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    Distribuzione e valutazione del rischio di composti perfluorati in bacini fluviali italiani.

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    Perfluoroalkyl substances (PFASs) are emerging pollutants with so peculiar physico-chemical characteristics that these compounds found wide applications in several industrial processes and daily products. Their characteristics and the wide use make them widespread in all environmental compartments, very persistent and partially bioaccumulable. A past survey at the basin closures of the main European rivers highlighted that river Po was the most contaminated (200 ng/L) by perfluorooctanoic acid (PFOA), the currently most diffused perfluoroalkyl acid (PFAA). This evidence led to a funded project which aimed to evaluate the PFAA distribution in main Italian river basins and to assess the correlated environmental and sanitary risks. An UHPLC-MS/MS multi-residue method based on an on-line SPE procedure was developed for the simultaneous determination of 12 PFAAs to support the sampling program in river basins that covered about 40% of the Italian surface area and about 45% of the Italian population. In Italy the most important sources of PFAA are fluorochemical plants, followed by discharges from tannery and textile industrial districts, while the contribution of urban areas is limited. Considering the most populated and industrialized Italian area, the river Lambro basin, Lombardy, detailed mass balance of the emission sources have been carried out. The environmental risks for the aquatic ecosystem were evaluated in river Bormida (Piedmont) downstream the discharge of a fluoropolymer plant which is the most significant source of PFOA in Italy. An effect-based approach was applied to the study of macrobenthic community, evaluating the ecological quality, the community structure and the genetic variance

    Structured matrices coming from PDE approximation theory: spectral analysis, spectral symbol and design of fast iterative solvers.

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    Partial Differential Equations (PDE) are extensively used in Applied Sciences to model real-world problems. The solution u of a PDE is normally not available in closed form, and so it is necessary to approximate it by means of some numerical method. Despite the differences among the various methods, the principle on which all of them are based is essentially the same: they first discretize the PDE by introducing a mesh, related to some discretization parameter n, and then they compute the corresponding numerical solution u_n, which will converge to u when n tends to infinity, i.e., when the mesh is progressively refined. Now, if both the PDE and the numerical method are linear, the computation of u_n reduces to solving a certain linear system A_n * u_n = f_n whose size d_n tends to infinity with n. In addition, the sequence of discretization matrices A_n often enjoys an asymptotic spectral distribution described by a certain matrix-valued function f, which takes values in the space of Hermitian matrices of a certain size s. This means that, for large n, the eigenvalues of A_n are approximately given by a uniform sampling of the eigenvalue functions lambda_i(f), i=1,...,s, over the domain of f. In this situation, f is called the (spectral) symbol of the sequence of matrices A_n. The identification and the study of the symbol are two interesting issues in themselves, because they provide an accurate information about the asymptotic global behavior of the eigenvalues of A_n. In particular, the number s coincides with the number of "branches" that compose the asymptotic spectrum of A_n. However, the knowledge of the symbol f and of its properties is not only interesting in itself, but can also be used for practical purposes. In particular, it can be used to design effective preconditioned Krylov and multigrid solvers for the linear systems associated with A_n. The reason is clear: the convergence properties of preconditioned Krylov and multigrid methods strongly depend on the spectral features of the matrix to which they are applied. Hence, the spectral information provided by the symbol can be conveniently used for designing fast solvers of this kind. The purpose of this thesis is to present some specific examples, of interest in practical applications, in which the above philosophical discussion comes to life. As our model PDE, we consider classical second-order elliptic differential equations. Concerning the numerical methods that we employ for their solution, we make three choices: the classical Qp Lagrangian Finite Element Method (FEM), the Galerkin B-spline Isogeometric Analysis (IgA) and the B-spline IgA Collocation Method. We first identify and study the symbol f that characterizes the asymptotic spectrum of the discretization matrices A_n arising from these approximation techniques. Then, by exploiting the properties of the symbol, we design fast iterative solvers for the matrices A_n associated with the two numerical methods based on IgA (the Galerkin B-spline IgA and the B-spline IgA Collocation Method)

    Effect of hypercaloric and isocaloric diets different in fatty acid content on the endo cannabinoid system in pregnant dams and their offspring.

