| 1. |
- Romagnoni, A, et al.
(författare)
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Comparative performances of machine learning methods for classifying Crohn Disease patients using genome-wide genotyping data
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10351-
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Tidskriftsartikel (refereegranskat)abstract
- Crohn Disease (CD) is a complex genetic disorder for which more than 140 genes have been identified using genome wide association studies (GWAS). However, the genetic architecture of the trait remains largely unknown. The recent development of machine learning (ML) approaches incited us to apply them to classify healthy and diseased people according to their genomic information. The Immunochip dataset containing 18,227 CD patients and 34,050 healthy controls enrolled and genotyped by the international Inflammatory Bowel Disease genetic consortium (IIBDGC) has been re-analyzed using a set of ML methods: penalized logistic regression (LR), gradient boosted trees (GBT) and artificial neural networks (NN). The main score used to compare the methods was the Area Under the ROC Curve (AUC) statistics. The impact of quality control (QC), imputing and coding methods on LR results showed that QC methods and imputation of missing genotypes may artificially increase the scores. At the opposite, neither the patient/control ratio nor marker preselection or coding strategies significantly affected the results. LR methods, including Lasso, Ridge and ElasticNet provided similar results with a maximum AUC of 0.80. GBT methods like XGBoost, LightGBM and CatBoost, together with dense NN with one or more hidden layers, provided similar AUC values, suggesting limited epistatic effects in the genetic architecture of the trait. ML methods detected near all the genetic variants previously identified by GWAS among the best predictors plus additional predictors with lower effects. The robustness and complementarity of the different methods are also studied. Compared to LR, non-linear models such as GBT or NN may provide robust complementary approaches to identify and classify genetic markers.
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| 2. |
- Chauvin, G., et al.
(författare)
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Discovery of a warm, dusty giant planet around HIP 65426
- 2017
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 605
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Tidskriftsartikel (refereegranskat)abstract
- Aims. The SHINE program is a high-contrast near-infrared survey of 600 young, nearby stars aimed at searching for and characterizing new planetary systems using VLT/SPHERE's unprecedented high-contrast and high-angular-resolution imaging capabilities. It is also intended to place statistical constraints on the rate, mass and orbital distributions of the giant planet population at large orbits as a function of the stellar host mass and age to test planet-formation theories.Methods. We used the IRDIS dual-band imager and the IFS integral field spectrograph of SPHERE to acquire high-contrast coronagraphic differential near-infrared images and spectra of the young A2 star HIP 65426. It is a member of the similar to 17 Myr old Lower Centaurus-Crux association. Results. At a separation of 830 mas (92 au projected) from the star, we detect a faint red companion. Multi-epoch observations confirm that it shares common proper motion with HIP 65426. Spectro-photometric measurements extracted with IFS and IRDIS between 0.95 and 2.2 mu m indicate a warm, dusty atmosphere characteristic of young low-surface-gravity L5-L7 dwarfs. Hot-start evolutionary models predict a luminosity consistent with a 6-12 M-Jup, T-eff = 1300-1600K and R = 1.5 +/- 0.1 R-Jup giant planet. Finally, the comparison with Exo-REM and PHOENIX BT-Settl synthetic atmosphere models gives consistent effective temperatures but with slightly higher surface gravity solutions of log(g) = 4.0-5.0 with smaller radii (1.0-1.3 R-Jup).Conclusions. Given its physical and spectral properties, HIP 65426 b occupies a rather unique placement in terms of age, mass, and spectral-type among the currently known imaged planets. It represents a particularly interesting case to study the presence of clouds as a function of particle size, composition, and location in the atmosphere, to search for signatures of non-equilibrium chemistry, and finally to test the theory of planet formation and evolution.
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| 3. |
- Keppler, M., et al.
(författare)
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Discovery of a planetary-mass companion within the gap of the transition disk around PDS 70
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 617
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Tidskriftsartikel (refereegranskat)abstract
- Context. Young circumstellar disks are the birthplaces of planets. Their study is of prime interest to understand the physical and chemical conditions under which planet formation takes place. Only very few detections of planet candidates within these disks exist, and most of them are currently suspected to be disk features.Aims. In this context, the transition disk around the young star PDS 70 is of particular interest, due to its large gap identified in previous observations, indicative of ongoing planet formation. We aim to search for the presence of an embedded young planet and search for disk structures that may be the result of disk-planet interactions and other evolutionary processes.Methods. We analyse new and archival near-infrared images of the transition disk PDS 70 obtained with the VLT/SPHERE, VLT/NaCo, and Gemini/NICI instruments in polarimetric differential imaging and angular differential imaging modes.Results. We detect a point source within the gap of the disk at about 195 mas (similar to 22 au) projected separation. The detection is confirmed at five different epochs, in three filter bands and using different instruments. The astrometry results in an object of bound nature, with high significance. The comparison of the measured magnitudes and colours to evolutionary tracks suggests that the detection is a companion of planetary mass. The luminosity of the detected object is consistent with that of an L-type dwarf, but its IR colours are redder, possibly indicating the presence of warm surrounding material. Further, we confirm the detection of a large gap of similar to 54 au in size within the disk in our scattered light images, and detect a signal from an inner disk component. We find that its spatial extent is very likely smaller than similar to 17 au in radius, and its position angle is consistent with that of the outer disk. The images of the outer disk show evidence of a complex azimuthal brightness distribution which is different at different wavelengths and may in part be explained by Rayleigh scattering from very small grains.Conclusions. The detection of a young protoplanet within the gap of the transition disk around PDS 70 opens the door to a so far observationally unexplored parameter space of planetary formation and evolution. Future observations of this system at different wavelengths and continuing astrometry will allow us to test theoretical predictions regarding planet-disk interactions, planetary atmospheres, and evolutionary models.
