Estimation of infection rate in epidemic models with multiple populations

Dissertação para obtenção do Grau de Mestre em Matemática e Aplicações Especialização em Actuariado, Estatística e Investigação OperacionalThe e ect of infectious diseases on human development throughout history is well established, and investigation on the causes of infectious epidemics { and plagues in particular { dates back at least to Hippocrates,the father of Western medicine. The mechanisms by which diseases spread, however, could not be fully understood until the late nineteenth century, with the discovery of microorganisms and the understanding of their role as infectious agents. Eventually, at the turn of the twentieth century, the foundations of the mathematical epidemiology of infectious diseases were laid by the seminal work of En'ko, Ross, and Kermack and McKendrick. More recently, the application of graph theory to epidemiology has given rise to models that consider the spread of diseases not only at the level of individuals belonging to a single population (population models), but also in systems with multiple populations linked by a transportation network(meta-population models). The aim of meta-populations models is to understand how movement of individuals between populations generates the geographical spread of diseases, a challenging goal whose importance is all the greater now that long-range displacements are facilitated by inexpensive air travel possibilities. A problem of particular interest in all epidemic models is the estimation of parameters from sparse and inaccurate real-world data, especially the socalled infection rate, whose estimation cannot be carried out directly through clinical observation. Focusing on meta-population models, in this thesis we introduce a new estimation method for this crucial parameter that is able to accurately infer it from the arrival times of the rst infective individual in each population. Moreover, we test our method and its accuracy by means of computer simulations

The TimeMachine for Inference on Stochastic Trees

The simulation of genealogical trees backwards in time, from observations up to the most recent common ancestor (MRCA), is hindered by the fact that, while approaching the root of the tree, coalescent events become rarer, with a corresponding increase in computation time. The recently proposed "Time Machine" tackles this issue by stopping the simulation of the tree before reaching the MRCA and correcting for the induced bias. We present a computationally efficient implementation of this approach that exploits multithreading

Friction Stir Welding of Ti6Al4V complex geometries for aeronautical applications: a feasibility study

While Friction Stir Welding (FSW) of aluminium alloys can be considered a mature technology, even for complex joint morphologies, as T joints welded “in transparency”, welding of hard material still presents several open issues. In fact, welding of titanium alloys is a challenging process due to the chemical, mechanical and thermal characteristics of such materials which are subjected to atmosphere contamination resulting in joint hydrogen, oxygen and nitrogen embrittlement; additionally, due to the high melting temperature, large distortion and residual stress are found in joints obtained by traditional fusion welding processes as gas metal arc welding, electron beam welding and laser welding. In this way a solid-state process, as FSW, represents a valid choice in order to overcome problems related to the material melting. It should be noticed that FSW of titanium alloys is definitely more complex than the same process referred to aluminium alloys. In the proposed paper, a feasibility study on the production of Ti6Al4V T-joints in one welding pass, i.e. the so-called transparency welding, is presented. The main process parameters, i.e. tool rotation and feed rate have been fixed, and the main metallurgical and mechanical properties of the joint have been analysed. Macro and micro observations of the joints have been performed relating the final microstructure to the input process parameters utilized

Investigation of refractive index sensing based on Fano resonance in fiber Bragg grating ring resonators.

In this paper we theoretically investigate a ring resonant cavity obtained by closing on itself a pi-shifted fiber Bragg grating, to be used for refractive index sensing applications. Differently from a conventional pi-shifted fiber Bragg grating, the spectral structure of this cavity is characterized by an asymmetric splitting doublet composed by a right side resonance having an asymmetric Fano profile and a left side resonance having a symmetric Lorentzian profile. The right side resonance shows a narrower and sharper peak than all the other kinds of resonance achievable with both conventional ring resonators and pi-shifted fiber Bragg gratings. A reduction of the resonant linewidth with respect to a conventional pi-shifted Fiber Bragg grating and a fiber ring resonator, having the same physical parameters, is theoretically proved, achieving up to five orders of magnitude improvement with respect to the usual ring resonator. Due to these resonance features, the pi-shifted Bragg grating ring resonator results suitable for RI sensing applications requiring extremely narrow resonances for high resolution measurements. In particular, by assuming a refractive index sensing to detect the presence of sugar in water, the sensor can show a theoretical resolution better than 10(-9) RIU. (C)2015 Optical Society of Americ