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    Lipid molecules are the building blocks of all cell membranes and provide essential secondary metabolites. The central nervous system is enriched in polyunsaturated fatty acids (PUFAs): arachidonic acid (AA) and docosahexaenoic acid (DHA). During brain development, PUFAs play a critical role in determining neuronal structure, particularly axonal outgrowth. In mammals, AA and DHA cannot be synthesized de novo and must be obtained largely from dietary sources. Moreover, during pregnancy and lactation, fetuses and infants rely on PUFAs from their mothers through the placenta and breast milk, respectively. Thus, the maternal diet needs to contain an appropriate omega-3/omega-6 PUFAs ratio to help child development. Based on these premises, we investigated the consequences of maternal malnutrition, defined as a shifted dietary ratio of omega-3 or omega-6 PUFAs on the brain of the offspring. In particular, we modeled human relevance by manipulating both the content and time of daily diets, with a keen focus on endocannabinoid (eCB) system given the critical roles of this AA-derived neuromodulator system during pre- and postnatal brain development. In the first approach of this project we fed female mice with hypercaloric diets, rich in omega-3 or in omega-6 PUFA, for two (short-term diet) or nine weeks (long-term diet) before mating and during gestation. We found that, levels of endocannabinoids (AEA, 2-AG) and AEA-like mediators (PEA, OEA) did not change with short-term diet in pregnant dams. Moreover, only omega-3 diet induced a significant increase of 2-AG levels, after long-term protocol. In embryos, we found that the short-term exposure of two weeks of omega-3 and omega-6 diet feeding is already sufficient to allow alteration of endocannabinoid system, especially FAAH and CB1R. In fact, in female embryos, we found down-regulation of CB1R and increase of FAAH after treatment with both diets. Interestingly, both enzyme and receptor levels are normalized after high-fat diet administration for a long period, where AEA levels were found decreased. By contrast, in males the alterations found in CB1R after the shorter protocol persist also after the prolongation of the treatment. In line with this, these data suggest a relationship among AEA, CB1R and FAAH, and an important link between PUFAs and endocannabinoid system. The second approach of this project was based on the administration of isocaloric diets, different in omega-3 levels but not in omega-6 PUFAs throughout gestation and until adulthood. We discovered that during gestation, not only the increase but also the decrease of omega-3 levels markedly affected the eCB system in the hippocampus of embryos. Furthermore, our in vivo results strongly suggest that omega-3 diets enriched and deficient affect the principal presynaptic marker in embryonic hippocampus but not in adult, where maternal malnutrition leads to long-term behavioral alterations in adult rats characterized by the presence of recognition memory deficits. As a whole, the second approach of this study supports our hypothesis about a relationship between PUFAs and the endocannabinoid system and provides further evidence on the importance of omega-3 PUFA on hippocampal development and functioning. All together, our results suggest that changes in dietary omega-3/omega-6 PUFAs ratio during gestation affect the endocannabinoid system in the brain of the offspring and the major effects of diets are present at the beginning of the treatment (i.e during gestation). Moreover, these data suggest that not only lipids but also fat can have a role in these changes

    Urban water services in Sub Saharan Africa: access, private sector involvement and technical paradigm.

