Impact of HSD11B1 polymorphisms on BMI and components of the metabolic syndrome in patients receiving psychotropic treatments.

BACKGROUND: Metabolic syndrome (MetS) associated with psychiatric disorders and psychotropic treatments represents a major health issue. 11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is an enzyme that catalyzes tissue regeneration of active cortisol from cortisone. Elevated enzymatic activity of 11β-HSD1 may lead to the development of MetS. METHODS: We investigated the association between seven HSD11B1 gene (encoding 11β-HSD1) polymorphisms and BMI and MetS components in a psychiatric sample treated with potential weight gain-inducing psychotropic drugs (n=478). The polymorphisms that survived Bonferroni correction were analyzed in two independent psychiatric samples (nR1=168, nR2=188) and in several large population-based samples (n1=5338; n2=123 865; n3>100 000). RESULTS: HSD11B1 rs846910-A, rs375319-A, and rs4844488-G allele carriers were found to be associated with lower BMI, waist circumference, and diastolic blood pressure compared with the reference genotype (Pcorrected<0.05). These associations were exclusively detected in women (n=257) with more than 3.1 kg/m, 7.5 cm, and 4.2 mmHg lower BMI, waist circumference, and diastolic blood pressure, respectively, in rs846910-A, rs375319-A, and rs4844488-G allele carriers compared with noncarriers (Pcorrected<0.05). Conversely, carriers of the rs846906-T allele had significantly higher waist circumference and triglycerides and lower high-density lipoprotein-cholesterol exclusively in men (Pcorrected=0.028). The rs846906-T allele was also associated with a higher risk of MetS at 3 months of follow-up (odds ratio: 3.31, 95% confidence interval: 1.53-7.17, Pcorrected=0.014). No association was observed between HSD11B1 polymorphisms and BMI and MetS components in the population-based samples. CONCLUSIONS: Our results indicate that HSD11B1 polymorphisms may contribute toward the development of MetS in psychiatric patients treated with potential weight gain-inducing psychotropic drugs, but do not play a significant role in the general population.

