Approccio multidisciplinare per le valutazioni ambientali: Problematiche e sinergie in un uso combinato delle metodologie life cycle assessment (lca) e risk assessment (ra)

In questo lavoro di tesi si è elaborato un quadro di riferimento per l’utilizzo combinato di due metodologie di valutazione di impatti LCA e RA, per tecnologie emergenti. L’originalità dello studio sta nell’aver proposto e anche applicato il quadro di riferimento ad un caso studio, in particolare ad una tecnologia innovativa di refrigerazione, basata su nanofluidi (NF), sviluppata da partner del progetto Europeo Nanohex che hanno collaborato all’elaborazione degli studi soprattutto per quanto riguarda l’inventario dei dati necessari. La complessità dello studio è da ritrovare tanto nella difficile integrazione di due metodologie nate per scopi differenti e strutturate per assolvere a quegli scopi, quanto nel settore di applicazione che seppur in forte espansione ha delle forti lacune di informazioni circa processi di produzione e comportamento delle sostanze. L’applicazione è stata effettuata sulla produzione di nanofluido (NF) di allumina secondo due vie produttive (single-stage e two-stage) per valutare e confrontare gli impatti per la salute umana e l’ambiente. Occorre specificare che il LCA è stato quantitativo ma non ha considerato gli impatti dei NM nelle categorie di tossicità. Per quanto concerne il RA è stato sviluppato uno studio di tipo qualitativo, a causa della problematica di carenza di parametri tossicologici e di esposizione su citata avente come focus la categoria dei lavoratori, pertanto è stata fatta l’assunzione che i rilasci in ambiente durante la fase di produzione sono trascurabili. Per il RA qualitativo è stato utilizzato un SW specifico, lo Stoffenmanger-Nano che rende possibile la prioritizzazione dei rischi associati ad inalazione in ambiente di lavoro. Il quadro di riferimento prevede una procedura articolata in quattro fasi: DEFINIZIONE SISTEMA TECNOLOGICO, RACCOLTA DATI, VALUTAZIONE DEL RISCHIO E QUANTIFICAZIONE DEGLI IMPATTI, INTERPRETAZIONE.

A Web GIS Decision Support System For Coastal Risk Assessment and Mitigation Planning

Coastal flooding poses serious threats to coastal areas around the world, billions of dollars in damage to property and infrastructure, and threatens the lives of millions of people. Therefore, disaster management and risk assessment aims at detecting vulnerability and capacities in order to reduce coastal flood disaster risk. In particular, non-specialized researchers, emergency management personnel, and land use planners require an accurate, inexpensive method to determine and map risk associated with storm surge events and long-term sea level rise associated with climate change. This study contributes to the spatially evaluation and mapping of social-economic-environmental vulnerability and risk at sub-national scale through the development of appropriate tools and methods successfully embedded in a Web-GIS Decision Support System. A new set of raster-based models were studied and developed in order to be easily implemented in the Web-GIS framework with the purpose to quickly assess and map flood hazards characteristics, damage and vulnerability in a Multi-criteria approach. The Web-GIS DSS is developed recurring to open source software and programming language and its main peculiarity is to be available and usable by coastal managers and land use planners without requiring high scientific background in hydraulic engineering. The effectiveness of the system in the coastal risk assessment is evaluated trough its application to a real case study.

Interaction between APOE4 genotype and environmental risk factors in Alzheimer's disease

