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Therapy with Elexacaftor/Tezacaftor/Ivacaftor (ETI) was recently approved for adult cystic fibrosis (CF) patients with at least one F508del mutation. However, its effects on structural and functional lung abnormalities and chronic rhinosinusitis have not been studied by imaging.19 adults with CF (mean age 31±9y, range 19-55y) underwent standardized chest magnetic resonance imaging (MRI), and nine also same-session sinonasal MRI, before (MRI1) and after (MRI2) at least one month (mean duration 5 ± 3mon) on ETI. 24 control CF patients (30±7y, range 20-44y) without ETI underwent longitudinal chest MRI, and eleven also sinonasal MRI, twice (mean interval 40±15mon). MRI was assessed using the validated chest MRI score and chronic rhinosinusitis (CRS)-MRI score. Forced expiratory volume in 1 s percent predicted (FEV1%) was measured in all patients.In controls, the chest MRI global score and CRS-MRI sum score were stable from MRI1 to MRI2. In patients under ETI, the chest MRI global score improved (-11.4 ± 4.6, P0.001), mainly due to reduction of bronchiectasis/wall thickening and mucus plugging subscores (-3.3 ± 2.2 and -5.2 ± 1.5, P0.001, respectively). The improvement in chest MRI score correlated well with improved FEV1% (r=-0.703, P0.001). The CRS-MRI sum score also improved in patients under ETI (-6.9 ± 3.0, P0.001), mainly due to a reduction of mucopyoceles in the maxillary and ethmoid sinus (-50% and -39%, P0.05, respectively).MRI detects improvements of chest MRI and CRS-MRI scores in adult CF patients who first received ETI, demonstrating reversibility of structural lung and paranasal sinus abnormalities in patients with established disease.

Traditionally-suggested combustion time of 1 h at 550°C) with the sealed-tube combustion method for determining the 13C/ 12C ratio of cellulose nitrate or other nitrogen-containing components could produce large negative deviation up to 1°. Three types of cellulose are used to ascertain possible causes. The presence of nitrous oxide (N2O) formed during combustion is most likely responsible for this deviation. Prolongation of the combustion time (at least 5 h at 550°C) and intimate contact between copper oxide and organic matter can greatly improve the analysis precision and effectively reduce this deviation to an acceptable level. Regardless of scattered carbon isotope data, hydrogen isotope data are all reproducible within 2° when this method is coupled with the high temperature uranium reduction method. Thus, care should be taken for determining carbon and nitrogen isotope compositions of nitrogen-containing substances using the low temperature sealed-tube combustion method.

The 13 C/ 12 C ratios of leaves of the conifer morphotype Frenelopsis were measured to decipher the influences of water and salt stress on stomatal density (SD), epidermal cell density (ECD) and stomatal index (SI). Three morphospecies were analyzed: F . ugnaensis from freshwater fluvio-lacustrine deposits (Upper Barremian), F . turolensis and alata from coastal deposits (Lower-Middle Albian and Upper Albian respectively). The cuticle δ 13 C values show a large variation from − 28‰ to − 21‰. Comparison with previously published marine carbonate δ 13 C records indicate that the difference in cuticle δ 13 C between the different deposits are mainly due to difference in CO 2 -plant isotope fractionation rather than to change in isotopic composition of inorganic carbon in the atmosphere and ocean. The less negative δ 13 C and wide range in δ 13 C of F . turolensis and alata (− 27.5 to − 21‰), compared to F . ugnaensis , (− 28 to − 25‰) are interpreted as a result of salt and/or water stress. The data as a whole yield a good relationship between the 13 C/ 12 C ratio and SD ( r = 0.67, n = 42, p r = 0.53, n = 41, p F. ugnaensis decreases with increasing δ 13 C value ( r = − 0.57, n = 15, p = 0.026) as well as a decrease of SI ( r = − 0.62, n = 15, p = 0.013), possibly reflecting warmer and drier conditions. Average SI of F. alata does not significantly change with δ 13 C and inferred soil salinity in contrast to SD ( p

