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Surface wave dispersion measurements from ambient seismic noise and array‐based measurements from teleseismic earthquakes observed with the EarthScope/USArray Transportable Array (TA) are inverted using a Monte Carlo method for a 3‐D VS model of the crust and uppermost mantle beneath the western United States. The combination of data from these methods produces exceptionally broadband dispersion information from 6 to 100 s period, which constrains shear wave velocity structures in the crust and uppermost mantle to a depth of more than 100 km. The high lateral resolution produced by the TA network and the broadbandedness of the dispersion information motivate the question of the appropriate parameterization for a 3‐D model, particularly for the crustal part of the model. We show that a relatively simple model in which VS increases monotonically with depth in the crust can fit the data well across more than 90% of the study region, except in eight discrete areas where greater crustal complexity apparently exists. The regions of greater crustal complexity are the Olympic Peninsula, the MendocinoTriple Junction, the Yakima Fold Belt, the southern Cascadia back arc, the Great Central Valley of California, the Salton Trough, the Snake River Plain, and the Wasatch Mountains. We also show that a strong Rayleigh‐Love discrepancy exists across much of the western United States, which can be resolved by introducing radial anisotropy in both the mantle and notably the crust. We focus our analysis on demonstrating the existence of crustal radial anisotropy and primarily discuss the crustal part of the isotropic model that results from the radially anisotropic model by Voigt averaging. Model uncertainties from the Monte Carlo inversion are used to identify robust isotropic features in the model. The uppermost mantle beneath the western United States is principally composed of four large‐scale shear wave velocity features, but lower crustal velocity structure exhibits far greater heterogeneity. We argue that these lower crustal structures are predominantly caused by interactions with the uppermost mantle, including the intrusion and underplating of mafic mantle materials and the thermal depression of wave speeds caused by conductive heating from the mantle. Upper and middle crustal wave speeds are generally correlated, and notable anomalies are inferred to result from terrane accretion at the continental margin and volcanic intrusions.

Crustal deformation runs deep Morgan Moschetti and colleagues use ambient noise tomography data from the western United States to show that strong radial seismic anisotropy exists in the deep crust, confined mainly to the geological provinces that have undergone significant extension during the Cenozoic era, since about 65 million years ago. The coincidence of crustal radial anisotropy with these extensional provinces supports the hypothesis that the deep crust within these regions has undergone widespread and relatively uniform strain in response to crustal thinning and extension. Here a method of seismic wave imaging known as 'ambient noise' tomography is used to generate high-resolution images of seismic wave speeds in the crust and uppermost mantle. The observations reveal strong and uniform anisotropy — where waves travel through rock at different speeds depending on direction — in the deep crust in areas of the western United States that have undergone significant extension during the past 65 million years. Laboratory experiments have established that many of the materials comprising the Earth are strongly anisotropic in terms of seismic-wave speeds 1 . Observations of azimuthal 2 , 3 and radial 4 , 5 anisotropy in the upper mantle are attributed to the lattice-preferred orientation of olivine caused by the shear strains associated with deformation, and provide some of the most direct evidence for deformation and flow within the Earth’s interior. Although observations of crustal radial anisotropy would improve our understanding of crustal deformation and flow patterns resulting from tectonic processes, large-scale observations have been limited to regions of particularly thick crust 6 . Here we show that observations from ambient noise tomography in the western United States reveal strong deep (middle to lower)-crustal radial anisotropy that is confined mainly to the geological provinces that have undergone significant extension during the Cenozoic Era (since ∼65 Myr ago) 7 , 8 . The coincidence of crustal radial anisotropy with the extensional provinces of the western United States suggests that the radial anisotropy results from the lattice-preferred orientation of anisotropic crustal minerals caused by extensional deformation. These observations also provide support for the hypothesis that the deep crust within these regions has undergone widespread and relatively uniform strain in response to crustal thinning and extension 9 , 10 , 11 .