Localized strain sensing with fiber Bragg-grating ring cavities

We report the theoretical description and the experimental demonstration of an optical resonator formed by inserting a Fiber Bragg Grating (FBG) in a closed fiber loop. The spectral characteristics of such a resonator strongly depend on the reflectivity of the FBG. In the wavelength region where the FBG reflectivity R is negligible, the system behaves like a conventional ring resonator. On the other hand, when R is not vanishing, a split-mode structure can be observed, associated to the degeneracy removal of two counterpropagating resonant modes. The magnitude of the mode splitting can be used to sense small variations of the FBG physical parameters, such as length, temperature or group index. An example of strain sensing with this setup is reported, showing that the mode splitting is sensitive to a mechanical strain applied to the FBG, while it is almost insensitive to a strain applied to any other point of the resonator. This peculiar feature allows to perform cavity-enhanced, local strain measurements with a reduced sensitivity to environmental perturbations, which represents an important improvement in the framework of the fiber-optic sensors. (C)2013 Optical Society of Americ

Dynamics of the Risk of Smoking-Induced Lung Cancer A Compartmental Hidden Markov Model for Longitudinal Analysis

n/

Differentially methylated microRNAs in prediagnostic samples of subjects who developed breast cancer in the european prospective investigation into nutrition and cancer (EPIC-Italy) cohort

The crosstalk between microRNAs (miRNAs) and other epigenetic factors may lead to novel hypotheses about carcinogenesis identifying new targets for research. Because a single miRNA can regulate multiple downstream target genes, its altered expression may potentially be a sensitive biomarker to detect early malignant transformation and improve diagnosis and prognosis. In the current study, we tested the hypothesis that altered methylation of miRNA encoding genes, associated with deregulated mature miRNA expression, may be related to dietary and lifestyle factors and may contribute to cancer development. In a case-control study nested in a prospective cohort (EPIC-Italy), we analysed DNA methylation levels of miRNA encoding genes (2191 CpG probes related to 517 genes) that are present in the Infinium Human Methylation450 BeadChip array in prediagnostic peripheral white blood cells of subjects who developed colorectal cancer (CRC, n = 159) or breast cancer (BC, n = 166) and matched subjects who remained clinically healthy. In the whole cohort, several differentially methylated miRNA genes were observed in association with age, sex, smoking habits and physical activity. Interestingly, in the case-control study, eight differentially methylated miRNAs were identified in subjects who went on to develop BC (miR-328, miR-675, miR-1307, miR-1286, miR-1275, miR-1910, miR-24-1 and miR-548a-1; all Bonferroni-adjusted P < 0.05). No significant associations were found with CRC. Assuming that altered methylation of miRNAs detectable in blood may be present before diagnosis, it may represent a biomarker for early detection or risk of cancer and may help to understand the cascade of events preceding tumour onset

Life-course socioeconomic status and DNA methylation of genes regulating inflammation

Background: In humans, low socioeconomic status (SES) across the life course is associated with greater diurnal cortisol production, increased inflammatory activity and higher circulating antibodies for several pathogens, all suggesting a dampened immune response. Recent evidence suggests that DNA methylation of pro-inflammatory genes may be implicated in the biological embedding of the social environment. Methods: The present study examines the association between life-course SES and DNA methylation of candidate genes, selected on the basis of their involvement in SES-related inflammation, in the context of a genome-wide methylation study. Participants were 857 healthy individuals sampled from the EPIC Italy prospective cohort study. Results: Indicators of SES were associated with DNA methylation of genes involved in inflammation. NFATC1, in particular, was consistently found to be less methylated in individuals with low vs high SES, in a dose-dependent manner. IL1A, GPR132 and genes belonging to the MAPK family were also less methylated among individuals with low SES. In addition, associations were found between SES and CXCL2 and PTGS2, but these genes were consistently more methylated among low SES individuals. Conclusions: Our findings support the hypothesis that the social environment leaves an epigenetic signature in cells. Although the functional significance of SES-related DNA methylation is still unclear, we hypothesize that it may link SES to chronic disease ris

Beyond BRCA1 and BRCA2: deleterious variants in DNA repair pathway genes in italian families with breast/ovarian and pancreatic cancers

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches

Biological marks of early-life socioeconomic experience is detected in the adult inflammatory transcriptome.

Consistent evidence is accumulating to link lower socioeconomic position (SEP) and poorer health, and the inflammatory system stands out as a potential pathway through which socioeconomic environment is biologically embedded. Using bloodderived genome-wide transcriptional profiles from 268 Italian participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we evaluated the association between early life, young and later adulthood SEP and the expression of 845 genes involved in human inflammatory responses. These were examined individually and jointly using several inflammatory scores. Our results consistently show that participants whose father had a manual (as compared to nonmanual) occupation exhibit, later in life, a higher inflammatory score, hence indicating an overall increased level of expression for the selected inflammatory-related genes. Adopting a life course approach, these associations remained statistically significant upon adjustment for later-in-life socioeconomic experiences. Sensitivity analyses indicated that our findings were not affected by the way the inflammatory score was calculated, and were replicated in an independent study. Our study provides additional evidence that childhood SEP is associated with a sustainable upregulation of the inflammatory transcriptome, independently of subsequent socioeconomic experiences. Our results support the hypothesis that early social inequalities impacts adult physiology