Alzheimer's disease (AD) is probably caused by both genetic and environmental risk factors. The major genetic risk factor is the E4 variant of apolipoprotein E gene called apoE4. Several risk factors for developing AD have been identified including lifestyle, such as dietary habits. The mechanisms behind the AD pathogenesis and the onset of cognitive decline in the AD brain are presently unknown. In this study we wanted to characterize the effects of the interaction between environmental risk factors and apoE genotype on neurodegeneration processes, with particular focus on behavioural studies and neurodegenerative processes at molecular level. Towards this aim, we used 6 months-old apoE4 and apoE3 Target Replacement (TR) mice fed on different diets (high intake of cholesterol and high intake of carbohydrates). These mice were evaluated for learning and memory deficits in spatial reference (Morris Water Maze (MWM)) and contextual learning (Passive Avoidance) tasks, which involve the hippocampus and the amygdala, respectively. From these behavioural studies we found that the initial cognitive impairments manifested as a retention deficit in apoE4 mice fed on high carbohydrate diet. Thus, the genetic risk factor apoE4 genotype associated with a high carbohydrate diet seems to affect cognitive functions in young mice, corroborating the theory that the combination of genetic and environmental risk factors greatly increases the risk of developing AD and leads to an earlier onset of cognitive deficits. The cellular and molecular bases of the cognitive decline in AD are largely unknown. In order to determine the molecular changes for the onset of the early cognitive impairment observed in the behavioural studies, we performed molecular studies, with particular focus on synaptic integrity and Tau phosphorylation. The most relevant finding of our molecular studies showed a significant decrease of Brain-derived Neurotrophic Factor (BDNF) in apoE4 mice fed on high carbohydrate diet. Our results may suggest that BDNF decrease found in apoE4 HS mice could be involved in the earliest impairment in long-term reference memory observed in behavioural studies. The second aim of this thesis was to study possible involvement of leptin in AD. There is growing evidence that leptin has neuroprotective properties in the Central Nervous System (CNS). Recent evidence has shown that leptin and its receptors are widespread in the CNS and may provide neuronal survival signals. However, there are still numerous questions, regarding the molecular mechanism by which leptin acts, that remain unanswered. Thus, given to the importance of the involvement of leptin in AD, we wanted to clarify the function of leptin in the pathogenesis of AD and to investigate if apoE genotype affect leptin levels through studies in vitro, in mice and in human. Our findings suggest that apoE4 TR mice showed an increase of leptin in the brain. Leptin levels are also increased in the cerebral spinal fluid of AD patients and apoE4 carriers with AD have higher levels of leptin than apoE3 carriers. Moreover, leptin seems to be expressed by reactive glial cells in AD brains. In vitro, ApoE4 together with Amyloid beta increases leptin production by microglia and astrocytes. Taken together, all these findings suggest that leptin replacement might not be a good strategy for AD therapy. Our results show that high leptin levels were found in AD brains. These findings suggest that, as high leptin levels do not promote satiety in obese individuals, it might be possible that they do not promote neuroprotection in AD patients. Therefore, we hypothesized that AD brain could suffer from leptin resistance. Further studies will be critical to determine whether or not the central leptin resistance in SNC could affect its potential neuroprotective effects.

Cellular and Molecular Biomarkers for Risk Assessment of Colorectal cancer

The detection of Colorectal Cancer (CRC), at early stages, is one of the proven strategies resulting in a higher cure rate. In recent years, several studies have appeared identifying potential cancer markers in serum, plasma and stool in an attempt to improve actual screening procedures. Thus, the aim of the study was (1) Evaluate MN frequency, (2) Evaluate plasma ultrafiltrate capacity to induce MN formation, (3) Evaluate SEPT9 and NOTCH3 promoter methylation profile in peripheral blood lymphocytes from subjects resulted positive to fecal occult blood test and examined by colonoscopy. MN frequency was significantly higher in subjects with histological diagnosis of CRC and adenoma than control (p ≤ 0.001 and p ≤ 0.01, respectively). About, CF-MN analysis, a statistically significant difference was observed between CRC and control (p ≤ 0.05). On the other hand, SEPT9 and NOTCH3 promoter methylation status was significantly lower in CRC subjects than controls; additionally, NOTCH3 promoter methylation status was significantly lower in CRC subjects than adenoma subjects (p ≤ 0.01). The results obtained allow conclude that MN frequency varies according CRC pathologic status and, together with other variables, is a valid biomarker for adenoma and CRC risk. Additionally, the plasma of patients affected with CRC not only serve as a biomarker for oxidative stress but also as biomarker of genetic damage correlated with the carcinogenic process that verifies in colon-rectum. SEPT9 and NOTCH3 promoter methylation status, at peripheral blood level, varies according hystopathological changes observed in colon-rectum, suggesting that promoter methylation profile of these genes could be a reliable biomarker for CRC risk.