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    The thesis analyses the water supply sector in the Sub Saharan African region, focusing on the challenges experienced by the water utilities to fulfil their mandates, in a context of rapid urbanization. In September 2000, building upon a decade of major United Nations (UN) conferences and summits, world leaders came together at UN Headquarters in New York to adopt the Resolution A/RES/55/2, committing their nations to a new global partnership to reduce extreme poverty and setting out a series of time-bound targets - with a deadline in 2015 - that have become known as the Millennium Development Goals (MDG). The goal number 7 was “Ensure environmental sustainability” and it included the Target 7.C which is to “halve, by 2015, the proportion of the population without sustainable access to safe drinking water and basic sanitation”. The water MDG is dramatically off track in Sub Saharan Africa, with only 64% of the population covered in 2012 instead of the expected 77.5% (WHO and UNICEF 2014). These poor performances are driven by urban areas, where the water supply coverage through household connections declined while the access through other improved sources, like public taps, private hand pumps and protected wells, hardly compensated for that. This calls for a reconsideration of the policies implemented in the sector following the prescriptions of the neoliberal agenda for the sector. In the ‘80s and ‘90s policymakers from International Financial Institutions (IFIs) and donors agencies designed a set of recipes to address poor performances of the urban water services in the developing world. This happened in the context of structural adjustment policies, such as trade liberalization, labor market reforms, financial deregulation and privatization of State Owned Enterprises (SOE). In the water sector, these orientations were translated into decentralization, private sector participation, commercialization and corporatization of water utilities, with the shift of governments from providers to regulators. The thesis studies some of the devices and solutions typically adopted by the reformed utilities and justified by the expectation of positive outcomes for the access to water by the poor The work shows however that some of these devices gained a certain degree of autonomy from access goals and became a priority as such, to be pursued by water utilities regardless their impacts and interaction with key social dimensions. This phenomenon was in some cases favoured by a biased attitude of water sector practitioners, benchmarking regulation and donors. The work highlights that in some cases the reform solutions do not contribute to the achievement of the declared objectives, while their implementation can divert scarce resources and attention from key sector priorities. Cost recovery, Private Sector Participation and household level metering issues are analysed. The work is organized in three parts. The first part proposes a review of the main notions and issues addressed by water economics (chapter 1), with particular attention to developing countries. The second part is divided into three chapters, closely linked together for their arguments but conceived as autonomous papers and characterized by different methodological approaches: the first is quantitative, the second and the third are more qualitative in nature and they include original findings from interviews on the Lilongwe Water Board, a water utility from Malawi. The second chapter focuses on the problems of cost recovery and access to drinking water in Sub Saharan Africa. A model explaining the dynamics in water coverage which accounts for financial performances of utilities is proposed. The data set covers 25 countries in the Sub Saharan region from 1995 to 2012. The results suggest that the access to water depends upon financial results, but this relationship is not linear: with increasing returns for relatively low levels of cost recovery and decreasing returns beyond a certain threshold. The results are consistent with the literature about the risks associated with corporatization and neoliberal reforms in the water sector, and they provide some supporting quantitative evidence and recommendations for sector policies in the region. The third chapter refers to the Light Private Sector Involvement initiatives in the Sub Saharan Africa water supply sector, considering in particular efficiency improvements, aid effectiveness and related policy implications. The study analyses the determinants that can incentivize or discourage the partners of light forms of Private Sector Involvement (PSI) initiatives to achieve the expected results in the water supply sector in the Sub Saharan Africa region. This is done through a review of case studies involving management and service contracts, which are the lightest and lower risk forms of public-private partnership. While five cases are taken from the available literature, the sixth includes contributions from original research on Lilongwe Water Board (Malawi). The chapter considers the incentives to perform for both the private and the public partner, as determined by the contracts and by the wider context. The incentives necessary for both parties to engage in the partnership are also considered, jointly with the costs of creating these preconditions. The study concludes that the allocation of risks and decision making power are among the drivers of poor performances by light PSI initiatives. Moreover, as most partnerships are financed by development projects, the study discusses the policy implications of promoting these PSI initiatives. The fourth chapter analyses the priorities and tools for Water Demand Management in urban Africa, focusing on household level water metering. The study presents an analysis of the issues associated with water metering at household level by utilities in low income areas or informal settlements of Sub Saharan African cities. Metering is considered a key tool for water demand management and recommended as a good practice in the water supply sector but, while its benefits are clearly spelled out by donors and development agencies, its costs and shortcomings are seldom considered. The chapter analyses such challenges, based on the available literature and on an original case study on Lilongwe Water Board (Malawi). It is argued that the technical paradigm of metered household level connection can be in some cases a constraint to the connection of low income households, due to the high cost and complexity of the practices associated to this paradigm, while the benefits in terms of demand management are not straightforward. Some alternatives to universal household level metering are also identified. Finally, in the last part of the work the findings from the studies presented are summarized and some conclusions and recommendations are drawn about the importance of better focusing on the priority of water access, encompassing a wider set of operational solutions

    Ensembles of segmentation algorithms for figure-ground segmentation.

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    Studio prospettico multicentrico di efficacia della chirurgia laparoscopica colorettale per patologia neoplastica nel paziente grande anziano

