An aperture masking mode for the MICADO instrument

MICADO is a near-IR camera for the Europea ELT, featuring an extended field (75" diameter) for imaging, and also spectrographic and high contrast imaging capabilities. It has been chosen by ESO as one of the two first-light instruments. Although it is ultimately aimed at being fed by the MCAO module called MAORY, MICADO will come with an internal SCAO system that will be complementary to it and will deliver a high performance on axis correction, suitable for coronagraphic and pupil masking applications. The basis of the pupil masking approach is to ensure the stability of the optical transfer function, even in the case of residual errors after AO correction (due to non common path errors and quasi-static aberrations). Preliminary designs of pupil masks are presented. Trade-offs and technical choices, especially regarding redundancy and pupil tracking, are explained.Comment: SPIE 2014 Proceeding -- Montrea

Shadows and spirals in the protoplanetary disk HD 100453

Understanding the diversity of planets requires to study the morphology and the physical conditions in the protoplanetary disks in which they form. We observed and spatially resolved the disk around the ~10 Myr old protoplanetary disk HD 100453 in polarized scattered light with SPHERE/VLT at optical and near-infrared wavelengths, reaching an angular resolution of ~0.02", and an inner working angle of ~0.09". We detect polarized scattered light up to ~0.42" (~48 au) and detect a cavity, a rim with azimuthal brightness variations at an inclination of 38 degrees, two shadows and two symmetric spiral arms. The spiral arms originate near the location of the shadows, close to the semi major axis. We detect a faint spiral-like feature in the SW that can be interpreted as the scattering surface of the bottom side of the disk, if the disk is tidally truncated by the M-dwarf companion currently seen at a projected distance of ~119 au. We construct a radiative transfer model that accounts for the main characteristics of the features with an inner and outer disk misaligned by ~72 degrees. The azimuthal brightness variations along the rim are well reproduced with the scattering phase function of the model. While spirals can be triggered by the tidal interaction with the companion, the close proximity of the spirals to the shadows suggests that the shadows could also play a role. The change in stellar illumination along the rim, induces an azimuthal variation of the scale height that can contribute to the brightness variations. Dark regions in polarized images of transition disks are now detected in a handful of disks and often interpreted as shadows due to a misaligned inner disk. The origin of such a misalignment in HD 100453, and of the spirals, is unclear, and might be due to a yet-undetected massive companion inside the cavity, and on an inclined orbit.Comment: A&A, accepte

SPHERE: the exoplanet imager for the Very Large Telescope

Observations of circumstellar environments to look for the direct signal of exoplanets and the scattered light from disks has significant instrumental implications. In the past 15 years, major developments in adaptive optics, coronagraphy, optical manufacturing, wavefront sensing and data processing, together with a consistent global system analysis have enabled a new generation of high-contrast imagers and spectrographs on large ground-based telescopes with much better performance. One of the most productive is the Spectro-Polarimetic High contrast imager for Exoplanets REsearch (SPHERE) designed and built for the ESO Very Large Telescope (VLT) in Chile. SPHERE includes an extreme adaptive optics system, a highly stable common path interface, several types of coronagraphs and three science instruments. Two of them, the Integral Field Spectrograph (IFS) and the Infra-Red Dual-band Imager and Spectrograph (IRDIS), are designed to efficiently cover the near-infrared (NIR) range in a single observation for efficient young planet search. The third one, ZIMPOL, is designed for visible (VIR) polarimetric observation to look for the reflected light of exoplanets and the light scattered by debris disks. This suite of three science instruments enables to study circumstellar environments at unprecedented angular resolution both in the visible and the near-infrared. In this work, we present the complete instrument and its on-sky performance after 4 years of operations at the VLT.Comment: Final version accepted for publication in A&