Eretria - Nea Psara : eine klassizistische Stadtanlage über der antiken Polis

Résumé: Le présent ouvrage propose une histoire de l'Erétrie moderne, de la redécouverte du site antique au projet urbanistique de 1834 pour une ville nouvelle destinée à accueillir les réfugiés de l'île de Psara - anéantie en 1824 par les Ottomans - et au développement urbain d'Erétrie/Nea Psara au XIXe et au XXe siècles. Le nom d'Erétrie englobe trois couches historiques distinctes: la cité antique, la ville néoclassique, dessinée par l'architecte allemand Eduard Schaubert (1804-1860), et le village moderne, issu de son projet. Chacune de ces strates - vestiges antiques, tissu urbain néoclassique et constructions plus récentes - est perceptible au sein de cet ensemble urbain et se trouve en relation constante avec les autres. L'exposé des recherches archéologiques - depuis la redécouverte du site antique par Ciriaco de' Pizzicolli d'Ancona (Cyriaque d'Ancône) en 1436 déjà, puis de manière systématique par des voyageurs-archéologues dès le XIXe siècle - comble une lacune dans l'historiographie de la cité antique. Cette approche met également en lumière la relation étroite entre archéologie et urbanisme au XIXe siècle. Si l'exploration de la Grèce avait été jusqu'à son indépendance en 1827 essentiellement le fait des archéologues, des historiens et des philologues, après cette date, des géologues, des ingénieurs et des topographes travaillant pour le développement économique du jeune Etat se mirent également à parcourir le pays, le regard tourné non plus seulement vers l'Antiquité, mais aussi vers l'avenir. L'histoire de la redécouverte d'Erétrie permet ainsi d'éclairer divers aspects liés à la gestation de l'Etat grec. Le projet conçu en 1834 par Ecluard Schaubert de ville néoclassique superposée aux ruines de la cité antique d'Erétrie s'inscrit dans un réseau de créations de villes nouvelles et de modernisations de villes existantes par le nouvel Etat grec, qui cherchait à fonder sa légitimité et son identité, après la domination ottomane, sur les valeurs idéales (ou idéalisées) de l'Antiquité classique. Dans le projet de développement urbain d'Erétrie, la relation étroite entre archéologie et urbanisme et, par conséquent, la référence à l'Antiquité sont évidentes: Eduard Schaubert commença par tracer sur son plan toutes les ruines antiques, dressant ainsi l'état des connaissances archéologiques du site. Sur cette base, l'architecte conçut la ville néoclassique en y incluant les principales ruines, qui devaient servir de repères visuels et qui concrétisaient ainsi le lien idéologique de la monarchie absolue avec l'Antiquité. A Erétrie, deux perspectives principales reliaient le port à l'acropole et l'Ecole navale au théâtre antique. L'intégration de ruines antiques dans un projet urbanistique avait été réalisée par Stamatios Kleanthes et Eduard Schaubert en 1831-1832 dans le plan de l'Athènes moderne, avant que celle-ci n'ait été promue capitale de la Grèce. Les deux architectes ont ainsi anticipé le caractère idéal d'Athènes dans le processus de gestation de l'Etat grec. L'importance de ce plan et de celui qu'ifs ont établi sur le même modèle pour le Pirée a été reconnue par les historiens de l'urbanisme. En revanche, le plan d'Erétrie, qui suit pourtant les mêmes principes, n'a été que partiellement étudié. Cette monographie montre que le projet d'Erétrie était le plus abouti des trois, qui tous se caractérisent par un système de routes rayonnant depuis le siège du gouvernement (résidences royales à Athènes et au Pirée, mairie à Erétrie). Cet éventail de rues ou u patte d'oie» embrasse à Athènes l'acropole et au Pirée fa baie du port, alors qu'a Erétrie il est double, axé en raison de la topographie sur l'acropole et sur Pa baie du port. Cette double patte d'oie crée ainsi le lien idéologique avec l'Antiquité et témoigne, par son ouverture sur le port, de l'essor économique souhaité par le gouvernement. Le plan d'Erétrie représente de manière exemplaire l'urbanisme programmatique de la Grèce sous Othon ler (1832-1862). L'ouvrage s'intéresse ensuite à la réalisation du projet de Schaubert, dont la mise en oeuvre n'a pas répondu aux attentes du Gouvernement. Le faible développement d'Erétrie s'explique principalement par le surdimensionnement du projet, des finances publiques modestes, la malaria endémique et une politique économique inadaptée aux traditions commerciales des Psariotes. Les lenteurs dans la réalisation du projet et même des régressions au cours du XIXe siècle et au début du XXe siècle, puis l'urbanisation accélérée d'Erétrie à partir des années 1960, ont eu pour conséquence que les historiens de l'urbanisme et les urbanistes ont sous-estimé, voire ignoré la valeur historique de ce concept Cependant, l'exécution du projet néoclassique s'est poursuivie de manière continue et des références au plan de Schaubert peuvent être observées dans l'aménagement récent de la localité aujourd'hui encore. Ainsi, des arbres ont été plantés dans les années 1960 le long de l'enceinte urbaine antique, à l'emplacement où Schaubert avait prévu la création d'une promenade arborée. Au centre d'Erétrie, là où l'agora principale aurait dû être aménagée, une grande place publique servant au marché hebdomadaire a été créée. Dans le quartier oriental, une petite église dédiée à la Pan hagia Paravouniotissa a été construite en 2001 sur la parcelle où Schaubert en avait prévue une. D'importants éléments des projets de Schaubert, qui ne sont actuellement plus guère perceptibles à Athènes et au Pirée, le sont toujours à Erétrie. Les espaces verts, par exemple, occupent une place importante dans le domaine privé: malgré la densification du tissu urbain, des parcelles caractéristiques contiennent encore des maisons isolées d'un ou de deux niveaux côté rue, avec un grand jardin à l'arrière, séparé des parcelles voisines par un mur en pierre ou en brique crue. Erétrie mérite donc une reconnaissance plus considérable dans l'histoire de l'urbanisme, puisqu'elle contribue à faire mieux comprendre les projets de ses deux villes soeurs. L'étude du projet urbanistique est complétée par une approche typologique des constructions néoclassiques d'Erétrie qui souligne encore la valeur historique de cet ensemble. Comme la plupart des édifices sont, menacés de démolition, à l'exception d'un petit nombre d'entre eux qui bénéficient d'un bon entretien, un inventaire photographique des constructions d'Erétrie datant du XIXe et du début du XXe siècle a été constitué entre 1994 et 2005, complété par des photographies anciennes. Il en ressort que les formes et les techniques de construction sont représentatives de l'architecture privée à l'époque de la création de l'Etat. Enfin, le plan directeur d'Erétrie, réalisé en 1975-1976 par un séminaire du Département d'architecture de l'Ecole polytechnique fédérale de Zurich avec l'appui de l'Ecole suisse d'archéologie en Grèce, est publié ici intégralement pour la première fois. Le présent ouvrage rend ses lettres de noblesse à un ensemble urbain néoclassique, certes modeste, mais issu d'un projet urbanistique ambitieux, témoin significatif du programme politique du nouvel Etat grec. SUMMARY