Equine and human mutual welfare: a whole subject? Critical aspects and possible strategies in equine-assisted activities and therapies

General aim of the study is equine welfare, particularly concerning different husbandry methodic and inter-specific relational factors. Specific aim is the evaluation of possible mutual (to humans and to equines) benefits and the analysis of critical factors/strength points, of human-horse relationship within Therapeutic Riding context (TR). The peculiarities of human-horse relationship (compared to the bond with “Pet”) are analyzed, concerning their socio-anthropological, psychological, psycho-dynamic distinctive characteristics. 8 European representative therapeutic riding centers (TRC) were therefore selected (on the basis of their different animals’ husbandry criteria, and of the different rehabilitative methodologies adopted). TRC were investigated through 2 different questionnaires, specifically settled to access objective/subjective animal welfare parameters; the quality of human-horse relationship; technicians’ emotional experienced. 3 Centers were further selected, and behavioral (145 hours of behavioral recording) and physiological parameters (heart rate and heart rate variability) were evaluated, aimed to access equine welfare and horses’ adaptive responses/coping (towards general environment and towards TR job). Moreover a specific “handling-task” was ideated and experimented, aimed to measure the quality of TR technicians-horses relationship. We did therefore evaluate both the individual horses’ responses and the possible differences among Centers. Data collected highlight the lack of univocal standardized methodic, concerning the general animals’ management and the specific methodologies (aimed to improve animal welfare and to empower TR efficacy). Some positive and some critical aspects were detected concerning TR personnel-horse relationship. Another experimental approach did evaluate the efficacy (concerning the mutual benefits’ empowerment) of an “ethologically-fitted” TR intervention, aimed to educate children to and through the relationship with horses. Our data evidenced that the improvement of human horse relationship, through structured educational programs for TR personnel might have important consequences both to human and equine welfare.

La responsabilità civile da prodotto farmaceutico

Il tema della ricerca ha riguardato preliminarmente la definizione di farmaco descritta nel d.lgs. n. 219 del 2006 (Codice dei farmaci per uso umano). Oltre al danno prodotto da farmaci, la ricerca ha approfondito anche la tutela ex ante ed ex post riguardante la produzione di dispositivi medici (Direttiva della Comunità Economica Europea n. 42 del 1993 e Direttiva della Comunità Economica Europea n. 374 del 1985). E’ stato necessario soffermarsi sull’analisi del concetto di precauzione per il quale nell’ambito di attività produttive, come quelle che cagionano inquinamento ambientale, o “pericolose per la salute umana” come quelle riguardanti la produzione di alimenti e farmaci, è necessario eliminare i rischi non conosciuti nella produzione di questi ultimi al fine di garantire una tutela completa della salute. L’analisi della Direttiva della Comunità Economica Europea n. 374 del 1985 nei suoi aspetti innovativi ha riguardato l’esame dei casi di danno da farmaco (Trib. Roma, 20 Giugno 2002, Trib. Roma 27 Giugno 1987, Trib. Milano 19 Novembre 1987, Cassazione Civile n. 6241 del 1987): profilo critico è quello riguardante la prova liberatoria, mentre l'art. 2050 prevede che «si debbano adottare tutte le misure necessarie per evitare il danno», l'art. 118, lett. e), c. cons.) prevede una serie di casi di esonero di responsabilità del produttore (tra cui il rischio di sviluppo). Dall'analisi emerge poi la necessità da parte del produttore di continuo utilizzo del duty to warn (Art. 117 del Codice del Consumo lett. A e B ): esso consiste nel dovere continuo di informazione del produttore tramite i suoi rappresentanti e il bugiardino presente nelle confezioni dei farmaci. Tale dovere è ancor più importante nel caso della farmacogenetica, infatti, al fine di evitare reazioni avverse nel bugiardino di alcuni farmaci verrà prescritta la necessità di effettuare un test genetico prima dell’assunzione.