Post conjunction detection of β\beta Pictoris b with VLT/SPHERE

With an orbital distance comparable to that of Saturn in the solar system, \bpic b is the closest (semi-major axis $\simeq$\,9\,au) exoplanet that has been imaged to orbit a star. Thus it offers unique opportunities for detailed studies of its orbital, physical, and atmospheric properties, and of disk-planet interactions. With the exception of the discovery observations in 2003 with NaCo at the Very Large Telescope (VLT), all following astrometric measurements relative to \bpic have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters. We aimed at further constraining \bpic b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit. We used SPHERE at the VLT to precisely monitor the orbital motion of beta \bpic b since first light of the instrument in 2014. We were able to monitor the planet until November 2016, when its angular separation became too small (125 mas, i.e., 1.6\,au) and prevented further detection. We redetected \bpic b on the northeast side of the disk at a separation of 139\,mas and a PA of 30$^{\circ}$ in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of $a = 9.0 \pm 0.5$ au (1 $\sigma$), it definitely excludes previously reported possible long orbital periods, and excludes \bpic b as the origin of photometric variations that took place in 1981. We also refine the eccentricity and inclination of the planet. From an instrumental point of view, these data demonstrate that it is possible to detect, if they exist, young massive Jupiters that orbit at less than 2 au from a star that is 20 pc away.Comment: accepted by A&

Transiting exoplanets from the CoRoT space mission VIII. CoRoT-7b: the first Super-Earth with measured radius

We report the discovery of very shallow (DF/F = 3.4 10-4), periodic dips in the light curve of an active V = 11.7 G9V star observed by the CoRoT satellite, which we interpret as due to the presence of a transiting companion. We describe the 3-colour CoRoT data and complementary ground-based observations that support the planetary nature of the companion. Methods. We use CoRoT color information, good angular resolution ground-based photometric observations in- and out- of transit, adaptive optics imaging, near-infrared spectroscopy and preliminary results from Radial Velocity measurements, to test the diluted eclipsing binary scenarios. The parameters of the host star are derived from optical spectra, which were then combined with the CoRoT light curve to derive parameters of the companion. We examine carefully all conceivable cases of false positives, and all tests performed support the planetary hypothesis. Blends with separation larger than 0.40 arcsec or triple systems are almost excluded with a 8 10-4 risk left. We conclude that, as far as we have been exhaustive, we have discovered a planetary companion, named CoRoT-7b, for which we derive a period of 0.853 59 +/- 3 10-5 day and a radius of Rp = 1.68 +/- 0.09 REarth. Analysis of preliminary radial velocity data yields an upper limit of 21 MEarth for the companion mass, supporting the finding. CoRoT-7b is very likely the first Super-Earth with a measured radius.Comment: Accepted in Astronomy and Astrophysics; typos and language corrections; version sent to the printer w few upgrade

Effectiveness and safety of obeticholic acid in a Southern European multicenter cohort of patients with primary biliary cholangitis and suboptimal response to ursodeoxycholic acid

Background Obeticholic acid (OCA) was recently approved as the only on-label alternative for patients with primary biliary cholangitis (PBC) with intolerance or suboptimal response to ursodeoxycholic acid (UDCA). However, few data are available outside clinical trials. Aim To assess the effectiveness and safety of OCA in a real-world cohort of patients with non-effective UDCA therapy. Methods Open-label, prospective, real-world, multicentre study, enrolling consecutive patients who did not meet Paris II criteria, from 18 institutions in Spain and Portugal. Effectiveness was assessed by the changes in GLOBE and UK-PBC scores from baseline. POISE and Paris II criteria were evaluated after 12 months of OCA . Liver fibrosis was evaluated by FIB-4 and AST to platelet ratio index (APRI). Results One hundred and twenty patients were eligible, median time since PBC diagnosis 9.3 (4.0-13.8) years, 21.7% had cirrhosis, and 26.7% received had previous or concomitant treatment with fibrates. Seventy-eight patients completed at least 1 year of OCA. The Globe-PBC score decreased to 0.17 (95% CI 0.05 to 0.28; P = 0.005) and the UK-PBC score decreased to 0.81 (95% CI -0.19 to 1.80; P = 0.11). There was a significant decrease in alkaline phosphatase of 81.3 U/L (95% CI 42.5 to 120; P < 0.001), ALT 22.1 U/L (95% CI 10.4 to 33.8; P < 0.001) and bilirubin 0.12 mg/dL (95% CI 0 to 0.24; P = 0.044). FIB-4 and APRI remained stable. According to the POISE criteria, 29.5% (23 out of 78) achieved response. The adverse events rate was 35%; 11.67% discontinued (8.3% due to pruritus). Conclusions This study supports data from phase III trials with significant improvement of PBC-Globe continuous prognostic marker score among OCA-treated patients with good tolerability

