Essays in Applied Health Economics: Evidence on Health and Health Care in Italy and UK

This thesis is the result of my experience as a PhD student taking part in the Joint Doctoral Programme at the University of York and the University of Bologna. In my thesis I deal with topics that are of particular interest in Italy and in Great Britain. Chapter 2 focuses on the empirical test of the existence of the relationship between technological profiles and market structure claimed by Sutton’s theory (1991, 1998) in the specific economic framework of hospital care services provided by the Italian National Health Service (NHS). In order to test the empirical predictions by Sutton, we identify the relevant markets for hospital care services in Italy in terms of both product and geographic dimensions. In particular, the Elzinga and Hogarty (1978) approach has been applied to data on patients’ flows across Italian Provinces in order to derive the geographic dimension of each market. Our results provide evidence in favour of the empirical predictions of Sutton. Chapter 3 deals with the patient mobility in the Italian NHS. To analyse the determinants of patient mobility across Local Health Authorities, we estimate gravity equations in multiplicative form using a Poisson pseudo maximum likelihood method, as proposed by Santos-Silva and Tenreyro (2006). In particular, we focus on the scale effect played by the size of the pool of enrolees. In most of the cases our results are consistent with the predictions of the gravity model. Chapter 4 considers the effects of contractual and working conditions on selfassessed health and psychological well-being (derived from the General Health Questionnaire) using the British Household Panel Survey (BHPS). We consider two branches of the literature. One suggests that “atypical” contractual conditions have a significant impact on health while the other suggests that health is damaged by adverse working conditions. The main objective of our paper is to combine the two branches of the literature to assess the distinct effects of contractual and working conditions on health. The results suggest that both sets of conditions have some influence on health and psychological well-being of employees.

Cognitive and affective processes in social actions and decisions

The question of how we make, and how we should make judgments and decisions has occupied thinkers for many centuries. This thesis has the aim to add new evidences to clarify the brain’s mechanisms for decisions. The cognitive and the emotional processes of social actions and decisions are investigated with the aim to understand which brain areas are mostly involved. Four experimental studies are presented. A specific kind of population is involved in the first study (as well as in study III) concerning patients with lesion of ventromedial prefrontal cortex (vmPFC). This region is collocated in the ventral surface of frontal lobe, and it seems have an important role in social and moral decision in forecasting the negative emotional consequences of choice. In study I, it is examined whether emotions, specifically social emotions subserved by the vmPFC, affect people’s willingness to trust others. In study II is observed how incidental emotions could encourage trusting behaviour, especially when individuals are not aware of emotive stimulation. Study III has the aim to gather a direct psychophysiological evidence, both in healthy and neurologically impaired individuals, that emotions are crucially involved in shaping moral judgment, by preventing moral violations. Study IV explores how the moral meaning of a decision and its subsequent action can modulate the basic component of action such as sense of agency.

Genetic Manipulation, Gene Silencing and Biomarker Development in Multiple Experimental Models.

The thesis is set in three different parts, according to the relative experimental models. First, the domestic pig (Sus scrofa) is part of the study on reproductive biotechnologies: the transgenesis technique of Sperm Mediated Gene Transfer is widely studied starting from the quality of the semen, through the study of multiple uptakes of exogenous DNA and lastly used in the production of multi-transgenic blastocysts. Finally we managed to couple the transgenesis pipeline with sperm sorting and therefore produced transgenic embryos of predetermined sex. In the second part of the thesis the attention is on the fruit fly (Drosophila melanogaster) and on its derived cell line: the S2 cells. The in vitro and in vivo models are used to develop and validate an efficient way to knock down the myc gene. First an efficient in vitro protocol is described, than we demonstrate how the decrease in myc transcript remarkably affects the ribosome biogenesis through the study of Polysome gradients, rRNA content and qPCR. In vivo we identified two optimal drivers for the conditional silencing of myc, once the flies are fed with RU486: the first one is throughout the whole body (Tubulin), while the second is a head fat body driver (S32). With these results we present a very efficient model to study the role of myc in multiple aspects of translation. In the third and last part, the focus is on human derived lung fibroblasts (hLF-1), mouse tail fibroblasts and mouse tissues. We developed an efficient assay to quantify the total protein content of the nucleus on a single cell level via fluorescence. We coupled the protocol with classical immunofluorescence so to have at the same time general and particular information, demonstrating that during senescence nuclear proteins increase by 1.8 fold either in human cells, mouse cells and mouse tissues.