Translated by William Eisler This book gives an account of the history of modern Eretria. It encompasses the rediscovery of the ancient city, the 1834 urban plan for the new town designed to accommodate the refugees from the island of Psara - destroyed by the Ottomans in 1824 - and also the urban development of Eretria/Nea Psara in the 19th and 20th centuries. The name Eretria carries a rich heritage: the ancient city, the neoclassical town designed by the Germen architect Eduard Schaubert (1804-1860), and the modern village. These three distinct historical layers ancient ruins, neoclassical plan and more recent constructions - can be seen within this urban area and are interlinked with each other. The account of the archeological investigations fills a gap in the historiography of the ancient city. This started with the early rediscovery of the ancient site by Ciriaco de'Pizzicolli d'Ancona in 1436, and was followed by systematic research by travellers/ archeologists from the 19th century onward. Furthermore, this shows the close relationship between archeology and urbanism in the 19th century. The exploration of Greece prier te its independence in 1827 was mainly red by archeologists, historians and philologists. Subsequently, geologists, engineers and topographers working for the young state's economic development travelled across the country, with their attention focused not only on Antiquity but are on the future. The history of Eretria's rediscovery gives new insights on various aspects related to the development of the Greek state. In 1834, Eduard Schaubert's project, planning a neoclassical town built upon the ancient Eretria, took place alongside the development of other new cities and the modernization of existing ones du ring the Ottoman domination. By doing so, the new Greek state wanted to build its legitimacy and identity, based upon the ideal (or idealized) values of Classical Antiquity. In the urban development of Eretria, the close connection between archeology and urbanism, and the reference to Antiquity, are obvious. Eduard Schaubert began by tracing on his plan ail of the ancient ruins, thus showing the knowledge of the archeological site at that time. On this basis, the architect planned the neoclassical town, incorporating the principal ruins which were to serve as visual references embodying the ideological link between Antiquity and King Otto's absolute monarchy. In Eretria, two principal visual axes linked the port to the acropolis and the Naval School to the ancient theatre. The integration of ancient ruins in an urban project had already been achieved by Stamatios Kleanthes and Eduard Schaubert in 1831-1832 in their plan for modern Athens, before it became the capital of Greece. The two architects had therefore anticipated the ideal character of Athens at the beginning of the Greek state. The importance of this plan and that of Piraeus (designed along the same model) has long been recognized by urban historians. By contrast, the plan of Eretria based open the same principles has been only partly studied. This book explains clearly that the Eretria project was the most elaborate. The three cities are characterized by a system of roads radiating from the seat of government (the royal residences in Athens and Piraeus, the town hall in Eretria). This fan-like arrangement of streets includes the Acropolis in Athens and the harbour in Piraeus, whereas in Eretria it is twofold, orientated towards the acropolis and the harbour on account of the topography. This double fan-like arrangement shows the ideological link with Antiquity and, with its opening onto the harbour, the government's desire for economic development. The plan of Eretria is a typical ex- ample of the programmatic urbanism of Greece under Otto I (1832-1862). The book discusses the completion of Schaubert's project, which was not fully carried out as expected by the government. The poor development of Eretria can be explained primarily by the excessive scale of the project, the modest public finances, the endemic malaria and an economic policy unsuitable to the commercial traditions of the Psariotes. Delays, even regressions in the implementation of the project in the course of the 19th and the beginning of the 20th centuries, followed by the growing urbanization of Eretria starting in the 1960's, led urban historians and town planners to underestimate or even to ignore the historical value of this concept. Nevertheless, the neoclassical project was carried out steadfastly, and references to the Schaubert plan can still be seen in the modern layout of the town. Trees were planted in the 1960's all along the circumference of the ancient city, where Schaubert had planned a tree-lined promenade. A big public square serving as a weekly market place was created in the centre of Eretria, where the principal agora had been originally planned. In 2001 a small church dedicated to the Panhagia Paravouniotissa was built on a plot of land in the eastern district, where this had been intended by Schaubert. Important elements of Schaubert's projects, which are barely perceptible in modern-day Athens and Piraeus, remain visible in Eretria. Green areas, for example, occupy a significant place within the private properties. In spite of the urban densification, characteristic plots still include isolated houses of one or two stories facing the street, with large gardens in the rear, separated from neighbours by stone or mudbrick walls. Eretria therefore deserves a more prominent position in the history of urbanism, as it contributes to a better understanding of ifs two sister cities. The study of the urban project is enriched by a typological approach to the neoclassical constructions of Eretria, underlining once again the historical value of this heritage. Since only a small number of the buildings have benefited from good maintenance and the greater part is threatened with demolition, a photographic inventory of the constructions of Eretria dating from the 19tIt and early 20th centuries was produced between 1994 and 2005, supplemented by old photographs. This documentation clearly shows that the forms and techniques of construction are characteristic of private architecture at the beginning of modern Greece. Finally, the master plan of Eretria drafted in 1975-1976 by a seminar of the Department of Architecture of the Swiss Federal Institute of Technology, Zurich, with the support of the Swiss School of Archeology in Greece, is published here in full for the first time. This book gives credit to a neoclassical urban heritage which, although modest in scale, derives from an ambitious project that embodies the political programme of the new Greek state. ΠΕΡΙΛΗΨΗ Μετάβραση Ελενή Δημητρακοπούλου Η παρούσα εργασία προτείνει μια. ιστορία της σύγχρονης πόλης της Ερέτριας, ξεκινώντας από την αποκάλύψη του αρχαιολογικού χώρου, περνώντας από την σύνταξη, το 1834, του ρυμοτομικού σχεδίου για μια νέα. πόλη που σκοπό είχε να υποδεχθεί τούς πρόσφυγες από τα Ψαρά. - που καταστράφηκαν ολοσχερώς το 1824 από τούς Οθωμανούς - και εξετάζοντας τέλος την πολεοδομική εξέλιξη της Ερέτριας/Νέων Ψαρών κατά τον 19° και τον 20° αι. Πίσω από