Surrogate markers for atheriosclerosis in overweight subjects with atherogenic dyslipidemia : the GEMS project

Rapport de synthèseLe syndrome métabolique (défini par les critères ATP III par la présence au minimum de 3 des facteurs suivants : taux plasmatiques d'HDL-cholestérol < 1,04 mmol/1 chez l'homme et < 1.29 mmol/1 chez la femme, taux plasmatiques de triglycérides > 1,69 mmol/1, tension artérielle > 130/85 mmHg, glycémie >6,1 mmol/1, tour de taille > 108 cm chez l'homme et > 88 cm chez la femme) représente une constellation de facteurs de risque majeurs pour le développement de maladies cardiovascu-laires. Il n'est pas encore établi actuellement quelle composante de ce syndrome contribue de manière plus marquée au risque de développer une athérosclérose. Dans le but d'éclaircir la pathogenèse de ce syndrome, une étude multicentrique intitulée GEMS (« Genetic Epidemiology of Metabolic Syndrome ») a été initiée afin de déterminer si la constellation d'une dyslipidémie avec HDL-C bas et TG élevé est un marqueur sensible de l'homogénéité génétique chez les individus atteints de syndrome métabolique.Dans l'étude menée à Lausanne (multicentrique), la contribution de la dyslipidémie avec HDL-C bas et TG élevé dans la pathogenèse de l'athérosclérose a été évaluée par 2 examens, reconnus comme marqueurs fiables de la vasculopathie : la mesure de l'épaisseur intima média carotidienne par ultrasonographic et l'évaluation de la dysfonction endothéliale de la microcirculation cutanée. Deux groupes de sujets comparables en terme d'âge et de sexe et souffrant d'un excès pondéral (BMI > 25 kg/m2) mais normoglycémiques ont été comparés. Ces deux groupes (étude cas-témoins) étaient uniquement discordants quant à leurs profils lipidiques. Ainsi, 120 cas, définis comme ayant un HDL-cholestérol bas (< 25 percentile pour l'âge et le sexe dans la population générale) et des TG élevés (> 75 percentile) ont été comparés à 120 contrôles avec un HDL-cholestérol haut (> 50 percentile) et des TG bas (< 50 percentile). Un doppler des artères carotides et fémorales a été effectué pour déterminer l'épaisseur de l'intima média et la présence ou non de plaques d'athérome. La fonction endothéliale a été évaluée par un laser doppler sur la micro-circulation cutanée (réponse hyperémique à une occlusion transitoire de la circulation de l'avant-bras par une manchette à pression et mesure de la vasodilatation induite par un échauffement local de la peau avec de l'eau). Un enregistrement de la pression artérielle ambulatoire sur la journée (Remler) a été pratiqué chez tous les sujets.Les résultats obtenus montrent que les cas ont une prévalence plus élevée de plaques d'athérome (médiane 1,5 ± 0,15 vs 0,8 > 0,15, p<.001), une épaisseur intima média plus importante (médiane 0,66 ± 0,15 vs 0,61 ± 0,15, p<.01), ainsi qu'une réduction significative de la vasodilatation endothéliale induite par la chaleur et post-ischémique comparativement aux contrôles.En conclusion, le profil lipidique associant un HDL-cholestérol bas et des triglycérides élevés représente un risque majeur de développer une maladie athéromateuse périphérique et est associée à une augmentation de l'épaisseur intima média et une altération de la fonction endothéliale chez les individus en surcharge pondérale. Bien qu'un HDL-cholestérol bas soit fréquemment associé à une hypertriglycéridémie, les résultats de notre étude peuvent suggérer un rôle potentiel de la fraction HDL-cholestérol comme un puissant agent anti-athérogénique.

Genome-wide linkage and association analyses to identify genes influencing adiponectin levels: the GEMS Study.

