Improved virological outcome in White patients infected with HIV-1 non-B subtypes compared to subtype B.

BACKGROUND: Antiretroviral compounds have been predominantly studied in human immunodeficiency virus type 1 (HIV-1) subtype B, but only ~10% of infections worldwide are caused by this subtype. The analysis of the impact of different HIV subtypes on treatment outcome is important. METHODS: The effect of HIV-1 subtype B and non-B on the time to virological failure while taking combination antiretroviral therapy (cART) was analyzed. Other studies that have addressed this question were limited by the strong correlation between subtype and ethnicity. Our analysis was restricted to white patients from the Swiss HIV Cohort Study who started cART between 1996 and 2009. Cox regression models were performed; adjusted for age, sex, transmission category, first cART, baseline CD4 cell counts, and HIV RNA levels; and stratified for previous mono/dual nucleoside reverse-transcriptase inhibitor treatment. RESULTS: Included in our study were 4729 patients infected with subtype B and 539 with non-B subtypes. The most prevalent non-B subtypes were CRF02_AG (23.8%), A (23.4%), C (12.8%), and CRF01_AE (12.6%). The incidence of virological failure was higher in patients with subtype B (4.3 failures/100 person-years; 95% confidence interval [CI], 4.0-4.5]) compared with non-B (1.8 failures/100 person-years; 95% CI, 1.4-2.4). Cox regression models confirmed that patients infected with non-B subtypes had a lower risk of virological failure than those infected with subtype B (univariable hazard ratio [HR], 0.39 [95% CI, .30-.52; P < .001]; multivariable HR, 0.68 [95% CI, .51-.91; P = .009]). In particular, subtypes A and CRF02_AG revealed improved outcomes (multivariable HR, 0.54 [95% CI, .29-.98] and 0.39 [95% CI, .19-.79], respectively). CONCLUSIONS: Improved virological outcomes among patients infected with non-B subtypes invalidate concerns that these individuals are at a disadvantage because drugs have been designed primarily for subtype B infections.

Amputations du membre inférieur [Amputations of the lower extremity]

Still nowadays amputations are frequently performed in our country. In diabetic patients the incidence of an amputation is 25 times higher than in the normal population. All possibilities of revascularisation or limb salvage must be excluded by a multidisciplinary approach before choosing an amputation. Once the decision is taken the good level of amputation and the correct technique have to determined. The goal of this article is to describe which clinical and paraclinical parameters will help the surgeon to choose the best level of amputation, which techniques are to be used for the amputation and to finally give some information about re-education and the fitting of an orthesis or prosthesis.

Traitement de l'ischémie critique chronique des membres inférieurs en 2014 [Treatment of critical lower limb ischemia].

Critical limb ischemia is a major public health problem in our western countries due to the epidemia of (diabesity). The outcome of patients suffering from critical limb ischemia reains poor with an amputation free survival rate at one year of about 50%. The treatment should be multidiciplinary and done in emergency in specialized centers to ensure the limb salvage: this management should be centered aroud 3 axis: the screening of the cardiovascular risk factors, the best medical treatment and the invasive approaches. Due to multiple endovascular technical innovations, more frail patients with com plex diseases can be treated with good results. Therefore, the endovascular treatment is essential in the management of such patients by vascular surgeons.

Timing of Palaeozoic magmatism in the Maggia and Sambuco nappes and paleogeographic implications (Central Lepontine Alps)