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| 4. |
- Lagrange, A. -M., et al.
(författare)
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Post-conjunction detection of beta Pictoris b with VLT/SPHERE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 621
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Tidskriftsartikel (refereegranskat)abstract
- Context. With an orbital distance comparable to that of Saturn in the solar system, beta Pictoris b is the closest (semi-major axis similar or equal to 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 beta Pictoris have been obtained in the southwestern part of the orbit, which severely limits the determination of the planet's orbital parameters.Aims. We aimed at further constraining beta Pictoris b orbital properties using more data, and, in particular, data taken in the northeastern part of the orbit.Methods. We used SPHERE at the VLT to precisely monitor the orbital motion of beta beta Pictoris b since first light of the instrument in 2014.Results. 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 beta Pictoris b on the northeast side of the disk at a separation of 139 mas and a PA of 30 degrees in September 2018. The planetary orbit is now well constrained. With a semi-major axis (sma) of a = 9.0 +/- 0.5 au (1 sigma), it definitely excludes previously reported possible long orbital periods, and excludes beta Pictoris 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.
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| 5. |
- Desidera, S., et al.
(författare)
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The SPHERE infrared survey for exoplanets (SHINE) I. Sample definition and target characterization
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- Context. Large surveys with new-generation high-contrast imaging instruments are needed to derive the frequency and properties of exoplanet populations with separations from ~5 to 300 au. A careful assessment of the stellar properties is crucial for a proper understanding of when, where, and how frequently planets form, and how they evolve. The sensitivity of detection limits to stellar age makes this a key parameter for direct imaging surveys.Aims. We describe the SpHere INfrared survey for Exoplanets (SHINE), the largest direct imaging planet-search campaign initiated at the VLT in 2015 in the context of the SPHERE Guaranteed Time Observations of the SPHERE consortium. In this first paper we present the selection and the properties of the complete sample of stars surveyed with SHINE, focusing on the targets observed during the first phase of the survey (from February 2015 to February 2017). This early sample composed of 150 stars is used to perform a preliminary statistical analysis of the SHINE data, deferred to two companion papers presenting the survey performance, main discoveries, and the preliminary statistical constraints set by SHINE.Methods. Based on a large database collecting the stellar properties of all young nearby stars in the solar vicinity (including kinematics, membership to moving groups, isochrones, lithium abundance, rotation, and activity), we selected the original sample of 800 stars that were ranked in order of priority according to their sensitivity for planet detection in direct imaging with SPHERE. The properties of the stars that are part of the early statistical sample wererevisited, including for instance measurements from the Gaia Data Release 2. Rotation periods were derived for the vast majority of the late-type objects exploiting TESS light curves and dedicated photometric observations.Results. The properties of individual targets and of the sample as a whole are presented.
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| 6. |
- Langlois, M., et al.
(författare)
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The SPHERE infrared survey for exoplanets (SHINE) : II. Observations, data reduction and analysis, detection performances, and initial results
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- Context. In recent decades, direct imaging has confirmed the existence of substellar companions (exoplanets or brown dwarfs) on wide orbits (>10 au) around their host stars. In striving to understand their formation and evolution mechanisms, in 2015 we initiated the SPHERE infrared survey for exoplanets (SHINE), a systematic direct imaging survey of young, nearby stars that is targeted at exploring their demographics.Aims. We aim to detect and characterize the population of giant planets and brown dwarfs beyond the snow line around young, nearby stars. Combined with the survey completeness, our observations offer the opportunity to constrain the statistical properties (occurrence, mass and orbital distributions, dependency on the stellar mass) of these young giant planets.Methods. In this study, we present the observing and data analysis strategy, the ranking process of the detected candidates, and the survey performances for a subsample of 150 stars that are representative of the full SHINE sample. Observations were conducted in a homogeneous way between February 2015 and February 2017 with the dedicated ground-based VLT/SPHERE instrument equipped with the IFS integral field spectrograph and the IRDIS dual-band imager, covering a spectral range between 0.9 and 2.3 μm. We used coronographic, angular, and spectral differential imaging techniques to achieve the best detection performances for this study, down to the planetary mass regime.Results. We processed, in a uniform manner, more than 300 SHINE observations and datasets to assess the survey typical sensitivity as a function of the host star and of the observing conditions. The median detection performance reached 5σ-contrasts of 13 mag at 200 mas and 14.2 mag at 800 mas with the IFS (YJ and YJH bands), and of 11.8 mag at 200 mas, 13.1 mag at 800 mas, and 15.8 mag at 3 as with IRDIS in H band, delivering one of the deepest sensitivity surveys thus far for young, nearby stars. A total of sixteen substellar companions were imaged in this first part of SHINE: seven brown dwarf companions and ten planetary-mass companions.These include two new discoveries, HIP 65426 b and HIP 64892 B, but not the planets around PDS70 that had not been originally selected for the SHINE core sample. A total of 1483 candidates were detected, mainly in the large field of view that characterizes IRDIS. The color-magnitude diagrams, low-resolution spectrum (when available with IFS), and follow-up observations enabled us to identify the nature (background contaminant or comoving companion) of about 86% of our subsample. The remaining cases are often connected to crowded-field follow-up observations that were missing. Finally, even though SHINE was not initially designed for disk searches, we imaged twelve circumstellar disks, including three new detections around the HIP 73145, HIP 86598, and HD 106906 systems.Conclusions. Nowadays, direct imaging provides a unique opportunity to probe the outer part of exoplanetary systems beyond 10 au to explore planetary architectures, as highlighted by the discoveries of: one new exoplanet, one new brown dwarf companion, and three new debris disks during this early phase of SHINE. It also offers the opportunity to explore and revisit the physical and orbital properties of these young, giant planets and brown dwarf companions (relative position, photometry, and low-resolution spectrum in near-infrared, predicted masses, and contrast in order to search for additional companions). Finally, these results highlight the importance of finalizing the SHINE systematic observation of about 500 young, nearby stars for a full exploration of their outer part to explore the demographics of young giant planets beyond 10 au and to identify the most interesting systems for the next generation of high-contrast imagers on very large and extremely large telescopes.