το όνομα της Ερέτριας κρύβονται τρία διαφορετικά. ιστορικά στρώματα,: η αρχαία πόλη, η νεοκλασική πόλη πού σχεδιάστηκε από τον γερμανό αρχιτε κτονα "Εντοναρντ Σάουμπερτ (1804-1860) και η σύγχρονη πόλη που κτίστηκε πάνω στά. σχέδια του τελευταίού. Κάθε ένα από αυτά τα στρώματα - αρχαία κατάλοιπα. νεοκλασικός πολεοδομικός ιστός και νεώτερα κτίσματα - γίνεται αντιληπτό στο πλαίσιο αυτού του πολεοδομικού συνόλου και βρίσκεται σε άμεση σχέση με τα άλλα δύο. Ηπαρονσίαση των αρχαιολογικών ερευνών, που ξεκινούν το 1436 με την αποκάλυψη τον αρχαιολογικού χώρού από τον Ciriaco de' Pizzicolli d'Ancona (Κυριάκος ο Αγκωνίτης) και συνεχίζονται συστηματικά. από περιηγητές_αρχαιολόγούς κατά το 19° αι., καλύπτει ένα κενό στην ιστοριογραφία της έρεύνας της αρχαίας πύλης. Η προσέγγιση αυτή φωτίζει επίσης τη στενή σχέσημεταξύαρχαιολογίας και πολεοδομίας κατά τον 190 αι. Αν η εξερεύνηση της Ελλάδος, ως την ανεξαρτησία της το 1827, ήταν έργο κνρϊως αρχαιολόγων, ιστορικών και φιλολόγων, μετά από αυτήν την χρονολογία., γεωλόγοι, μηχανικοί και τοπογράφοι που εργάζονταν για την οικονομική ανάπτυξη τον νεοσύστατου Ελληνικού Κράτούς, άρχισαν επίσης να περιτρέχονν όλη την χώρα., με το βλέμμα. στραμμένο όχι μόνο προς την Αρχαιότητα, αλλά και προς το μέλλον. Η ιστορία της αποκάλυψης της Ερέτριας φωτίζει έτσι και διάφορες όψεις που συνδέονται με την γένεση του Ελληνικού Κράτους. Το 1834, υ 'Εντοναρντ Σάουμπερτ εκπόνησε το σχέδιο μιας νεοκλασικής πόλης που Θα επικαθόταν στα; ερείπια. της αρχαίας Ερέτριας?το έργο εντάσσεται στο δίκτυο δημιουργίας νέων πόλεων και εκσυγχρονισμού των υπαρχυυσών από το νεοσύστατο Ελληνικό Κράτος. το οποίο, μετά την Οθωμανική κυριαρχία, επεδίωκε να Θεμελιώσει την νομιμότητα και την ταυτότητά του πάνω στις ιδανικές ή εξιδανικευμένες αξίες της κλασικής αρχαιότητας. Στο σχέδιο της πολεοδομικής ανάπτυξης της Ερέτριας, η στενή σχέση μεταξύ αρχαιολογίας και πολεοδομίας και, κατ επέκταση. οι σαφείς αναφορές στην Αρχαιότητα. είναι εμφανείς: ο Εντοναρντ Σάουμπερτ άρχισε σχεδιάζοντας στο τοπογραφικό τον όλα τα αρχαία. ερείπια, καταγράφοντας έτσι τις τότε αρχαιολογικές γνώσεις για, το χώρο. Σε αυτή τη βάση, ο αρχιτέκτονας συνέλαβε την νεοκλασική πόλη εντάσσοντας σε αυτήν τα κυριότερα αρχαία μνημεία, τα οποία χρησίμευαν ως οπτικά σημεία αναφοράς, ενώ συγχρόνως υλοποιούσαν την ιδεολογική σχέση της απόλύτης μοναρχίας με την Αρχαιότητα. Στην Ερέτρια, δυο βασικοί άξονες συνέδεαν το λιμάνι με την Ακρόπολη και τη Ναυτική Σχολή με το Αρχαίο Θέατρο. Η ένταξη αρχαίων ερειπίων σε ένα πολεοδομικό σχέδιο είχε ήδη πραγματοποιηθεί από τούς Σταμάτιο Κλεάνθη και'Εντουαρντ Σάουμπερτ στα 1831-1832, στον σχεδιασμό της νέας Αθήνας, πριν αυτή ανακηρυχθεί σε πρωτεύουσα. της Ελλάδος. Οι δυο αρχιτέκτονες προεξόφλησαν έτσι τον συμβολικό χαρακτήρα της Αθήνας στην διαδικασία. γένεσης του Ελληνικού Κράτούς, Η σημασία αυτού τον σχεδίου καθώς και εκείνου που συνέταξαν, πάνω στο ίδιο πνεύμα, για τον Πειραιά έχει αναγνωριστεί από τους σύγχρονούς πολεοδόμους. Αντίθετα, το σχέδιο της Ερέτριας, παρ όλο που ακολούθεί τις ίδιες αρχές, μελετήθηκε πολύ λίγο. Η παρούσα μονογραφία δείχνει ότι το σχέδιο της Ερέτριας ήταν το πιο ολοκληρωμένο από τα τρία. Βασικό χαρακτηριστικό των σχεδίων αυτών είναι ένα σύστημα οδών που αναπτύσσονται ακτινωτά από το κέντρο εξουσίας (βασιλική κατοικία στην Αθήνα και τον Πειραιά, δημαρχείο στην Ερέτρια). Αυτή η ακτινωτή διάταξη των οδών συμπεριλαμβάνει στην Αθήνα την Ακρόπολη και στον Πειραιά το λιμάνι, ενώ στην Ερέτρια είναι αμφίροπη, προσανατολισμένη, λόγω της τοπογραφίας, προς την ακρόπολη αλλά και προς τον όρμο του λιμανιού. Αυτή η διπλή ακτινωτή διάταξη από τη μια δημιούργεί τον ιδεολογικό δεσμό ιιε την Αρχαιότητα, ενώ από την άλλη τονίζει, με το άνοιγμά της προς το λιμάνι, την οικονομική άνθηση της πόλης που επιθυμούσε η κεντρική εξουσία. Τα σχέδιο της Ερέτριας αποτελεί αντιπροσωπευτικό δείγμα της προγραμματικής πολεοδομίας της Ελλάδος κατά τα, χρόνια της Βασιλείας του "Οθωνος (1832-1862). Η υλοποίηση του σχεδίου του Σάουμπερτ δεν ανταποκρίθηκε στις προσδοκίες της κυβέρνησης. Η μικρή ανάπτύξη της Ερέτριας οφείλεται κυρίως στούς ανεδαφικούς, μεγαλεπί βολονς στόχους του σχεδίού, στα μέτρια δημόσια οικονομικά, στην ενδημική ελονοσία λόγω των υφισταμένων ελών καθώς και σε μια, οικονομική πολιτική που ήταν ξένη στις εμπορικές παραδόσεις των Ψαριανών. Οι αργοί ρυθμοί της πραγματοποίησης του σχεδίού και μάλιστα κάποιες περικοπές τον κατά τη διάρκεια τον 19°ν και στις αρχές του 2θ αι., και στη συνέχεια η ταχεία πολεοδομική εξέλιξη της Ερέτριας από τη δεκαετία του 1960, είχαν σαν συνέπεια να υποτιμηθεί ή κατ να αγνοηθεί η ιστορική αξία του πολεοδομικού σχεδίου από τους ιστορικούς της πολεοδομίας. Ωστόσο, η εκτέλεση τον νεοκλασικού σχεδίου ακολουθήθηκε με συνέπεια, ενώ αναφορές στο σχέδιο του Σάουμπερτ μπορούν να παρατηρηθούν, ακόμα. και σήμερα. στις νεώτερες διευθετήσεις τον χώρου. Ετσι, στη δεκαετία του 1960, κατά μήκος του αρχαίού τείχούς της πόλης φυτεύθηκαν δέντρα, στη Θέση όπού ο Σάουμπερτ είχε προβλέψει τη δημιουργία ενός δεντροφυτεμένου περιπάτου. Στο κέντρο της Ερέτριας, εκεί όπου Θα έπρεπε να διαμορφωθεί η κύρια αγορά της πόλης, δημιουργήθηκε μια μεγάλη δημόσια πλατεία όπου γίνεται η εβδομαδιαία λαϊκή αγορά. Στην ανατολική συνοικία, χτίστηκε, το 2001, μια μικρή εκκλησία αφιερωμένη στην Παναγία, την Παραβοννιώτισσα, στο οικόπεδο όπου ο Σάουμπερτ είχε προβλέψει μια εκκλησία. Σημαντικά στοιχεία των σχεδίων του Σάουμπερτ, που δεν γίνονται πια καθόλου αντιληπτά στην ΑΘήνα και στον Πειραιά, μπορούν να παρατηρηθούν στην Ερέτρια. Το πράσινο, για παράδειγμα, καταλαμβάνει σημαντική Θέση τον ιδιωτικού χώρου: παρά την πύκνωση τον πολεοδομικού ιστού, χαρακτηριστικά είναι τα οικόπεδα που περιέχούν ακόμα μεμονωμένα σπίτια, μονώροφα ή διώροφα, επί προσώπου οδού, με ένα μεγάλο κήπο στο πίσω μέρος, που χωρίζονται από τα, γειτονικά οικόπεδα με ένα μαντρότοιχο πέτρινο ή από ωμές πλίνθους. Η Ερέτρια οφείλει λοιπόν να λάβει τη Θέση που της αξίζει στην ιστορία της Νεοελληνικής πολεοδομίας, εφόσον συμβάλλει στην καλύτερη κατανόηση των σχεδίων των δυο αυτών αδελφών πόλεων. Η μελέτη τον πολεοδομικού σχεδίού συμπληρώνεται από μια τυπολογική προσέγγιση των νεοκλασικών κτηρίων της Ερέτριας, η οποία υπογραμμίζει ακόμα περισσότερο την ιστορική αξία του συνόλου αυτού. Καθώς τα περισσότερα κτήρια απειλούνται με κατεδάφιση, με εξαίρεση λίγα από αυτά που είχαν την τύχη να συντηρούνται σωστά, μεταξύ 1994 και 2005, καταρτίστηκε ένα φωτογραφικό αρχείο των κτιρίων της Ερέτριας που χρονολογούνται στο 19° και στις αρχές τον 200υ αι., συμπληρωμένο και από παλιές φωτογραφίες. Από αυτό προκύπτει ότι οι μορφές κατ οι τεχνικές δομήσεως είναι αντιπροσωπευτικές της ιδιωτικής αρχιτεκτονικής κατά την εποχή της σύστασης τον Ελληνικού Κράτους. Τέλος, το γενικό ρυθμιστικό σχέδιο της Ερέτριας, που εκπονήθηκε στα 1975-1976 από μελετητική ομάδατης σχολής Αρχιτεκτόνων του Ομοσπονδιακού Πολυτεχνείου της Ζυρίχης, με την υποστήριξη της Ελβετικής Αρχαιολογικής Σχολής στην Ελλάδα., δημοσιεύεται εδώ για πρώτη φορά στην πλήρη μορφή του. Η παρούσα εργασία, αφορά ένα νεοκλασικό πολεοδομικό σύνολο, ταπεινό ίσως, αλλά αποτέλεσμα ενός φιλόδοξου πολεοδομικού σχεδιασμού, ο οποίος αποτελεί σημαντικό μάρτυρα του πολιτικού προγράμματος τον νεοσύστατού Ελληνικού Κράτους.