From fall-risk assessment to fall detection: inertial sensors in the clinical routine and daily life

Falls are caused by complex interaction between multiple risk factors which may be modified by age, disease and environment. A variety of methods and tools for fall risk assessment have been proposed, but none of which is universally accepted. Existing tools are generally not capable of providing a quantitative predictive assessment of fall risk. The need for objective, cost-effective and clinically applicable methods would enable quantitative assessment of fall risk on a subject-specific basis. Tracking objectively falls risk could provide timely feedback about the effectiveness of administered interventions enabling intervention strategies to be modified or changed if found to be ineffective. Moreover, some of the fundamental factors leading to falls and what actually happens during a fall remain unclear. Objectively documented and measured falls are needed to improve knowledge of fall in order to develop more effective prevention strategies and prolong independent living. In the last decade, several research groups have developed sensor-based automatic or semi-automatic fall risk assessment tools using wearable inertial sensors. This approach may also serve to detect falls. At the moment, i) several fall-risk assessment studies based on inertial sensors, even if promising, lack of a biomechanical model-based approach which could provide accurate and more detailed measurements of interests (e.g., joint moments, forces) and ii) the number of published real-world fall data of older people in a real-world environment is minimal since most authors have used simulations with healthy volunteers as a surrogate for real-world falls. With these limitations in mind, this thesis aims i) to suggest a novel method for the kinematics and dynamics evaluation of functional motor tasks, often used in clinics for the fall-risk evaluation, through a body sensor network and a biomechanical approach and ii) to define the guidelines for a fall detection algorithm based on a real-world fall database availability.

Effects of pesticides on honey bees (Apis mellifera L.): study of a specific route of exposure and evaluation of biochemical-physiological changes in the assessment of the pesticides toxicity

In this study, some important aspects of the relationship between honey bees (Apis mellifera L.) and pesticides have been investigated. In the first part of the research, the effects of the exposure of honey bees to neonicotinoids and fipronil contaminated dusts were analyzed. In fact, considerable amounts of these pesticides, employed for maize seed dressing treatments, may be dispersed during the sowing operations, thus representing a way of intoxication for honey bees. In particular, a specific way of exposure to this pesticides formulation, the indirect contact, was taken into account. To this aim, we conducted different experimentations, in laboratory, in semi-field and in open field conditions in order to assess the effects on mortality, foraging behaviour, colony development and capacity of orientation. The real dispersal of contaminated dusts was previously assessed in specific filed trials. In the second part, the impact of various pesticides (chemical and biological) on honey bee biochemical-physiological changes, was evaluated. Different ways and durations of exposure to the tested products were also employed. Three experimentations were performed, combining Bt spores and deltamethrin, Bt spores and fipronil, difenoconazole and deltamethrin. Several important enzymes (GST, ALP, SOD, CAT, G6PDH, GAPDH) were selected in order to test the pesticides induced variations in their activity. In particular, these enzymes are involved in different pathways of detoxification, oxidative stress defence and energetic metabolism. The results showed a significant effect on mortality of neonicotinoids and fipronil contaminated dusts, both in laboratory and in semi-field trials. However, no effects were evidenced in honey bees orientation capacity. The analysis of different biochemical indicators highlighted some interesting physiological variations that can be linked to the pesticide exposure. We therefore stress the attention on the possibility of using such a methodology as a novel toxicity endpoint in environmental risk assessment.

The challenges and the limitations in Life Cycle Impact Assessment for metal oxide nanoparticles, a case study on nano- TiO2