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| 7. |
- Momozawa, Y, et al.
(författare)
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IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 2427-
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Tidskriftsartikel (refereegranskat)abstract
- GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach.
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| 8. |
- Vigan, A., et al.
(författare)
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The SPHERE infrared survey for exoplanets (SHINE) : III. The demographics of young giant exoplanets below 300 au with SPHERE
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 651
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Tidskriftsartikel (refereegranskat)abstract
- The SpHere INfrared Exoplanet (SHINE) project is a 500-star survey performed with SPHERE on the Very Large Telescope for the purpose of directly detecting new substellar companions and understanding their formation and early evolution. Here we present an initial statistical analysis for a subsample of 150 stars spanning spectral types from B to M that are representative of the full SHINE sample. Our goal is to constrain the frequency of substellar companions with masses between 1 and 75 MJup and semimajor axes between 5 and 300 au. For this purpose, we adopt detection limits as a function of angular separation from the survey data for all stars converted into mass and projected orbital separation using the BEX-COND-hot evolutionary tracks and known distance to each system. Based on the results obtained for each star and on the 13 detections in the sample, we use a Markov chain Monte Carlo tool to compare our observations to two different types of models. The first is a parametric model based on observational constraints, and the second type are numerical models that combine advanced core accretion and gravitational instability planet population synthesis. Using the parametric model, we show that the frequencies of systems with at least one substellar companion are 23.0−9.7+13.5, 5.8−2.8+4.7, and 12.6−7.1+12.9% for BA, FGK, and M stars, respectively. We also demonstrate that a planet-like formation pathway probably dominates the mass range from 1–75 MJup for companions around BA stars, while for M dwarfs, brown dwarf binaries dominate detections. In contrast, a combination of binary star-like and planet-like formation is required to best fit the observations for FGK stars. Using our population model and restricting our sample to FGK stars, we derive a frequency of 5.7−2.8+3.8%, consistent with predictions from the parametric model. More generally, the frequency values that we derive are in excellent agreement with values obtained in previous studies.
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| 9. |
- Cheetham, A., et al.
(författare)
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Discovery of a brown dwarf companion to the star HIP 64892
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 615
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery of a bright, brown dwarf companion to the star HIP 64892, imaged with VLT/SPHERE during the SHINE exoplanet survey. The host is a B9.5V member of the Lower-Centaurus-Crux subgroup of the Scorpius Centaurus OB association. The measured angular separation of the companion (1.2705 +/- 0.0023) corresponds to a projected distance of 159 +/- 12AU. We observed the target with the dual-band imaging and long-slit spectroscopy modes of the IRDIS imager to obtain its spectral energy distribution (SED) and astrometry. In addition, we reprocessed archival NACO L-band data, from which we also recover the companion. Its SED is consistent with a young (<30 Myr), low surface gravity object with a spectral type of M9 gamma +/- 1. From comparison with the BT-Settl atmospheric models we estimate an effective temperature of T-eff = 2600 +/- 100 K, and comparison of the companion photometry to the COND evolutionary models yields a mass of similar to 29-37 M-J at the estimated age of 16(-7)(+15) Myr for the system. The star HIP 64892 is a rare example of an extreme-mass ratio system (q similar to 0.01) and will be useful for testing models relating to the formation and evolution of such low-mass objects.
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| 10. |
- Vigan, A., et al.
