Multilevel Analysis in Household Survey: An Application to Health Condition Data

The aim of this thesis is to apply multilevel regression model in context of household surveys. Hierarchical structure in this type of data is characterized by many small groups. In last years comparative and multilevel analysis in the field of perceived health have grown in size. The purpose of this thesis is to develop a multilevel analysis with three level of hierarchy for Physical Component Summary outcome to: evaluate magnitude of within and between variance at each level (individual, household and municipality); explore which covariates affect on perceived physical health at each level; compare model-based and design-based approach in order to establish informativeness of sampling design; estimate a quantile regression for hierarchical data. The target population are the Italian residents aged 18 years and older. Our study shows a high degree of homogeneity within level 1 units belonging from the same group, with an intraclass correlation of 27% in a level-2 null model. Almost all variance is explained by level 1 covariates. In fact, in our model the explanatory variables having more impact on the outcome are disability, unable to work, age and chronic diseases (18 pathologies). An additional analysis are performed by using novel procedure of analysis :"Linear Quantile Mixed Model", named "Multilevel Linear Quantile Regression", estimate. This give us the possibility to describe more generally the conditional distribution of the response through the estimation of its quantiles, while accounting for the dependence among the observations. This has represented a great advantage of our models with respect to classic multilevel regression. The median regression with random effects reveals to be more efficient than the mean regression in representation of the outcome central tendency. A more detailed analysis of the conditional distribution of the response on other quantiles highlighted a differential effect of some covariate along the distribution.

Approccio agli spostamenti per la valutazione della vulnerabilità sismica di telai in conglomerato cementizio armato.

Il presente lavoro ha lo scopo di presentare gli studi e i risultati ottenuti durante l’attività di ricerca svolta sul Displacement-based Assessment (DBA) dei telai in cemento armato. Dopo alcune considerazioni iniziali sul tema della vulnerabilità sismica e sui metodi di analisi e verifica, si procede alla descrizione teorica del metodo. Sono stati analizzati tre casi studio di telai piani, progettati per soli carichi verticali e secondo normative non più in vigore che non prevedevano l’applicazione della gerarchia delle resistenze. I telai considerati, destinati ad abitazione civile, hanno diversa altezza e numero di piani, e diverso numero di campate. Si è proceduto all’applicazione del metodo, alla valutazione della vulnerabilità sismica in base alla domanda in termini di spostamento costituita da uno spettro elastico previsto dall’EC8 e alla validazione dei risultati ottenuti mediante analisi non lineari statiche e dinamiche e mediante l’applicazione dei teoremi dell’Analisi limite dei telai, proposta come procedura alternativa per la determinazione del meccanismo anelastico e della capacità in termini di taglio alla base. In ultimo si è applicata la procedura DBA per la valutazione della vulnerabilità sismica di un edificio scolastico, realizzato tra il 1969 e il 1975 in un sito caratterizzato da una accelerazione di picco orizzontale pari a 0,24g e una probabilità di superamento del 10% in 75 anni.

New computational biology tools for the systematic analysis of the structure and expression of human genes

From the late 1980s, the automation of sequencing techniques and the computer spread gave rise to a flourishing number of new molecular structures and sequences and to proliferation of new databases in which to store them. Here are presented three computational approaches able to analyse the massive amount of publicly avalilable data in order to answer to important biological questions. The first strategy studies the incorrect assignment of the first AUG codon in a messenger RNA (mRNA), due to the incomplete determination of its 5' end sequence. An extension of the mRNA 5' coding region was identified in 477 in human loci, out of all human known mRNAs analysed, using an automated expressed sequence tag (EST)-based approach. Proof-of-concept confirmation was obtained by in vitro cloning and sequencing for GNB2L1, QARS and TDP2 and the consequences for the functional studies are discussed. The second approach analyses the codon bias, the phenomenon in which distinct synonymous codons are used with different frequencies, and, following integration with a gene expression profile, estimates the total number of codons present across all the expressed mRNAs (named here "codonome value") in a given biological condition. Systematic analyses across different pathological and normal human tissues and multiple species shows a surprisingly tight correlation between the codon bias and the codonome bias. The third approach is useful to studies the expression of human autism spectrum disorder (ASD) implicated genes. ASD implicated genes sharing microRNA response elements (MREs) for the same microRNA are co-expressed in brain samples from healthy and ASD affected individuals. The different expression of a recently identified long non coding RNA which have four MREs for the same microRNA could disrupt the equilibrium in this network, but further analyses and experiments are needed.