Idarucizumab is a monoclonal antibody fragment that binds dabigatran with high affinity in a 1:1 molar ratio. We investigated the safety, tolerability, and efficacy of increasing doses of idarucizumab for the reversal of anticoagulant effects of dabigatran in a two-part phase 1 study (rising-dose assessment and dose-finding, proof-of-concept investigation). Here we present the results of the proof-of-concept part of the study. In this randomised, placebo-controlled, double-blind, proof-of-concept phase 1 study, we enrolled healthy volunteers (aged 18–45 years) with a body-mass index of 18·5–29·9 kg/m2 into one of four dose groups at SGS Life Sciences Clinical Research Services, Belgium. Participants were randomly assigned within groups in a 3:1 ratio to idarucizumab or placebo using a pseudorandom number generator and a supplied seed number. Participants and care providers were masked to treatment assignment. All participants received oral dabigatran etexilate 220 mg twice daily for 3 days and a final dose on day 4. Idarucizumab (1 g, 2 g, or 4 g 5-min infusion, or 5 g plus 2·5 g in two 5-min infusions given 1 h apart) was administered about 2 h after the final dabigatran etexilate dose. The primary endpoint was incidence of drug-related adverse events, analysed in all randomly assigned participants who received at least one dose of dabigatran etexilate. Reversal of diluted thrombin time (dTT), ecarin clotting time (ECT), activated partial thromboplastin time (aPTT), and thrombin time (TT) were secondary endpoints assessed by measuring the area under the effect curve from 2 h to 12 h (AUEC2–12) after dabigatran etexilate ingestion on days 3 and 4. This trial is registered with ClinicalTrials.gov, number NCT01688830. Between Feb 23, and Nov 29, 2013, 47 men completed this part of the study. 12 were enrolled into each of the 1 g, 2 g, or 5 g plus 2·5 g idarucizumab groups (nine to idarucizumab and three to placebo in each group), and 11 were enrolled into the 4 g idarucizumab group (eight to idarucizumab and three to placebo). Drug-related adverse events were all of mild intensity and reported in seven participants: one in the 1 g idarucizumab group (infusion site erythema and hot flushes), one in the 5 g plus 2·5 g idarucizumab group (epistaxis); one receiving placebo (infusion site haematoma), and four during dabigatran etexilate pretreatment (three haematuria and one epistaxis). Idarucizumab immediately and completely reversed dabigatran-induced anticoagulation in a dose-dependent manner; the mean ratio of day 4 AUEC2–12 to day 3 AUEC2–12 for dTT was 1·01 with placebo, 0·26 with 1 g idarucizumab (74% reduction), 0·06 with 2 g idarucizumab (94% reduction), 0·02 with 4 g idarucizumab (98% reduction), and 0·01 with 5 g plus 2·5 g idarucizumab (99% reduction). No serious or severe adverse events were reported, no adverse event led to discontinuation of treatment, and no clinically relevant difference in incidence of adverse events was noted between treatment groups. These phase 1 results show that idarucizumab was associated with immediate, complete, and sustained reversal of dabigatran-induced anticoagulation in healthy men, and was well tolerated with no unexpected or clinically relevant safety concerns, supporting further testing. Further clinical studies are in progress. Boehringer Ingelheim Pharma GmbH & Co KG.