(författare)
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First light of the VLT planet finder SPHERE I. Detection and characterization of the substellar companion GJ 758 B
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Tidskriftsartikel (refereegranskat)abstract
- GJ 758 B is a brown dwarf companion to a nearby (15.76%) solar-type, metal-rich (M/H = +0.2 dex) main-sequence star (G9V) that was discovered with Subaru/HiCIAO in 2009. From previous studies, it has drawn attention as being the coldest (similar to 600 K) companion ever directly imaged around a neighboring star. We present new high-contrast data obtained during the commissioning of the SPHERE instrument at the Very Large Telescope (VLT). The data was obtained in Y-, J-, H-, and K-s-bands with the dual-band imaging (DBI) mode of IRDIS, thus providing a broad coverage of the full near-infrared (near-IR) range at higher contrast and better spectral sampling than previously reported. In this new set of high-quality data, we report the re-detection of the companion, as well as the first detection of a new candidate closer-in to the star. We use the new eight photometric points for an extended comparison of GJ 758 B with empirical objects and four families of atmospheric models. From comparison to empirical object, we estimate a T8 spectral type, but none of the comparison objects can accurately represent the observed near-IR fluxes of GJ 758 B. From comparison to atmospheric models, we attribute a T-eff = 600 +/- 100 K, but we find that no atmospheric model can adequately fit all the fluxes of GJ 758 B. The lack of exploration of metal enrichment in model grids appears as a major limitation that prevents an accurate estimation of the companion physical parameters. The photometry of the new candidate companion is broadly consistent with L-type objects, but a second epoch with improved photometry is necessary to clarify its status. The new astrometry of GJ 758 B shows a significant proper motion since the last epoch. We use this result to improve the determination of the orbital characteristics using two fitting approaches: Least-Squares Monte Carlo and Markov chain Monte Carlo. We confirm the high-eccentricity of the orbit (peak at 0.5), and find a most likely semi-major axis of 46.05 AU. We also use our imaging data, as well as archival radial velocity data, to reject the possibility that this is a false positive effect created by an unseen, closer-in, companion. Finally, we analyze the sensitivity of our data to additional closer-in companions and reject the possibility of other massive brown dwarf companions down to 4-5 AU.
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| 11. |
- Zurlo, A., et al.
(författare)
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First light of the VLT planet finder SPHERE III. New spectrophotometry and astrometry of the HR 8799 exoplanetary system
- 2016
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 587
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Tidskriftsartikel (refereegranskat)abstract
- Context. The planetary system discovered around the young A-type HR8799 provides a unique laboratory to: a) test planet formation theories; b) probe the diversity of system architectures at these separations, and c) perform comparative (exo)planetology.Aims. We present and exploit new near-infrared images and integral-field spectra of the four gas giants surrounding HR8799 obtained with SPHERE, the new planet finder instrument at the Very Large Telescope, during the commissioning and science verification phase of the instrument (July-December 2014). With these new data, we contribute to completing the spectral energy distribution (SED) of these bodies in the 1.0-2.5 mu m range. We also provide new astrometric data, in particular for planet e, to further constrain the orbits.Methods. We used the infrared dual-band imager and spectrograph (IRDIS) subsystem to obtain pupil-stabilized, dual-band H2H3 (1.593 mu m, 1.667 mu m), K1K2 (2.110 mu m, 2.251 mu m), and broadband J (1.245 mu m) images of the four planets. IRDIS was operated in parallel with the integral field spectrograph (IFS) of SPHERE to collect low-resolution (R similar to 30), near-infrared (0.94-1.64 mu m) spectra of the two innermost planets HR8799 d and e. The data were reduced with dedicated algorithms, such as the Karhunen-Loeve image projection (KLIP), to reveal the planets. We used the so-called negative planets injection technique to extract their photometry, spectra, and measure their positions. We illustrate the astrometric performance of SPHERE through sample orbital fits compatible with SPHERE and literature data.Results. We demonstrated the ability of SPHERE to detect and characterize planets in this kind of systems, providing spectra and photometry of its components. The spectra improve upon the signal-to-noise ratio of previously obtained data and increase the spectral coverage down to the Y band. In addition, we provide the first detection of planet e in the J band. Astrometric positions for planets HR8799 bcde are reported for the epochs of July, August, and December 2014. We measured the photometric values in J, H2H3, K1K2 bands for the four planets with a mean accuracy of 0.13 mag. We found upper limit constraints on the mass of a possible planet f of 3-7 M-Jup. Our new measurements are more consistent with the two inner planets d and e being in a 2d:1e or 3d:2e resonance. The spectra of HR8799 d and e are well matched by those of L6-8 field dwarfs. However, the SEDs of these objects are redder than field L dwarfs longward of 1.6 mu m.
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| 12. |
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| 13. |
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| 14. |
- Cugno, G., et al.
(författare)
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A search for accreting young companions embedded in circumstellar disks High-contrast H alpha imaging with VLT/SPHERE
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 622
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Tidskriftsartikel (refereegranskat)abstract
- Context. In recent years, our understanding of giant planet formation progressed substantially. There have even been detections of a few young protoplanet candidates still embedded in the circumstellar disks of their host stars. The exact physics that describes the accretion of material from the circumstellar disk onto the suspected circumplanetary disk and eventually onto the young, forming planet is still an open question.Aims. We seek to detect and quantify observables related to accretion processes occurring locally in circumstellar disks, which could be attributed to young forming planets. We focus on objects known to host protoplanet candidates and/or disk structures thought to be the result of interactions with planets.Methods. We analyzed observations of six young stars (age 3.5-10 Myr) and their surrounding environments with the SPHERE/ZIMPOL instrument on the Very Large Telescope (VLT) in the H alpha filter (656 nm) and a nearby continuum filter (644.9 nm). We applied several point spread function (PSF) subtraction techniques to reach the highest possible contrast near the primary star, specifically investigating regions where forming companions were claimed or have been suggested based on observed disk morphology.Results. We redetect the known accreting M-star companion HD142527 B with the highest published signal to noise to date in both H alpha and the continuum. We derive new astrometry (r = 62.8(-2.7)(+2.1)mas and PA = (98.7 +/- 1.8)degrees) and photometry (Delta N_Ha = 6.3-(+0.2)(0.3) mag, Delta B_Ha = 6.7 +/- 0.2 mag and Delta Cnt_Ha= 7.3(-0.2)(+0.3) mag) for the companion in agreement with previous studies, and estimate its mass accretion rate (M approximate to 1-2 x 10(-10) M-circle dot yr(-1)). A faint point-like source around HD135344 B (SA0206462) is also investigated, but a second deeper observation is required to reveal its nature. No other companions are detected. In the framework of our assumptions we estimate detection limits at the locations of companion candidates around HD100546, HD169142, and MWC 758 and calculate that processes involving Ha fluxes larger than similar to 8 x 10(-14)-10(-15) erg s(-1) cm(-2) (M > 10(-10)-10(-12) M-circle dot yr(-1)) can be excluded. Furthermore, flux upper limits of similar to 10(-14)-10(-15)erg s(-1) cm(-2) (M < 10(-11) -10(-12)M(circle dot )yr(-1)) are estimated within the gaps identified in the disks surrounding HD135344 B and TW Hya. The derived luminosity limits exclude H alpha signatures at levels similar to those previously detected for the accreting planet candidate LkCa15 b.