Life Cycle Assessment (LCA) is a chain-oriented tool to evaluate the environment performance of products focussing on the entire life cycle of these products: from the extraction of resources, via manufacturing and use, to the final processing of the disposed products. Through all these stages consumption of resources and pollutant releases to air, water, soil are identified and quantified in Life Cycle Inventory (LCI) analysis. Subsequently to the LCI phase follows the Life Cycle Impact Assessment (LCIA) phase; that has the purpose to convert resource consumptions and pollutant releases in environmental impacts. The LCIA aims to model and to evaluate environmental issues, called impact categories. Several reports emphasises the importance of LCA in the field of ENMs. The ENMs offer enormous potential for the development of new products and application. There are however unanswered questions about the impacts of ENMs on human health and the environment. In the last decade the increasing production, use and consumption of nanoproducts, with a consequent release into the environment, has accentuated the obligation to ensure that potential risks are adequately understood to protect both human health and environment. Due to its holistic and comprehensive assessment, LCA is an essential tool evaluate, understand and manage the environmental and health effects of nanotechnology. The evaluation of health and environmental impacts of nanotechnologies, throughout the whole of their life-cycle by using LCA methodology. This is due to the lack of knowledge in relation to risk assessment. In fact, to date, the knowledge on human and environmental exposure to nanomaterials, such ENPs is limited. This bottleneck is reflected into LCA where characterisation models and consequently characterisation factors for ENPs are missed. The PhD project aims to assess limitations and challenges of the freshwater aquatic ecotoxicity potential evaluation in LCIA phase for ENPs and in particular nanoparticles as n-TiO2.

Environmental Assessment of the Agricultural Sector

One of the main problems recognized in sustainable development goals and sustainable agricultural objectives is Climate change. Farming contributes significantly to the overall Greenhouse gases (GHG) in the atmosphere, which is approximately 10-12 percent of total GHG emissions, but when taking in consideration also land-use change, including deforestation driven by agricultural expansion for food, fiber and fuel the number rises to approximately 30 percent (Smith et. al., 2007). There are two distinct methodological approaches for environmental impact assessment; Life Cycle Assessment (a bottom up approach) and Input-Output Analysis (a top down approach). The two methodologies differ significantly but there is not an immediate choice between them if the scope of the study is on a sectorial level. Instead, as an alternative, hybrid approaches which combine these two approaches have emerged. The aim of this study is to analyze in a greater detail the agricultural sectors contribution to Climate change caused by the consumption of food products. Hence, to identify the food products that have the greatest impact through their life cycle, identifying their hotspots and evaluating the mitigation possibilities for the same. At the same time evaluating methodological possibilities and models to be applied for this purpose both on a EU level and on a country level (Italy).

Sviluppo di tecniche di analisi ifenate per la quantificazione di biomarcatori di esposizione a tossici ambientali: gli acidi mercapturici

Human biomonitoring (HBM) is an ideal tool for evaluating toxicant exposure in health risk assessment. Chemical substances or their metabolites related to environmental pollutants can be detected as biomarkers of exposure using a wide variety of biological fluids. Individual exposure to aromatic hydrocarbon compounds (benzene, toluene, and o-xylene –“BTX”) were analysed with a liquid chromatography coupled to electrospray ionisation-mass spectrometry (μHPLC-ESI-MS/MS) method for the simultaneous quantitative detection of the BTX exposure biomarker SPMA, SBMA and o-MBMA in human urine. Urinary S-phenylmercapturic acid (SPMA) is a biomarker proposed by the American Conference of Governmental Industrial Hygienists (ACGIH) for assessing occupational exposure to benzene (Biological Exposure Index of 25 microg/g creatinine). Urinary S-benzylmercapturic (SBMA) and o-methyl S-benzyl mercapturic acid (o-MBMA) are specific toluene and o-xylene metabolites of glutathione detoxicant pathways, proposed as reliable biomarkers of exposure. To this aim a pre-treatment of the urine with solid phase extraction (SPE) and an evaporation step were necessary to concentrate the mercapturic acids before instrumental analysis. A liquid chromatography separation was carried out with a reversed phase capillary column (Synergi 4u Max-RP) using a binary gradient composed of an acquous solution of formic acid 0.07% v/v and methanol. The mercapturic acids were determinated by negative-ion-mass spectrometry and the data were corrected using isotope-labelled analogs as internal standards. The analytical method follows U.S. Food and Drug Administration guidance and was applied to assess exposure to BTX in a group of 396 traffic wardens. The association between biomarker results and individual factors, such as age, sex and tobacco smoke were also investigated. The present work also included improvements in the methods used by modifying various chromatographic parameters and experimental procedures. A partial validation was conducted to evaluate LOD, precision, accuracy, recovery as well as matrix effects. Higher sensitivity will be possible in future biological monitoring programmes, allowing evaluation of very low level of BTX human exposure. Keywords: Human biomonitoring, aromatic hydrocarbons, biomarker of exposure, HPLC-MS/MS.