Magmatic rocks from the pre-Mesozoic basements of the Sambuco and Maggia nappes have been dated by U-Pb zircon ages with the LA-ICPMS technique. Several magmatic events have been identified in the Sambuco nappe. The mafic banded calc-alkaline suite of Scheggia is dated at 540 Ma, an age comparable to that of mafic rocks in the Austroalpine Silvretta nappe. The Sasso Nero peraluminous augengneiss has an age of 480-470 Ma, like many other ``older orthogneisses'' in Alpine basement units. It hosts a large proportion of inherited zircons, which were dated around 630 Ma, a Panafrican age indicating the Gondwanan affiliation of the Sambuco basement. The calc-alkaline Matorello pluton yielded ages around 300 Ma, similar to numerous Late Carboniferous intrusions in other basement units of the Lower Penninic (Monte Leone, Antigorio, Verampio) and Helvetic domains (Gotthard and other External Crystalline Massifs). Associated lamprophyric dykes are slightly younger (300-290 Ma), like similar dykes sampled in gneiss blocks included in the sedimentary cover of the underlying Antigorio nappe (290-285 Ma). The Cocco granodiorite and Ruscada leucogranite, both intruding the basement of the neighbouring Maggia nappe, yielded ages of ca. 300-310 Ma, identical within errors to the age of the Matorello pluton. They are significantly older than former age determinations. This age coincidence, coupled with remarkable petrologic similarities between the Cocco and Matorello granodiorites, strongly suggests paleogeographic proximity of the Sambuco and Maggia nappes in Late Carboniferous times. In recent publications these two nappes have been interpreted as belonging to distinct Mesozoic paleogeographic domains: ``European'' for Sambuco and ``Brian double dagger onnais'' for Maggia, separated by the ``Valais'' oceanic basin. In this case, the similarity of the Matorello and Cocco intrusions would demonstrate the absence of any significant transcurrent movement between these two continental domains. Alternatively, according to a more traditional view, Sambuco and Maggia might belong to a single large Alpine tectonic unit.

The quality of primary care in a country with universal health care coverage.

BACKGROUND: Standard indicators of quality of care have been developed in the United States. Limited information exists about quality of care in countries with universal health care coverage.OBJECTIVE: To assess the quality of preventive care and care for cardiovascular risk factors in a country with universal health care coverage.DESIGN AND PARTICIPANTS: Retrospective cohort of a random sample of 1,002 patients aged 50-80 years followed for 2 years from all Swiss university primary care settings.MAIN MEASURES: We used indicators derived from RAND's Quality Assessment Tools. Each indicator was scored by dividing the number of episodes when recommended care was delivered by the number of times patients were eligible for indicators. Aggregate scores were calculated by taking into account the number of eligible patients for each indicator.KEY RESULTS: Overall, patients (44% women) received 69% of recommended preventive care, but rates differed by indicators. Indicators assessing annual blood pressure and weight measurements (both 95%) were more likely to be met than indicators assessing smoking cessation counseling (72%), breast (40%) and colon cancer screening (35%; all p < 0.001 for comparisons with blood pressure and weight measurements). Eighty-three percent of patients received the recommended care for cardiovascular risk factors, including > 75% for hypertension, dyslipidemia and diabetes. However, foot examination was performed only in 50% of patients with diabetes. Prevention indicators were more likely to be met in men (72.2% vs 65.3% in women, p < 0.001) and patients < 65 years (70.1% vs 68.0% in those a parts per thousand yen65 years, p = 0.047).CONCLUSIONS: Using standardized tools, these adults received 69% of recommended preventive care and 83% of care for cardiovascular risk factors in Switzerland, a country with universal coverage. Prevention indicator rates were lower for women and the elderly, and for cancer screening. Our study helps pave the way for targeted quality improvement initiatives and broader assessment of health care in Continental Europe.

Etiology of ethnic differences in childhood spirometry.

OBJECTIVES: Age- and height-adjusted spirometric lung function of South Asian children is lower than those of white children. It is unclear whether this is purely genetic, or partly explained by the environment. In this study, we assessed whether cultural factors, socioeconomic status, intrauterine growth, environmental exposures, or a family and personal history of wheeze contribute to explaining the ethnic differences in spirometric lung function. METHODS: We studied children aged 9 to 14 years from a population-based cohort, including 1088 white children and 275 UK-born South Asians. Log-transformed spirometric data were analyzed using multiple linear regressions, adjusting for anthropometric factors. Five different additional models adjusted for (1) cultural factors, (2) indicators of socioeconomic status, (3) perinatal data reflecting intrauterine growth, (4) environmental exposures, and (5) personal and family history of wheeze. RESULTS: Height- and gender-adjusted forced vital capacity (FVC) and forced expired volume in 1 second (FEV1) were lower in South Asian than white children (relative difference -11% and -9% respectively, P < .001), but PEF and FEF50 were similar (P ≥ .5). FEV1/FVC was higher in South Asians (1.8%, P < .001). These differences remained largely unchanged in all 5 alternative models. CONCLUSIONS: Our study confirmed important differences in lung volumes between South Asian and white children. These were not attenuated after adjustment for cultural and socioeconomic factors and intrauterine growth, neither were they explained by differences in environmental exposures nor a personal or family history of wheeze. This suggests that differences in lung function may be mainly genetic in origin. The implication is that ethnicity-specific predicted values remain important specifically for South Asian children.

