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 représentation du pathétique masculin dans le roman sentimental européen: une réflexion sur l'imaginaire littéraire

Ce travail est une analyse de la représentation du pathétique masculin dans le roman dit sentimental dans la deuxième moitié du dix-huitième siècle en Europe, ou plutôt dans les littératures anglaise, française, allemande et italienne. La thèse soutenue est celle de la dérivation du pathétique romanesque de l’âge des Lumières des pratiques de prédication religieuse du siècle précédent et donc de la valeur normative du roman sentimental à ses débuts : celui-ci aurait relayé le rôle des manuels de conduite des siècles précédents et se serait posé comme un répertoire d’exempla comportementaux adaptés aux différentes situations de la vie. Nous avons suivi les évolutions historiques du genre à travers l’analyse thématique du motif des larmes masculines. Pour ce faire, nous avons examiné la complexe proxémique de représentation de l’émotion et la diégèse qui en résulte, qui peut être nuancée, selon une terminologie récente, en pathétique attendrissant, sentimental et spectaculaire. Cela a entraîne la prise en compte de diverses formes artistiques, de la peinture au théâtre. La méthodologie utilisé conjugue l’histoire des idées et l’étude des formes de l’imaginaire, le pathétique appartenant au domaine de la philosophie autant qu’à celui de la représentation artistique : le concept glisse au dix-huitième siècle du champ rhétorique et stylistique à une dimension esthétique et anthropologique. Le travail a donc été divisé en trois grandes parties qui analysent les trois dimensions anthropologiques fondamentales : l’imaginaire religieux et l’héritage des anciens, c’est–à-dire le rapport que l’époque établit avec la tradition culturelle qui la précède ; l’imaginaire amoureux, qui se concentre sur les rapports entre les deux sexes et sur la « féminisation » du héros romanesque sentimental ; l’imaginaire familial, qui aborde les conséquences de ce changement dans la représentation de la masculinité au sein de la représentation de la famille et des rapports intergénérationnels.

La ville picaresque

Cet extrait (le début du projet) peut être essentiellement considéré comme un travail de synthèse, de traduction et d’argumentation concernant un des textes de référence parmi les plus importants au sujet de la littérature picaresque : “La literatura picaresca desde la historia social” écrit par Jose Antonio Maravall. Mon but en développant ce projet était de me focaliser sur les idées principales contenues dans ce volume et en particulier sur la relation existante entre la littérature picaresque et le concept de ville, en termes urbanistiques. Je tiens à souligner le fait que ce travail a été longuement approfondi dans mes nombreuses activités d’étude et de recherche et en me référant, volontairement, au texte lui-même. La raison fondamentale de mon désir de rester près du texte se justifie par le fait que je venais de commence ce qui seraient mes futures activités de recherche de doctorat. J’ai utilisé ces idées à propos de la littérature picaresque, idées qui sont aujourd’hui universellement acceptées, afin de m’orienter moi-même dans ce genre littéraire. Les autres idées que j’ai étudiées et décrites au cours de mes activités de recherche successives sont plus personnelles, car j’avais eu l’occasion de les analyser auparavant. Ce travail n’inclut pas seulement des activités de recherche , mais il s’est agi aussi d’un projet de traduction puisque j’ai dû traduire de l’espagnol(texte original) en italien, pour ensuite concevoir et puis rédiger ma synthèse et mon argumentation en langue française. En conclusion, je peux affirmer que j’ai été capable de construire de solides bases pour élaborer et planifier ma thèse de Doctorat, avec les typiques thèmes de la littérature picaresque, pour exemple la recherche de la nourriture dans la ville.

La tutela dei lavoratori a tempo determinato in Italia, Francia e Spagna, con spunti per un'analisi comparata

L’attività di ricerca è focalizzata sull’analisi delle normative in materia di contratto di lavoro a termine in Italia, Francia e Spagna. Si tratta di Stati che, al pari del nostro, fanno un grandissimo uso di tale fattispecie, divenuta nei fatti il principale canale di ingresso nel mondo del lavoro, con percentuali complessive di rapporti a tempo determinato anche superiori a quelle italiane. Il confronto con due Paesi a noi vicini da un punto di vista giuridico, culturale e sociale è servito allo scopo di valutare la razionalità e l’opportunità delle profonde modifiche apportate alla disciplina generale da parte del decreto-legge n. 34/2014 (c.d. Decreto Poletti) ed ancora prima dalla riforma del sistema risarcitorio ad opera della legge n. 183/2010. Per ciascun ordinamento sono prese in considerazione le regole finalizzate alla tutela dei diritti dei lavoratori a termine, nonché gli orientamenti giurisprudenziali che hanno contribuito, specie in materia di non discriminazione, ad implementare il livello di protezione della posizione dei lavoratori stessi. Specifica attenzione viene dedicata, inoltre, alla disciplina del pubblico impiego, settore in cui si riscontra spesso un uso distorto delle assunzioni a tempo determinato, come testimoniano le vicende degli agents contractuels francesi e dei lavoratori c.d. indefinidos no fijos de plantilla. La conclusione della tesi è affidata allo studio del contenzioso originato dai tre Stati avanti alla Corte di Giustizia dell’Unione Europea, al fine di isolare eventuali momenti di sintesi delle differenze delle rispettive regolamentazioni. L’elemento aggregante che affiora dai dicta del supremo organo di giustizia comunitario è il principio di stabilità dell’impiego, la cui portata generale e trasversale può essere utile al fine di orientare l’attività produttiva e interpretativa delle norme nazionali nella direzione di un’implementazione delle tutele spettanti ai prestatori di lavoro a termine.