Food safety and zoonotic enteric pathogens: sources, risk factors and transmission routes of human salmonellosis and campylobacteriosis

Salmonella and Campylobacter are common causes of human gastroenteritis. Their epidemiology is complex and a multi-tiered approach to control is needed, taking into account the different reservoirs, pathways and risk factors. In this thesis, trends in human gastroenteritis and food-borne outbreak notifications in Italy were explored. Moreover, the improved sensitivity of two recently-implemented regional surveillance systems in Lombardy and Piedmont was evidenced, providing a basis for improving notification at the national level. Trends in human Salmonella serovars were explored: serovars Enteritidis and Infantis decreased, Typhimurium remained stable and 4,[5],12:i:-, Derby and Napoli increased, suggesting that sources of infection have changed over time. Attribution analysis identified pigs as the main source of human salmonellosis in Italy, accounting for 43–60% of infections, followed by Gallus gallus (18–34%). Attributions to pigs and Gallus gallus showed increasing and decreasing trends, respectively. Potential bias and sampling issues related to the use of non-local/non-recent multilocus sequence typing (MLST) data in Campylobacter jejuni/coli source attribution using the Asymmetric Island (AI) model were investigated. As MLST data become increasingly dissimilar with increasing geographical/temporal distance, attributions to sources not sampled close to human cases can be underestimated. A combined case-control and source attribution analysis was developed to investigate risk factors for human Campylobacter jejuni/coli infection of chicken, ruminant, environmental, pet and exotic origin in The Netherlands. Most infections (~87%) were attributed to chicken and cattle. Individuals infected from different reservoirs had different associated risk factors: chicken consumption increased the risk for chicken-attributed infections; animal contact, barbecuing, tripe consumption, and never/seldom chicken consumption increased that for ruminant-attributed infections; game consumption and attending swimming pools increased that for environment-attributed infections; and dog ownership increased that for environment- and pet-attributed infections. Person-to-person contacts around holiday periods were risk factors for infections with exotic strains, putatively introduced by returning travellers.

Assimilation of Meteosat Second Generation (MSG) satellite data in a regional numerical weather prediction model using a one-dimensional variational approach

The quality of temperature and humidity retrievals from the infrared SEVIRI sensors on the geostationary Meteosat Second Generation (MSG) satellites is assessed by means of a one dimensional variational algorithm. The study is performed with the aim of improving the spatial and temporal resolution of available observations to feed analysis systems designed for high resolution regional scale numerical weather prediction (NWP) models. The non-hydrostatic forecast model COSMO (COnsortium for Small scale MOdelling) in the ARPA-SIM operational configuration is used to provide background fields. Only clear sky observations over sea are processed. An optimised 1D–VAR set-up comprising of the two water vapour and the three window channels is selected. It maximises the reduction of errors in the model backgrounds while ensuring ease of operational implementation through accurate bias correction procedures and correct radiative transfer simulations. The 1D–VAR retrieval quality is firstly quantified in relative terms employing statistics to estimate the reduction in the background model errors. Additionally the absolute retrieval accuracy is assessed comparing the analysis with independent radiosonde and satellite observations. The inclusion of satellite data brings a substantial reduction in the warm and dry biases present in the forecast model. Moreover it is shown that the retrieval profiles generated by the 1D–VAR are well correlated with the radiosonde measurements. Subsequently the 1D–VAR technique is applied to two three–dimensional case–studies: a false alarm case–study occurred in Friuli–Venezia–Giulia on the 8th of July 2004 and a heavy precipitation case occurred in Emilia–Romagna region between 9th and 12th of April 2005. The impact of satellite data for these two events is evaluated in terms of increments in the integrated water vapour and saturation water vapour over the column, in the 2 meters temperature and specific humidity and in the surface temperature. To improve the 1D–VAR technique a method to calculate flow–dependent model error covariance matrices is also assessed. The approach employs members from an ensemble forecast system generated by perturbing physical parameterisation schemes inside the model. The improved set–up applied to the case of 8th of July 2004 shows a substantial neutral impact.