Food lipids: their effects on quality and oxidative stability of animal tissues and emulsions

Lipolysis and oxidation of lipids in foods are the major biochemical and chemical processes that cause food quality deterioration, leading to the characteristic, unpalatable odour and flavour called rancidity. In addition to unpalatability, rancidity may give rise to toxic levels of certain compounds like aldehydes, hydroperoxides, epoxides and cholesterol oxidation products. In this PhD study chromatographic and spectroscopic techniques were employed to determine the degree of lipid oxidation in different animal products and its relationship with technological parameters like feeding fat sources, packaging, processing and storage conditions. To achieve this goal capillary gas chromatography (CGC) was employed not only to determine the fatty acids profile but also, after solid phase extraction, the amount of sterols (cholesterol and phytosterols) and cholesterol oxidation products (COPs). To determine hydroperoxides, primary products of oxidation and quantify secondary products UV/VIS absorbance spectroscopy was applied. Beef and pork meat in this study were analysed. In actual fact, lipid oxidation is a major deterioration reaction in meat, meat products and results in adverse changes in the colour, flavour, texture of meat and develops different compounds which should be a risk to human health as oxysterols. On beef and pork meat, a study of lipid fraction during storage was carried out to evaluate its shelf-life and some nutritional features life saturated/unsaturated fatty acids ratio and sterols content, in according to the interest that has been growing around functional food in the last years. The last part of this research was focused on the study of lipid oxidation in emulsions. In oil-in-water emulsions antioxidant activity of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) was evaluated. The rates of lipid oxidation of 1.0% stripped soybean oil-in-water emulsions with DOPC were followed by monitoring lipid hydroperoxide and hexanal as indicators of primary and secondary oxidation products and the droplet surface charge or zeta potential (ζ) of the emulsions with varying concentrations of DOPC were tested. This manuscript reports the main results obtained in the three activities briefly summarized as follows: 1. study on effects of feeding composition on the photoxidative stability of lipids from beef meat, evaluated during storage under commercial retail conditions; 2. evaluation of effects of diets and storage conditions on the oxidative stability of pork meat lipids; 3. study on oxidative behavior of DOPC in stripped soybean oil-in-water emulsions stabilized by nonionic surfactant.

Application of chromatographic and spectroscopic techniques in the evaluation of the lipid fraction of animal products

Lipolysis and oxidation of lipids in foods are the major biochemical and chemical processes that cause food quality deterioration, leading to the characteristic, unpalatable odour and flavour called rancidity. In addition to unpalatability, rancidity may give rise to toxic levels of certain compounds like aldehydes, hydroperoxides, epoxides and cholesterol oxidation products. In this PhD study chromatographic and spectroscopic techniques were employed to determine the degree of rancidity in different animal products and its relationship with technological parameters like feeding fat sources, packaging, processing and storage conditions. To achieve this goal capillary gas chromatography (CGC) was employed not only to determine the fatty acids profile but also, after solid phase extraction, the amount of free fatty acids (FFA), diglycerides (DG), sterols (cholesterol and phytosterols) and cholesterol oxidation products (COPs). To determine hydroperoxides, primary products of oxidation and quantify secondary products UV/VIS absorbance spectroscopy was applied. Most of the foods analysed in this study were meat products. In actual fact, lipid oxidation is a major deterioration reaction in meat and meat products and results in adverse changes in the colour, flavour and texture of meat. The development of rancidity has long recognized as a serious problem during meat handling, storage and processing. On a dairy product, a vegetal cream, a study of lipid fraction and development of rancidity during storage was carried out to evaluate its shelf-life and some nutritional features life saturated/unsaturated fatty acids ratio and phytosterols content. Then, according to the interest that has been growing around functional food in the last years, a new electrophoretic method was optimized and compared with HPLC to check the quality of a beehive product like royal jelly. This manuscript reports the main results obtained in the five activities briefly summarized as follows: 1) comparison between HPLC and a new electrophoretic method in the evaluation of authenticity of royal jelly; 2) study of the lipid fraction of a vegetal cream under different storage conditions; 3) study of lipid oxidation in minced beef during storage under a modified atmosphere packaging, before and after cooking; 4) evaluation of the influence of dietary fat and processing on the lipid fraction of chicken patties; 5) study of the lipid fraction of typical Italian and Spanish pork dry sausages and cured hams.