Silicon Photonics Integrated Circuits for Flexible Optical Systems

This dissertation deals with the design and the characterization of novel reconfigurable silicon-on-insulator (SOI) devices to filter and route optical signals on-chip. Design is carried out through circuit simulations based on basic circuit elements (Building Blocks, BBs) in order to prove the feasibility of an approach allowing to move the design of Photonic Integrated Circuits (PICs) toward the system level. CMOS compatibility and large integration scale make SOI one of the most promising material to realize PICs. The concepts of generic foundry and BB based circuit simulations for the design are emerging as a solution to reduce the costs and increase the circuit complexity. To validate the BB based approach, the development of some of the most important BBs is performed first. A novel tunable coupler is also presented and it is demonstrated to be a valuable alternative to the known solutions. Two novel multi-element PICs are then analysed: a narrow linewidth single mode resonator and a passband filter with widely tunable bandwidth. Extensive circuit simulations are carried out to determine their performance, taking into account fabrication tolerances. The first PIC is based on two Grating Assisted Couplers in a ring resonator (RR) configuration. It is shown that a trade-off between performance, resonance bandwidth and device footprint has to be performed. The device could be employed to realize reconfigurable add-drop de/multiplexers. Sensitivity with respect to fabrication tolerances and spurious effects is however observed. The second PIC is based on an unbalanced Mach-Zehnder interferometer loaded with two RRs. Overall good performance and robustness to fabrication tolerances and nonlinear effects have confirmed its applicability for the realization of flexible optical systems. Simulated and measured devices behaviour is shown to be in agreement thus demonstrating the viability of a BB based approach to the design of complex PICs.

La globalizzazione della bioetica: Analisi della bioetica latinoamericana

La tesi esplora la riflessione bioetica latino-americana e la sua evoluzione, valutandone i legami, intenzionali e non, con le posizioni bioetiche più consolidate e tendenzialmente dominanti del panorama internazionale. La trattazione indaga lo sviluppo della bioetica nel sub-continente latinoamericano, ponendo in evidenza lo sviluppo delle teorie morali che definiscono l'orizzonte interpretativo del dibattito contemporaneo, come pure le peculiarità della produzione sudamericana in materia di bioetica e la casistica tipica di questi territori. Per una comprensione delle caratteristiche di un pensiero bioetico, tipico di un territorio in via di sviluppo, la tesi presenta la trattazione di due precisi case studies: A- Il progetto peruviano: Propuesta de incorporación del enfoque intercultural y de representantes indígenas en los comités de ética en países multiculturales; B- La biomedicina e gli xenotrapianti in Messico. L'analisi dei casi studio è funzionale alla messa in luce delle caratteristiche costitutive del pensiero latinoamericano e della casistica tipica del territorio. La bioetica Latinoamericana, infatti, sviluppatasi circa con vent'anni di ritardo rispetto ai luoghi di nascita di questa disciplina (Gran Bretagna e USA), rivendica l'esigenza di un dibattito e di una prassi bioetica autoctone, capaci quindi di riassumere in sé stesse concetti e principi declinabili all'interno delle esperienze e delle concrete esigenze che prendono forma nella realtà culturale e socio-economica. Per questo motivo si discosta dalle cosiddette teorie bioetiche classiche rivendicando una bioetica di contestazione che si vincola costitutivamente al linguaggio dei diritti umani. La tesi propone inoltre l'utilizzo dei dati emersi dai casi studio per sviluppare una riflessione sulle modalità e su alcuni esiti della globalizzazione della bioetica. L’analisi si avvale di strumenti e categorie proprie della sociologia, dell’economia e della politica al fine di mettere in evidenza le diverse componenti costitutive e le criticità della bioetica globalizzata.