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| 15. |
- Ruemmele, F M, et al.
(författare)
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Consensus guidelines of ECCO/ESPGHAN on the medical management of pediatric Crohn's disease.
- 2014
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Ingår i: Journal of Crohn's & Colitis. - : Oxford University Press (OUP). - 1873-9946 .- 1876-4479. ; 8:10, s. 1179-207
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Tidskriftsartikel (refereegranskat)abstract
- Children and adolescents with Crohn's disease (CD) present often with a more complicated disease course compared to adult patients. In addition, the potential impact of CD on growth, pubertal and emotional development of patients underlines the need for a specific management strategy of pediatric-onset CD. To develop the first evidenced based and consensus driven guidelines for pediatric-onset CD an expert panel of 33 IBD specialists was formed after an open call within the European Crohn's and Colitis Organisation and the European Society of Pediatric Gastroenterolog, Hepatology and Nutrition. The aim was to base on a thorough review of existing evidence a state of the art guidance on the medical treatment and long term management of children and adolescents with CD, with individualized treatment algorithms based on a benefit-risk analysis according to different clinical scenarios. In children and adolescents who did not have finished their growth, exclusive enteral nutrition (EEN) is the induction therapy of first choice due to its excellent safety profile, preferable over corticosteroids, which are equipotential to induce remission. The majority of patients with pediatric-onset CD require immunomodulator based maintenance therapy. The experts discuss several factors potentially predictive for poor disease outcome (such as severe perianal fistulizing disease, severe stricturing/penetrating disease, severe growth retardation, panenteric disease, persistent severe disease despite adequate induction therapy), which may incite to an anti-TNF-based top down approach. These guidelines are intended to give practical (whenever possible evidence-based) answers to (pediatric) gastroenterologists who take care of children and adolescents with CD; they are not meant to be a rule or legal standard, since many different clinical scenario exist requiring treatment strategies not covered by or different from these guidelines.
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| 16. |
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| 17. |
- Hugot, J-P, et al.
(författare)
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Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease
- 2001
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 411:6837, s. 599-603
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease and ulcerative colitis, the two main types of chronic inflammatory bowel disease, are multifactorial conditions of unknown aetiology. A susceptibility locus for Crohn's disease has been mapped to chromosome 16. Here we have used a positional-cloning strategy, based on linkage analysis followed by linkage disequilibrium mapping, to identify three independent associations for Crohn's disease: a frameshift variant and two missense variants of NOD2, encoding a member of the Apaf-1/Ced-4 superfamily of apoptosis regulators that is expressed in monocytes. These NOD2 variants alter the structure of either the leucine-rich repeat domain of the protein or the adjacent region. NOD2 activates nuclear factor NF-?B, this activating function is regulated by the carboxy-terminal leucine-rich repeat domain, which has an inhibitory role and also acts as an intracellular receptor for components of microbial pathogens. These observations suggest that the NOD2 gene product confers susceptibility to Crohn's disease by altering the recognition of these components and/or by over-activating NF-?B in monocytes, thus documenting a molecular model for the pathogenic mechanism of Crohn's disease that can now be further investigated.
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| 18. |
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| 19. |
- Peretti, S., et al.
(författare)
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Orbital and spectral analysis of the benchmark brown dwarf HD 4747B
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 631
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Tidskriftsartikel (refereegranskat)abstract
- Context. The study of high-contrast imaged brown dwarfs and exoplanets depends strongly on evolutionary models. To estimate the mass of a directly imaged substellar object, its extracted photometry or spectrum is used and adjusted with model spectra together with the estimated age of the system. These models still need to be properly tested and constrained. HD 4747B is a brown dwarf close to the H burning mass limit, orbiting a nearby (d = 19.25 +/- 0.58 pc), solar-type star (G9V); it has been observed with the radial velocity method for over almost two decades. Its companion was also recently detected by direct imaging, allowing a complete study of this particular object.Aims. We aim to fully characterize HD 4747B by combining a well-constrained dynamical mass and a study of its observed spectral features in order to test evolutionary models for substellar objects and to characterize its atmosphere.Methods. We combined the radial velocity measurements of High Resolution Echelle Spectrometer (HIRES) and CORALIE taken over two decades and high-contrast imaging of several epochs from NACO, NIRC2, and SPHERE to obtain a dynamical mass. From the SPHERE data we obtained a low-resolution spectrum of the companion from Y to H band, and two narrow band-width photometric measurements in the K band. A study of the primary star also allowed us to constrain the age of the system and its distance.Results. Thanks to the new SPHERE epoch and NACO archival data combined with previous imaging data and high-precision radial velocity measurements, we were able to derive a well-constrained orbit. The high eccentricity (e = 0.7362 +/- 0.0025) of HD 4747B is confirmed, and the inclination and the semi-major axis are derived (i = 47.3 +/- 1.6 degrees, a = 10.01 +/- 0.21 au). We derive a dynamical mass of m(B) = 70.0 +/- 1.6 M-Jup, which is higher than a previous study but in better agreement with the models. By comparing the object with known brown dwarfs spectra, we derive a spectral type of L9 and an effective temperature of 1350 +/- 50 K. With a retrieval analysis we constrain the oxygen and carbon abundances and compare them with the values from the HR 8799 planets.