Surface wave dispersion measurements from ambient seismic noise and array‐based measurements from teleseismic earthquakes observed with the EarthScope/USArray Transportable Array (TA) are inverted using a Monte Carlo method for a 3‐D V S model of the crust and uppermost mantle beneath the western United States. The combination of data from these methods produces exceptionally broadband dispersion information from 6 to 100 s period, which constrains shear wave velocity structures in the crust and uppermost mantle to a depth of more than 100 km. The high lateral resolution produced by the TA network and the broadbandedness of the dispersion information motivate the question of the appropriate parameterization for a 3‐D model, particularly for the crustal part of the model. We show that a relatively simple model in which V S increases monotonically with depth in the crust can fit the data well across more than 90% of the study region, except in eight discrete areas where greater crustal complexity apparently exists. The regions of greater crustal complexity are the Olympic Peninsula, the MendocinoTriple Junction, the Yakima Fold Belt, the southern Cascadia back arc, the Great Central Valley of California, the Salton Trough, the Snake River Plain, and the Wasatch Mountains. We also show that a strong Rayleigh‐Love discrepancy exists across much of the western United States, which can be resolved by introducing radial anisotropy in both the mantle and notably the crust. We focus our analysis on demonstrating the existence of crustal radial anisotropy and primarily discuss the crustal part of the isotropic model that results from the radially anisotropic model by Voigt averaging. Model uncertainties from the Monte Carlo inversion are used to identify robust isotropic features in the model. The uppermost mantle beneath the western United States is principally composed of four large‐scale shear wave velocity features, but lower crustal velocity structure exhibits far greater heterogeneity. We argue that these lower crustal structures are predominantly caused by interactions with the uppermost mantle, including the intrusion and underplating of mafic mantle materials and the thermal depression of wave speeds caused by conductive heating from the mantle. Upper and middle crustal wave speeds are generally correlated, and notable anomalies are inferred to result from terrane accretion at the continental margin and volcanic intrusions.

ESPRESSO is the new high-resolution spectrograph of ESO's Very-Large Telescope (VLT). It was designed for ultra-high radial-velocity precision and extreme spectral fidelity with the aim of performing exoplanet research and fundamental astrophysical experiments with unprecedented precision and accuracy. It is able to observe with any of the four Unit Telescopes (UT) of the VLT at a spectral resolving power of 140,000 or 190,000 over the 378.2 to 788.7 nm wavelength range, or with all UTs together, turning the VLT into a 16-m diameter equivalent telescope in terms of collecting area, while still providing a resolving power of 70,000. We provide a general description of the ESPRESSO instrument, report on the actual on-sky performance, and present our Guaranteed-Time Observation (GTO) program with its first results. ESPRESSO was installed on the Paranal Observatory in fall 2017. Commissioning (on-sky testing) was conducted between December 2017 and September 2018. The instrument saw its official start of operations on October 1st, 2018, but improvements to the instrument and re-commissioning runs were conducted until July 2019. The measured overall optical throughput of ESPRESSO at 550 nm and a seeing of 0.65 arcsec exceeds the 10% mark under nominal astro-climatic conditions. We demonstrate a radial-velocity precision of better than 25 cm/s during one night and 50 cm/s over several months. These values being limited by photon noise and stellar jitter show that the performanceis compatible with an instrumental precision of 10 cm/s. No difference has been measured across the UTs neither in throughput nor RV precision. The combination of the large collecting telescope area with the efficiency and the exquisite spectral fidelity of ESPRESSO opens a new parameter space in RV measurements, the study of planetary atmospheres, fundamental constants, stellar characterisation and many other fields.