Global and regional sea level variations in the recent past and future: insight from observations and modeling

This work is focused on the analysis of sea–level change (last century), based mainly on instrumental observations. During this period, individual components of sea–level change are investigated, both at global and regional scales. Some of the geophysical processes responsible for current sea-level change such as glacial isostatic adjustments and current melting terrestrial ice sources, have been modeled and compared with observations. A new value of global mean sea level change based of tide gauges observations has been independently assessed in 1.5 mm/year, using corrections for glacial isostatic adjustment obtained with different models as a criterion for the tide gauge selection. The long wavelength spatial variability of the main components of sea–level change has been investigated by means of traditional and new spectral methods. Complex non–linear trends and abrupt sea–level variations shown by tide gauges records have been addressed applying different approaches to regional case studies. The Ensemble Empirical Mode Decomposition technique has been used to analyse tide gauges records from the Adriatic Sea to ascertain the existence of cyclic sea-level variations. An Early Warning approach have been adopted to detect tipping points in sea–level records of North East Pacific and their relationship with oceanic modes. Global sea–level projections to year 2100 have been obtained by a semi-empirical approach based on the artificial neural network method. In addition, a model-based approach has been applied to the case of the Mediterranean Sea, obtaining sea-level projection to year 2050.

Exploring host-pathogen interactions through protein microarray. Large-scale protein microarray analysis revealed novel human receptors for the staphylococcal immune evasion protein FLIPr and for the neisserial adhesin NadA

Adhesion, immune evasion and invasion are key determinants during bacterial pathogenesis. Pathogenic bacteria possess a wide variety of surface exposed and secreted proteins which allow them to adhere to tissues, escape the immune system and spread throughout the human body. Therefore, extensive contacts between the human and the bacterial extracellular proteomes take place at the host-pathogen interface at the protein level. Recent researches emphasized the importance of a global and deeper understanding of the molecular mechanisms which underlie bacterial immune evasion and pathogenesis. Through the use of a large-scale, unbiased, protein microarray-based approach and of wide libraries of human and bacterial purified proteins, novel host-pathogen interactions were identified. This approach was first applied to Staphylococcus aureus, cause of a wide variety of diseases ranging from skin infections to endocarditis and sepsis. The screening led to the identification of several novel interactions between the human and the S. aureus extracellular proteomes. The interaction between the S. aureus immune evasion protein FLIPr (formyl-peptide receptor like-1 inhibitory protein) and the human complement component C1q, key players of the offense-defense fighting, was characterized using label-free techniques and functional assays. The same approach was also applied to Neisseria meningitidis, major cause of bacterial meningitis and fulminant sepsis worldwide. The screening led to the identification of several potential human receptors for the neisserial adhesin A (NadA), an important adhesion protein and key determinant of meningococcal interactions with the human host at various stages. The interaction between NadA and human LOX-1 (low-density oxidized lipoprotein receptor) was confirmed using label-free technologies and cell binding experiments in vitro. Taken together, these two examples provided concrete insights into S. aureus and N. meningitidis pathogenesis, and identified protein microarray coupled with appropriate validation methodologies as a powerful large scale tool for host-pathogen interactions studies.

Assessment of gait spatio-temporal parameters in neurological disorders using wearable inertial sensors

Movement analysis carried out in laboratory settings is a powerful, but costly solution since it requires dedicated instrumentation, space and personnel. Recently, new technologies such as the magnetic and inertial measurement units (MIMU) are becoming widely accepted as tools for the assessment of human motion in clinical and research settings. They are relatively easy-to-use and potentially suitable for estimating gait kinematic features, including spatio-temporal parameters. The objective of this thesis regards the development and testing in clinical contexts of robust MIMUs based methods for assessing gait spatio-temporal parameters applicable across a number of different pathological gait patterns. First, considering the need of a solution the least obtrusive as possible, the validity of the single unit based approach was explored. A comparative evaluation of the performance of various methods reported in the literature for estimating gait temporal parameters using a single unit attached to the trunk first in normal gait and then in different pathological gait conditions was performed. Then, the second part of the research headed towards the development of new methods for estimating gait spatio-temporal parameters using shank worn MIMUs on different pathological subjects groups. In addition to the conventional gait parameters, new methods for estimating the changes of the direction of progression were explored. Finally, a new hardware solution and relevant methodology for estimating inter-feet distance during walking was proposed. Results of the technical validation of the proposed methods at different walking speeds and along different paths against a gold standard were reported and showed that the use of two MIMUs attached to the lower limbs associated with a robust method guarantee a much higher accuracy in determining gait spatio-temporal parameters. In conclusion, the proposed methods could be reliably applied to various abnormal gaits obtaining in some cases a comparable level of accuracy with respect to normal gait.