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| 20. |
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| 21. |
- Zouali, H, et al.
(författare)
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CARD4/NOD1 in inflammatory bowel disease.
- 2002
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Ingår i: American Journal of Human Genetics. - 0002-9297 .- 1537-6605. ; 71:4, s. 1877-
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)
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| 22. |
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| 23. |
- Franke, Andre, et al.
(författare)
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Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1118-1125
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Tidskriftsartikel (refereegranskat)abstract
- We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.
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| 24. |
- Hugot, JP, et al.
(författare)
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Clustering of Crohn's disease within affected sibships
- 2003
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 11:2, s. 179-184
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease (CD) is a complex genetic disorder for which aetiology is unknown. Recently, genetic factors for susceptibility have been described. Several genetic loci have been mapped and partially explain the familial aggregations of the disease. However, environmental factors may also contribute to these aggregations. We considered that if the role of non-genetic factors was negligible, CD patients would be randomly distributed in sibships with multiple affected siblings. On the other hand if there was a significant environmental contribution, the siblings would be affected non-randomly over exposure status. In order to test this hypothesis, we studied 102 sibships with two or more affected siblings. A statistical test, named Cluster of Affected Sibling Test or CAST, was developed, based on the exact calculation of the probability of observing a given number of clusters of affected siblings in multiplex families. The null hypothesis of a random distribution of affected siblings was rejected (P=0,005). The observed excess of affected sibling clusters indicates that birth order influences the disease status. Considering that an adjacent order of birth is a global estimate of environmental sharing, this observation strongly suggests that environmental factors contribute to the observed familial aggregations of the disease. This observation provides evidence that familial CD is a relevant tool for further studies of environmental factors and gene-environment interaction. More generally, the CAST statistics may be widely applicable to estimate the involvement of environmental factors in the aetiology of other binary traits which may be observed in multiple members of the same sibship.
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| 25. |
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| 26. |
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| 27. |
- Thiébaut, R., et al.
(författare)
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TNFSF15 polymorphisms are associated with susceptibility to inflammatory bowel disease in a new European cohort
- 2009
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Ingår i: American Journal of Gastroenterology. - : Ovid Technologies (Wolters Kluwer Health). - 0002-9270 .- 1572-0241. ; 104:2, s. 384-391
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Inflammatory bowel disease (IBD), e.g., Crohn's disease (CD) and ulcerative colitis (UC), is a complex genetic disorder. Tumor necrosis factor (ligand) superfamily, member 15 (TNFSF15) has been previously identified as a susceptibility gene for CD in Japanese and UK cohorts. This replication study was designed in order to confirm and further validate the role of TNFSF15 in IBD. METHODS: A total of 666 IBD families (corresponding to 2,982 relatives) with European ancestry were genotyped for the rs6478108 and rs7869487 polymorphisms, which define the main TNFSF15 haplotypes previously associated with CD. An association between the main haplotypes and CD, UC and IBD was tested using the Genehunter TDT and Unphased statistics. Caspase recruitment domain 15 (CARD15)/TNFSF15 interaction and genotype/phenotype correlations were also studied. RESULTS: The previously reported "high-risk" haplotype (A) was associated with IBD (P=0.001) (OR=1.25 (1.05-1.50)) and CD (P=0.02) (OR=1.31 (1.03-1.67)) whereas the "protective" (B) haplotype was significantly less transmitted to IBD and CD patients. No interaction between CARD15 and TNFSF15 was detected. We also failed to define a clinical subgroup of CD patients specifically associated with TNFSF15 haplotype A. CONCLUSIONS: This study confirms that TNFSF15 or a closely linked gene is involved in the genetic predisposition to CD.
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| 28. |
- Zouali, H, et al.
(författare)
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CARD4/NOD1 is not involved in inflammatory bowel disease
- 2003
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Ingår i: Gut. - : BMJ. - 0017-5749 .- 1468-3288. ; 52:1, s. 71-74
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Tidskriftsartikel (refereegranskat)abstract
- Background and aims: Inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are complex genetic disorders. CARD15/NOD2, a member of the Ced4 superfamily which includes Apaf-1 and CARD4/NOD1, has recently been associated with genetic predisposition to CD but additional genetic Factors remain to be identified. Because CARD4/NOD1 shares many structural and functional similarities with CARD15, we tested its putative role in IBD. Patients and methods: The 11 exons of CARD4 were screened for the presence of variants in 63 unrelated IBD patients. The only non-private genetic variation encoding for a substitution in the peptidic chain was genotyped in 381 IBD families (235 CD, 58 UC, 81 mixed, and seven indeterminate colitis families) using a polymerase chain reaction-restriction fragment length polymorphism procedure. Genotyping data were analysed by the transmission disequilibrium test. Results: Five of nine sequence variations identified in the coding sequence of the gene encoded for non-conservative changes (E266K, D372N, R705Q, T787M, and T787K). Four were present in only one family. The remaining variant (E266K), which exhibited an allele frequency of 0.28, was not associated with CD, UC, or IBD. Furthermore, IBD patients carrying sequence variations in their CARD4 gene had a similar phenotype to those with a normal sequence. Conclusion: Our results suggest that CARD4 does not play a major role in genetic susceptibility to IBD.