Filiera corta: percorsi di innovazione tecnici, organizzativi e sociali nella gestione strategica delle nicchie. Esperienze in Toscana e in Provenza

There is a widening consensus around the fact that, in many developed countries, food production-consumption patterns are in recent years interested by a process of deep change towards diversification and re-localisation practices, as a counter-tendency to the trend to the increasing disconnection between farming and food, producers and consumers. The relevance of these initiatives doesn't certainly lie on their economic dimension, but rather in their intense diffusion and growth rate, their spontaneous and autonomous nature and, especially, their intrinsic innovative potential. These dynamics involve a wide range of actors around local food patterns, embedding short food supply chains initiatives within a more complex and wider process of rural development, based on principles of sustainability, multifunctionality and valorisation of endogenous resources. In this work we have been analysing these features through a multi-level perspective, with reference to the dynamics between niche and regime and the inherent characteristics of the innovation paths. We apply this approach, through a qualitative methodology, to the analysis of the experience of farmers’ markets and Solidarity-Based Consumers Groups (Gruppi di Acquisto Solidale) ongoing in Tuscany, seeking to highlight the dynamics that are affecting the establishment of this alternative food production-consumption model (and its related innovative potential) from within and from without. To verify if and in which conditions they can constitute a niche, a protected space where radical innovations can develop, we make reference to the three interrelated analytic dimensions of socio-technical systems: the actors (i.e. individuals. social groups, organisations), the rules and institutions system, and the artefacts (i.e. the material and immaterial contexts in which the actors move). Through it, we analyse the innovative potential of niches and the level of their structuration and , then, the mechanisms of system transition, focusing on the new dynamics within the niche and between the niche and the policy regime emerging after the growth of interest by mass-media and public institutions and their direct involvement in the initiatives. Following the development of these significant experiences, we explore more deeply social, economic, cultural, political and organisational factors affecting innovations in face-to-face interactions, underpinning the critical aspects (sharing of alternative values, coherence at individual choices level, frictions on organisational aspects, inclusion/exclusion, attitudes towards integration at territorial level), towards uncovering until to the emergence of tensions and the risks of opportunistic behaviours that might arise from their growth. Finally, a comparison with similar experiences abroad is drawn (specifically with Provence), in order to detect food for thought, potentially useful for leading regional initiativestowards transition path.

Development of Clinical Decision Support Systems based on Mathematical Models of Physiological Systems