Genetic and environmental factors associated with cardiovascular diseases and acute myocardial infarction

Acute myocardial infarction (AMI) is a multifactorial disease with a complex pathogenesis where lifestyle, individual genetic background and environmental risk factors are involved. Altered inflammatory responses seems to be implicated in the pathogenesis of atherosclerosis. To understand which genes may predispose to increased risk of cardiovascular disease gene polymorphism of immune regulatory genes, and clinical events from the Offs of parents with an early AMI were investigated. Genetics data from Offs were compared with those obtained from healthy subjects and an independent cohort of patients with clinical sporadic AMI. Rates of clinical events during a 24 years follow up from Offs and from an independent Italian population survey were also evaluated. This study showed that a genetic signature consisting of the concomitant presence of the CC genotype of VEGF, the A allele of IL-10 and the A allele of IFN-γ was indeed present in the Offs population. During the 24-year follow-up, Offs with a positive familiarity in spite of a relatively young age showed an increased prevalence of diabetes, ischemic heart disease and stroke. In these patients with the genetic signature the EBV and HHV-6 herpes virus were also investigated and founded. These findings reinforce the notion that subjects with a familial history of AMI are at risk of an accelerated aging of cardiovascular system resulting in cardiovascular events. These data suggest that selected genes with immune regulatory functions and envoronmental factors are part of the complex genetic background contributing to familiarity for cardiovascular diseases.N

Stream sediments analysis for geochemical mapping of Romagna Apennines (Northern Italy): monitoring and management tool of environmental resources at various scales

Geochemical mapping is a valuable tool for the control of territory that can be used not only in the identification of mineral resources and geological, agricultural and forestry studies but also in the monitoring of natural resources by giving solutions to environmental and economic problems. Stream sediments are widely used in the sampling campaigns carried out by the world's governments and research groups for their characteristics of broad representativeness of rocks and soils, for ease of sampling and for the possibility to conduct very detailed sampling In this context, the environmental role of stream sediments provides a good basis for the implementation of environmental management measures, in fact the composition of river sediments is an important factor in understanding the complex dynamics that develop within catchment basins therefore they represent a critical environmental compartment: they can persistently incorporate pollutants after a process of contamination and release into the biosphere if the environmental conditions change. It is essential to determine whether the concentrations of certain elements, in particular heavy metals, can be the result of natural erosion of rocks containing high concentrations of specific elements or are generated as residues of human activities related to a certain study area. This PhD thesis aims to extract from an extensive database on stream sediments of the Romagna rivers the widest spectrum of informations. The study involved low and high order stream in the mountain and hilly area, but also the sediments of the floodplain area, where intensive agriculture is active. The geochemical signals recorded by the stream sediments will be interpreted in order to reconstruct the natural variability related to bedrock and soil contribution, the effects of the river dynamics, the anomalous sites, and with the calculation of background values be able to evaluate their level of degradation and predict the environmental risk.

The use of satellite remote sensing for flood risk management

Over the last decades the impact of natural disasters to the global environment is becoming more and more severe. The number of disasters has dramatically increased, as well as the cost to the global economy and the number of people affected. Among the natural disaster, flood catastrophes are considered to be the most costly, devastating, broad extent and frequent, because of the tremendous fatalities, injuries, property damage, economic and social disruption they cause to the humankind. In the last thirty years, the World has suffered from severe flooding and the huge impact of floods has caused hundreds of thousands of deaths, destruction of infrastructures, disruption of economic activity and the loss of property for worth billions of dollars. In this context, satellite remote sensing, along with Geographic Information Systems (GIS), has become a key tool in flood risk management analysis. Remote sensing for supporting various aspects of flood risk management was investigated in the present thesis. In particular, the research focused on the use of satellite images for flood mapping and monitoring, damage assessment and risk assessment. The contribution of satellite remote sensing for the delineation of flood prone zones, the identification of damaged areas and the development of hazard maps was explored referring to selected cases of study.