L'a(rche)tipico Brian O'Nolan. Comico e riso dalla tradizione al post-

This study aims at analysing Brian O'Nolans literary production in the light of a reconsideration of the role played by his two most famous pseudonyms ,Flann Brien and Myles na Gopaleen, behind which he was active both as a novelist and as a journalist. We tried to establish a new kind of relationship between them and their empirical author following recent cultural and scientific surveys in the field of Humour Studies, Psychology, and Sociology: taking as a starting point the appreciation of the comic attitude in nature and in cultural history, we progressed through a short history of laughter and derision, followed by an overview on humour theories. After having established such a frame, we considered an integration of scientific studies in the field of laughter and humour as a base for our study scheme, in order to come to a definition of the comic author as a recognised, powerful and authoritative social figure who acts as a critic of conventions. The history of laughter and comic we briefly summarized, based on the one related by the French scholar Georges Minois in his work (Minois 2004), has been taken into account in the view that humorous attitude is one of man’s characteristic traits always present and witnessed throughout the ages, though subject in most cases to repression by cultural and political conservative power. This sort of Super-Ego notwithstanding, or perhaps because of that, comic impulse proved irreducible exactly in its influence on the current cultural debates. Basing mainly on Robert R. Provine’s (Provine 2001), Fabio Ceccarelli’s (Ceccarelli 1988), Arthur Koestler’s (Koestler 1975) and Peter L. Berger’s (Berger 1995) scientific essays on the actual occurrence of laughter and smile in complex social situations, we underlined the many evidences for how the use of comic, humour and wit (in a Freudian sense) could be best comprehended if seen as a common mind process designed for the improvement of knowledge, in which we traced a strict relation with the play-element the Dutch historian Huizinga highlighted in his famous essay, Homo Ludens (Huizinga 1955). We considered comic and humour/wit as different sides of the same coin, and showed how the demonstrations scientists provided on this particular subject are not conclusive, given that the mental processes could not still be irrefutably shown to be separated as regards graduations in comic expression and reception: in fact, different outputs in expressions might lead back to one and the same production process, following the general ‘Economy Rule’ of evolution; man is the only animal who lies, meaning with this that one feeling is not necessarily biuniquely associated with one and the same outward display, so human expressions are not validation proofs for feelings. Considering societies, we found that in nature they are all organized in more or less the same way, that is, in élites who govern over a community who, in turn, recognizes them as legitimate delegates for that task; we inferred from this the epistemological possibility for the existence of an added ruling figure alongside those political and religious: this figure being the comic, who is the person in charge of expressing true feelings towards given subjects of contention. Any community owns one, and his very peculiar status is validated by the fact that his place is within the community, living in it and speaking to it, but at the same time is outside it in the sense that his action focuses mainly on shedding light on ideas and objects placed out-side the boundaries of social convention: taboos, fears, sacred objects and finally culture are the favourite targets of the comic person’s arrow. This is the reason for the word a(rche)typical as applied to the comic figure in society: atypical in a sense, because unconventional and disrespectful of traditions, critical and never at ease with unblinkered respect of canons; archetypical, because the “village fool”, buffoon, jester or anyone in any kind of society who plays such roles, is an archetype in the Jungian sense, i.e. a personification of an irreducible side of human nature that everybody instinctively knows: a beginner of a tradition, the perfect type, what is most conventional of all and therefore the exact opposite of an atypical. There is an intrinsic necessity, we think, of such figures in societies, just like politicians and priests, who should play an elitist role in order to guide and rule not for their own benefit but for the good of the community. We are not naïve and do know that actual owners of power always tend to keep it