Suchergebnisse

Autoimmune Addisons disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population. ; Funding Agencies|Swedish Research Council; Torsten and Ragnar Soderberg Foundations; European Union Seventh Framework Programme [201167]; Stockholm County Council; Karolinska Institutet; Swedish Society for Medical Research; Swedish Society of Medicine; NovoNordisk Foundation; Tore Nilsons Foundation for Medical Research; Swedish Research Council Formas; Knut and Alice Wallenberg Foundation; Marianne and Marcus Wallenberg Foundation; Swedish Reumatism Foundation; King Gustaf Vs 80-year Foundation; Ake Wiberg Foundation

Dottorato di ricerca in Storia e cultura del viaggio e dell'odeporica nell'età moderna ; Le Remarks on several parts of Italy & c. in the years 1701, 1702, 1703, pubblicate a Londra per la prima volta nel 1705 sono il resoconto del viaggio italiano di Joseph Addison, moralista inglese. Le Remarks sono state spesso considerate come il punto di origine di uno stereotipo sull'Italia, intesa solo come land der klassik; ciò facendo, si sono sottovalutate le riflessioni morali, frutto di una sensibilità da diplomatico e da futuro politico; uno sguardo sull'altro e sull'altrove attento e curioso, interessato. Questo studio ha l'obiettivo di chiarire il senso storico e culturale di quel viaggio, limitatamente alle repubbliche italiane ancora esistenti a quel tempo ovvero, Genova, Lucca e San Marino, oltre a Livorno, città granducale e porto franco, sede di una importante British factory. Il viaggio in queste città è analizzato sia da un punto di vista socio-politico che artistico e storico-culturale, ponendo le parole dell'autore a confronto con le testimonianze di altri viaggiatori rintracciando il contesto storico, politico, religioso e culturale attraverso fonti storiche e documentarie, contemporanee e non. Il tentativo è quello di guardare alle sue riflessioni da una prospettiva storica e culturale, mettendo in luce l'ammirazione non solo del grand tourist ma anche del fine osservatore, per l'istituto repubblicano e la bontà di questo ancora riscontrabile, con varie modalità e con diverse prospettive e conseguenti esiti, negli ultimi esempi reali. La tesi è suddivisa in tre capitoli: nel Capitolo primo trova spazio l'esposizione semantica e teorica sul viaggio, inquadrato come categoria conoscitiva dell'altro e dell'altrove; inoltre, si propongono testimonianze antiche e moderne, storiche e letterarie per mostrare tutta la complessità del genere odeporico. Nel Capitolo secondo si ripercorre la fenomenologia del Grand Tour inteso come esperienza culturale europea e si presenta la biografia di Addison per meglio comprendere la genesi del suo viaggio in Italia, cercando di far luce attraverso quale background culturale, storico e sociale nasce il desiderio di partire per l'Italia. Nel Capitolo terzo si analizzano più specificamente i brani delle Remarks relativi a Genova, Lucca, San Marino e Livorno, e lì si potranno concretamente apprezzare le sue impressioni storiche, politiche, culturali e morali. Il resoconto delle città italiane sarà preceduto da un'analisi sulle teorie del repubblicanesimo presenti e passate, per meglio inquadrare il contesto storico di Addison e il suo percorso ideologico. In Appendice si troveranno la Lettera dedicatoria, la Prefazione e le parti relative alle repubbliche di Genova, Lucca e San Marino e le pagine relative a Livorno nella traduzione italiana da me effettuata. ; Remarks on several parts of Italy & c. in the years 1701, 1702, 1703, written by Joseph Addison, are the account of a Grand Tour in Italy. Remarks have often been considered as the origin of a stereotype on Italy, for the content of Addison's reflections about the land der klassik, and their impact on XVIII and XIX-century readers. Addison travelled in Italy paying attention on manners, political troubles and cultural aspects, as well. His curious glance was attracted by the artistic beauties and the unique landscapes; his acute speculations pertained to political considerations. Scholars have often underestimated his insight and potentiality as a politician, notwithstanding his background as a Secretary of State in England. This study aims to clarify the historical and cultural sense of that travel around the Italian republics, notably, Genoa, Lucca and San Marino, together with Leghorn, an important free port at that time, local seat of an important British factory. Addison's republican interest is motivated by his Oxonian classical studies, and the particular attention about these towns is justified by the fact that they seemed preserve the antique spirit of the Roman republic and he, true empiricist as he was, wanted to see it from life, on the spot, checking the practicality of this institution and the pragmatic effects of it, as well. Addison was a grand tourist and a good political observer, as well, seeking to go back over all the good of republicanism and its moral values. In Chapter one semantic and theoretical analysis of the travel, as a cognitive category of the other and the elsewhere, has been carried out; ancient and modern reflections, in order to demonstrate the complexity of travel literature as a genre, have been quoted. In Chapter two phenomenology of the Grand Tour as a European cultural experience has been analysed, together with relevant aspects of Addison's biography, in order to understand the genesis of his travel in Italy, and the cultural meaning of it in Addison's life. In Chapter three important passages of Remarks about Genoa, Lucca, San Marino and Leghorn have been examined, Addison's impressions on them can be appreciated; they have been compared and juxtaposed to contemporary and XIX-century historians' judgments. Report of the Italian towns is anticipated by a short presentation of current and past theories on republicanism. Travels in those towns have been always analysed from a historical and cultural point of view, and Addison's reflections have been compared to other important journals, written by many famous XVI to XIX-century travellers, in order to support or confute them. Dedication to Lord Somers, Preface and the whole passages on Genoa, Lucca, San Marino and Leghorn from the Remarks have been translated into Italian, and you can find all of them in the Appendix.

"In this incisive biography, Paul Addison examines both the life of the most iconic figure in twentieth-century British history, and the battle over his reputation, which continues to this day."--Jacket