Adiponectin has a variety of metabolic effects on obesity, insulin sensitivity, and atherosclerosis. To identify genes influencing variation in plasma adiponectin levels, we performed genome-wide linkage and association scans of adiponectin in two cohorts of subjects recruited in the Genetic Epidemiology of Metabolic Syndrome Study. The genome-wide linkage scan was conducted in families of Turkish and southern European (TSE, n = 789) and Northern and Western European (NWE, N = 2,280) origin. A whole genome association (WGA) analysis (500K Affymetrix platform) was carried out in a set of unrelated NWE subjects consisting of approximately 1,000 subjects with dyslipidemia and 1,000 overweight subjects with normal lipids. Peak evidence for linkage occurred at chromosome 8p23 in NWE subjects (lod = 3.10) and at chromosome 3q28 near ADIPOQ, the adiponectin structural gene, in TSE subjects (lod = 1.70). In the WGA analysis, the single-nucleotide polymorphisms (SNPs) most strongly associated with adiponectin were rs3774261 and rs6773957 (P < 10(-7)). These two SNPs were in high linkage disequilibrium (r(2) = 0.98) and located within ADIPOQ. Interestingly, our fourth strongest region of association (P < 2 x 10(-5)) was to an SNP within CDH13, whose protein product is a newly identified receptor for high-molecular-weight species of adiponectin. Through WGA analysis, we confirmed previous studies showing SNPs within ADIPOQ to be strongly associated with variation in adiponectin levels and further observed these to have the strongest effects on adiponectin levels throughout the genome. We additionally identified a second gene (CDH13) possibly influencing variation in adiponectin levels. The impact of these SNPs on health and disease has yet to be determined.

Genetic and phenotypic architecture of metabolic syndrome-associated components in dyslipidemic and normolipidemic subjects: the GEMS Study.

Atherogenic dyslipidemia, manifest by low HDL-cholesterol and high TG levels, is an important component of ATP-III defined metabolic syndrome. Here, we dissected the phenotypic and genetic architecture of these traits by assessing their relationships with other metabolically relevant measures, including plasma adipo-cytokines, highly sensitive C-reactive protein (hsCRP) and LDL particle size, in a large family data set (n=2800) and in an independent set of dyslipidemic cases (n=716) and normolipidemic controls (n=1073). We explored the relationships among these phenotypes using variable clustering and then estimated their genetic heritabilities and cross-trait correlations. In families, four clusters explained 61% of the total variance, with one adiposity-related cluster (including hsCRP), one BP-related cluster, and two lipid-related clusters (HDL-C, TG, adiponectin and LDL particle size; apoB and non-HDL-C). A similar structure was observed in dyslipidemic cases and normolipidemic controls. The genetic correlations in the families largely paralleled the phenotype clustering results, suggesting that common genes having pleiotropic effects contributed to the correlations observed. In summary, our analyses support a model of metabolic syndrome with two major components, body fat and lipids, each with two subcomponents, and quantifies their degree of overlap with each other and with metabolic-syndrome related measures (adipokines, LDL particle size and hsCRP).

The casket of poetical gems

UANL

The casket of literary gems : containing tales and sketches, choice selections, anecdotes, wit and humor

UANL

Requirements definition and testing of the new version of multi-mission generic monitoring system (GEMS) v 4.4 for operations at Eumetsat

