Real‐world effectiveness of ustekinumab and vedolizumab in TNF‐exposed pediatric patients with ulcerative colitis

ObjectivesVedolizumab (VDZ) and ustekinumab (UST) are second-line treatments in pediatric patients with ulcerative colitis (UC) refractory to antitumor necrosis factor (anti-TNF) therapy. Pediatric studies comparing the effectiveness of these medications are lacking. Using a registry from ImproveCareNow (ICN), a global research network in pediatric inflammatory bowel disease, we compared the effectiveness of UST and VDZ in anti-TNF refractory UC.MethodsWe performed a propensity-score weighted regression analysis to compare corticosteroid-free clinical remission (CFCR) at 6 months from starting second-line therapy. Sensitivity analyses tested the robustness of our findings to different ways of handling missing outcome data. Secondary analyses evaluated alternative proxies of response and infection risk.ResultsOur cohort included 262 patients on VDZ and 74 patients on UST. At baseline, the two groups differed on their mean pediatric UC activity index (PUCAI) (p = 0.03) but were otherwise similar. At Month 6, 28.3% of patients on VDZ and 25.8% of those on UST achieved CFCR (p = 0.76). Our primary model showed no difference in CFCR (odds ratio: 0.81; 95% confidence interval [CI]: 0.41-1.59) (p = 0.54). The time to biologic discontinuation was similar in both groups (hazard ratio: 1.26; 95% CI: 0.76-2.08) (p = 0.36), with the reference group being VDZ, and we found no differences in clinical response, growth parameters, hospitalizations, surgeries, infections, or malignancy risk. Sensitivity analyses supported these findings of similar effectiveness.ConclusionsUST and VDZ are similarly effective for inducing clinical remission in anti-TNF refractory UC in pediatric patients. Providers should consider safety, tolerability, cost, and comorbidities when deciding between these therapies

The global dust SED: Tracing the nature and evolution of dust with DustEM

The Planck and Herschel missions are currently measuring the farIR-mm emission of dust, which combined with existing IR data, will for the first time provide the full SED of the galactic ISM dust emission with an unprecedented sensitivity and angular resolution. It will allow a systematic study of the dust evolution processes that affect the SED. Here we present a versatile numerical tool, DustEM, that predicts the emission and extinction of dust given their size distribution and their optical and thermal properties. In order to model dust evolution, DustEM has been designed to deal with a variety of grain types, structures and size distributions and to be able to easily include new dust physics. We use DustEM to model the dust SED and extinction in the diffuse interstellar medium at high-galactic latitude (DHGL), a natural reference SED. We present a coherent set of observations for the DHGL SED. The dust components in our DHGL model are (i) PAHs, (ii) amorphous carbon and (iii) amorphous silicates. We use amorphous carbon dust, rather than graphite, because it better explains the observed high abundances of gas-phase carbon in shocked regions of the interstellar medium. Using the DustEM model, we illustrate how, in the optically thin limit, the IRAS/Planck HFI (and likewise Spitzer/Herschel for smaller spatial scales) photometric band ratios of the dust SED can disentangle the influence of the exciting radiation field intensity and constrain the abundance of small grains relative to the larger grains. We also discuss the contributions of the different grain populations to the IRAS, Planck and Herschel channels. Such information is required to enable a study of the evolution of dust as well as to systematically extract the dust thermal emission from CMB data and to analyze the emission in the Planck polarized channels. The DustEM code described in this paper is publically available.Comment: accepted for publication in A&

Determination of the gas-to-dust ratio in nearby dense clouds using X-ray absorption measurements

We present a comparison of the gas and dust properties of the dense interstellar matter in six nearby star-forming regions (d<500 pc): rho Oph, Cha I, R CrA, IC 348, NGC 1333, and Orion. We measure from Chandra and XMM-Newton observations the X-ray absorption toward pre-main sequence stars (PMS) without accretion disks (i.e., Class III sources) to obtain the total hydrogen column density N_{H,X}. For these sources we take from the literature the corresponding dust extinction in the near-infrared, A_J, or when unavailable we derive it from SED fitting using the available DENIS, 2MASS, ISOCAM and other data. We then compare N_{H,X} and A_J for each object, up to unprecedently high extinction. For the rho Oph dark cloud with a relatively large sample of 20 bona-fide Class III sources, we probe the extinction up to A_J <~ 14 (A_V <~ 45), and find a best-fit linear relation N_{H,X}/A_J = 5.6 (+/- 0.4)x10^{21} cm^{-2} mag^{-1}, adopting standard ISM abundances. The other regions reveal a large dispersion in the N_{H,X}/A_J ratio for each source but for lack of adequate IR data these studies remain limited to moderate extinctions (A_J <~ 1.5 or A_V ~2 sigma) than the galactic value, derived using the standard extinction curve (R_V = 3.1). This result is consistent with the recent downwards revision of the metallicity of the Sun and stars in the solar vicinity. We find that the rho Oph dense cloud has the same metallicity than the local ISM when assuming that the galactic gas-to-dust ratio remains unchanged. The difference between galactic and local values of the gas-to-dust ratio can thus be attributed entirely to a difference in metallicity.Comment: 21 Pages including 12 figures. Accepted for publication in Astronomy and Astrophysic