Sedimentology, geochemistry and mineralogy of the Paleocene-Eocene thermal maximum (PETM) : sediment records from Egypt, India and Spain

A gradual increase in Earth's surface temperatures marking the transition from the late Paleocene to early Eocene (55.8±0.2Ma), represents an extraordinary warming event known as Paleocene-Eocene Thermal Maximum (PETM). Both marine and continental sedimentary records during this period reveal evidences for the massive injection of isotopically light carbon. The carbon dioxide injection from multiple potential sources may have triggered the global warming. The importance of the PETM studies is due to the fact that the PETM bears some striking resemblances to the human-caused climate change unfolding today. Most notably, the culprit behind it was a massive injection of heat-trapping greenhouse gases into the atmosphere and oceans, comparable in volume to what our persistent burning of fossil fuels could deliver in coming centuries. The exact knowledge of what went on during the PETM could help us to foresee the future climate change. The response of the oceanic and continental environments to the PETM is different. Many factors might control the response of the environments to the PETM such as paleogeography, paleotopography, paleoenvironment, and paleodepth. To better understand the mechanisms triggering PETM events, two different environments were studied: 1) shallow marine to inner shelf environment (Wadi Nukhul, Sinai; and the Dababiya GSSP, Luxor, Egypt), and 2) terrestrial environments (northwestern India lignite mines) representing wetland, and fluvial environments (Esplugafreda, Spain) both highlighting the climatic changes observed in continental conditions. In the marine realm, the PETM is characterized by negative ö13Ccar and ô13Corg excursions and shifts in Ô15N to ~0%o values above the P/E boundary and persisting along the interval suggesting a bloom and high production of atmospheric N2-fixers. Decrease in carbonate contents could be due to dissolution and/or dilution by increasing detrital input. High Ti, K and Zr and decreased Si contents at the P/E boundary indicate high weathering index (CIA), which coincides with significant kaolinite input and suggests intense chemical weathering under humid conditions at the beginning of the PETM. Two anoxic intervals are observed along the PETM. The lower one may be linked to methane released from the continental shelf with no change in the redox proxies, where the upper anoxic to euxinic conditions are revealed by increasing U, Mo, V, Fe and the presence of small size pyrite framboids (2-5fim). Productivity sensitive elements (Cu, Ni, and Cd) show their maximum concentrated within the upper anoxic interval suggesting high productivity in surface water. The obtained data highlight that intense weathering and subsequent nutrient inputs are crucial parameters in the chain of the PETM events, triggering productivity during the recovery phase. In the terrestrial environments, the establishment of wetland conditions and consequence continental climatic shift towards more humid conditions led to migration of modern mammals northward following the extension of the tropical belts. Relative ages of this mammal event based on bio-chemo- and paleomagnetic stratigraphy support a migration path originating from Asia into Europe and North America, followed by later migration from Asia into India and suggests a barrier to migration that is likely linked to the timing of the India-Asia collision. In contrast, at Esplugafereda, northeastern Spain, the terrestrial environment reacted differently. Two significant S13C shifts with the lower one linked to the PETM and the upper corresponding to the Early Eocene Thermal Maximum (ETM2); 180/160 paleothermometry performed on two different soil carbonate nodule reveal a temperature increase of around 8°C during the PETM. The prominent increase in kaolinite content within the PETM is linked to increased runoff and/or weathering of adjacent and coeval soils. These results demonstrate that the PETM coincides globally with extreme climatic fluctuations and that terrestrial environments are very likely to record such climatic changes. - La transition Paléocène-Eocène (55,8±0,2 Ma) est marquée par un réchauffement extraordinaire communément appelé « Paleocene-Eocene Thermal Maximum » (PETM). Les données géochimiques caractérisant les sédiments marins et continentaux de cette période indiquent que ce réchauffement a été déclenché par une augmentation massive de CO2 lié à la déstabilisation des hydrates de méthane stockés le long des marges océaniques. L'étude des événements PETM constitue donc un bon analogue avec le réchauffement actuel. Le volume de CO2 émis durant le PETM est comparable avec le CO2 lié à l'activité actuelle humaine. La compréhension des causes du réchauffement du PETM peut être cruciale pour prévoir et évaluer les conséquences du réchauffement anthropogénique, en particulier les répercussions d'un tel réchauffement sur les domaines continentaux et océaniques. De nombreux facteurs entrent en ligne de compte dans le cas du PETM, tels que la paléogéographie, la paléotopographie et les paléoenvironnement. Pour mieux comprendre les réponses environnementales aux événements du PETM, 2 types d'environnements ont été choisis : (1) le domaine marin ouvert mais relativement peu profond (Wadi Nukhul. Sinai, Dababiya, Luxor, Egypte), (2) le milieu continental marécageux humide (mines de lignite, Inde) et fluviatile, semi-aride (Esplugafreda, Pyrénées espagnoles). Dans le domaine marin, le PETM est caractérisé par des excursions négatives du ô13Ccar et ô13Corg et un shift persistant des valeurs de 815N à ~ 0 %o indiquant une forte activité des organismes (bactéries) fixant l'azote. La diminution des carbonates observée durant le PETM peut-être due à des phénomènes de dissolution ou une augmentation des apports terrigènes. Des taux élevés en Ti, K et Zr et une diminution des montants de Si, reflétés par des valeurs des indices d'altération (CIA) qui coïncident avec une augmentation significative des apports de kaolinite impliquent une altération chimique accrue, du fait de conditions plus humides au début du PETM. Deux événements anoxiques globaux ont été mis en évidence durant le PETM. Le premier, situé dans la partie inférieur du PETM, serait lié à la libération des hydrates de méthane stockés le long des talus continentaux et ne correspond pas à des variations significatives des éléments sensibles aux changements de conditions redox. Le second est caractérisé par une augmentation des éléments U, Mo, V et Fe et la présence de petit framboids de pyrite dont la taille varie entre 2 et 5pm. Le second épisode anoxique est caractérisé par une forte augmentation des éléments sensibles aux changements de la productivité (Cu, Ni et Co), indiquant une augmentation de la productivité dans les eaux de surface. Les données obtenues mettent en évidence le rôle crucial joué par l'altération et les apports en nutriments qui en découlent. Ces paramètres sont cruciaux pour la succession des événements qui ont conduit au PETM, et plus particulièrement l'augmentation de la productivité dans la phase de récupération. Durant le PETM, le milieu continental est caractérisé par l'établissement de conditions humides qui ont facilité voir provoqué la migration des mammifères modernes qui ont suivi le déplacement de ces ceintures climatiques. L'âge de cette migration est basé sur des arguments chimiostratigraphiques (isotopes stables), biostratigraphiques et paléomagnétiques. Les données bibliographiques ainsi que celles que nous avons récoltées en Inde, montrent que les mammifères modernes ont d'abord migré depuis l'Asie vers l'Europe, puis dans le continent Nord américain. Ces derniers ne sont arrivés en Inde que plus tardivement, suggérant que le temps de leur migration est lié à la collision Inde-Asie. Dans le Nord-Est de l'Espagne (Esplugafreda), la réponse du milieu continental aux événements PETM est assez différente. Comme en Inde, deux excursions signicatives en ô13C ont été observées. La première correspond au PETM et la seconde est corrélée avec l'optimum thermique de l'Eocène précoce (ETM2). Les isotopes stables de l'oxygène mesurés 2 différents types de nodules calcaires provenant de paléosols suggère une augmentation de 10°C pendant le PETM. Une augmentation simultanée des taux de kaolinite indique une intensification de l'altération chimique et/ou de l'érosion de sols adjacents. Ces résultats démontrent que le PETM coïncide globalement avec des variations climatiques extrêmes qui sont très aisément reconnaissables dans les dépôts continentaux.

