Studio e validazione di una nuova metodica per la valutazione dello stato di forma

We observed 82 healthy subjects, from both sexes, aged between 19 and 77 years. All subjects performed two different tests: for being scientifically acknowledged, the first one was used as a reference and it was a stress test (CPX). During the entire test, heart rate and gas exchange were recorded continuously; the second, the actual object of this study, was a submaximal test (TOP). Only heart rate was recorded continuously. The main purpose was to determinate an index of physical fitness as result of TOP. CPX test allowed us to individuate anaerobic threshold. We used an incremental protocol of 10/20 Watt/min, different by age. For our TOP test we used an RHC400 UPRIGHT BIKE, by Air Machine. Each subject was monitored for heart frequency. After 2 minutes of resting period there was a first step: 3 minutes of pedalling at a constant rate of 60 RPM, (40 watts for elder subjects and 60 watts for the younger ones). Then, the subject was allowed to rest for a recovery phase of 5 minutes. Third and last step consisted of 3 minutes of pedalling again at 60 RPM but now set to 60 watts for elder subjects and 80 watts for the young subjects. Finally another five minutes of recovery. A good correlation was found between TOP and CPX results especially between punctua l heart rate reserve (HRR’) and anaerobic threshold parameters such as Watt, VO2, VCO2 . HRR’ was obtained by subtracting maximal heart rate during TOP from maximal theoretic heart rate (206,9-(0,67*age)). Data were analyzed through cluster analysis in order to obtain 3 homogeneous groups. The first group contains the least fit subjects (inactive, women, elderly). The other groups contain the “average fit” and the fittest subjects (active, men, younger). Concordance between test resulted in 83,23%. Afterwards, a linear combinations of the most relevant variables gave us a formula to classify people in the correct group. The most relevant result is that this submaximal test is able to discriminate subjects with different physical condition and to provide information (index) about physical fitness through HRR’. Compared to a traditional incremental stress test, the very low load of TOP, short duration and extended resting period, make this new method suitable to very different people. To better define the TOP index, it is necessary to enlarge our subject sample especially by diversifying the age range.

The Integrated European Project "GEHA - GEnetics of Healthy Aging": recruitment, health status assessment and survival of the Italian 90+ sibpairs