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| 29. |
- Zouali, H, et al.
(författare)
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Genetic refinement and physical mapping of a chromosome 16q candidate region for inflammatory bowel disease
- 2001
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Ingår i: European Journal of Human Genetics. - : Springer Science and Business Media LLC. - 1018-4813 .- 1476-5438. ; 9:10, s. 731-742
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Tidskriftsartikel (refereegranskat)abstract
- Crohn's disease (CD) is a complex genetic disorder for which a susceptibility gene, IBD1, has been mapped within the pericentromeric region of chromosome 16. In order to refine the location of IBD1, 77 multiplex CD families were genotyped for 26 microsatellite markers evenly spaced by approximately 1 cM. Nonparametric linkage analyses exhibited a maximum NPL score of 3.49 (P=2.37 ╫ 10-4) in a region centred by markers D16S3136, D16S3117 and D16S770. Simulation studies showed that the probability for IBD1 to be located in a 5 cM region around these markers was 70%. A 2.5 Mb YAC and BAC contig map spanning this genetic region on chromosome band 16q12 was built. TDT analyses demonstrated suggestive association between the 207 bp allele of D16S3136 (P<0.05) and a new biallellic marker hb27g11f-end (P=0.01). These markers were located in the hb27g11 and hb87b10 BAC clones from the contig. Taken together, the present results provide a crucial preliminary step before an exhaustive linkage disequilibrium mapping of putatively transcribed regions to identify IBD1.
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| 30. |
- Chassaing, Benoit, et al.
(författare)
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Crohn disease-associated adherent-invasive E. coli bacteria target mouse and human Peyers patches via long polar fimbriae
- 2011
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Ingår i: JOURNAL OF CLINICAL INVESTIGATION. - : American Society for Clinical Investigation. - 0021-9738. ; 121:3, s. 966-975
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Tidskriftsartikel (refereegranskat)abstract
- Crohn disease (CD) is a multifactorial disease in which an abnormal immune response in the gastrointestinal (GI) tract leads to chronic inflammation. The small intestine, particularly the ileum, of patients with CD is colonized by adherent-invasive E. coil (AIEC) a pathogenic group of E. coil able to adhere to and invade intestinal epithelial cells. As the earliest inflammatory lesions are microscopic erosions of the epithelium lining the Peyers patches (PPs), we investigated the ability of AIEC bacteria to interact with PPs and the virulence factors involved. We found that AIEC bacteria could interact with mouse and human PPs via long polar fimbriae (LPF). An LPF-negative AIEC mutant was highly impaired in its ability to interact with mouse and human PPs and to translocate across monolayers of M cells, specialized epithelial cells at the surface of PPs. The prevalence of AIEC strains harboring the lpf operon was markedly higher in CD patients compared with controls. In addition, increased numbers of AIEC, but not LPF-deficient AIEC, bacteria were found interacting with PPs from Nod2(-/-) mice compared with WT mice. In conclusion, we have identified LPF as a key factor for AIEC to target PPs. This could be the missing link between AIEC colonization and the presence of early lesions in the PPs of CD patients.
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| 31. |
- Hawkey, Christopher J, et al.
(författare)
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Less small-bowel injury with lumiracoxib compared with naproxen plus omeprazole
- 2008
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Ingår i: Clinical Gastroenterology and Hepatology. - : Elsevier BV. - 1542-7714 .- 1542-3565. ; 6:5, s. 536-544
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Tidskriftsartikel (refereegranskat)abstract
- Background & Aims: The selective cyclooxygenase-2 inhibitor lumiracoxib has been shown to reduce endoscopically detected ulcers and ulcer complications in the upper gastrointestinal tract compared with nonselective nonsteroidal anti-inflammatory drugs. We investigated whether lumiracoxib would reduce small-bowel injury compared with naproxen plus omeprazole. Methods: Healthy volunteers were randomized to receive lumiracoxib, 100 mg once daily, naproxen 500 mg twice daily plus omeprazole 20 mg once daily, or placebo in a 16-day double-blind, parallel-group study. Small-bowel mucosal injury and inflammation were assessed by video capsule endoscopy, the lactulose:L-rhamnose permeability assessment, and the fecal calprotectin test. Results: Of 152 randomized subjects, 139 completed the study with valid video capsule endoscopies (lumiracoxib, n = 47; naproxen plus omeprazole, n = 45; placebo, n = 47). Compared with placebo, an increased number of subjects on naproxen plus omeprazole had small-bowel mucosal breaks (77.8% vs 40.4%, P < .001), with increased permeability (P = .023) and increased fecal calprotectin (increase, 96.8 vs 14.5 mg/kg for placebo; P < .001). With lumiracoxib, 27.7% of subjects had small-bowel mucosal breaks (P = .196 vs placebo; P < .001 vs naproxen), there was no increase in permeability (P = .157 vs placebo; P = .364 vs naproxen), and no increase in fecal calprotectin (-5.7 mg/kg; P = .377 vs placebo; P < .001 vs naproxen). Conclusions: As assessed by 3 different measures, acute small-bowel injury on lumiracoxib treatment is less frequent than with naproxen plus omeprazole and similar to placebo.