Effect of antenatal corticosteroids on fetal growth and gestational age at birth.

OBJECTIVE: To estimate the effect of multiple courses of antenatal corticosteroids on neonatal size, controlling for gestational age at birth and other confounders, and to determine whether there was a dose-response relationship between number of courses of antenatal corticosteroids and neonatal size. METHODS: This is a secondary analysis of the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study, a double-blind randomized controlled trial of single compared with multiple courses of antenatal corticosteroids in women at risk for preterm birth and in which fetuses administered multiple courses of antenatal corticosteroids weighed less, were shorter, and had smaller head circumferences at birth. All women (n=1,858) and children (n=2,304) enrolled in the Multiple Courses of Antenatal Corticosteroids for Preterm Birth Study were included in the current analysis. Multiple linear regression analyses were undertaken. RESULTS: Compared with placebo, neonates in the antenatal corticosteroids group were born earlier (estimated difference and confidence interval [CI]: -0.428 weeks, CI -0.10264 to -0.75336; P=.01). Controlling for gestational age at birth and confounding factors, multiple courses of antenatal corticosteroids were associated with a decrease in birth weight (-33.50 g, CI -66.27120 to -0.72880; P=.045), length (-0.339 cm, CI -0.6212 to -0.05676]; P=.019), and head circumference (-0.296 cm, -0.45672 to -0.13528; P<.001). For each additional course of antenatal corticosteroids, there was a trend toward an incremental decrease in birth weight, length, and head circumference. CONCLUSION: Fetuses exposed to multiple courses of antenatal corticosteroids were smaller at birth. The reduction in size was partially attributed to being born at an earlier gestational age but also was attributed to decreased fetal growth. Finally, a dose-response relationship exists between the number of corticosteroid courses and a decrease in fetal growth. The long-term effect of these findings is unknown. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00187382. LEVEL OF EVIDENCE: II.

A CMR study of the effects of tissue edema and necrosis on left ventricular dyssynchrony in acute myocardial infarction: implications for cardiac resynchronization therapy.

ABSTRACT: BACKGROUND: In acute myocardial infarction (AMI), both tissue necrosis and edema are present and both might be implicated in the development of intraventricular dyssynchrony. However, their relative contribution to transient dyssynchrony is not known. Cardiovascular magnetic resonance (CMR) can detect necrosis and edema with high spatial resolution and it can quantify dyssynchrony by tagging techniques. METHODS: Patients with a first AMI underwent percutaneous coronary interventions (PCI) of the infarct-related artery within 24 h of onset of chest pain. Within 5-7 days after the event and at 4 months, CMR was performed. The CMR protocol included the evaluation of intraventricular dyssynchrony by applying a novel 3D-tagging sequence to the left ventricle (LV) yielding the CURE index (circumferential uniformity ratio estimate; 1 = complete synchrony). On T2-weighted images, edema was measured as high-signal (>2 SD above remote tissue) along the LV mid-myocardial circumference on 3 short-axis images (% of circumference corresponding to the area-at-risk). In analogy, on late-gadolinium enhancement (LGE) images, necrosis was quantified manually as percentage of LV mid-myocardial circumference on 3 short-axis images. Necrosis was also quantified on LGE images covering the entire LV (expressed as %LV mass). Finally, salvaged myocardium was calculated as the area-at-risk minus necrosis (expressed as % of LV circumference). RESULTS: After successful PCI (n = 22, 2 female, mean age: 57 ± 12y), peak troponin T was 20 ± 36ug/l and the LV ejection fraction on CMR was 41 ± 8%. Necrosis mass was 30 ± 10% and CURE was 0.91 ± 0.05. Edema was measured as 58 ± 14% of the LV circumference. In the acute phase, the extent of edema correlated with dyssynchrony (r2 = -0.63, p < 0.01), while extent of necrosis showed borderline correlation (r2 = -0.19, p = 0.05). PCI resulted in salvaged myocardium of 27 ± 14%. LV dyssynchrony (=CURE) decreased at 4 months from 0.91 ± 0.05 to 0.94 ± 0.03 (p < 0.004, paired t-test). At 4 months, edema was absent and scar %LV slightly shrunk to 23.7 ± 10.0% (p < 0.002 vs baseline). Regression of LV dyssynchrony during the 4 months follow-up period was predicted by both, the extent of edema and its necrosis component in the acute phase. CONCLUSIONS: In the acute phase of infarction, LV dyssynchrony is closely related to the extent of edema, while necrosis is a poor predictor of acute LV dyssynchrony. Conversely, regression of intraventricular LV dyssynchrony during infarct healing is predicted by the extent of necrosis in the acute phase.

Closure of large intrathoracic airway defects using extrathoracic muscle flaps.

BACKGROUND: Prospective assessment of pedicled extrathoracic muscle flaps for the closure of large intrathoracic airway defects after noncircumferential resection in situations where an end-to-end reconstruction seemed risky (defects of > 4-cm length, desmoplastic reactions after previous infection or radiochemotherapy). METHODS: From 1996 to 2001, 13 intrathoracic muscle transpositions (6 latissimus dorsi and 7 serratus anterior muscle flaps) were performed to close defects of the intrathoracic airways after noncircumferential resection for tumor (n = 5), large tracheoesophageal fistula (n = 2), delayed tracheal injury (n = 1) and bronchopleural fistula (n = 5). In 2 patients, the extent of the tracheal defect required reinforcement of the reconstruction by use of a rib segment embedded into the muscle flap followed by temporary tracheal stenting. Patient follow-up was by clinical examination bronchoscopy and biopsy, pulmonary function tests, and dynamic virtual bronchoscopy by computed tomographic (CT) scan during inspiration and expiration. RESULTS: The airway defects ranged from 2 x 1 cm to 8 x 4 cm and involved up to 50% of the airway circumference. They were all successfully closed using muscle flaps with no mortality and all patients were extubated within 24 hours. Bronchoscopy revealed epithelialization of the reconstructions without dehiscence, stenosis, or recurrence of fistulas. The flow-volume loop was preserved in all patients and dynamic virtual bronchoscopy revealed no significant difference in the endoluminal cross surface areas of the airway between inspiration and expiration above (45 +/- 21 mm(2)), at the site (76 +/- 23 mm(2)) and below the reconstruction (65 +/- 40 mm(2)). CONCLUSIONS: Intrathoracic airway defects of up to 50% of the circumference may be repaired using extrathoracic muscle flaps when an end-to-end reconstruction is not feasible.

Multiple courses of antenatal corticosteroids for preterm birth (MACS): a randomised controlled trial.

BACKGROUND: One course of antenatal corticosteroids reduces the risk of respiratory distress syndrome and neonatal death. Weekly doses given to women who remain undelivered after a single course may have benefits (less respiratory morbidity) or cause harm (reduced growth in utero). We aimed to find out whether multiple courses of antenatal corticosteroids would reduce neonatal morbidity and mortality without adversely affecting fetal growth. METHODS: 1858 women at 25-32 weeks' gestation who remained undelivered 14-21 days after an initial course of antenatal corticosteroids and continued to be at high risk of preterm birth were randomly assigned to multiple courses of antenatal corticosteroids (n=937) or placebo (n=921), every 14 days until week 33 or delivery, whichever came first. The primary outcome was a composite of perinatal or neonatal mortality, severe respiratory distress syndrome, intraventricular haemorrhage (grade III or IV), periventricular leucomalacia, bronchopulmonary dysplasia, or necrotising enterocolitis. Analysis was by intention to treat. All patients and caregivers were unaware of the treatment given. This trial is registered as number ISRCTN2654148. FINDINGS: Infants exposed to multiple courses of antenatal corticosteroids had similar morbidity and mortality to those exposed to placebo (150 [12.9%] vs 143 [12.5%]). Those receiving multiple doses of corticosteroids also weighed less at birth than those exposed to placebo (2216 g vs 2330 g, p=0.0026), were shorter (44.5 cm vs 45.4 cm, p<0.001), and had a smaller head circumference (31.1 cm vs 31.7 cm, p<0.001). INTERPRETATION: Multiple courses of antenatal corticosteroids, every 14 days, do not improve preterm-birth outcomes, and are associated with a decreased weight, length, and head circumference at birth. Therefore, this treatment schedule is not recommended. FUNDING: Canadian Institutes of Health Research.