The present study is part of the EU Integrated Project “GEHA – Genetics of Healthy Aging” (Franceschi C et al., Ann N Y Acad Sci. 1100: 21-45, 2007), whose aim is to identify genes involved in healthy aging and longevity, which allow individuals to survive to advanced age in good cognitive and physical function and in the absence of major age-related diseases. Aims The major aims of this thesis were the following: 1. to outline the recruitment procedure of 90+ Italian siblings performed by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The procedures related to the following items necessary to perform the study were described and commented: identification of the eligible area for recruitment, demographic aspects related to the need of getting census lists of 90+siblings, mail and phone contact with 90+ subjects and their families, bioethics aspects of the whole procedure, standardization of the recruitment methodology and set-up of a detailed flow chart to be followed by the European recruitment centres (obtainment of the informed consent form, anonimization of data by using a special code, how to perform the interview, how to collect the blood, how to enter data in the GEHA Phenotypic Data Base hosted at Odense). 2. to provide an overview of the phenotypic characteristics of 90+ Italian siblings recruited by the recruiting units of the University of Bologna (UNIBO) and Rome (ISS). The following items were addressed: socio-demographic characteristics, health status, cognitive assessment, physical conditions (handgrip strength test, chair-stand test, physical ability including ADL, vision and hearing ability, movement ability and doing light housework), life-style information (smoking and drinking habits) and subjective well-being (attitude towards life). Moreover, haematological parameters collected in the 90+ sibpairs as optional parameters by the Bologna and Rome recruiting units were used for a more comprehensive evaluation of the results obtained using the above mentioned phenotypic characteristics reported in the GEHA questionnaire. 3. to assess 90+ Italian siblings as far as their health/functional status is concerned on the basis of three classification methods proposed in previous studies on centenarians, which are based on: • actual functional capabilities (ADL, SMMSE, visual and hearing abilities) (Gondo et al., J Gerontol. 61A (3): 305-310, 2006); • actual functional capabilities and morbidity (ADL, ability to walk, SMMSE, presence of cancer, ictus, renal failure, anaemia, and liver diseases) (Franceschi et al., Aging Clin Exp Res, 12:77-84, 2000); • retrospectively collected data about past history of morbidity and age of disease onset (hypertension, heart disease, diabetes, stroke, cancer, osteopororis, neurological diseases, chronic obstructive pulmonary disease and ocular diseases) (Evert et al., J Gerontol A Biol Sci Med Sci. 58A (3): 232-237, 2003). Firstly these available models to define the health status of long-living subjects were applied to the sample and, since the classifications by Gondo and Franceschi are both based on the present functional status, they were compared in order to better recognize the healthy aging phenotype and to identify the best group of 90+ subjects out of the entire studied population. 4. to investigate the concordance of health and functional status among 90+ siblings in order to divide sibpairs in three categories: the best (both sibs are in good shape), the worst (both sibs are in bad shape) and an intermediate group (one sib is in good shape and the other is in bad shape). Moreover, the evaluation wanted to discover which variables are concordant among siblings; thus, concordant variables could be considered as familiar variables (determined by the environment or by genetics). 5. to perform a survival analysis by using mortality data at 1st January 2009 from the follow-up as the main outcome and selected functional and clinical parameters as explanatory variables. Methods A total of 765 90+ Italian subjects recruited by UNIBO (549 90+ siblings, belonging to 258 families) and ISS (216 90+ siblings, belonging to 106 families) recruiting units are included in the analysis. Each subject was interviewed according to a standardized questionnaire, comprising extensively utilized questions that have been validated in previous European studies on elderly subjects and covering demographic information, life style, living conditions, cognitive status (SMMSE), mood, health status and anthropometric measurements. Moreover, subjects were asked to perform some physical tests (Hand Grip Strength test and Chair Standing test) and a sample of about 24 mL of blood was collected and then processed according to a common protocol for the preparation and storage of DNA aliquots. Results From the analysis the main findings are the following: - a standardized protocol to assess cognitive status, physical performances and health status of European nonagenarian subjects was set up, in respect to ethical requirements, and it is available as a reference for other studies in this field; - GEHA families are enriched in long-living members and extreme survival, and represent an appropriate model for the identification of genes involved in healthy aging and longevity; - two simplified sets of criteria to classify 90+ sibling according to their health status were proposed, as operational tools for distinguishing healthy from non healthy subjects; - cognitive and functional parameters have a major role in categorizing 90+ siblings for the health status; - parameters such as education and good physical abilities (500 metres walking ability, going up and down the stairs ability, high scores at hand grip and chair stand tests) are associated with a good health status (defined as “cognitive unimpairment and absence of disability”); - male nonagenarians show a more homogeneous phenotype than females, and, though far fewer in number, tend to be healthier than females; - in males the good health status is not protective for survival, confirming the male-female health survival paradox; - survival after age 90 was dependent mainly on intact cognitive status and absence of functional disabilities; - haemoglobin and creatinine levels are both associated with longevity; - the most concordant items among 90+ siblings are related to the functional status, indicating that they contain a familiar component. It is still to be investigated at what level this familiar component is determined by genetics or by environment or by the interaction between genetics, environment and chance (and at what level). Conclusions In conclusion, we could state that this study, in accordance with the main objectives of the whole GEHA project, represents one of the first attempt to identify the biological and non biological determinants of successful/unsuccessful aging and longevity. Here, the analysis was performed on 90+ siblings recruited in Northern and Central Italy and it could be used as a reference for others studies in this field on Italian population. Moreover, it contributed to the definition of “successful” and “unsuccessful” aging and categorising a very large cohort of our most elderly subjects into “successful” and “unsuccessful” groups provided an unrivalled opportunity to detect some of the basic genetic/molecular mechanisms which underpin good health as opposed to chronic disability. Discoveries in the topic of the biological determinants of healthy aging represent a real possibility to identify new markers to be utilized for the identification of subgroups of old European citizens having a higher risk to develop age-related diseases and disabilities and to direct major preventive medicine strategies for the new epidemic of chronic disease in the 21st century.

La psicologia della Gestalt. Ricerche teoriche e sperimentali sulla percezione sonora e musicale (1890-1939)

The aim of the present work is a historical survey on Gestalt trends in psychological research between late 19th and the first half of 20th century with privileged reference to sound and musical perception by means of a reconsideration of experimental and theoretical literature. Ernst Mach and Christian von Ehrenfels gave rise to the debate about Gestaltqualität which notably grew thanks to the ‘Graz School’ (Alexius Meinong, Stephan Witasek, Anton Faist, Vittorio Benussi), where the object theory and the production theory of perception were worked out. Stumpf’s research on Tonpsychologie and Franz Brentano’s tradition of ‘act psychology’ were directly involved in this debate, opposing to Wilhelm Wundt’s conception of the discipline; this clearly came to light in Stumpf’s controversy with Carl Lorenz and Wundt on Tondistanzen. Stumpf’s concept of Verschmelzung and his views about consonance and concordance led him to some disputes with Theodor Lipps and Felix Krueger, lasting more than two decades. Carl Stumpf was responsible for education of a new generation of scholars during his teaching at the Berlin University: his pupils Wolfgang Köhler, Kurt Koffka and Max Wertheimer established the so-called ‘Berlin School’ and promoted the official Gestalt theory since the 1910s. After 1922 until 1938 they gave life and led together with other distinguished scientists the «Psychologische Forschung», a scientific journal in which ‘Gestalt laws’ and many other acoustical studies on different themes (such as sound localization, successive comparison, phonetic phenomena) were exposed. During the 1920s Erich Moritz von Hornbostel gave important contributions towards the definition of an organic Tonsystem in which sound phenomena could find adequate arrangement. Last section of the work contains descriptions of Albert Wellek’s studies, Kurt Huber’s vowel researches and aspects of melody perception, apparent movement and phi-phenomenon in acoustical field. The work contains also some considerations on the relationships among tone psychology, musical psychology, Gestalt psychology, musical aesthetics and musical theory. Finally, the way Gestalt psychology changed earlier interpretations is exemplified by the decisive renewal of perception theory, the abandon of Konstanzannahme, some repercussions on theory of meaning as organization and on feelings in musical experience.