he class Betaproteobacteria contains several related genera that associate closely (and non-pathogenically) with plants. Recent studies have highlighted the emerging importance of newly-discovered legume-nodulating bacteria in the genera Burkholderia and Cupriavidus, the so-called “beta-rhizobia”. Nine species of nodulating burkholderias have been described so far, most being ancient (ca. 50 my) symbionts of many of the 500 species in the large genus Mimosa, but also of several other species of the legume tribe Mimoseae (Mimosoideae). Nodulation in these species by beta-rhizobia is thought to have emerged through the ancient lateral transfer of nodulation genes to their endophytic ancestors, followed by mainly vertical transfer (horizontal transfer being also detected in a few species), as illustrated by the parallelism between phylogenies of taxonomic and symbiotic markers. In contrast to Burkholderia, the most studied Cupriavidus species, C. taiwanensis, is considered to be a very recent legume symbiont that only nodulates a few invasive Mimosa spp. On the plant side, genera belonging to the tribe Mimoseae (especially those in the Piptadenia Group, which includes the genera Mimosa and Piptadenia) and several species in Papilionoid genera endemic to the Fynbos in the Cape region of South Africa exhibit particular affinities for beta-rhizobia. Legume taxonomy thus appears to give some insights into the potential nodulation of plants by beta-rhizobia. This is particularly exemplified by the genus Mimosa, within which there are clades of geographically-isolated endemics that clearly have evolved to have preferences for specific symbiont types (either alpha- or beta-proteobacterial). On the other hand, although many of the relatives of Mimosa (e.g., species in Piptadenia) share their preferences for beta-rhizobial symbionts, this is not always the case, and, indeed, there is no obvious strict pattern of coevolution between species in the wider tribe Mimoseae and their symbionts (beta-rhizobial or otherwise). This is discussed in terms of the broad host ranges of both symbiotic partners, and the horizontal transfer of nodulation genes between the Burkholderia species.

Some mantle-derived Kerguelen harzburgite and dunite xenoliths have bulk-rock and mineral trace element compositions that provide evidence of carbonatitic metasomatism similar to that described in some continental and other oceanic settings. Rare xenoliths contain carbonates that are highly enriched in rare earth elements (REE), interpreted to be quenched, evolved carbonatitic melts. One amphibole-bearing dunite mantle wall-rock containing carbonates in small interstitial pockets (100–500 μm across) has been studied in detail. Mg-bearing calcite (MgO

This study investigates the controls on the stable isotope composition of shell nacreous layer of a modern Nautilus macromphalus from New Caledonia. Closely spaced samples were taken both along growth lines (isochrons) and growth axis (time series). Carbon isotope compositions ( δ 13 C=−0.3‰ to 1‰ PDB) of the shell decrease in the domains of maximal growth (−0.3‰) and muscle insertion (−0.4‰). Maximal δ 13 C variations of about 1 ‰ are recorded in time series. A global ontogenetic decrease of δ 13 C values is observed for both dorsal and ventral areas (0.4‰ to 0.8‰) and can be ascribed to a metabolic effect with age or to changes in the food source. By contrast, oxygen isotope compositions are quite constant (1.1 δ 18 O