PDRs4All III: JWST's NIR spectroscopic view of the Orion Bar

(Abridged) We investigate the impact of radiative feedback from massive stars on their natal cloud and focus on the transition from the HII region to the atomic PDR (crossing the ionisation front (IF)), and the subsequent transition to the molecular PDR (crossing the dissociation front (DF)). We use high-resolution near-IR integral field spectroscopic data from NIRSpec on JWST to observe the Orion Bar PDR as part of the PDRs4All JWST Early Release Science Program. The NIRSpec data reveal a forest of lines including, but not limited to, HeI, HI, and CI recombination lines, ionic lines, OI and NI fluorescence lines, Aromatic Infrared Bands (AIBs including aromatic CH, aliphatic CH, and their CD counterparts), CO2 ice, pure rotational and ro-vibrational lines from H2, and ro-vibrational lines HD, CO, and CH+, most of them detected for the first time towards a PDR. Their spatial distribution resolves the H and He ionisation structure in the Huygens region, gives insight into the geometry of the Bar, and confirms the large-scale stratification of PDRs. We observe numerous smaller scale structures whose typical size decreases with distance from Ori C and IR lines from CI, if solely arising from radiative recombination and cascade, reveal very high gas temperatures consistent with the hot irradiated surface of small-scale dense clumps deep inside the PDR. The H2 lines reveal multiple, prominent filaments which exhibit different characteristics. This leaves the impression of a "terraced" transition from the predominantly atomic surface region to the CO-rich molecular zone deeper in. This study showcases the discovery space created by JWST to further our understanding of the impact radiation from young stars has on their natal molecular cloud and proto-planetary disk, which touches on star- and planet formation as well as galaxy evolution.Comment: 52 pages, 30 figures, submitted to A&

PDRs4All IV. An embarrassment of riches: Aromatic infrared bands in the Orion Bar

(Abridged) Mid-infrared observations of photodissociation regions (PDRs) are dominated by strong emission features called aromatic infrared bands (AIBs). The most prominent AIBs are found at 3.3, 6.2, 7.7, 8.6, and 11.2 $\mu$m. The most sensitive, highest-resolution infrared spectral imaging data ever taken of the prototypical PDR, the Orion Bar, have been captured by JWST. We provide an inventory of the AIBs found in the Orion Bar, along with mid-IR template spectra from five distinct regions in the Bar: the molecular PDR, the atomic PDR, and the HII region. We use JWST NIRSpec IFU and MIRI MRS observations of the Orion Bar from the JWST Early Release Science Program, PDRs4All (ID: 1288). We extract five template spectra to represent the morphology and environment of the Orion Bar PDR. The superb sensitivity and the spectral and spatial resolution of these JWST observations reveal many details of the AIB emission and enable an improved characterization of their detailed profile shapes and sub-components. While the spectra are dominated by the well-known AIBs at 3.3, 6.2, 7.7, 8.6, 11.2, and 12.7 $\mu$m, a wealth of weaker features and sub-components are present. We report trends in the widths and relative strengths of AIBs across the five template spectra. These trends yield valuable insight into the photochemical evolution of PAHs, such as the evolution responsible for the shift of 11.2 $\mu$m AIB emission from class B$_{11.2}$ in the molecular PDR to class A$_{11.2}$ in the PDR surface layers. This photochemical evolution is driven by the increased importance of FUV processing in the PDR surface layers, resulting in a "weeding out" of the weakest links of the PAH family in these layers. For now, these JWST observations are consistent with a model in which the underlying PAH family is composed of a few species: the so-called 'grandPAHs'.Comment: 25 pages, 10 figures, to appear in A&

PDRs4All II: JWST's NIR and MIR imaging view of the Orion Nebula

The JWST has captured the most detailed and sharpest infrared images ever taken of the inner region of the Orion Nebula, the nearest massive star formation region, and a prototypical highly irradiated dense photo-dissociation region (PDR). We investigate the fundamental interaction of far-ultraviolet photons with molecular clouds. The transitions across the ionization front (IF), dissociation front (DF), and the molecular cloud are studied at high-angular resolution. These transitions are relevant to understanding the effects of radiative feedback from massive stars and the dominant physical and chemical processes that lead to the IR emission that JWST will detect in many Galactic and extragalactic environments. Due to the proximity of the Orion Nebula and the unprecedented angular resolution of JWST, these data reveal that the molecular cloud borders are hyper structured at small angular scales of 0.1-1" (0.0002-0.002 pc or 40-400 au at 414 pc). A diverse set of features are observed such as ridges, waves, globules and photoevaporated protoplanetary disks. At the PDR atomic to molecular transition, several bright features are detected that are associated with the highly irradiated surroundings of the dense molecular condensations and embedded young star. Toward the Orion Bar PDR, a highly sculpted interface is detected with sharp edges and density increases near the IF and DF. This was predicted by previous modeling studies, but the fronts were unresolved in most tracers. A complex, structured, and folded DF surface was traced by the H2 lines. This dataset was used to revisit the commonly adopted 2D PDR structure of the Orion Bar. JWST provides us with a complete view of the PDR, all the way from the PDR edge to the substructured dense region, and this allowed us to determine, in detail, where the emission of the atomic and molecular lines, aromatic bands, and dust originate

A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photo-dissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, impacting planet formation within the disks. We report JWST and Atacama Large Millimetere Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modelling their kinematics and excitation allows us to constrain the physical conditions within the gas. We quantify the mass-loss rate induced by the FUV irradiation, finding it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk