for UWB radars. In particular, we develop tracking algorithms based on particle filtering, which is the most common approximation of Bayesian filtering, for both single and multiple target scenarios. Also, we propose some effective detection and tracking algorithms based on image processing tools. We evaluate the performance of our proposed approaches by numerical simulations. Moreover, we provide experimental results by channel measurements for tracking a person walking in an indoor area, with the presence of a significant clutter. We discuss the existing practical issues and address them by proposing more robust algorithms.

Study of 3 Lambda H and 4 Lambda H in the reaction of 6 Li + 12 C at 2 A GeV

Die Produktion von Hyperkernen wurde in peripheren Schwerionenreaktionen untersucht, bei denen eine Kohlenstofffolie mit $^6$Li Projektilen mit einer Strahlenergie von $2 A$~GeV bestrahlt wurde. Es konnten klare Signale f{"{u}}r $Lambda$, $^3_{Lambda}$H, $^4_{Lambda}$H in deren jeweiligen invarianten Massenverteilungen aus Mesonenzerfall beobachtet werden.rnrnIn dieser Arbeit wird eine unabh{"{a}}ngige Datenauswertung vorgelegt, die eine Verifizierung fr"{u}herer Ergebnisse der HypHI Kollaboration zum Ziel hatte. Zu diesem Zweck wurde eine neue Track-Rekonstruktion, basierend auf einem Kalman-Filter-Ansatz, und zwei unterschiedliche Algorithmen zur Rekonstruktion sekund"{a}rer Vertices entwickelt.rn%-Rekonstruktionsalgorithmen .rnrnDie invarianten Massen des $Lambda$-Hyperon und der $^3_{Lambda}$H- und $^4_{Lambda}$H-Hyperkerne wurden mit $1109.6 pm 0.4$, $2981.0 pm 0.3$ und $3898.1 pm 0.7$~MeV$/c^2$ und statistischen Signifikanzen von $9.8sigma$, $12.8sigma$ beziehungsweise $7.3sigma$ bestimmt. Die in dieser Arbeit erhaltenen Ergebnisse stimmen mit der fr{"{u}}heren Auswertung {"{u}}berein.rnrnDas Ausbeutenverh{"{a}}ltnis der beiden Hyperkerne wurde als $N(^3_{Lambda}$H)/$N(^4_{Lambda}$H)$ sim 3$ bestimmt. Das deutet darauf hin, dass der Produktionsmechanismus f{"{u}}r Hyperkerne in Schwerionen-induzierten Reaktionen im Projektil-Rapidit{"{a}}tsbereich nicht allein durch einen Koaleszenzmechanismus beschrieben werden kann, sondern dass auch sekund{"{a}}re Pion-/Kaon-induzierte Reaktionen und Fermi-Aufbruch involviert sind.rn

Studio ed implementazione di algoritmi per la navigazione inerziale di velivoli autonomi ad ala rotante

I sistemi di navigazione inerziale, denominati INS, e quelli di navigazione inerziale assistita, ovvero che sfruttano anche sensori di tipo non inerziale come ad esempio il GPS, denominati in questo caso INS/GPS, hanno visto un forte incremento del loro utilizzo soprattutto negli ultimi anni. I filtri complementari sfruttano segnali in ingresso che presentano caratteristiche complementari in termine di banda. Con questo lavoro di tesi mi sono inserito nel contesto del progetto SHERPA (Smart collaboration between Humans and ground-aErial Robots for imProving rescuing activities in Alpine environments), un progetto europeo, coordinato dall'Università di Bologna, che prevede di mettere a punto una piattaforma robotica in grado di aiutare i soccorritori che operano in ambienti ostili, come quelli del soccorso alpino, le guardie forestali, la protezione civile. In particolare è prevista la possibilità di lanciare i droni direttamente da un elicottero di supporto, per cui potrebbe essere necessario effettuare l'avvio del sistema in volo. Ciò comporta che il sistema di navigazione dovrà essere in grado di convergere allo stato reale del sistema partendo da un grande errore iniziale, dal momento che la fase di inizializzazione funziona bene solo in condizioni di velivolo fermo. Si sono quindi ricercati, in special modo, schemi che garantissero la convergenza globale. Gli algoritmi implementati sono alla base della navigazione inerziale, assistita da GPS ed Optical Flow, della prima piattaforma aerea sviluppata per il progetto SHERPA, soprannominata DreamDroneOne, che include una grande varietà di hardware appositamente studiati per il progetto, come il laser scanner, la camera termica, ecc. Dopo una panoramica dell'architettura del sistema di Guida, Navigazione e Controllo (GNC) in cui mi sono inserito, si danno alcuni cenni sulle diverse terne di riferimento e trasformazioni, si descrivono i diversi sensori utilizzati per la navigazione, si introducono gli AHRS (Attitude Heading Rference System), per la determinazione del solo assetto sfruttando la IMU ed i magnetometri, si analizza l'AHRS basato su Extended Kalman Filter. Si analizzano, di seguito, un algoritmo non lineare per la stima dell'assetto molto recente, e il sistema INS/GPS basato su EKF, si presenta un filtro complementare molto recente per la stima di posizione ed assetto, si presenta un filtro complementare per la stima di posizione e velocità, si analizza inoltre l'uso di un predittore GPS. Infine viene presentata la piattaforma hardware utilizzata per l'implementazione e la validazione, si descrive il processo di prototipazione software nelle sue fasi e si mostrano i risultati sperimentali.