Body mass index, abdominal adiposity and blood pressure: consistency of their association across developing and developed countries.

BACKGROUND: Obesity is increasing worldwide because developing countries are adopting Western high-fat foods and sedentary lifestyles. In parallel, in many of them, hypertension is rising more rapidly, particularly with age, than in Western countries. OBJECTIVE: To assess the relationship between adiposity and blood pressure (BP) in a developing country with high average BP (The Seychelles, Indian Ocean, population mainly of African origin) in comparison to a developed country with low average BP (Switzerland, population mainly of Caucasian origin). DESIGN: Cross-sectional health examination surveys based on population random samples. SETTING: The main Seychelles island (Mahé) and two Swiss regions (Vaud-Fribourg and Ticino). SUBJECTS: Three thousand one hundred and sixteen adults (age range 35-64) untreated for hypertension. MEASUREMENTS: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), systolic and diastolic blood pressure (SBP and DBP, mean of two measures). METHODS: Scatterplot smoothing techniques and gender-specific linear regression models. RESULTS: On average, SBP and DBP were found to increase linearly over the whole variation range of BMI, WHR and WC. A modest, but statistically significant linear association was found between each indicator of adiposity and BP levels in separate regression models controlling for age. The regression coefficients were not significantly different between the Seychelles and the two Swiss regions, but were generally higher in women than in men. For the latter, a gain of 1.7 kg/m(2) in BMI, of 4.5 cm in WC or of 3.4% in WHR corresponded to an elevation of 1 mmHg in SBP. For women, corresponding figures were 1.25 kg/m(2), 2.5 cm and 1.8% respectively. Regression coefficients for age reflected a higher effect of this variable on both SBP and DBP in the Seychelles than in Switzerland. CONCLUSION: These findings suggest a stable linear relation of adiposity with BP, independent of age and body fat distribution, across developed and developing countries. The more rapid increase of BP with age observed in the latter countries are likely to reflect higher genetic susceptibility and/or higher cumulative exposure to another risk factor than adiposity.

Analysis of selectin ligands supporting hematologic malignancy cell interactions with their microenvironment : focus on leukemia and multiple myeloma

CONTEXTE: Les sélectines sont une famille de trois protéines qui règlent la capture et le roulement des leucocytes et qui initient la cascade d'adhésion. Elles contrôlent également la migration des leucocytes en réponse à un stimulus physiologique ou inflammatoire pour atteindre un organe cible. Le rôle des sélectines et des leurs ligands est bien connu dans l'adhésion des leucocytes normaux à l'endothélium; en revanche, la nature des ligands des sélectines exprimés par les cellules leucémiques et le myélome multiple est peu connue. La récente découverte que la E- et la P-sélectine sont exprimées par les cellules endothéliales et du stroma de la moelle osseuse, nous a incité à examiner leur rôle dans les interactions des cellules malignes avec leur environnement médullaire. RÉSULTATS: Les analyses ont été conduites sur les cellules du sang ou de la moelle osseuse prélevées à des patients atteints de leucémie aiguë ou de myélome multiple et sur des lignées cellulaires. Les ligands des sélectines qui ont été identifiés sur les blastes leucémiques ou les plasmocytes, sont « P-selectin glycoprotein ligand-1 » (PSGL-1), CD44, CD43 et l'endoglycan (EGC), ainsi que les saccharides fucosylés sLex et CLA. Nous avons vérifié dans des expériences d'adhésion cellulaire effectuées dans des conditions de flux que ces ligands sont fonctionnels, étant porteurs des sucres mentionnés, et qu'ils sont capables de supporter le roulement cellulaire dépendant des sélectines. De plus, nous avons montré que la liaison de ces ligands génère des signaux intracellulaires favorisant la prolifération et la survie des cellules de myélome. CONCLUSION. Les données présentées ici montrent que la E- et la P- sélectine du microenvironnement médullaire interagissent avec les cellules leucémiques et de myélome multiple, et que ces interactions activent des voies de signalisation contrôlant la prolifération et la survie cellulaire. Ces effets protecteurs sont impliqués dans la persistance de clones cellulaires malins résistant aux traitements et peuvent conduire à la récidive de la maladie. L'inhibition de ces interactions pourrait fournir de nouvelles options thérapeutiques pour le traitement de ces maladies de mauvais pronostic. - BACKGROUND: Selectins are a family of glycoproteins involved in the first steps of the adhesion cascade, tethering and rolling, during which leukocytes sense tissue specific signals and commit the cells to enter in a particular organ or inflammation site. While the role of selectins and their ligands is well established in supporting normal leukocyte adhesion to vascular endothelium, our knowledge of selectin ligands in two hematological malignancies, acute leukemia and multiple myeloma, is incomplete. The recent discovery that E- and P- selectin are also expressed on bone marrow (BM) endothelial and stromal cells, prompted us to investigate a potential role in selectin-mediated interaction of malignant cells with its protective BM microenvironment. RESULTS. Using cells obtained from blood or BM of patients affected by acute myeloid or lymphoblastic leukemia, or multiple myeloma, as well as cell lines, we characterized the expression of selectin ligands on blasts and plasma cells and identified P-selectin glycoprotein ligand-1 (PSGL-1), CD44, CD43 and endoglycan (EGC), as well as sLex/CLA determinants. Rolling assays under flow conditions allowed us to verify that these ligands are functional, i.e. correctly glycosylated and able to support selectin-mediated rolling. Moreover, we demonstrated that these ligands trigger proliferation and pro-survival signals upon engagement on myeloma cells. CONCLUSIONS. Data presented here demonstrate that E- and P-selectin in the BM microenvironment interact with leukemia and myeloma cells, and suggest that they have an impact on proliferation and survival of malignant plasma cells. These protective effects may induce drug resistance in malignant clones, leading to disease relapse. Interfering with these interactions could provide new therapeutic options. - Le corps humain dépend du système immunitaire pour sa protection face aux agressions, notamment des bactéries ou des virus, ou face à une dysfonction de l'organisme. Ce système est composé de plusieurs types cellulaires, regroupés sous le nom de leucocytes, qui participent à son fonctionnement. Ces cellules se développent à partir d'une cellule souche hématopo'iétique commune qui réside dans la moelle osseuse. Comme c'est le cas dans les autres tissus, les cellules du système immunitaire peuvent aussi développer des cancers, appelés tumeurs hématopoïétiques ou tumeurs du sang. Bien que ces maladies puissent être traitées avec succès grâce à de fortes doses de chimiothérapies ou à d'autres moyens comme les greffes, les patients connaissent un fort taux de rechute. La raison de ces récidives est la survie d'une partie des cellules malignes dans la moelle osseuse, où elles reçoivent une protection au traitement par le biais de l'interaction avec d'autres cellules. Les sélectines (E-, P- et L-sélectine) régulent l'interaction des leucocytes avec l'endothélium (la paroi des vaisseaux sanguins), d'autres leucocytes et les plaquettes ; ces interactions surviennent quand les leucocytes atteignent un site d'inflammation ou un organe cible. Dans la moelle osseuse, la E- et la P-sélectine se trouvent sur les cellules de l'endothélium et sur les macrophages, qui sont d'autres leucocytes faisant partie du stroma de la moelle. Elles pourraient être impliquées dans la protection des cellules cancéreuses évoquée plus haut. Les molécules d'adhésion avec lesquelles les sélectines s'associent, autrement dit les ligands des sélectines, sont des glycoprotéines. Ces protéines ont besoin de sucres spécifiques pour acquérir une telle capacité d'adhésion. Dans le cadre de cette thèse, nous avons étudié deux types de cellules extraites du sang et de la moelle osseuse des patients atteints d'une leucémie aiguë (les blastes) ou de myélome multiple (les plasmocytes), et leur capacité à se lier aux sélectines. Nous avons démontré une interaction entre ces cellules malignes et la E- et/ou la P-sélectine, à condition que les ligands soient correctement décorés. De plus, lors que les plasmocytes se lient aux sélectines, une cascade de signaux à l'intérieur des cellules stimule leur prolifération et leur survie. L'ensemble de ces résultats permet l'identification de nouvelles cibles thérapeutiques potentielles de ces hémopathies de mauvais pronostic.