indefinitely: the ‘social comic’ as a role of power has nonetheless the distinctive feature of being the only job whose tension is not towards stability. It has got in itself the rewarding permission of contradiction, for the very reason we exposed before that the comic must cast an eye both inside and outside society and his vision may be perforce not consistent, then it is satisfactory for the popularity that gives amongst readers and audience. Finally, the difference between governors, priests and comic figures is the seriousness of the first two (fundamentally monologic) and the merry contradiction of the third (essentially dialogic). MPs, mayors, bishops and pastors should always console, comfort and soothe popular mood in respect of the public convention; the comic has the opposite task of provoking, urging and irritating, accomplishing at the same time a sort of control of the soothing powers of society, keepers of the righteousness. In this view, the comic person assumes a paramount importance in the counterbalancing of power administration, whether in form of acting in public places or in written pieces which could circulate for private reading. At this point comes into question our Irish writer Brian O'Nolan(1911-1966), real name that stood behind the more famous masks of Flann O'Brien, novelist, author of At Swim-Two-Birds (1939), The Hard Life (1961), The Dalkey Archive (1964) and, posthumously, The Third Policeman (1967); and of Myles na Gopaleen, journalist, keeper for more than 25 years of the Cruiskeen Lawn column on The Irish Times (1940-1966), and author of the famous book-parody in Irish An Béal Bocht (1941), later translated in English as The Poor Mouth (1973). Brian O'Nolan, professional senior civil servant of the Republic, has never seen recognized his authorship in literary studies, since all of them concentrated on his alter egos Flann, Myles and some others he used for minor contributions. So far as we are concerned, we think this is the first study which places the real name in the title, this way acknowledging him an unity of intents that no-one before did. And this choice in titling is not a mere mark of distinction for the sake of it, but also a wilful sign of how his opus should now be reconsidered. In effect, the aim of this study is exactly that of demonstrating how the empirical author Brian O'Nolan was the real Deus in machina, the master of puppets who skilfully directed all of his identities in planned directions, so as to completely fulfil the role of the comic figure we explained before. Flann O'Brien and Myles na Gopaleen were personae and not persons, but the impression one gets from the critical studies on them is the exact opposite. Literary consideration, that came only after O'Nolans death, began with Anne Clissmann’s work, Flann O'Brien: A Critical Introduction to His Writings (Clissmann 1975), while the most recent book is Keith Donohue’s The Irish Anatomist: A Study of Flann O'Brien (Donohue 2002); passing through M.Keith Booker’s Flann O'Brien, Bakhtin and Menippean Satire (Booker 1995), Keith Hopper’s Flann O'Brien: A Portrait of the Artist as a Young Post-Modernist (Hopper 1995) and Monique Gallagher’s Flann O'Brien, Myles et les autres (Gallagher 1998). There have also been a couple of biographies, which incidentally somehow try to explain critical points his literary production, while many critical studies do the same on the opposite side, trying to found critical points of view on the author’s restless life and habits. At this stage, we attempted to merge into O'Nolan's corpus the journalistic articles he wrote, more than 4,200, for roughly two million words in the 26-year-old running of the column. To justify this, we appealed to several considerations about the figure O'Nolan used as writer: Myles na Gopaleen (later simplified in na Gopaleen), who was the equivalent of the street artist or storyteller, speaking to his imaginary public and trying to involve it in his stories, quarrels and debates of all kinds. First of all, he relied much on language for the reactions he would obtain, playing on, and with, words so as to ironically unmask untrue relationships between words and things. Secondly, he pushed to the limit the convention of addressing to spectators and listeners usually employed in live performing, stretching its role in the written discourse to come to a greater effect of involvement of readers. Lastly, he profited much from what we labelled his “specific weight”, i.e. the potential influence in society given by his recognised authority in determined matters, a position from which he could launch deeper attacks on conventional beliefs, so