Statistical mapping of real environments with uwb radars

In this master thesis I evaluated the performance of a Ultra-Wide Bandwidth (UWB) radar system for indoor environments mapping. In particular, I used a statistical Bayesian approach which is able to combine all the measurements collected by the radar, including system non-idealities such as the error on the estimated antenna pointing direction or on the estimated radar position. First I verified through simulations that the system was able to provide a sufficiently accurate reconstruction of the surrounding environment despite the limitations imposed by the UWB technology. In fact, the emission of UWB pulses is limited in terms of transmitted power by international regulations. Motivated by the promising results obtained through simulations, I successively carried out a measurement campaign in a real indoor environment using a UWB commercial device. The obtained results showed that the UWB radar system is capable of providing an accurate reconstruction of indoor environments also adopting not directional antennas.

Sviluppo e validazione di una App Android per il riconoscimento dell'attivita motoria tramite Smartphones e Smartwatch

In questo progetto di tesi saranno applicate tecniche appartenenti al campo della bioingegneria, indirizzate al riconoscimento delle attività motorie e all’analisi del movimento umano. E' stato definito un protocollo di ricerca necessario per il raggiungimento degli obiettivi finali. Si è quindi implementata un’App Android per l’acquisizione e il salvataggio dei dati provenienti dai principali sensori di Smartwatch e Smartphone, utilizzati secondo le modalità indicate nel protocollo. Successivamente i dati immagazzinati nei dispositivi vengono trasferiti al Pc per effettuarne l’elaborazione off-line, in ambiente Matlab. Per facilitare la seguente procedura di sincronizzazione dei dati intra e inter-device, tutti i sensori sono stati salvati, dall’App Android, secondo uno schema logico definito. Si è perciò verificata la possibilità del riconoscimento del contesto e dell’attività nell’uso quotidiano dei dispositivi. Inoltre si è sviluppato un algoritmo per la corretta identificazione del numero dei passi, indipendentemente dall’orientamento del singolo dispositivo. Infatti è importante saper rilevare in maniera corretta il numero di passi effettuati, soprattutto nei pazienti che, a causa di diverse patologie, non riescono ad effettuare una camminata fluida, regolare. Si è visto come il contapassi integrato nei sistemi commerciali per il fitness più diffusi (Smartwatch), pecca soprattutto in questa valutazione, mentre l’algoritmo, appositamente sviluppato, è in grado di garantire un’analisi accettabile a prescindere dal tipo di attività svolta, soprattutto per i dispositivi posizionati in L5. Infine è stato implementato un algoritmo, che sfrutta il filtro di Kalman e un modello biomeccanico appositamente sviluppato, per estrapolare l’evoluzione dell’angolo Tronco-Coscia. Avere a disposizione tale informazione e perciò conoscere la biomeccanica e la cinematica del corpo umano, rende possibile l’applicazione di questa procedura in svariati campi in ambito clinico e non.

Studio della cinematica del nuoto a stile libero attraverso sensori inerziali

Analisi cinematica delle fasi del nuoto, velocità in vasca e body roll attraverso l'uso di sensori inerziali. Implementazione di innovativi algoritmi di calcolo con l'utilizzo del filtro di Kalman 3D, matrici di rotazione e quaternioni per la determinazione dei parametri fondamentali del nuoto e della posizione del polso nel sistema di riferimento di torace. Confronto dei risultati ottenuti mediante i diversi algoritmi e loro validazione con quelli ottenuti con l'uso della stereofotogrammetria. Gli algoritmi possono essere generalizzati ad altri gesti motori.