Esophageal leaks repaired by a muscle onlay approach in the presence of mediastinal sepsis.

BACKGROUND: Nineteen patients were evaluated after closure of intrathoracic esophageal leaks by a pediculated muscle flap onlay repair in the presence of mediastinal and systemic sepsis. METHODS: Intrathoracic esophageal leaks with mediastinitis and systemic sepsis occurred after delayed spontaneous perforations (n = 7) or surgical and endoscopic interventions (n = 12). Six patients presented with fulminant anastomotic leaks. Seven patients had previous attempts to close the leak by surgery (n = 4) or stenting (2) or both (n = 1). The debrided defects measured up to 2 x 12 cm or involved three quarters of the anastomotic circumference and were closed either by a full thickness diaphragmatic flap (n = 13) or a pediculated intrathoracically transposed extrathoracic muscle flap (n = 6). All patients had postoperative contrast esophagography between days 7 and 10 and an endoscopic evaluation 4 to 6 months after surgery. RESULTS: There was no 30-day mortality. During follow-up (4 to 42 months), 16 patients (84%) revealed functional and morphological restoration of the esophagointestinal integrity without further interventions. One patient required serial dilatations for a stricture, and 1 underwent temporary stenting for a persistent fistula; both patients had normal control endoscopy during follow-up. A third patient requiring permanent stenting for stenosis died from gastrointestinal bleeding due to stent erosion during follow-up. CONCLUSIONS: Intrathoracic esophageal leaks may be closed efficiently by a muscle flap onlay approach in the presence of mediastinitis and where a primary repair seems risky. The same holds true for fulminant intrathoracic anastomotic leaks after esophagectomy or other surgical interventions at the gastroesophageal junction.

Quantitative ultrasound of bone in institutionalized elderly women: a cross-sectional and longitudinal study.

Quantitative ultrasound of bone is a promising method for bone assessment: radiation-free, portable and predictive of hip fracture. Its portability allowed us to study the relationships between ultrasonic parameters of bone with age and with non-vertebral fractures in elderly women living in 19 nursing homes. Broadband ultrasound attenuation (BUA) and speed of sound (SOS) of the calcaneus were measured (and the stiffness index calculated) in a sample of 270 institutionalized women, aged 85 +/- 7 years, using an Achilles bone densitometer (Lunar). The effects of age, history of non-vertebral and non-traumatic fractures, body mass index, triceps skinfold and arm circumference were assessed on BUA, SOS and stiffness index. Furthermore, to evaluate longitudinally the influence of aging on the ultrasound parameters of bone, 60 subjects from the same group had a second ultrasound measurement after 1 year. The cross-sectional analysis of the data on all 270 women showed a significant decrease (p < 0.001) with age in BUA, SOS and stiffness index (-0.47%, -0.06%, and -1.01% respectively per year). In the 94 women, (35%) with a history of previous non-vertebral fractures, ultrasound parameters were significantly lower (p < 0.0001) than in the 176 women with no history of fracture (-8.3% for BUA, -1.3% for SOS, -18.9% for stiffness index). In contrast, there was no significant difference in anthropometric measurements between the groups with and without previous non-vertebral fractures, although the measurements decreased significantly with age. In the longitudinal study, repeated quantitative ultrasound after 11.4 +/- 0.8 months showed no significant decrease in BUA (-1%) but a significant decrease in SOS (-0.3%, p < 0.0001) and in stiffness index (-3.6%, p < 0.0002). In conclusion, quantitative ultrasound of the calcaneus measures properties of bone which continue to decline in institutionalized elderly women, and is able to discriminate women with previous non-vertebral fractures.

Effects of a lifestyle intervention on adiposity and fitness in overweight or low fit preschoolers (Ballabeina).

OBJECTIVE: Overweight (OW) and low fit children represent cardiovascular high-risk groups. A multidimensional school-based lifestyle intervention performed in 652 preschoolers reduced skinfold thickness and waist circumference, and improved fitness, but did not affect BMI. The objective of this study is to examine whether the intervention was equally effective in OW (≥90th national percentile) and/or low fit (lowest sex- and age-adjusted quartile of aerobic fitness) children compared to their normal weight and normal fit counterparts. DESIGN AND METHODS: Cluster randomized controlled single blinded trial, conducted in 2008/09 in 40 randomly selected preschool classes in Switzerland. The intervention included a playful physical activity program and lessons on nutrition, media use and sleeps. Primary outcomes were BMI and aerobic fitness; secondary outcomes included sum of four skinfolds, waist circumference and motor agility. Modification of intervention effects by BMI-group and fitness-group was tested by interaction terms. RESULTS: Compared to their counterparts, OW children (n = 130) had more beneficial effects on waist circumference (p for interaction = 0.001) and low fit children (n = 154) more beneficial effects on all adiposity outcomes (p for interaction ≤0.03). The intervention effects on both fitness outcomes were not modified by BMI- or fitness-group (all p for interaction ≥0.2). Average intervention effect sizes for BMI were -0.12, -0.05, -0.26 and -0.02 kg/m(2) and for aerobic fitness were 0.40, 0.30, 0.12 and 0.36 stages for OW, normal weight, low fit and normal fit children, respectively. Conclusions: This multidimensional intervention was equally and for some adiposity measures even more effective in high-risk preschoolers and represents a promising option for these children.