Intra-tooth δ18O variations within the carbonate (δ18Oc) and phosphate (δ18Op) components of tooth apatite were measured for Miocene and Pliocene hypsodont mammals from Afghanistan, Greece and Chad in order to evaluate the resistance of enamel to diagenetic alteration. Application of water-apatite interaction models suggest that the different kinetic behaviours of the phosphate-water and carbonate-water systems can be used to detect subtle oxygen isotope disequilibria in fossil enamel when intra-individual variations are considered. Selective alteration of the oxygen isotope composition from the carbonate component of Afghan and Greek enamels suggests inorganic isotopic exchange processes. Microbially-induced isotopic exchange for phosphate is demonstrated for the first time in enamel samples from Chad, in association with extensive recrystallization. In Chad, δ18Op values were derived from partial isotopic exchange with fossil groundwater during early diagenesis. Mass balance calculations using average carbonate content in enamel as a proxy for recrystallization, and the lowest δ18Op value of dentine as a proxy for the isotopic composition of the diagenetic fluid, indicate that diagenesis can alter δ18Op by as much as 3‰ in some enamel samples. This diagenetic alteration is also responsible for a decrease in intra-individual variations of up to 1‰ in affected specimens. The effects of diagenesis on δ18Op values of fossil enamel are not systematic, however, and can only be estimated if sequential δ18Op and δ18Oc analyses are performed on fossil enamel and dentine. Reconstruction of large temporal- or spatial-scale paleoclimates based on δ18Op analyses from mammalian teeth cannot be considered valid if enamel has been affected by bacterial activity or if the data cannot be corrected for diagenetic effects.

The relationship between the δ13C of dissolved inorganic carbon (DIC) and modern mollusk aragonite from rivers was calibrated for the purpose of reconstructing DIC paleochemistry from the shell record. The δ13C values of aragonitic bivalves (Dreissena polymorpha, Corbicula fluminea), prosobranch gastropods (Bithynia tentaculata, Theodoxus fluviatilis, Viviparus viviparus), and an air-breathing pulmonate gastropod (Limnea auricularia) were analyzed from several locations on the Rhone River (—13.7‰ to —6.0‰) and its major tributary, the Saone River (—11.4‰ to —10.2‰). The δ13CDIC varied from —11.5‰ to —7.5‰, and the δ13C of particulate inorganic matter (POM) varied from —31.7‰ to —25.4‰. At a given site, the δ13C of all species except the pulmonate were within 1‰ of each other. Whole-shell δ13C correlated positively with δ13CDIC, with a slope close to unity. Bioaragonite—DIC fractionations were 0–1.5‰ for bivalves and 0–2.7‰ for gastropods (excluding the pulmonates). Applying these fractionations, bivalves that live in open water are a reliable proxy, monitoring the average δ13CDIC value to within its natural ~2‰ temporal variation within the growth period. For the suspension feeders (bivalves) using POM as a food source, the δ13C of whole shells and bulk POM indicated that the incorporation of carbon derived from respiratory sources lay in the range 10–30%. Fine-scale analyses of growth increments of C. fluminea could not be related simply to δ13CDIC because metabolic and seasonal variations in δ13CDIC produced similar isotopic fluctuations (≤2.5‰).

A compilation of new and published stratigraphic, paleontological and geochemical data is used to detect the reciprocal influences of carbon cycling and global environmental changes in the Jurassic. A major perturbation of the surface carbon cycling accompanied by pronounced climate and sea level fluctuations (waxing and waning of continental ice?) affected Earth history around the Middle/Late Jurassic transition (MLJT). We establish the respective timing of changes of carbonate and organic matter sedimentation, and global fluctuations of sea surface temperatures (paleobiogeography and O-isotope paleothermometry) and sea level (sequence stratigraphy), so that causative mechanisms and feedback effects can be considered. It is apparent that the global sea level rise and warming initiated in the Late Bathonian led to a constriction of carbonate platforms to low latitudes and enhanced marine organic deposition. Sea level and temperature optima were achieved several million-years later during the Middle Callovian. A detailed record of sea surface temperatures in the Northern Hemisphere based on migration of marine fauna and isotopic thermometry indicates that a drastic climatic decline set in during the early Late Callovian, just post-dating the increased capture of organic matter by marine sediments. This decline in temperature is interpreted in terms of an inverse greenhouse effect, triggered by drawdown of CO 2 consequent upon excess carbon burial. The magnitude of refrigeration and its coincidence in time with an abrupt global-scale fall of sea level are both suggestive of continental ice formation at this time. Carbonate sedimentation was jeopardized at the MLJT as a result of both global cooling and presumed P C O 2 lowering, and resumed abruptly during the Middle Oxfordian by spreading again over mid-latitude zones. Salient conclusions are that (1) the pattern of excess carbon burial, coincident with elevated temperature but followed by climatic deterioration supports the general hypothesis that a major control on Mesozoic climate was the abundance of atmospheric CO 2 ; (2) significant masses of continental ice may have formed during this part of the Jurassic and correlatively, high CO 2 levels were certainly not sustained throughout this period; (3) the global carbonate sedimentation budget correlated with the surface temperature and sea level, but the latitudinal spreading of type-tropical carbonates was not simply related to the thermal status of seawaters; (4) on a global scale, the C o r g and C i n o r g burial rates were coupled, apparently through the correlation existing between the CO 2 level and surface temperature.