Triassic stratigraphic evolution of the Arabian-Greater India embayment of the southern Tethys margin

An exceptional, tectonically remarkably unaffected, nearly 200 m-thick continuous section of hemipelagic and turbiditic sediments, covering most of the Triassic is described from the Batain Complex of north-eastern Oman. According to conodont and radiolarian data the sequence spans the late Scythian to the early Norian, a time period of nearly 30 M. Coupled with a high resolution stratigraphy, the lithostratigraphy, sedimentology, as well as sequence and isotope stratigraphy of the section are documented. For the Triassic of the Batain Plain we propose the new name Sal Formation, which replaces the formerly used Matbat Formation, and subdivide it into three new members. The Sal Formation was deposited on the proximal continental margin of northeastern Arabia and records various depositional environments. The lower member is interpreted as the distal part of a homoclinal ramp which evolves to a distally steepened ramp during time of deposition of the middle member. The upper member displays a toe of slope position which is indicated by an increase of proximal turbidites. These sediments form part of a segment of the Neo-Tethyan embayment between Arabia and India. The stratigraphic analysis indicates highly varying sedimentation rates from a minimum of 2 m/M gamma around the Anisian/Ladinian boundary up to 15 m/M gamma during the Lower and Upper Triassic. Sequence-stratigraphically, the Sal section is subdivided into six third order cycles which are biochronologically well integrated into the global Triassic cycle chart. The mixed siliciclastic-calcareous upper member of the Sal Formation typically shows highstand related carbonate shedding. It is, therefore, an important test case for sequence-stratigraphic controlled carbonate export to mixed basin fills. The well developed sequence stratigraphic cycles are mirrored in the isotope patterns. Additionally, the carbon and oxygen isotope data from the Sal Formation record the same chemostratigraphic marker at the Spathian/Anisian boundary known from other Tethyan sections.

Trace-element and phosphorus contents in sediment associated with Cretaceous oceanic anoxic events

ABSTRACT : During my SNSF-funded Ph.D. thesis project, I studied the evolution of redox conditions and organic-carbon preservation in the western Tethyan realm during three major positive excursions in the Cretaceous δ13C record, corresponding to the Valanginian, Early Aptian and Late Cenomanian. These periods were characterized by important global environmental and climate change, which was associated with perturbations in the carbon cycle. For the period of the Valanginian δ13C excursion, total organic carbon (TOC) contents and the quality of preserved organic matter are typical of oxic pelagic settings in the western Tethys. This is confirmed by the absence of major excursions in the stratigraphic distribution of RSTE during the δ13C shift. Published TOC data from other parts of the Valanginian oceans indicate that dys- to anaerobic zones were restricted to marginal seas within the Atlantic and Southern Ocean, and to the Pacific. Phosphorus (P) and mineralogical contents suggest a stepwise climatic evolution during the Valanginian, with a humid and warm climate prior to the δ13C shift leading to an increase in continental runoff. During the δ13C shift, a decrease in detrital input and P contents suggests a change in the climate towards more and conditions. During the early Aptian oceanic anoxic event (OAE 1a), a general increase followed by a rapid decrease in P contents suggests enhanced nutrient input at the beginning of OAE 1a. The return to lower values during OAE 1 a, associated with an increase in RSTE contents, may have been related to the weakened capacity to retain P in the sedimentary reservoir due to bottom-water oxygen depletion. In basinal settings, the RSTE distribution indicates well-developed anoxic conditions during OAE la, whereas in the shallower-water environments, conditions were oxic to suboxic, rather than anoxic. Furthermore, in the deeper part of the Tethys, two distinct enrichments have been observed, indicating fluctuations in the intensity of water column anoxia during the δ73C excursion. We also studied the effect of the end-Cenomanian oceanic anoxic event (OAE 2) on an expanded section in the Chrummflueschlucht (E of Euthal, Ct Switzerland). The goal here was to identify paleoceanographic and paleoenvironmental