In the last years of research, I focused my studies on different physiological problems. Together with my supervisors, I developed/improved different mathematical models in order to create valid tools useful for a better understanding of important clinical issues. The aim of all this work is to develop tools for learning and understanding cardiac and cerebrovascular physiology as well as pathology, generating research questions and developing clinical decision support systems useful for intensive care unit patients. I. ICP-model Designed for Medical Education We developed a comprehensive cerebral blood flow and intracranial pressure model to simulate and study the complex interactions in cerebrovascular dynamics caused by multiple simultaneous alterations, including normal and abnormal functional states of auto-regulation of the brain. Individual published equations (derived from prior animal and human studies) were implemented into a comprehensive simulation program. Included in the normal physiological modelling was: intracranial pressure, cerebral blood flow, blood pressure, and carbon dioxide (CO2) partial pressure. We also added external and pathological perturbations, such as head up position and intracranial haemorrhage. The model performed clinically realistically given inputs of published traumatized patients, and cases encountered by clinicians. The pulsatile nature of the output graphics was easy for clinicians to interpret. The manoeuvres simulated include changes of basic physiological inputs (e.g. blood pressure, central venous pressure, CO2 tension, head up position, and respiratory effects on vascular pressures) as well as pathological inputs (e.g. acute intracranial bleeding, and obstruction of cerebrospinal outflow). Based on the results, we believe the model would be useful to teach complex relationships of brain haemodynamics and study clinical research questions such as the optimal head-up position, the effects of intracranial haemorrhage on cerebral haemodynamics, as well as the best CO2 concentration to reach the optimal compromise between intracranial pressure and perfusion. We believe this model would be useful for both beginners and advanced learners. It could be used by practicing clinicians to model individual patients (entering the effects of needed clinical manipulations, and then running the model to test for optimal combinations of therapeutic manoeuvres). II. A Heterogeneous Cerebrovascular Mathematical Model Cerebrovascular pathologies are extremely complex, due to the multitude of factors acting simultaneously on cerebral haemodynamics. In this work, the mathematical model of cerebral haemodynamics and intracranial pressure dynamics, described in the point I, is extended to account for heterogeneity in cerebral blood flow. The model includes the Circle of Willis, six regional districts independently regulated by autoregulation and CO2 reactivity, distal cortical anastomoses, venous circulation, the cerebrospinal fluid circulation, and the intracranial pressure-volume relationship. Results agree with data in the literature and highlight the existence of a monotonic relationship between transient hyperemic response and the autoregulation gain. During unilateral internal carotid artery stenosis, local blood flow regulation is progressively lost in the ipsilateral territory with the presence of a steal phenomenon, while the anterior communicating artery plays the major role to redistribute the available blood flow. Conversely, distal collateral circulation plays a major role during unilateral occlusion of the middle cerebral artery. In conclusion, the model is able to reproduce several different pathological conditions characterized by heterogeneity in cerebrovascular haemodynamics and can not only explain generalized results in terms of physiological mechanisms involved, but also, by individualizing parameters, may represent a valuable tool to help with difficult clinical decisions. III. Effect of Cushing Response on Systemic Arterial Pressure. During cerebral hypoxic conditions, the sympathetic system causes an increase in arterial pressure (Cushing response), creating a link between the cerebral and the systemic circulation. This work investigates the complex relationships among cerebrovascular dynamics, intracranial pressure, Cushing response, and short-term systemic regulation, during plateau waves, by means of an original mathematical model. The model incorporates the pulsating heart, the pulmonary circulation and the systemic circulation, with an accurate description of the cerebral circulation and the intracranial pressure dynamics (same model as in the first paragraph). Various regulatory mechanisms are included: cerebral autoregulation, local blood flow control by oxygen (O2) and/or CO2 changes, sympathetic and vagal regulation of cardiovascular parameters by several reflex mechanisms (chemoreceptors, lung-stretch receptors, baroreceptors). The Cushing response has been described assuming a dramatic increase in sympathetic activity to vessels during a fall in brain O2 delivery. With this assumption, the model is able to simulate the cardiovascular effects experimentally observed when intracranial pressure is artificially elevated and maintained at constant level (arterial pressure increase and bradicardia). According to the model, these effects arise from the interaction between the Cushing response and the baroreflex response (secondary to arterial pressure increase). Then, patients with severe head injury have been simulated by reducing intracranial compliance and cerebrospinal fluid reabsorption. With these changes, oscillations with plateau waves developed. In these conditions, model results indicate that the Cushing response may have both positive effects, reducing the duration of the plateau phase via an increase in cerebral perfusion pressure, and negative effects, increasing the intracranial pressure plateau level, with a risk of greater compression of the cerebral vessels. This model may be of value to assist clinicians in finding the balance between clinical benefits of the Cushing response and its shortcomings. IV. Comprehensive Cardiopulmonary Simulation Model for the Analysis of Hypercapnic Respiratory Failure We developed a new comprehensive cardiopulmonary model that takes into account the mutual interactions between the cardiovascular and the respiratory systems along with their short-term regulatory mechanisms. The model includes the heart, systemic and pulmonary circulations, lung mechanics, gas exchange and transport equations, and cardio-ventilatory control. Results show good agreement with published patient data in case of normoxic and hyperoxic hypercapnia simulations. In particular, simulations predict a moderate increase in mean systemic arterial pressure and heart rate, with almost no change in cardiac output, paralleled by a relevant increase in minute ventilation, tidal volume and respiratory rate. The model can represent a valid tool for clinical practice and medical research, providing an alternative way to experience-based clinical decisions. In conclusion, models are not only capable of summarizing current knowledge, but also identifying missing knowledge. In the former case they can serve as training aids for teaching the operation of complex systems, especially if the model can be used to demonstrate the outcome of experiments. In the latter case they generate experiments to be performed to gather the missing data.

Technological innovation in Emilia-Romagna: knowledge, practice, strategies

The present study aims at assessing the innovation strategies adopted within a regional economic system, the Italian region Emilia-Romagna, as it faced the challenges of a changing international scenario. As the strengthening of the regional innovative capabilities is regarded as a keystone to foster a new phase of economic growth, it is important also to understand how the local industrial, institutional, and academic actors have tackled the problem of innovation in the recent past. In this study we explore the approaches to innovation and the strategies adopted by the main regional actors through three different case studies. Chapter 1 provides a general survey of the innovative performance of the regional industries over the past two decades, as it emerges from statistical data and systematic comparisons at the national and European levels. The chapter also discusses the innovation policies that the regional government set up since 2001 in order to strengthen the collaboration among local economic actors, including universities and research centres. As mechanics is the most important regional industry, chapter 2 analyses the combination of knowledge and practices utilized in the period 1960s-1990s in the design of a particular kind of machinery produced by G.D S.p.A., a world-leader in the market of tobacco packaging machines. G.D is based in Bologna, the region’s capital, and is at the centre of the most important Italian packaging district. In chapter 3 the attention turns to the institutional level, focusing on how the local public administrations, and the local, publicly-owned utility companies have dealt with the creation of new telematic networks on the regional territory during the 1990s and 2000s. Finally, chapter 4 assesses the technology transfer carried out by the main university of the region – the University of Bologna – by focusing on the patenting activities involving its research personnel in the period 1960-2010.