A detailed record of sea surface temperatures in the Northern Hemisphere based on migration of marine invertebrate fauna (ammonites) and isotopic thermometry (δ18O values of shark tooth enamel) indicates a severe cooling at the Middle–Late Jurassic transition (MLJT), about 160 Ma ago. The magnitude of refrigeration (1–3°C for lower middle latitudes) and its coincidence in time with an abrupt global-scale fall of sea level documented through sequence stratigraphy are both suggestive of continental ice formation at this time. Ice sheets may have developed over the high-latitude mountainous regions of Far-East Russia. The drastic cooling just post-dated the Middle–Late Callovian widespread deposition of organic-rich marine sediments (e.g. northwestern Europe, Central Atlantic, and Arabian Peninsula). This thermal deterioration can thus be ascribed to a downdraw in atmospheric CO2 via enhanced organic carbon burial which acted as a negative feedback effect (i.e. the inverse greenhouse effect). The glacial episode of the MLJT climaxed in the Late Callovian, lasted about 2.6 Myr, and had a pronounced asymmetrical pattern composed of an abrupt (∼0.8 Myr) temperature fall opposed to a long-term (∼1.8 Myr), stepwise recovery. The glacial conditions at the MLJT reveal that atmospheric CO2 levels could have dropped temporarily to values lower than 500 ppmv during Mesozoic times.

We studied the changes in major elements and organic carbon concentrations during the initial stage of the mixing of the black (Rio Negro) and the White (Rio Solimoes) waters in the Amazon River basin to understand the geochemical processes that could control the redistribution between particulate and dissolved fractions. Water samples were collected at six stations including the Rio Negro and the Rio Solimoes and four stations downstream from the confluence. The relative contributions of the two tributaries were determined using a triple tracer approach (d 18 O, dD, Cl � ). Particulate (>0.2 Am) and dissolved (

The rare earth element (REE) chemistry of Jurassic shelf seawater from western Europe (Anglo-Paris Basin) was investigated by analyzing the fish and reptile teeth deposited in shallow to deeper water (

International audience; Numerous observations indicate that faults play a major role on the migration pathways of fluids in the Bolivian sub-Andean Zone. Most oil seeps in the foothills are located on faults, but oil fields in the foredeep are closed by faults. In the foothills, analysis of cements in fractures inside and around fault zones indicates that the faults act as barriers for transversal migration but can be preferential lateral migration pathways for both hydrocarbons and water. A detailed study of these apparent contradictions suggests that the hydraulic behaviour of faults changes with depth in relation with sandstone diagenesis, but it is strain-independent. From microstructural analyses of fault zones, we suggest that the main controlling factor is temperature, which facilitates or inhibits quartz precipitation. This result implies that the same fault is a barrier for lateral and transversal migration at depths >3 km, due to sealing of fractures by authigenic quartz at T>80 °C, and is a lateral drain in its shallower parts. As a result, the various thrust sheets are isolated from a hydraulic point of view, whereas migration in the foreland may take place over long distances (>100 km).