complying with the duty of a comic we hypothesised before: that of criticising society even in threat of losing the benefits the post guarantees. That seemingly masochistic tendency has its rationale. Every representative has many privileges on the assumption that he, or she, has great responsibilities in administrating. The higher those responsibilities are, the higher is the reward but also the severer is the punishment for the misfits done while in charge. But we all know that not everybody accepts the rules and many try to use their power for their personal benefit and do not want to undergo law’s penalties. The comic, showing in this case more civic sense than others, helped very much in this by the non-accessibility to the use of public force, finds in the role of the scapegoat the right accomplishment of his task, accepting the punishment when his breaking of the conventions is too stark to be forgiven. As Ceccarelli demonstrated, the role of the object of laughter (comic, ridicule) has its very own positive side: there is freedom of expression for the person, and at the same time integration in the society, even though at low levels. Then the banishment of a ‘social’ comic can never get to total extirpation from society, revealing how the scope of the comic lies on an entirely fictional layer, bearing no relation with facts, nor real consequences in terms of physical health. Myles na Gopaleen, mastering these three characteristics we postulated in the highest way, can be considered an author worth noting; and the oeuvre he wrote, the whole collection of Cruiskeen Lawn articles, is rightfully a novel because respects the canons of it especially regarding the authorial figure and his relationship with the readers. In addition, his work can be studied even if we cannot conduct our research on the whole of it, this proceeding being justified exactly because of the resemblances to the real figure of the storyteller: its ‘chapters’ —the daily articles— had a format that even the distracted reader could follow, even one who did not read each and every article before. So we can critically consider also a good part of them, as collected in the seven volumes published so far, with the addition of some others outside the collections, because completeness in this case is not at all a guarantee of a better precision in the assessment; on the contrary: examination of the totality of articles might let us consider him as a person and not a persona. Once cleared these points, we proceeded further in considering tout court the works of Brian O'Nolan as the works of a unique author, rather than complicating the references with many names which are none other than well-wrought sides of the same personality. By putting O'Nolan as the correct object of our research, empirical author of the works of the personae Flann O'Brien and Myles na Gopaleen, there comes out a clearer literary landscape: the comic author Brian O'Nolan, self-conscious of his paramount role in society as both a guide and a scourge, in a word as an a(rche)typical, intentionally chose to differentiate his personalities so as to create different perspectives in different fields of knowledge by using, in addition, different means of communication: novels and journalism. We finally compared the newly assessed author Brian O'Nolan with other great Irish comic writers in English, such as James Joyce (the one everybody named as the master in the field), Samuel Beckett, and Jonathan Swift. This comparison showed once more how O'Nolan is in no way inferior to these authors who, greatly celebrated by critics, have nonetheless failed to achieve that great public recognition O’Nolan received alias Myles, awarded by the daily audience he reached and influenced with his Cruiskeen Lawn column. For this reason, we believe him to be representative of the comic figure’s function as a social regulator and as a builder of solidarity, such as that Raymond Williams spoke of in his work (Williams 1982), with in mind the aim of building a ‘culture in common’. There is no way for a ‘culture in common’ to be acquired if we do not accept the fact that even the most functional society rests on conventions, and in a world more and more ‘connected’ we need someone to help everybody negotiate with different cultures and persons. The comic gives us a worldly perspective which is at the same time comfortable and distressing but in the end not harmful as the one furnished by politicians could be: he lets us peep into parallel worlds without moving too far from our armchair and, as a consequence, is the one who does his best for the improvement of our understanding of things.