Solving the cooling flow problem through mechanical AGN feedback

A fundamental gap in the current understanding of collapsed structures in the universe concerns the thermodynamical evolution of the ordinary, baryonic component. Unopposed radiative cooling of plasma would lead to the cooling catastrophe, a massive inflow of condensing gas toward the centre of galaxies, groups and clusters. The last generation of multiwavelength observations has radically changed our view on baryons, suggesting that the heating linked to the active galactic nucleus (AGN) may be the balancing counterpart of cooling. In this Thesis, I investigate the engine of the heating regulated by the central black hole. I argue that the mechanical feedback, based on massive subrelativistic outflows, is the key to solving the cooling flow problem, i.e. dramatically quenching the cooling rates for several billion years without destroying the cool-core structure. Using an upgraded version of the parallel 3D hydrodynamic code FLASH, I show that anisotropic AGN outflows can further reproduce fundamental observed features, such as buoyant bubbles, cocoon shocks, sonic ripples, metals dredge-up, and subsonic turbulence. The latter is an essential ingredient to drive nonlinear thermal instabilities, which cause cold gas condensation, a residual of the quenched cooling flow and, later, fuel for the AGN feedback engine. The self-regulated outflows are systematically tested on the scales of massive clusters, groups and isolated elliptical galaxies: in lighter less bound objects the feedback needs to be gentler and less efficient, in order to avoid drastic overheating. In this Thesis, I describe in depth the complex hydrodynamics, involving the coupling of the feedback energy to that of the surrounding hot medium. Finally, I present the merits and flaws of all the proposed models, with a critical eye toward observational concordance.

Hydrodynamical simulations of galaxy clusters in dark energy cosmologies

In this work we investigate the influence of dark energy on structure formation, within five different cosmological models, namely a concordance $\Lambda$CDM model, two models with dynamical dark energy, viewed as a quintessence scalar field (using a RP and a SUGRA potential form) and two extended quintessence models (EQp and EQn) where the quintessence scalar field interacts non-minimally with gravity (scalar-tensor theories). We adopted for all models the normalization of the matter power spectrum $\sigma_{8}$ to match the CMB data. For each model, we perform hydrodynamical simulations in a cosmological box of $(300 \ {\rm{Mpc}} \ h^{-1})^{3}$ including baryons and allowing for cooling and star formation. We find that, in models with dynamical dark energy, the evolving cosmological background leads to different star formation rates and different formation histories of galaxy clusters, but the baryon physics is not affected in a relevant way. We investigate several proxies for the cluster mass function based on X-ray observables like temperature, luminosity, $M_{gas}$, and $Y_{X}$. We confirm that the overall baryon fraction is almost independent of the dark energy models within few percentage points. The same is true for the gas fraction. This evidence reinforces the use of galaxy clusters as cosmological probe of the matter and energy content of the Universe. We also study the $c-M$ relation in the different cosmological scenarios, using both dark matter only and hydrodynamical simulations. We find that the normalization of the $c-M$ relation is directly linked to $\sigma_{8}$ and the evolution of the density perturbations for $\Lambda$CDM, RP and SUGRA, while for EQp and EQn it depends also on the evolution of the linear density contrast. These differences in the $c-M$ relation provide another way to use galaxy clusters to constrain the underlying cosmology.

Phenotypic characterization of the epithelial and myoepithelial components in canine and feline mammary tumours

In veterinary medicine, the ability to classify mammary tumours based on the molecular profile and also determine whether the immunophenotype of the regional lymph node and/or systemic metastases is equal to that of the primary tumor may be predictive on the estimation of the effectiveness of various cancer treatments that can be scheduled. Therefore, aims, developed as projects, of the past three years have been (1) to define the molecular phenotype of feline mammary carcinomas and their lymph node metastases according to a previous modified algorithm and to demonstrate the concordance or discordance of the molecular profile between the primary tumour and lymph node metastasis, (2) to analyze, in female dogs, the relationship between the primary mammary tumor and its lymph node metastasis based on immunohistochemical molecular characterization in order to develop the most specific prognostic-predictive models and targeted therapeutic options, and (3) to evaluate the molecular trend of cancer from its primary location to systemic metastases in three cats and two dogs with mammary tumors. The studies on mammary tumours, particularly in dogs, have drawn gradually increasing attention not exclusively to the epithelial component, but also to the myoepithelial cells. The lack of complete information on a valid panel of markers for the identification of these cells in the normal and neoplastic mammary gland and lack of investigation of immunohistochemical changes from an epithelial to a mesenchymal phenotype, was the aim of a parallel research. While investigating mammary tumours, it was noticed that only few studies had focused on the expression of CD117. Therefore, it was decided to further deepen the knowledge in order to characterize the immunohistochemical staining of CD117 in normal and neoplastic mammary tissue of the dog, and to correlate CD117 immunohistochemical results with mammary histotype, histological stage (invasiveness), Ki67 index and patient survival time.