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    Aim: to evaluate the effectiveness of laparoscopic surgery (LCS) for the treatment of colorectal cancer (CRC) in the very elderly over 80 years of age Methods: we performed a prospective multicentric analysis comparing patients over 80 yo and patients between 60 and 69 yo undergoing LCS for cancer from January 2008 to December 2013. We considered laparoscopic right colectomies, left colectomies, anterior rectal resections and other procedurel including segmental resections and Miles’ procedures. Colon and rectal cancers were analyzed separately. Preoperative workup, surgical techniques and instruments, peri-operative cares were standardized. Data on the patients’ demographics, disease features, operative details and short-term follow up were recorded and analyzed through an appropriate statistical comparison. Comorbidity and complications were classified using the Charlson Comorbidity index (CCI) and the Clavien Dindo classification system (CDCS) respectively. Oncological parameters included tumor-free resection margins, number of lymph nodes harvested and circumferential resection margin. Results: Group A included 96 and 33 patients, Group B 220 and 82 for colon and rectal cancers respectively. Groups were similar except for ASA score and CCI, as expected. We recorded a significant number of colonic in situ tumors Group B (0 vs 6.4%) and rectal T2 tumors (18.2 vs 39.0%) in Group B, a greater number of rectal T3 tumors (60.6 vs 26.8%) in Group A. There was no significant difference in operative time [Colon; Rectum] (178,0 ± 42,0 vs 185,3 ± 43,2 min; NS - 190,3 ± 52,5 vs 201,4 ± 54,9 min; NS), estimated blood loss (59,9 ± 51,8 vs 63,3 ± 60,1 mL; NS - 78,3 ± 81,9 vs 61,0 ± 55,6 mL; NS) and conversion rate (2,1 vs 2,7%; NS – 3,0 vs 2,4%; NS). Timing of first stool (3,1 ± 1,3 vs 3,5 ± 1,8 gg; NS - 3,3 ± 1,2 vs 3,3 ± 1,7 gg; NS), length of hospital stay (7,4 ± 2,1 vs 7,2 ± 2,1 gg; NS - 8,5 ± 1,7 vs 8,5 ± 2,8 gg; NS) and 30 days readmission rate (1,0 vs 0,45%; NS – 6,1 vs 1,2%; NS) were similar. Tumour-free margins were appropriate and positivity of CRM is poor (6.1 vs 4.9; NS). We didn’t record statistically significant differences in CDCS complications rate (47,9 vs 43,6%; NS – 63,6 vs 52,4%; NS). Conclusions: Laparoscopic surgery is effective for the treatment of colorectal cancer even in the very elderly. Age is not a risk factor or a limitation for LCS

    The Musso fault and its role in the evolution of the northern lake Como basement.