conditions during OAE 2 in this part of the northern Tethyan margin. The results show that this section is one of the most complete sections for the Cenomanian-Turonian boundary interval known from the Helvetic realm, despite a small hiatus between sediments corresponding to peaks 1 and 2 in the δ13C record. The evolution of P contents points to an increase in the input of this nutrient at the onset of OAE 2. The trends in RSTE contents show, however, that this part of the Helvetic realm was not affected by a strong depletion in oxygen conditions during OAE 2, despite its hemipelagic position. A further goal of this project was to submit the samples to a total extraction method (a combined HF/HNO3/HCI acid digestion) and compare the results obtained by the partial HNO3 acid extraction in order to standardize the analytical prócedures in the extraction of RSTE. The obtained results for samples of OAE 1 a suggest that RSTE trends using the partial HNO3 digestion are very comparable to those obtained by the total digestion method and subsequently normalized with regards to AI contents. RÉSUMÉ : Durant ce projet de thèse, financé par le Swiss National Science Funding (SNSF), j'ai étudié l'évolution des conditions redox et de la préservation de carbone organique dans le domnaine ouesttéthysien pendant trois excursions majeures du δ13C au Crétacé correspondant au Valanginien, à l'Aptien inférieur et à la limite Cénomanien-Turonien. Ces périodes sont caractérisées par des changements climatiques et environnementaux globaux associés à des perturbations dans le cylce du carbone. Pour L'excursion positive en δ13C du Valanginien, les analyses du carbone organique total (COT) et les observations palynologiques du domaine téthysien ont présenté des indications d'environnement pélagique relativementbienoxygéné. L'absence d'enrichissements en éléments traces sensibles aux conditions redox (TE) pendant l'excursion positive en δ13C confirme ces interprétations. Les données publiées de COT dans d'autres partie du globe indiquent cependant l'existence de conditions dys- à anaérobiques dans certains bassins restreints de l'Atlantique, l'Océan Austral et du Pacifique. L'évolution du phosphore (P) et la composition minéralogique des sédiments semblent indiquer un climat relativement chaud et humide avant l'excursion en δ13C entraînant une augmentation de l'altération continentale. Pendant le shift isotopique, une diminution des apports détritiques et du P suggèrent une transition vers des conditions plus arides. À l'Aptien Inférieur, le début de l'événement anoxique (OAE 1a) est marqué par une augmentation générale du P dans les sédiments indiquant une augmentation du niveau trophique à la base de l'excursion isotopique. Durant l'événement anoxique, les sédiments sont relativement appauvris en P. Cette diminution rapide associée à des enrichissements en TE est probablement liée à une remobilisation plus importante du P lors de la mise en place de conditions anoxiques dans les eaux de fond. Dans les environnements de bassin, le comportement des TE (enrichissements bien marqués) attestent de conditions réductrices bien marquées alors que dans les environnements moins profonds, les conditions semblent plutôt oxiques à dysoxiques. De plus, deux niveaux d'enrichissement en TE ont été observés dans la partie plus profonde de la Téthys, indiquant des fluctuations assez rapides dans l'intensité de l'anoxie de la colonne d'eau. Nous avons ensuite étudié les effets de l'événement anoxique de la fin du Cenomanien (OAE 2) dans un basin marginal de la marge nord de la Téthys avec la coupe de Chrummflueschlucht (à l'est de Euthal, Ct Schwyz). Les résultats ont montré que cette coupe présente un des enregistrements sédimentaires des plus complets de l'OAE 2 dans le domaine helvétique malgré un hiatus entre le pic 1 et 2 de l'excursion en δ13C. L'évolution du P montre une augmentation au début de l'OAE 2. Cependant, la distribution des TE indique que cette région n'a pas été affectée par des conditions réductrices trop importantes. Un second aspect de ce travail a été l'étude des différentes méthodes sur l'analyse de la distribution des TE. Des échantillons de l'OAE 1a ont été soumis à deux types d'extractions, l'une dite «totale » (attaque combinée d'acides HF/HNO3/HCI) et l'autre dite partielle » (HNO3). Les résultats obtenus suggèrent que les courbes de tendances des TE acquises par extraction partielle sont semblables à celle obtenues par extraction totale et normalisées par l'AI.