We characterized the transiting planetary system orbiting the G2V star K2-38 using the new-generation echelle spectrograph ESPRESSO. We carried out a photometric analysis of the available K2 photometric light curve of this star to measure the radius of its two known planets. Using 43 ESPRESSO high-precision radial velocity measurements taken over the course of 8 months along with the 14 previously published HIRES RV measurements, we modeled the orbits of the two planets through a MCMC analysis, significantly improving their mass measurements. Using ESPRESSO spectra, we derived the stellar parameters, \\(T_{\\rm eff}\\)=5731\\(\\pm\\)66, \\(\\log g\\)=4.38\\(\\pm\\)0.11~dex, and \\([Fe/H]\\)=0.26\\(\\pm\\)0.05~dex, and thus the mass and radius of K2-38, \\(M_{\\star}\\)=1.03 \\(^{+0.04}_{-0.02}\\)~M\\(_{\\oplus}\\) and \\(R_{\\star}\\)=1.06 \\(^{+0.09}_{-0.06}\\)~R\\(_{\\oplus}\\). We determine new values for the planetary properties of both planets. We characterize K2-38b as a super-Earth with \\(R_{\\rm P}\\)=1.54\\(\\pm\\)0.14~R\\(_{\\rm \\oplus}\\) and \\(M_{\\rm p}\\)=7.3\\(^{+1.1}_{-1.0}\\)~M\\(_{\\oplus}\\), and K2-38c as a sub-Neptune with \\(R_{\\rm P}\\)=2.29\\(\\pm\\)0.26~R\\(_{\\rm \\oplus}\\) and \\(M_{\\rm p}\\)=8.3\\(^{+1.3}_{-1.3}\\)~M\\(_{\\oplus}\\). We derived a mean density of \\(\\rho_{\\rm p}\\)=11.0\\(^{+4.1}_{-2.8}\\)~g cm\\(^{-3}\\) for K2-38b and \\(\\rho_{\\rm p}\\)=3.8\\(^{+1.8}_{-1.1}\\)~g~cm\\(^{-3}\\) for K2-38c, confirming K2-38b as one of the densest planets known to date. The best description for the composition of K2-38b comes from an iron-rich Mercury-like model, while K2-38c is better described by a rocky model with a H2 envelope. The maximum collision stripping boundary shows how giant impacts could be the cause for the high density of K2-38b. The irradiation received by each planet places them on opposite sides of the radius valley. We find evidence of a long-period signal in the radial velocity time-series whose origin could be linked to a 0.25-3~M\\(_{\\rm J}\\) planet or stellar activity.

Aims. We report on ESPRESSO high-resolution transmission spectroscopic observations of two primary transits of the highly-irradiated, ultra-hot Jupiter-size planet WASP-76b. We investigate the presence of several key atomic and molecular features of interest that may reveal the atmospheric properties of the planet. Methods. We extracted two transmission spectra of WASP-76b with R approx 140,000 using a procedure that allowed us to process the full ESPRESSO wavelength range (3800-7880 A) simultaneously. We observed that at a high signal-to-noise ratio, the continuum of ESPRESSO spectra shows wiggles that are likely caused by an interference pattern outside the spectrograph. To search for the planetary features, we visually analysed the extracted transmission spectra and cross-correlated the observations against theoretical spectra of different atomic and molecular species. Results. The following atomic features are detected: Li I, Na I, Mg I, Ca II, Mn I, K I, and Fe I. All are detected with a confidence level between 9.2 sigma (Na I) and 2.8 sigma (Mg I). We did not detect the following species: Ti I, Cr I, Ni I, TiO, VO, and ZrO. We impose the following 1 sigma upper limits on their detectability: 60, 77, 122, 6, 8, and 8 ppm, respectively. Conclusions. We report the detection of Li I on WASP-76b for the first time. In addition, we found the presence of Na I and Fe I as previously reported in the literature. We show that the procedure employed in this work can detect features down to the level of ~ 0.1 % in the transmission spectrum and ~ 10 ppm by means of a cross-correlation method. We discuss the presence of neutral and singly ionised features in the atmosphere of WASP-76b.

We aim to confirm the presence of Proxima b using independent measurements obtained with the new ESPRESSO spectrograph, and refine the planetary parameters taking advantage of its improved precision. We analysed 63 spectroscopic ESPRESSO observations of Proxima taken during 2019. We obtained radial velocity measurements with a typical radial velocity photon noise of 26 cm/s. We ran a joint MCMC analysis on the time series of the radial velocity and full-width half maximum of the cross-correlation function to model the planetary and stellar signals present in the data, applying Gaussian process regression to deal with stellar activity. We confirm the presence of Proxima b independently in the ESPRESSO data. The ESPRESSO data on its own shows Proxima b at a period of 11.218 \\(\\pm\\) 0.029 days, with a minimum mass of 1.29 \\(\\pm\\) 0.13 Me. In the combined dataset we measure a period of 11.18427 \\(\\pm\\) 0.00070 days with a minimum mass of 1.173 \\(\\pm\\) 0.086 Me. We find no evidence of stellar activity as a potential cause for the 11.2 days signal. We find some evidence for the presence of a second short-period signal, at 5.15 days with a semi-amplitude of merely 40 cm/s. If caused by a planetary companion, it would correspond to a minimum mass of 0.29 \\(\\pm\\) 0.08 Me. We find that the FWHM of the CCF can be used as a proxy for the brightness changes and that its gradient with time can be used to successfully detrend the radial velocity data from part of the influence of stellar activity. The activity-induced radial velocity signal in the ESPRESSO data shows a trend in amplitude towards redder wavelengths. Velocities measured using the red end of the spectrograph are less affected by activity, suggesting that the stellar activity is spot-dominated. The data collected excludes the presence of extra companions with masses above 0.6 Me at periods shorter than 50 days.