International audience; New geological, geochemical and geochronological data from the Southern Karakoram (NE Pakistan) indicate the presence of several unexpectedly old and well preserved units along the Asian margin: (1) a Precambrian basement, displaying a minimum amphibole Ar-Ar age of 651 Ma; (2) a thick Cambro-Ordovician platform-type sedimentary unit overlying the Precambrian basement. These series are dated by graptolite and crinoid faunas, and are confirmed by concordant 87Sr/ 86Sr and 13C "ages" of the marbles; (3) a dismembered ophiolitic series formed by slices of metagabbros and metabasalts separated by ultramafic lenses (the Masherbrum Greenstone Complex). The occurrence of such Cambro-Ordovician series overlying a Precambrian basement in south-eastern Karakoram similar to the south-western Karakoram shows that the Karakoram constitutes a continuous tectonic block. The petrology and geochemistry of the Masherbrum Greenstone Complex (mineral chemistry, major and trace element and Sr-Nd isotopic data) are indicative of a supra-subductive environment. The presence of LREE-enriched calc-alkaline rocks 〚(La/Yb) N = 4.4-5.6; (Nb/La) N = 0.2-0.3; ɛNd 565 = 5.1-7.1〛 and LREE-depleted tholeiitic rocks 〚(La/Yb) N = 0.5-1.3; (Nb/La) N = 0.6-0.9; ɛNd 565 = 5.6-7.8〛 are consistent with arc and back-arc settings, respectively. A high-Mg andesitic dolerite and an OIB-type metabasalt, with lower ɛNd ratios (ɛNd 565 = 0.5 and 4.5) are in accordance with source heterogeneity beneath the arc. The Masherbrum Greenstone Complex, along with other Cambro-Ordovician central-eastern volcanic series give evidence of a tectonic situation governed by micro-plate convergent-divergent systems with occurrence of arc - back-arc settings during the Lower Palaeozoic, comparable to that of the current SW Pacific area.

A basanite dyke in the Kerguelen Archipelago contains abundant INTRODUCTION composite mantle xenoliths consisting of spinel-bearing dunites Composite ultramafic xenoliths in volcanic rocks provide cross-cut by amphibole-rich veins. Two types of veins (thick and unique information about the extraction, interaction and thin) have been distinguished: the thick veins represent almost migration processes of melts in the upper mantle (e.g. complete crystallization products of highly alkaline melts similar Irving, 1980; Nielson & Wilshire, 1993; Witt-Eickschen to the host basanites, whereas thin veins are precipitates from et al., 1998). Studies of such xenoliths have improved our fractionates of the parental melts to the thick veins. These understanding of trace-element fractionation processes fractionated fluids are enriched in H2O relative to the parental involved in the geochemical evolution of the upper melts. The amphiboles in the thin veins are lower in Ti and mantle. In addition, amphibole, ilmenite and phlogopite higher in Nb, Ta, Zr and Hf than amphiboles in the thick are metasomatic phases that play a crucial role in the veins. This fractionation of high field strength elements (HFSE) dispersion and residence of trace elements in the upper is consistent with a combination of the changing composition of mantle because they incorporate (sometimes exclusively) the fractionated fluids and the change in intrinsic amphibole–fluid some of the important trace elements such as high field partition coefficients for HFSE in fluids with higher aH2O and strength elements (HFSE; Ti, Zr, Hf, Nb, Ta) or large ion lower aTiO2. The trace element content of amphiboles disseminated lithophile elements (LILE; Ba, Sr) that are incompatible in in dunitic wall-rocks is closely related to the composition of olivine–orthopyroxene–clinopyroxene–spinel peridotites adjacent veins and thus these amphiboles are precipitates from (e.g. Griffin et al., 1988; O’Reilly & Griffin, 1988; O’Reilly fluids percolating into the dunite from the veins. Disseminated et al., 1991; Ionov et al., 1997). amphibole reflects the composition of the percolating melt, which We report in this paper results of a majorand traceis similar to that of the associated veins. element study of constituent minerals in composite mantle xenoliths of spinel-bearing dunites cross-cut by amphibole-rich (± ilmenite ± phlogopite) veins. Our data

The analysis of macro- and microstructures and cement distribution in thrust fault zones of the Bolivian Sub-Andean Zone shows that fault zones are sealed by quartz at depths >∼2.5 km. Cementation occurred due to local silica transfer by pressure solution-precipitation activated at temperatures >80–90°C. At shallower depths, faults have remained open and could be preferential drains for lateral flow of allochthonous carbonated fluids. At a large-scale, the faults have a low transverse permeability and they separate thrust sheets with different fluid histories.