Liquid line of descent of a basanitic liquid at 1.5 GPa: Constraints for metasomatic vein formation

The metasomatism observed in the oceanic and continental lithosphere is generally interpreted to represent a continuous differentiation process forming anhydrous and hydrous veins plus a cryptic enrichment in the surrounding peridotite. In order to constrain the mechanisms of vein formation and potentially clarify the nature and origin of the initial metasomatic agent, we performed a series of high-pressure experiments simulating the liquid line of descent of a basanitic magma differentiating within continental or mature oceanic lithosphere. This series of experiments has been conducted in an end-loaded piston cylinder apparatus starting from an initial hydrous ne-normative basanite at 1.5 GPa and temperature varying between 1,250 and 980°C. Near-pure fractional crystallization process was achieved in a stepwise manner in 30°C temperature steps and starting compositions corresponding to the liquid composition of the previous, higher-temperature glass composition. Liquids evolve progressively from basanite to peralkaline, aluminum-rich compositions without significant SiO2 variation. The resulting cumulates are characterized by an anhydrous clinopyroxene + olivine assemblage at high temperature (1,250-1,160°C), while at lower temperature (1,130-980°C), hydrous cumulates with dominantly amphibole + minor clinopyroxene, spinel, ilmenite, titanomagnetite and apatite (1,130-980°C) are formed. This new data set supports the interpretation that anhydrous and hydrous metasomatic veins could be produced during continuous differentiation processes of primary, hydrous alkaline magmas at high pressure. However, the comparison between the cumulates generated by the fractional crystallization from an initial ne-normative liquid or from hy-normative initial compositions (hawaiite or picrobasalt) indicates that for all hydrous liquids, the different phases formed upon differentiation are mostly similar even though the proportions of hydrous versus anhydrous minerals could vary significantly. This suggests that the formation of amphibole-bearing metasomatic veins observed in the lithospheric mantle could be linked to the differentiation of initial liquids ranging from ne-normative to hy-normative in composition. The present study does not resolve the question whether the metasomatism observed in lithospheric mantle is a precursor or a consequence of alkaline magmatism; however, it confirms that the percolation and differentiation of a liquid produced by a low degree of partial melting of a source similar or slightly more enriched than depleted MORB mantle could generate hydrous metasomatic veins interpreted as a potential source for alkaline magmatism by various authors.