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| 32. |
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| 33. |
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| 34. |
- Margaritte-Jeannin, P, et al.
(författare)
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HLA-DQ relative risks for coeliac disease in European populations: a study of the European Genetics Cluster on Coeliac Disease.
- 2004
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Ingår i: Tissue antigens. - : Wiley. - 0001-2815 .- 1399-0039. ; 63:6, s. 562-7
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Tidskriftsartikel (refereegranskat)abstract
- Coeliac disease is an enteropathy due to an intolerance to gluten. The association between HLA-DQ genes and CD is well established. The majority of patients carry the HLA-DQ heterodimer encoded by DQA1*05/DQB1*02, either in cis or in trans. The remaining patients carry either part of the DQ heterodimer or DQA1*03-DQB1*0302. The aim of the study was to estimate the risks associated with different DQ genotypes in European populations. HLA information was available for 470 trio families from four countries: France (117), Italy (128), and Norway and Sweden (225). Five DQA1-DQB1 haplotypes were considered and control haplotype frequencies were estimated from the set of parental haplotypes not transmitted to the affected child. The possible genotypes were grouped into five genotype groups, based on the hierarchy of risk reported in the literature. A north-south gradient in the genotype group frequencies is observed in probands: homogeneity is strongly rejected between all country pairs. For each country, the relative risks associated with each genotype group were computed taking into account the control haplotype frequencies. Homogeneity of relative risks between countries was tested pairwise by maximum likelihood ratio statistics. The hypothesis of homogeneity of relative risks is rejected (P is approximately 10(-6)) for all country pairs. In conclusion, the gradient in the genotype group frequencies in probands is not only due to differences in haplotype frequencies but also due to differences in genotype relative risks in the studied populations; the relative risks associated with each DQ genotype group are different between northern and southern European countries; neither are they ordered in the same way.
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| 35. |
- Mesa, D., et al.
(författare)
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Signs of late infall and possible planet formation around DR Tau using VLT/SPHERE and LBTI/LMIRCam
- 2022
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 658
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Tidskriftsartikel (refereegranskat)abstract
- Context. Protoplanetary disks around young stars often contain substructures like rings, gaps, and spirals that could be caused by interactions between the disk and forming planets.Aims. We aim to study the young (1-3 Myr) star DR Tau in the near-infrared and characterize its disk, which was previously resolved through submillimeter interferometry with ALMA, and to search for possible substellar companions embedded into it.Methods. We observed DR Tau with VLT/SPHERE both in polarized light (H broad band) and total intensity (in Y, J, H, and K spectral bands). We also performed L' band observations with LBTI/LMIRCam on the Large Binocular Telescope (LBT). We applied differential imaging techniques to analyze both the polarized data, using dual beam polarization imaging, and the total intensity data, using angular and spectral differential imaging.Results. We found two previously undetected spirals extending north-east and south of the star, respectively. We further detected an arc-like structure north of the star. Finally a bright, compact and elongated structure was detected at a separation of 303 +/- 10 mas and a position angle 21.2 +/- 3.7 degrees, just at the root of the north-east spiral arm. Since this feature is visible both in polarized light and total intensity and has a blue spectrum, it is likely caused by stellar light scattered by dust.Conclusions. The two spiral arms are at different separations from the star, have very different pitch angles, and are separated by an apparent discontinuity, suggesting they might have a different origin. The very open southern spiral arm might be caused by infalling material from late encounters with cloudlets into the formation environment of the star itself. The compact feature could be caused by interaction with a planet in formation still embedded in its dust envelope and it could be responsible for launching the north-east spiral. We estimate a mass of the putative embedded object of the order of few M-Jup.
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| 36. |
- Rigliaco, E., et al.
(författare)
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Investigating the nature of the extended structure around the Herbig star RCrA using integral field and high-resolution spectroscopy
- 2019
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 632
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Tidskriftsartikel (refereegranskat)abstract
- Context. We present a detailed analysis of the extended structure detected around the young and close-by Herbig Ae/Be star R CrA. This is a young triple system with an intermediate mass central binary whose separation is of the order of a few tens of the radii of the individual components, and an M-star companion at about 30 au.Aims. Our aim is to understand the nature of the extended structure by means of combining integral-field and high-resolution spectroscopy.Methods. We conducted the analysis based on FEROS archival optical spectroscopy data and adaptive optics images and integral-field spectra obtained with SINFONI and SPHERE at the VLT.Results. The observations reveal a complex extended structure that is composed of at least two components: a non-uniform wide cavity whose walls are detected in continuum emission up to 400 au, and a collimated wiggling-jet detected in the emission lines of helium and hydrogen. Moreover, the presence of [Fe II] emission projected close to the cavity walls suggests the presence of a slower moving wind, most likely a disk wind. The multiple components of the optical forbidden lines also indicate the presence of a high-velocity jet co-existing with a slow wind. We constructed a geometrical model of the collimated jet flowing within the cavity using intensity and velocity maps, finding that its wiggling is consistent with the orbital period of the central binary. The cavity and the jet do not share the same position angle, suggesting that the jet is itself experiencing a precession motion possibly due to the wide M-dwarf companion.Conclusions. We propose a scenario that closely agrees with the general expectation of a magneto-centrifugal-launched jet. These results build upon the extensive studies already conducted on R CrA.
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