Effectiveness, safety/tolerability of OBV/PTV/r ± DSV in patients with HCV genotype 1 or 4 with/without HIV-1 co-infection, chronic kidney disease (CKD) stage IIIb/V and dialysis in Spanish clinical practice – preliminary data Vie-KinD study

Poster presentatio

Longitudinal outcomes of obeticholic acid therapy in ursodiol-nonresponsive primary biliary cholangitis: Stratifying the impact of add-on fibrates in real-world practice

Background Suboptimal response to ursodeoxycholic acid occurs in 40% of primary biliary cholangitis (PBC) patients, affecting survival. Achieving a deep response (normalisation of alkaline phosphatase [ALP] and bilirubin ≤0.6 upper limit of normal) improves survival. Yet, the long-term effectiveness of second-line treatments remains uncertain. Aims To evaluate the long-term effectiveness of obeticholic acid (OCA) ± fibrates. Focusing on biochemical response (ALP ≤1.67 times the upper limit of normal, with a decrease of at least 15% from baseline and normal bilirubin levels), normalisation of ALP, deep response and biochemical remission (deep response plus aminotransferase normalisation). Methods We conducted a longitudinal, observational, multicentre study involving ursodeoxyccholic acid non-responsive PBC patients (Paris-II criteria) from Spain and Portugal who received OCA ± fibrates. Results Of 255 patients, median follow-up was 35.1 months (IQR: 20.2–53). The biochemical response in the whole cohort was 47.2%, 61.4% and 68.6% at 12, 24 and 36 months. GLOBE-PBC and 5-year UK-PBC scores improved (p < 0.001). Triple therapy (ursodeoxycholic acid plus OCA plus fibrates) had significantly higher response rates than dual therapy (p = 0.001), including ALP normalisation, deep response and biochemical remission (p < 0.001). In multivariate analysis, triple therapy remained independently associated with biochemical response (p = 0.024), alkaline phosphatase normalisation, deep response and biochemical remission (p < 0.001). Adverse effects occurred in 41.2% of cases, leading to 18.8% discontinuing OCA. Out of 55 patients with cirrhosis, 12 developed decompensation. All with baseline portal hypertension. Conclusion Triple therapy was superior in achieving therapeutic goals in UDCA-nonresponsive PBC. Decompensation was linked to pre-existing portal hypertension

Tau Interaction with Tubulin and Microtubules: From Purified Proteins to Cells

International audienceMicrotubules (MTs) play an important role in many cellular processes and are dynamic structures regulated by an important network of microtubules-associated proteins, MAPs, such as Tau. Tau has been discovered as an essential factor for MTs formation in vitro, and its region implicated in binding to MTs has been identified. By contrast, the affinity, the stoichiometry, and the topology of Tau-MTs interaction remain controversial. Indeed, depending on the experiment conditions a wide range of values have been obtained. In this chapter, we focus on three biophysical methods, turbidimetry, cosedimentation assay, and Förster Resonance Energy Transfer to study Tau-tubulin interaction both in vitro and in cell. We highlight precautions that must be taken in order to avoid pitfalls and we detail the nature of the conclusions that can be drawn from these methods about Tau-tubulin interaction