Study of Candidate Genes for production and carcass traits in Italian Heavy Pigs: identification of a new DNA Markers, Expression Studies and Association Analysis using Different Experimental Design

Heavy pig breeding in Italy is mainly oriented for the production of high quality processed products. Of particular importance is the dry cured ham production, which is strictly regulated and requires specific carcass characteristics correlated with green leg characteristics. Furthermore, as pigs are slaughtered at about 160 kg live weight, the Italian pig breeding sector faces severe problems of production efficiency that are related to all biological aspects linked to growth, feed conversion, fat deposition and so on. It is well known that production and carcass traits are in part genetically determined. Therefore, as a first step to understand genetic basis of traits that could have a direct or indirect impact on dry cured ham production, a candidate gene approach can be used to identify DNA markers associated with parameters of economic importance. In this thesis, we investigated three candidate genes for carcass and production traits (TRIB3, PCSK1, MUC4) in pig breeds used for dry cured ham production, using different experimental approaches in order to find molecular markers associated with these parameters.

Integration of cognitive and affective processes in perception and decision-making

The relationship between emotion and cognition is a topic that raises great interest in research. Recently, a view of these two processes as interactive and mutually influencing each other has become predominant. This dissertation investigates the reciprocal influences of emotion and cognition, both at behavioral and neural level, in two specific fields, such as attention and decision-making. Experimental evidence on how emotional responses may affect perceptual and attentional processes has been reported. In addition, the impact of three factors, such as personality traits, motivational needs and social context, in modulating the influence that emotion exerts on perception and attention has been investigated. Moreover, the influence of cognition on emotional responses in decision-making has been demonstrated. The current experimental evidence showed that cognitive brain regions such as the dorsolateral prefrontal cortex are causally implicated in regulation of emotional responses and that this has an effect at both pre and post decisional stages. There are two main conclusions of this dissertation: firstly, emotion exerts a strong influence on perceptual and attentional processes but, at the same time, this influence may also be modulated by other factors internal and external to the individuals. Secondly, cognitive processes may modulate emotional prepotent responses, by serving a regulative function critical to driving and shaping human behavior in line with current goals.

The future in action: neurophysiological and behavioral evidence of anticipatory motor simulation.

The motor system can no longer be considered as a mere passive executive system of motor commands generated elsewhere in the brain. On the contrary, it is deeply involved in perceptual and cognitive functions and acts as an “anticipation device”. The present thesis investigates the anticipatory motor mechanisms occurring in two particular instances: i) when processing sensory events occurring within the peripersonal space (PPS); and ii) when perceiving and predicting others’actions. The first study provides evidence that PPS representation in humans modulates neural activity within the motor system, while the second demonstrates that the motor mapping of sensory events occurring within the PPS critically relies on the activity of the premotor cortex. The third study provides direct evidence that the anticipatory motor simulation of others’ actions critically relies on the activity of the anterior node of the action observation network (AON), namely the inferior frontal cortex (IFC). The fourth study, sheds light on the pivotal role of the left IFC in predicting the future end state of observed right-hand actions. Finally, the fifth study examines how the ability to predict others’ actions could be influenced by a reduction of sensorimotor experience due to the traumatic or congenital loss of a limb. Overall, the present work provides new insights on: i) the anticipatory mechanisms of the basic reactivity of the motor system when processing sensory events occurring within the PPS, and the same anticipatory motor mechanisms when perceiving others’ implied actions; ii) the functional connectivity and plasticity of premotor-motor circuits both during the motor mapping of sensory events occurring within the PPS and when perceiving others’ actions; and iii) the anticipatory mechanisms related to others’ actions prediction.

Residual function, spontaneous reorganisation and treatment plasticity in homonymous visual field defects

This thesis will focus on the residual function and visual and attentional deficits in human patients, which accompany damage to the visual cortex or its thalamic afferents, and plastic changes, which follow it. In particular, I will focus on homonymous visual field defects, which comprise a broad set of central disorders of vision. I will present experimental evidence that when the primary visual pathway is completely damaged, the only signal that can be implicitly processed via subcortical visual networks is fear. I will also present data showing that in a patient with relative deafferentation of visual cortex, changes in the spatial tuning and response gain of the contralesional and ipsilesional cortex are observed, which are accompanied by changes in functional connectivity with regions belonging to the dorsal attentional network and the default mode network. I will also discuss how cortical plasticity might be harnessed to improve recovery through novel treatments. Moreover, I will show how treatment interventions aimed at recruiting spared subcortical pathway supporting multisensory orienting can drive network level change.