Dissolved inorganic carbon (DIC) and particulate inorganic carbon (PIC) were sampled at 20 sites on the Rhone and its main tributaries from Switzerland to the Mediterranean, in March, September and July (flood event) 1996. Flux estimation and DIC and PIC values are used to trace watershed inputs and fluvial processes affecting the inorganic carbon budget. DIC concentration and values vary between ∼1 mM at −5‰ near the Rhone's source and ∼3 mM at −10‰ near its mouth, with tributaries draining lowland, carbonate-dominated areas at ∼3.8 mM and −11‰. There is an inverse relationship between river DIC concentration and DIC . The headwaters are characterized by high DIC values and low DIC, indicating a minor input of respired CO2. DIC should be mainly produced through the reaction of carbonate with atmospheric CO2 or organic/sulfuric acids. In lowland, carbonate-dominated areas, values of ∼−11‰ are consistent with production of DIC by weathering of limestone C (≈−1‰) with CO2 derived from the oxidation of organic matter (≈−21.5‰). The evolution of the Rhone's DIC concentration and appear to be largely determined by mixing between the Rhone and its main tributaries. The CO2 fluxes and DIC mass-balance, calculated for the different segments of the Rhone, point to a net, but very limited input of fluvial respired CO2 from the oxidation of organic C (

Oxygen isotope fractionations have been measured experimentally between dissolved orthophosphate ions H2PO4− and water from 50°C to 135°C. The derived equilibrium fractionation equation reveals that biogenic apatites are systematically 18O-depleted (8‰ at 20°C) compared with inorganic dissolved phosphate. The activation energy is relatively high at 134 kJmol−1 and the kinetics of the homogeneous inorganic exchange reaction are very slow (k = 10−13 to 10−11 s−1) when extrapolated to surface temperatures. In seawater, the oxygen isotope composition of dissolved phosphate is not in equilibrium with water; its composition should directly reflect source contributions or biological recycling. Any deviation from the composition of the inorganic sources may be attributed to biological recycling of this nutrient. The original isotopic compositions of fossils may be modified in less than 105 years at a temperature of 20°C through mechanisms of dissolution and precipitation in the presence of crustal aqueous fluids. The differences in oxygen isotope fractionations between biogenic or inorganic phosphate and water are applied to re-evaluate the significance of δ18O values of Phanerozoic and Precambrian phosphate deposits.

The nature of synmetamorphic fluids and their flow is examined in the granulitic lower crust of Madagascar, part of a Precambrian crustal-scale network of vertical ductile shear zones. Based on three independent data sets - field and satellite mapping, C-, O- and H-isotope geochemistry and gravimetry - this crust is divided into three zones: outside of shear zones, minor shear zones ( 350 km long and 20–35 km wide). The major shear zones are rooted in and are controlled by the mantle. They tapped mantle-derived CO2 with carbon fluxes of the same order of magnitude as oceanic ridge degassing. One major shear zone shows abundant phlogopite-diopside-apatite-calcite mineralizations (a well known paragenesis in mantle metasomatism) due to mantle-fluid infiltration and their interaction with the crust. Carbonatitic magmas possibly collected in the major shear zones at the base of the crust and may be the source for CO2 upwellings as well as other metasomatic agents. Small-scale minor shear zones were controlled by crustal deformation processes and focused crustally-derived H2O-rich fluids. Pervasive fluid circulation was restricted to the vicinity (