Application of different instrumental techniques to the selective evaluation of bio-sensible compounds in foodstuff of animal and vegetable origin

This PhD thesis describes the application of some instrumental analytical techniques suitable to the study of fundamental food products for the human diet, such as: extra virgin olive oil and dairy products. These products, widely spread in the market and with high nutritional values, are increasingly recognized healthy properties although their lipid fraction might contain some unfavorable components to the human health. The research activity has been structured in the following investigations: “Comparison of different techniques for trans fatty acids analysis” “Fatty acids analysis of outcrop milk cream samples, with particular emphasis on the content of Conjugated Linoleic Acid (CLA) and trans Fatty Acids (TFA), by using 100m high-polarity capillary column” “Evaluation of the oxidited fatty acids (OFA) content during the Parmigiano-Reggiano cheese seasoning” “Direct analysis of 4-desmethyl sterols and two dihydroxy triterpenes in saponified vegetal oils (olive oil and others) using liquid chromatography-mass spectrometry” “Quantitation of long chain poly-unsatured fatty acids (LC-PUFA) in base infant formulas by Gas Chromatography, and evaluation of the blending phases accuracy during their preparation” “Fatty acids composition of Parmigiano Reggiano cheese samples, with emphasis on trans isomers (TFA)”

The role of interleuchin 6 (IL-6) in the promotion of an aggressive and stem cell-like phenotype in human breast cancer cells and in stem/progenitor cells expanded in vitro as mammospheres

High serum levels of Interleukin-6 (IL-6) correlate with poor outcome in breast cancer patients. However no data are available on the relationship between IL-6 and stem/progenitor cells which may fuel the genesis of breast cancer in vivo. Herein, we address this issue in mammospheres (MS), multi-cellular structures enriched in stem/progenitor cells of the mammary gland, and also in MCF-7 breast cancer cells. We show that MS from node invasive breast carcinoma tissues express IL-6 mRNA at higher levels than MS from matched non-neoplastic mammary glands. We find that IL-6 mRNA is detectable only in basal-like breast carcinoma tissues, an aggressive variant showing stem cell features. Our results reveal that IL-6 triggers a Notch-3-dependent up-regulation of the Notch ligand Jagged-1, whose interaction with Notch-3 promotes the growth of MS and MCF-7 derived spheroids. Moreover, IL-6 induces a Notch-3-dependent up-regulation of the carbonic anhydrase IX gene, which promotes a hypoxia-resistant/invasive phenotype in MCF-7 cells and MS. Finally, an autocrine IL-6 loop relies upon Notch-3 activity to sustain the aggressive features of MCF-7-derived hypoxia-selected cells. In conclusion, our data support the hypothesis that IL-6 induces malignant features in Notch-3 expressing, stem/progenitor cells from human ductal breast carcinoma and normal mammary gland.

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.

Investigating the role of single point mutations in the human proteome: a computational study

In the post genomic era with the massive production of biological data the understanding of factors affecting protein stability is one of the most important and challenging tasks for highlighting the role of mutations in relation to human maladies. The problem is at the basis of what is referred to as molecular medicine with the underlying idea that pathologies can be detailed at a molecular level. To this purpose scientific efforts focus on characterising mutations that hamper protein functions and by these affect biological processes at the basis of cell physiology. New techniques have been developed with the aim of detailing single nucleotide polymorphisms (SNPs) at large in all the human chromosomes and by this information in specific databases are exponentially increasing. Eventually mutations that can be found at the DNA level, when occurring in transcribed regions may then lead to mutated proteins and this can be a serious medical problem, largely affecting the phenotype. Bioinformatics tools are urgently needed to cope with the flood of genomic data stored in database and in order to analyse the role of SNPs at the protein level. In principle several experimental and theoretical observations are suggesting that protein stability in the solvent-protein space is responsible of the correct protein functioning. Then mutations that are found disease related during DNA analysis are often assumed to perturb protein stability as well. However so far no extensive analysis at the proteome level has investigated whether this is the case. Also computationally methods have been developed to infer whether a mutation is disease related and independently whether it affects protein stability. Therefore whether the perturbation of protein stability is related to what it is routinely referred to as a disease is still a big question mark. In this work we have tried for the first time to explore the relation among mutations at the protein level and their relevance to diseases with a large-scale computational study of the data from different databases. To this aim in the first part of the thesis for each mutation type we have derived two probabilistic indices (for 141 out of 150 possible SNPs): the perturbing index (Pp), which indicates the probability that a given mutation effects protein stability considering all the “in vitro” thermodynamic data available and the disease index (Pd), which indicates the probability of a mutation to be disease related, given all the mutations that have been clinically associated so far. We find with a robust statistics that the two indexes correlate with the exception of all the mutations that are somatic cancer related. By this each mutation of the 150 can be coded by two values that allow a direct comparison with data base information. Furthermore we also implement computational methods that starting from the protein structure is suited to predict the effect of a mutation on protein stability and find that overpasses a set of other predictors performing the same task. The predictor is based on support vector machines and takes as input protein tertiary structures. We show that the predicted data well correlate with the data from the databases. All our efforts therefore add to the SNP annotation process and more importantly found the relationship among protein stability perturbation and the human variome leading to the diseasome.