Development and experimental validation of a knock induced damage model and real-time implementation of model-based strategies to control knock intensity in boosted gasoline engines

This PhD thesis reports the main activities carried out during the 3 years long “Mechanics and advanced engineering sciences” course, at the Department of Industrial Engineering of the University of Bologna. The research project title is “Development and analysis of high efficiency combustion systems for internal combustion engines” and the main topic is knock, one of the main challenges for boosted gasoline engines. Through experimental campaigns, modelling activity and test bench validation, 4 different aspects have been addressed to tackle the issue. The main path goes towards the definition and calibration of a knock-induced damage model, to be implemented in the on-board control strategy, but also usable for the engine calibration and potentially during the engine design. Ionization current signal capabilities have been investigated to fully replace the pressure sensor, to develop a robust on-board close-loop combustion control strategy, both in knock-free and knock-limited conditions. Water injection is a powerful solution to mitigate knock intensity and exhaust temperature, improving fuel consumption; its capabilities have been modelled and validated at the test bench. Finally, an empiric model is proposed to predict the engine knock response, depending on several operating condition and control parameters, including injected water quantity.

Study and experimental characterization of the laser welding process for the manufacturing of electric powertrain components in the automotive industry

The PhD project that will be presented in this thesis is focused on the study and optimization of the production process for the manufacturing of electrical powertrain components in the automotive field using the laser beam welding process (LBW). The objective is to define, through experimental activities, an optimized process condition for applications in the electrical field that can be generalized, that is, which guarantees its reproducibility as the types of connections vary and which represents the basis for extending the method to future applications in e-mobility sector. The work developed along two lines of research, the convergence of which made it possible to create prototypes of battery modules based on different types of lithium-ion cells and stator windings for electric motors. On the one hand, the different welding configurations involving the production of batteries based on pouch cells and therefore the welding of aluminum and copper in dissimilar configuration were studied, while for the prismatic cells only one configuration was analyzed. On the other hand, the welding of pure copper hairpins with rectangular shape in edge joint configuration was studied for the production of stator windings. The experimental tests carried out have demonstrated the feasibility of using the LBW process for the production of electric powertrain components entirely designed and developed internally as the types of materials and welding configurations vary; the methodologies required for the characterization methods, necessary for the end-of-line tests, for the evaluation of the properties of the different joint configurations and components (battery and electric motor) were also defined with the aim of obtaining the best performance. The entire doctorate program was conducted in collaboration with Ferrari Auto S.p.A. and the direct industrial application of the issues addressed has been faced.

Numerical modeling and experimental validation of the recrystallization behaviour in the extrusion of 6XXX aluminum alloys

The microstructure of 6XXX aluminum alloys deeply affects mechanical, crash, corrosion and aesthetic properties of extruded profiles. Unfortunately, grain structure evolution during manufacturing processes is a complex phenomenon because several process and material parameters such as alloy chemical composition, temperature, extrusion speed, tools geometries, quenching and thermal treatment parameters affect the grain evolution during the manufacturing process. The aim of the present PhD thesis was the analysis of the recrystallization kinetics during the hot extrusion of 6XXX aluminum alloys and the development of reliable recrystallization models to be used in FEM codes for the microstructure prediction at a die design stage. Experimental activities have been carried out in order to acquire data for the recrystallization models development, validation and also to investigate the effect of process parameters and die design on the microstructure of the final component. The experimental campaign reported in this thesis involved the extrusion of AA6063, AA6060 and AA6082 profiles with different process parameters in order to provide a reliable amount of data for the models validation. A particular focus was made to investigate the PCG defect evolution during the extrusion of medium-strength alloys such as AA6082. Several die designs and process conditions were analysed in order to understand the influence of each of them on the recrystallization behaviour of the investigated alloy. From the numerical point of view, innovative models for the microstructure prediction were developed and validated over the extrusion of industrial-scale profiles with complex geometries, showing a good matching in terms of the grain size and surface recrystallization prediction. The achieved results suggest the reliability of the developed models and their application in the industrial field for process and material properties optimization at a die-design stage.