Bridging innovation, nature and tradition: assessment of strategies for rural tourism development in Maramureş (Romania)

In the frame of EU rural policy, always more oriented towards environmental concerns and green livelihoods, Romania stands out for the predominance of rural areas and high nature value farming. The country has to face the challenge of joining the modernization process of rural farming systems with the valorization of local assets. Tourism has emerged as one of the main drivers of change and contributors for a sustainable exploitation of local resources. Rural tourism (RT) can foster the enhancement of the territorial capital (TC), the preservation of public goods (PGs) and the promotion of a more environmental oriented livelihood. The research focuses on a case study area, two valleys from Maramureş, where environmental approaches as diversification strategies are partially explored. The work investigates the role of tourism initiatives for the promotion of green oriented practices. The first part of the work is based on a literature review and interdisciplinary analysis of secondary data to identify the key issues: from rural development policy, to the concept of TC, of PGs and RT. The Romanian development programmes and related strategies are investigated; afterwards the characteristics of the County and the role of RT as diversification and valorisation policies is considered. The second part is based on the collection of primary data through interviews to different local stakeholders (farmers owners of rural guesthouses, local administrators, networks and artisans). The main frequencies are analyzed, a cluster analysis is computed to evaluate the similarities within the most representative groups and a comparative analysis is carried out between the two Valleys. The frame of the analysis is based on a set of indicators following the dimensions of the TC, to assess the characteristics of the local stakeholders and to outline the perception about the local PGs and on the adopted strategies to manage the territory. Final considerations are elaborated and few scenarios are outlined, giving relevance to the importance of improving awareness and creating embeddedness among public-private local stakeholders and resources as a tool for a socio-economic and environmental development of the area.

Spatial Disparity and Dynamic Trajectory of Convergence in China: Construction and Application of a Composite Index of Regional Development

China is a large country characterized by remarkable growth and distinct regional diversity. Spatial disparity has always been a hot issue since China has been struggling to follow a balanced growth path but still confronting with unprecedented pressures and challenges. To better understand the inequality level benchmarking spatial distributions of Chinese provinces and municipalities and estimate dynamic trajectory of sustainable development in China, I constructed the Composite Index of Regional Development (CIRD) with five sub pillars/dimensions involving Macroeconomic Index (MEI), Science and Innovation Index (SCI), Environmental Sustainability Index (ESI), Human Capital Index (HCI) and Public Facilities Index (PFI), endeavoring to cover various fields of regional socioeconomic development. Ranking reports on the five sub dimensions and aggregated CIRD were provided in order to better measure the developmental degrees of 31 or 30 Chinese provinces and municipalities over 13 years from 1998 to 2010 as the time interval of three “Five-year Plans”. Further empirical applications of this CIRD focused on clustering and convergence estimation, attempting to fill up the gap in quantifying the developmental levels of regional comprehensive socioeconomics and estimating the dynamic convergence trajectory of regional sustainable development in a long run. Four clusters were benchmarked geographically-oriented in the map on the basis of cluster analysis, and club-convergence was observed in the Chinese provinces and municipalities based on stochastic kernel density estimation.

Operational research applied to regional healthcare system

In this thesis we focus on optimization and simulation techniques applied to solve strategic, tactical and operational problems rising in the healthcare sector. At first we present three applications to Emilia-Romagna Public Health System (SSR) developed in collaboration with Agenzia Sanitaria e Sociale dell'Emilia-Romagna (ASSR), a regional center for innovation and improvement in health. Agenzia launched a strategic campaign aimed at introducing Operations Research techniques as decision making tools to support technological and organizational innovations. The three applications focus on forecast and fund allocation of medical specialty positions, breast screening program extension and operating theater planning. The case studies exploit the potential of combinatorial optimization, discrete event simulation and system dynamics techniques to solve resource constrained problem arising within Emilia-Romagna territory. We then present an application in collaboration with Dipartimento di Epidemiologia del Lazio that focuses on population demand of service allocation to regional emergency departments. Finally, a simulation-optimization approach, developed in collaboration with INESC TECH center of Porto, to evaluate matching policies for the kidney exchange problem is discussed.