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    The structural analysis of the MML and the surrounding basement lead to observe that: 1) The MML is completely bounded by main fragile fault planes and ductile structures. 2) The main foliation of the MML is only partly aligned to the regional E-W trending S2 foliation. 3) The MML has different N-S trending mylonitic foliation and fracture cleavage compared to S/SW dipping mylonitic foliation of the southern basement. 4) The apparent absence of garnet in the MML metabasites suggest a different metamorphic imprint in respect to the surrounding basements. 5) There are not sufficient petrographic data to determine the belonging of the MML to the different structural units recognized in the Southern Alpine basement. 6) The MML reached the Permo-Triassic thermal peak similar to that of surrounding basement. Within the MML, the marble-metabasite contact has locally characteristics that we interpreted as not correlated to the metamorphic evolution but resembling relicts of primary magmatic intrusion: i) lobes, ii) compositional layering parallel to the contact of the lobes, iii) diffuse sulphide mineralization at the metabasite-marble contact, iv) small interfingering of metabasite protruding within the marble resembling a fluidification of the hostrock, v) crosscutting of the dykes, vi) parallel tabular structures with geometry not related to any metamorphic event thus resembling dykes, vii) contact band characterized by mixing of phases suggesting a widespread mixing at the protoliths interface. The seven described structures, all found in the MML, resemble those of a basalt intrusion within a carbonatic sediment only partially lithified. Major, trace and REE elements of Musso and Lugano-Val Grande Fault Zone (LGFZ) metabasites, analyzed in this study, are compared to other metabasite and volcanics of the Southern Alps available in the literature: I) metabasites with and without cummingtonite from the Piona Peninsula (DOZ), II) metabasites from the Strona Ceneri Border Zone (SCBZ) and III) Triassic basaltic volcanics of the central Southern Alps. The LGFZ sample have very similar geochemical characteristics to SCBZ that allow to suppose a common origin. Musso samples show an in-between composition: they have similar Ba, Na, Al content to the SCBZ, LGFZ, and Triassic volcanics but have TiO2, Zr, Nb, MgO and SiO2 content similar to Anisian (a group belonging to the Triassic set) and part of the DOZ. This could be due to a partial metamorphic imprint with elements depletion, or a different volcano-tectonic origin, more similar to that of the Anisian basalts. Genetic diagrams, from literature, confirm the division between the DOZ and the SCBZ. SCBZ and LVGZ appear as a compact group with a MORB to tholeiitic composition. The Musso samples belong to intraplate products with alkali-basalt to tholeiitic composition. These data are only partially sufficient to suppose a particular role of the Musso marble lenses and the included metabasites but definitely testify the existence of this tectonic structure since at least Variscan age (Devonian-Early Carboniferous). In Chapter 3, the ductile and brittle structures mapped along the Musso Fault Zone (MFZ) are described and a hypothesis for the Musso fault evolution is presented, touching the following main stages: 1) Marble lenses (Musso marble) are boudinaged along the MFZ and represent the oldest rocks characterizing it. Their age is still not determined, but the included metabasites have unique geochemical characteristics that do not allow to attribute them nor to DOZ nor the Strona Ceneri Border Zone amphibolite suites. We speculate a Devonian perhaps to Early Carboniferous age for the marble and the included metabasites. 2) Geochronological and thermal data from literature shows that the Northern Lake Como region experienced a Triassic thermal peak and development of intra-basement shear zones, thinning the Adriatic crust. In this context the oldest structures directly and incontrovertibly connected to the MFZ are the Fe-carbonate veins, of Early Triassic age, which are preserved also boudinaged within the Musso mylonites. The same can be said also for the LGFZ, as demonstrated by extensive siderite mineralization presence in the Gaeta mine and Val Cavargna. 3) Fe-mineralized veins are found in similar extensional context in all the Southern Alps, along faults bordering Permo-Triassic continental basins. Therefore it is possible that also the MFZ was bordering a small basin to the N, nonetheless justifying the presence of the sedimentary Monte Pozzuolo and Sasso Pelo. In the Lake Como area continental extension started in the Norian and continued to Liassic. 4) The mylonites of the MFZ possibly developed after the Early Triassic thermal peak when temperature dropped to around 250-350°C allowing crystallization of quartz-albite-chlorite-sericite associations, before the emplacement of the 220Ma old Piona’s pegmatites which do not show mylonitization even near the MFZ. 5) From the Liassic to the onset of the Alpine compressive stage there is a long inactivity time span, with no records for the MFZ. 6) Alpine N-S contraction brought into a steep south dipping position the Paleozoic to Mesozoic rocks and lineaments and caused upper and middle crust to detach from their substratum along the MFZ. This contraction was responsible of the ductile-brittle deformation observed along the MFZ with development of widespread and abundant pseudotachylytes. Similar structures dated along the Orobic and Porcile thrusts yielded two sets of ages: an older Late Cretaceous and a younger Eocene ages. 7) Widespread distensive cataclastic bands along the Musso and contiguous faults, possibly indicating a distensive to transpressive stage, by correlation with nearby data of Val Morobbia, may belong to Oligocene. 8) Finally, right strike-slip dextral brittle deformation took place, visible along the largest fault planes, most probably driven by the Insubric Line

    The human T cell lymphotropic virus 1 (HTLV-1): cellular and molecular characterization of the HTLV-1 oncogenic protein HBZ.

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    T cell leukemia virus type 1 (HTLV-1 ) is the etiological agent responsible of a severe form of hematologic malignancy designated Adult T cell Leukemia/Lymphoma or ATLL and of aneurological syndrome designated HTLV Associated Myelopathy/Tropical SpasticParaparesis or HAM/TSP. Although the major documented viral oncogenic product ofHTLV-1 is the Tax-1 protein, it has been recently demonstrated that also HBZ (HTLV-1 bZIPfactor), a protein encoded by the minus strand of HTLV-1 genome, is involved in thepathogenesis of ATL. The full role played by HBZ in oncogenesis is still to be explored indetail mainly owing to the unavailability of tools to study this protein in naturally infectedcells and in ATLL cells and its interaction with other crucial cellular proteins involved in thehomeostasis of cell activation and proliferation. By the use of the first reported monoclonalantibody against HBZ generated in our laboratory we have carefully analyzed HBZ proteinexpression, sub-cellular localization as well as its interaction in vivo with endogenous cellfactors in various HBZ-expressing cells, including in particular HTLV-1-infected cells andATLL tumor cell lines. We also demonstrated the ability of this monoclonal antibody to detectHBZ in fresh PBMCs of HTLV-1 infected patients. The availability of this newly generated anti-HBZ mAb has allowed for the first time the quantization of HBZ at the single cell level in naturally infected cells and in neoplastic cells, a better definition of HBZ expression, localization and functional involvement in the biology of HTLV-1 infected cells. The findings described in this thesis may help to better understand the mechanisms through which viral oncogenes contribute to immortalization and neoplasti

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