The Role of Multiple Social Categorisation in Promoting the Inclusion in the Human Group of Outgroup Members

Rituali indigeni in Mesoamerica. La festa di Petición de Lluvias nella Montaña di Guerrero (Messico)

Questa tesi di carattere antropologico in ambito dottorale riguarda i rituali comunitari nelle comunità indigene messicane. Il principale oggetto della ricerca è il rituale della pioggia o di Petición de Lluvia, caratterizzato sia dal sacrificio animale che da una specifica relazione di causa-effetto con l’ambiente circostante. La ricerca etnografica è cominciata dall’ipotesi di voler verificare la persistenza nel tempo, e dunque nell’attualità, di procedure cerimoniali non appartenenti, almeno nella loro forma più lineare, alla religione cattolico-cristiana. Il luogo nel quale è avvenuta tale ricerca è la regione La Montaña di Guerrero, situata nel Messico sud-occidentale, e più precisamente la zona in cui vivono le comunità di etnia Nahua di San Pedro Petlacala, Acuilpa, e Xalpatláhuac che si trovano nelle vicinanze della cittadina di Tlapa de Comonfort. In un contesto ambientale profondamente rurale come quello della Montaña di Guerrero, la persistenza dei rituali evidenzia come le risorse naturali e gli agenti atmosferici - pioggia, vento, nubi - continuino a rappresentare gli elementi centrali che condizionano le variabili economiche di sussistenza e della riproduzione sociale. Il rituale di Petición de Lluvia rappresenta il momento di congiunzione tra la stagione secca e quella piovosa, tra la semina ed il raccolto del mais. Definito come una pratica religiosa nella quale il gruppo si identifica e partecipa con varie donazioni (ofrenda o deposito rituale), suddivisibili in alimenti/oggetti/preghiere ed azioni rituali, la cerimonia esprime l’auspicio di piogge abbondanti, con le quali irrigare i campi e continuare le attività umane. Il destinatario dell’offerta è la stessa divinità della pioggia, Tlaloc per le antiche civiltà mesoamericane, invocato sotto le mentite spoglie del santo patrono del 25 aprile, San Marcos. Il rituale è contraddistinto per tutta la sua durata dalla presenza del principale specialista religioso, sacerdote in lingua spagnola oppure «Tlahmáquetl» in lingua náhuatl.

Social learning and action understanding in human observers: contributions of sensori-motor constraints and prior information