EUMETSAT (www.eumetsat.int) e’ l’agenzia europea per operazioni su satelliti per monitorare clima, meteo e ambiente terrestre. Dal centro operativo situato a Darmstadt (Germania), si controllano satelliti meteorologici su orbite geostazionarie e polari che raccolgono dati per l’osservazione dell’atmosfera, degli oceani e della superficie terrestre per un servizio continuo di 24/7. Un sistema di monitoraggio centralizzato per programmi diversi all’interno dell’ambiente operazionale di EUMETSAT, e’ dato da GEMS (Generic Event Monitoring System). Il software garantisce il controllo di diverse piattaforme, cross-monitoring di diverse sezioni operative, ed ha le caratteristiche per potere essere esteso a future missioni. L’attuale versione della GEMS MMI (Multi Media Interface), v. 3.6, utilizza standard Java Server Pages (JSP) e fa uso pesante di codici Java; utilizza inoltre files ASCII per filtri e display dei dati. Conseguenza diretta e’ ad esempio, il fatto che le informazioni non sono automaticamente aggiornate, ma hanno bisogno di ricaricare la pagina. Ulteriori inputs per una nuova versione della GEMS MMI vengono da diversi comportamenti anomali riportati durante l’uso quotidiano del software. La tesi si concentra sulla definizione di nuovi requisiti per una nuova versione della GEMS MMI (v. 4.4) da parte della divisione ingegneristica e di manutenzione di operazioni di EUMETSAT. Per le attivita’ di supporto, i test sono stati condotti presso Solenix. Il nuovo software permettera’ una migliore applicazione web, con tempi di risposta piu’ rapidi, aggiornamento delle informazioni automatico, utilizzo totale del database di GEMS e le capacita’ di filtri, insieme ad applicazioni per telefoni cellulari per il supporto delle attivita’ di reperibilita’. La nuova versione di GEMS avra’ una nuova Graphical User Interface (GUI) che utilizza tecnologie moderne. Per un ambiente di operazioni come e’ quello di EUMETSAT, dove l’affidabilita’ delle tecnologie e la longevita’ dell’approccio scelto sono di vitale importanza, non tutti gli attuali strumenti a disposizione sono adatti e hanno bisogno di essere migliorati. Allo stesso tempo, un’ interfaccia moderna, in termini di visual design, interattivita’ e funzionalita’, e’ importante per la nuova GEMS MMI.

gems: An R Package for Simulating from Disease Progression Models

Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The R package gems is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.g., diagnosis, treatment and death), displayed in a directed acyclic graph. The vertices correspond to disease states and the directed edges represent events. The package gems allows simulations based on a generalized multistate model that can be described by a directed acyclic graph with continuous transition-specific hazard functions. The user can specify an arbitrary hazard function and its parameters. The model includes parameter uncertainty, does not need to be a Markov model, and may take the history of previous events into account. Applications are not limited to the medical field and extend to other areas where multistate simulation is of interest. We provide a technical explanation of the multistate models used by gems, explain the functions of gems and their arguments, and show a sample application.

GEMS-GLORI world river discharge database

The GEMS-GLORI register, circulated by UNEP for review in 1996, lists 555 world major rivers discharging to oceans (Q > 10 km**3/year, or A > 10 000 km**2, or sediment discharge > 5Mt/year, or basin population >5M people). Up to 48 river attributes are listed, including major ions and nutrients (C, N, P) in both dissolved, particulate, organic and inorganic forms. For many rivers, two or three sets of data are provided with relevant periods of records and references. Although half of the selected rivers are not yet documented for water quality, most of the first 40 rivers are well described (Irrawady, Zambezi, Ogooue, Magdalena, are noted exceptions). Altogether about 10 000 individual data from 500 references are listed. The global coverage in terms of river discharge and/or drainage area ranges from 40 to 67% for most major water quality attributes but drops to 25% for some organic and/or particulate forms of N and P. Planned development of the register includes collection of information on particulate chemistry and data on endorheic rivers and selected tributaries.

Gems of German song (revised edition) for low voice.

English and German words with piano accompaniment.

Glittering gems for willing workers /

Mode of access: Internet.

The Afro-American school speaker and gems of literature : for school commencements, literary circles, debating clubs, and rhetoricals generally /

Includes index.

Pearls of paradise : part one : a collection of the song-gems of the ages, containing hymns and music suited for every service of the Christian Church /

Mode of access: Internet.

Gems from The King's fool.

Composer's name on caption: Adolf Müller, Jr.

Cluster of gems : a choice collection of piano-forte pieces for advanced players.

Each piece paged separately.

The treasury of song, without words, for the home circle; the brighest [sic] best-loved gems, popular and classical.

Includes juvenile piano pieces and sketches and portraits of eminent musicians and singers.