The bright star \\(\\pi\\) Men was chosen as the first target for a radial velocity follow-up to test the performance of ESPRESSO, the new high-resolution spectrograph at the ESO's Very-Large Telescope (VLT). The star hosts a multi-planet system (a transiting 4 M\\(_\\oplus\\) planet at \\(\\sim\\)0.07 au, and a sub-stellar companion on a \\(\\sim\\)2100-day eccentric orbit) which is particularly appealing for a precise multi-technique characterization. With the new ESPRESSO observations, that cover a time span of 200 days, we aim to improve the precision and accuracy of the planet parameters and search for additional low-mass companions. We also take advantage of new photometric transits of \\(\\pi\\) Men c observed by TESS over a time span that overlaps with that of the ESPRESSO follow-up campaign. We analyse the enlarged spectroscopic and photometric datasets and compare the results to those in the literature. We further characterize the system by means of absolute astrometry with Hipparcos and Gaia. We used the spectra of ESPRESSO for an independent determination of the stellar fundamental parameters. We present a precise characterization of the planetary system around \\(\\pi\\) Men. The ESPRESSO radial velocities alone (with typical uncertainty of 10 cm/s) allow for a precise retrieval of the Doppler signal induced by \\(\\pi\\) Men c. The residuals show an RMS of 1.2 m/s, and we can exclude companions with a minimum mass less than \\(\\sim\\)2 M\\(_\\oplus\\) within the orbit of \\(\\pi\\) Men c). We improve the ephemeris of \\(\\pi\\) Men c using 18 additional TESS transits, and in combination with the astrometric measurements, we determine the inclination of the orbital plane of \\(\\pi\\) Men b with high precision (\\(i_{b}=45.8^{+1.4}_{-1.1}\\) deg). This leads to the precise measurement of its absolute mass \\(m_{b}=14.1^{+0.5}_{-0.4}\\) M\\(_{Jup}\\), and shows that the planetary orbital planes are highly misaligned.

Impaired immune function during the perioperative period may be associated with worse short- and long-term outcomes. Morphine is considered a major contributor to immune modulation. We performed a pilot study to investigate postoperative immune function by analyzing peripheral blood mononuclear cells' functionality and cytokine production in 16 patients undergoing major abdominal surgery. All patients were treated with intravenous (i.v.) patient-controlled analgesia with morphine and continuous wound infusion with ropivacaine+methylprednisolone for 24 hours. After 24 hours, patients were randomized into two groups, one continuing intrawound infusion and the other receiving only i.v. analgesia. We evaluated lymphoproliferation and cytokine production by peripheral blood mononuclear cells at the end of surgery and at 24 and 48 hours postoperatively. A significant reduction in TNF-α, IL-2, IFN-γ and lymphoproliferation was observed immediately after surgery, indicating impaired cell-mediated immunity. TNF-α and IFN-γ remained suppressed up to 48 hours after surgery, while a trend to normalization was observed for IL-2 and lymphoproliferation, irrespective of the treatment group. A significant inverse correlation was present between age and morphine and between age and lymphoproliferation. No negative correlation was present between morphine and cytokine production. We did not find any differences within the two groups between 24 and 48 hours in terms of morphine consumption and immune responses. A relevant depression of cell-mediated immunity is associated with major surgery and persists despite optimal analgesia. Even though morphine may participate in immunosuppression, we did not retrieve any dose-related effect.