The aim of this thesis was to investigate the respective contribution of prior information and sensorimotor constraints to action understanding, and to estimate their consequences on the evolution of human social learning. Even though a huge amount of literature is dedicated to the study of action understanding and its role in social learning, these issues are still largely debated. Here, I critically describe two main perspectives. The first perspective interprets faithful social learning as an outcome of a fine-grained representation of others’ actions and intentions that requires sophisticated socio-cognitive skills. In contrast, the second perspective highlights the role of simpler decision heuristics, the recruitment of which is determined by individual and ecological constraints. The present thesis aims to show, through four experimental works, that these two contributions are not mutually exclusive. A first study investigates the role of the inferior frontal cortex (IFC), the anterior intraparietal area (AIP) and the primary somatosensory cortex (S1) in the recognition of other people’s actions, using a transcranial magnetic stimulation adaptation paradigm (TMSA). The second work studies whether, and how, higher-order and lower-order prior information (acquired from the probabilistic sampling of past events vs. derived from an estimation of biomechanical constraints of observed actions) interacts during the prediction of other people’s intentions. Using a single-pulse TMS procedure, the third study investigates whether the interaction between these two classes of priors modulates the motor system activity. The fourth study tests the extent to which behavioral and ecological constraints influence the emergence of faithful social learning strategies at a population level. The collected data contribute to elucidate how higher-order and lower-order prior expectations interact during action prediction, and clarify the neural mechanisms underlying such interaction. Finally, these works provide/open promising perspectives for a better understanding of social learning, with possible extensions to animal models.

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.

Taste receptors in the gut: a chemosensitive mechanism from fish to human

The ingestion of a meal evokes a series of digestive processes, which consist of the essential functions of the digestive system: food transport, secretory activity, absorption of nutrients and the expulsion of undigested residues do not absorbed. The gastrointestinal chemosensitivity is characterized by cellular elements of the endocrine gastrointestinal mucosa and nerve fibers, in particular of vagal nature. A wide range of mediators endocrine and/or paracrine can be released from various endocrine cells in response to nutrients in the diet. These hormones, in addition to their direct activity, act through specific receptors activating some of the most important functions in the control of energy intake and energy homeostasis in the body. For integration of this complex system of control of gastrointestinal chemosensitivity, recent evidence demonstrates the presence of taste receptors (TR) belonging to the family of G proteins coupled receptor expressed in the mucosa of the gastrointestinal tract of different mammals and human. This thesis is divided into several research projects that have been conceived in order to clarify the relationship between TR and nutrients. To define this relationship I have used various scientific approaches, which have gone on to evaluate changes in signal molecules of TR, in particular of the α-transducin in the fasting state and after refeeding with standard diet in the gastrointestinal tract of the pig, the mapping of the same molecule signal in the gastrointestinal tract of fish (Dicentrarchus labrax), the signaling pathway of bitter TR in the STC-1 endocrine cell line and finally the involvement of bitter TR in particular of T2R38 in patients with an excessive caloric intake. The results showed how there is a close correlation between nutrients, TR and hormonal release and how they are useful both in taste perception but also likely to be involved in chronic diseases such as obesity.

Valorization of pomaces from the mechanical extraction of virgin olive oils in dairy animal feeding

This research work is aimed at the valorization of two types of pomace deriving from the extra virgin olive oil mechanical extraction process, such as olive pomace and a new by-product named “paté”, in the livestock sector as important sources of antioxidants and unsaturated fatty acids. In the first research the suitability of dried stoned olive pomace as a dietary supplement for dairy buffaloes was evaluated. The effectiveness of this utilization in modifying fatty acid composition and improving the oxidative stability of buffalo milk and mozzarella cheese have been proven by means of the analysis of qualitative and quantitative parameters. In the second research the use of paté as a new by-product in dietary feed supplementation for dairy ewes, already fed with a source of unsaturated fatty acids such as extruded linseed, was studied in order to assess the effect of this combination on the dairy products obtained. The characterization of paté as a new by-product was also carried out, studying the optimal conditions of its stabilization and preservation at the same time. The main results, common to both researches, have been the detection and the characterization of hydrophilic phenols in the milk. The analytical detection of hydroxytyrosol and tyrosol in the ewes’ milk fed with the paté and hydroxytyrosol in buffalo fed with pomace showed for the first time the presence in the milk of hydroxytyrosol, which is one of the most important bioactive compounds of the oil industry products; the transfer of these antioxidants and the proven improvement of the quality of milk fat could positively interact in the prevention of some human cardiovascular diseases and some tumours, increasing in this manner the quality of dairy products, also improving their shelf-life. These results also provide important information on the bioavailability of these phenolic compounds.