Malignant pleural mesothelioma: leukocyte recruitment is not required for drug delivery induced by photodynamic therapy in a human xenograft model

Objective: The pre-treatment of tumor neo-vessels by photodynamic therapy (PDT) was shown to improve the distribution of chemotherapy administered subsequently. However, the precise mechanism by which PDT modifies the tumor vasculature is unknown. We have recently shown that leukocyteendothelial cell interaction was essential for PDT induced drug delivery to normal tissue. Our purpose was to determine if PDT could enhance drug distribution in malignant mesothelioma and if a comparable role for leucocytes existed.Methods: We grew human mesothelioma xenografts (H-meso-1) in the dorsal skinfold chambers of nude mice (n = 28). The rolling, sticking and recruitment of leucocytes was assessed in tumor and normal vessels following PDT (Visudyne 0?4 mg/kg, fluence rate 200 mW/cm2, fluence 60 J/cm2) using intravital microscopy. In parallel, the distribution of a macromolecule (FITC dextran, 2000 kDa) administered after PDT was determined. We compared these variables in control (no PDT), PDT + IgG (non specific antibody) and PDT + pan-selectin antibody (monoclonal P-E-L selectin antibody).Results: PDT significantly enhanced the distribution of FITC dextran in mesothelioma xenografts compared to controls. Interestingly, PDT enhanced the leukocyte-endothelial interaction significantly (rolling and recruitment)in tumor and surrounding normal vessels compared to controls. Leukocyte recruitment was significantly down-regulated by pan-selectin antibodies in tumor tissues. However, the suppression of leucocyte recruitement did not affect the extravasation of FITC-dextran in tumor tissue.Conclusion:PDTpre-treatment of the mesothelioma vasculature can enhance the distribution of macromolecular drugs administered subsequently. However, unlike normal vessels, leukocyte-endothelial cell interaction is not required for PDT induced leakage.

Prediction of fat-free mass using bioelectrical impedance analysis in young adults from five populations of African origin.

Background/objectives:Bioelectrical impedance analysis (BIA) is used in population and clinical studies as a technique for estimating body composition. Because of significant under-representation in existing literature, we sought to develop and validate predictive equation(s) for BIA for studies in populations of African origin.Subjects/methods:Among five cohorts of the Modeling the Epidemiologic Transition Study, height, weight, waist circumference and body composition, using isotope dilution, were measured in 362 adults, ages 25-45 with mean body mass indexes ranging from 24 to 32. BIA measures of resistance and reactance were measured using tetrapolar placement of electrodes and the same model of analyzer across sites (BIA 101Q, RJL Systems). Multiple linear regression analysis was used to develop equations for predicting fat-free mass (FFM), as measured by isotope dilution; covariates included sex, age, waist, reactance and height(2)/resistance, along with dummy variables for each site. Developed equations were then tested in a validation sample; FFM predicted by previously published equations were tested in the total sample.Results:A site-combined equation and site-specific equations were developed. The mean differences between FFM (reference) and FFM predicted by the study-derived equations were between 0.4 and 0.6âeuro0/00kg (that is, 1% difference between the actual and predicted FFM), and the measured and predicted values were highly correlated. The site-combined equation performed slightly better than the site-specific equations and the previously published equations.Conclusions:Relatively small differences exist between BIA equations to estimate FFM, whether study-derived or published equations, although the site-combined equation performed slightly better than others. The study-derived equations provide an important tool for research in these understudied populations.

Association between obesity indices and cardiovascular risk factors in late adolescence in the Seychelles.

ABSTRACT: BACKGROUND: The ability of different obesity indices to predict cardiovascular risk is still debated in youth and few data are available in sub Saharan Africa. We compared the associations between several indices of obesity and cardiovascular risk factors (CVRFs) in late adolescence in the Seychelles. METHODS: We measured body mass index (BMI), waist circumference, waist/hip ratio (WHiR), waist/height ratio (WHtR) and percent fat mass (by bioimpedance) and 6 CVRFs (blood pressure, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting blood glucose and uric acid) in 423 youths aged 19-20 years from the general population. RESULTS: The prevalence of overweight/obesity and several CVRFs was high, with substantial sex differences. Except for glucose in males and LDL-cholesterol in females, all obesity indices were associated with CVRFs. BMI consistently predicted CVRFs at least as well as the other indices. Linear regression on BMI had standardized regression coefficients of 0.25-0.36 for most CVRFs (p<0.01) and ROC analysis had an AUC between 60%-75% for most CVRFs. BMI also predicted well various combinations of CVRFs: 36% of male and 16% of female lean subjects (BMI P90). CONCLUSION: There was an elevated prevalence of obesity and of several CVRFs in youths in Seychelles. BMI predicted single or combined CVRFs at least as well as other simple obesity indices.

Framingham risk score and alternatives for prediction of coronary heart disease in older adults.

BACKGROUND: Guidelines for the prevention of coronary heart disease (CHD) recommend use of Framingham-based risk scores that were developed in white middle-aged populations. It remains unclear whether and how CHD risk prediction might be improved among older adults. We aimed to compare the prognostic performance of the Framingham risk score (FRS), directly and after recalibration, with refit functions derived from the present cohort, as well as to assess the utility of adding other routinely available risk parameters to FRS.¦METHODS: Among 2193 black and white older adults (mean age, 73.5 years) without pre-existing cardiovascular disease from the Health ABC cohort, we examined adjudicated CHD events, defined as incident myocardial infarction, CHD death, and hospitalization for angina or coronary revascularization.¦RESULTS: During 8-year follow-up, 351 participants experienced CHD events. The FRS poorly discriminated between persons who experienced CHD events vs. not (C-index: 0.577 in women; 0.583 in men) and underestimated absolute risk prediction by 51% in women and 8% in men. Recalibration of the FRS improved absolute risk prediction, particulary for women. For both genders, refitting these functions substantially improved absolute risk prediction, with similar discrimination to the FRS. Results did not differ between whites and blacks. The addition of lifestyle variables, waist circumference and creatinine did not improve risk prediction beyond risk factors of the FRS.¦CONCLUSIONS: The FRS underestimates CHD risk in older adults, particularly in women, although traditional risk factors remain the best predictors of CHD. Re-estimated risk functions using these factors improve accurate estimation of absolute risk.