Association of CYP3A5 genotypes with blood pressure and renal function in African families.

OBJECTIVE: Renal cytochrome P450 3A5 (CYP3A5) activity has been associated with blood pressure and salt sensitivity in humans. We determined whether CYP3A5 polymorphisms are associated with ambulatory blood pressure (ABP) and with glomerular filtration rate (GFR) in African families. METHODS: Using a cross-sectional design, 375 individuals from 72 families, each with at least two hypertensive siblings, were recruited through a hypertension register in the Seychelles (Indian Ocean). We analyzed the association between the CYP3A5 alleles (*1, *3, *6 and *7) and ABP, GFR and renal sodium handling (fractional excretion of lithium), from pedigree data, allowing for other covariates and familial correlations. RESULTS: CYP3A5*1 carriers increased their daytime systolic and diastolic ABP with age (0.55 and 0.23 mmHg/year) more than non-carriers (0.21 and 0.04 mmHg/year). CYP3A5*1 had a significant main effect on daytime systolic/diastolic ABP [regression coefficient (SE): -29.6 (10.0)/-8.2 (4.1) mmHg, P = 0.003/0.045, respectively] and this effect was modified by age (CYP3A5*1 x age interactions, P = 0.017/0.018). For night-time ABP, the effect of CYP3A5*1 was modified by urinary sodium excretion, not by age. For renal function, CYP3A5*1 carriers had a 7.6(3.8) ml/min lower GFR (P = 0.045) than non-carriers. Proximal sodium reabsorption decreased with age in non-carriers, but not in CYP3A5*1 carriers (P for interaction = 0.02). CONCLUSIONS: These data demonstrate that CYP3A5 polymorphisms are associated with ambulatory BP, CYP3A5*1 carriers showing a higher age- and sodium- related increase in ABP than non-carriers. The age effect may be due, in part, to the action of CYP3A5 on renal sodium handling.

Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits: a multi-ethnic meta-analysis of 45,891 individuals.

Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.

Sedimentary record of the northward flight of India and its collision with Eurasia (Ladakh Himalaya, India)

Stratigraphic and petrographic analysis of the Cretaceous to Eocene Tibetan sedimentary succession has allowed us to reinterpret in detail the sequence of events which led to closure of Neotethys and continental collision in the NW Himalaya. During the Early Cretaceous, the Indian passive margin recorded basaltic magmatic activity. Albian volcanic arenites, probably related to a major extensional tectonic event, are unconformably overlain by an Upper Cretaceous to Paleocene carbonate sequence, with a major quartzarenite episode triggered by the global eustatic sea-level fall at the Cretaceous/Tertiary boundary. At the same time, Neotethyan oceanic crust was being subducted beneath Asia, as testified by calc-alkalic volcanism and forearc basin sedimentation in the Transhimalayan belt. Onset of collision and obduction of the Asian accretionary wedge onto the Indian continental rise was recorded by shoaling of the outer shelf at the Paleocene/Eocene boundary, related to flexural uplift of the passive margin. A few My later, foreland basin volcanic arenites derived from the uplifted Asian subduction complex onlapped onto the Indian continental terrace. All along the Himalaya, marine facies were rapidly replaced by continental redbeds in collisional basins on both sides of the ophiolitic suture. Next, foreland basin sedimentation was interrupted by fold-thrust deformation and final ophiolite emplacement. The observed sequence of events compares favourably with theoretical models of rifted margin to overthrust belt transition and shows that initial phases of continental collision and obduction were completed within 10 to 15 My, with formation of a proto-Himalayan chain by the end of the middle Eocene.