Novel lung imaging biomarkers and skin gene expression subsetting in dasatinib treatment of systemic sclerosis-associated interstitial lung disease.

BackgroundThere are no effective treatments or validated clinical response markers in systemic sclerosis (SSc). We assessed imaging biomarkers and performed gene expression profiling in a single-arm open-label clinical trial of tyrosine kinase inhibitor dasatinib in patients with SSc-associated interstitial lung disease (SSc-ILD).MethodsPrimary objectives were safety and pharmacokinetics. Secondary outcomes included clinical assessments, quantitative high-resolution computed tomography (HRCT) of the chest, serum biomarker assays and skin biopsy-based gene expression subset assignments. Clinical response was defined as decrease of >5 or >20% from baseline in the modified Rodnan Skin Score (MRSS). Pulmonary function was assessed at baseline and day 169.ResultsDasatinib was well-tolerated in 31 patients receiving drug for a median of nine months. No significant changes in clinical assessments or serum biomarkers were seen at six months. By quantitative HRCT, 65% of patients showed no progression of lung fibrosis, and 39% showed no progression of total ILD. Among 12 subjects with available baseline and post-treatment skin biopsies, three were improvers and nine were non-improvers. Improvers mapped to the fibroproliferative or normal-like subsets, while seven out of nine non-improvers were in the inflammatory subset (p = 0.0455). Improvers showed stability in forced vital capacity (FVC) and diffusing capacity for carbon monoxide (DLCO), while both measures showed a decline in non-improvers (p = 0.1289 and p = 0.0195, respectively). Inflammatory gene expression subset was associated with higher baseline HRCT score (p = 0.0556). Non-improvers showed significant increase in lung fibrosis (p = 0.0313).ConclusionsIn patients with SSc-ILD dasatinib treatment was associated with acceptable safety profile but no significant clinical efficacy. Patients in the inflammatory gene expression subset showed increase in skin fibrosis, decreasing pulmonary function and worsening lung fibrosis during the study. These findings suggest that target tissue-specific gene expression analyses can help match patients and therapeutic interventions in heterogeneous diseases such as SSc, and quantitative HRCT is useful for assessing clinical outcomes.Trial registrationClinicaltrials.gov NCT00764309

The JCMT Gould Belt Survey: Evidence for radiative heating in Serpens MWC 297 and its influence on local star formation

We present SCUBA-2 450micron and 850micron observations of the Serpens MWC 297 region, part of the JCMT Gould Belt Survey of nearby star-forming regions. Simulations suggest that radiative feedback influences the star-formation process and we investigate observational evidence for this by constructing temperature maps. Maps are derived from the ratio of SCUBA-2 fluxes and a two component model of the JCMT beam for a fixed dust opacity spectral index of beta = 1.8. Within 40 of the B1.5Ve Herbig star MWC 297, the submillimetre fluxes are contaminated by free-free emission with a spectral index of 1.03+-0.02, consistent with an ultra-compact HII region and polar winds/jets. Contamination accounts for 73+-5 per cent and 82+-4 per cent of peak flux at 450micron and 850micron respectively. The residual thermal disk of the star is almost undetectable at these wavelengths. Young Stellar Objects are confirmed where SCUBA-2 850micron clumps identified by the fellwalker algorithm coincide with Spitzer Gould Belt Survey detections. We identify 23 objects and use Tbol to classify nine YSOs with masses 0.09 to 5.1 Msun. We find two Class 0, one Class 0/I, three Class I and three Class II sources. The mean temperature is 15+-2K for the nine YSOs and 32+-4K for the 14 starless clumps. We observe a starless clump with an abnormally high mean temperature of 46+-2K and conclude that it is radiatively heated by the star MWC 297. Jeans stability provides evidence that radiative heating by the star MWC 297 may be suppressing clump collapse.Comment: 24 pages, 13 figures, 7 table

The JCMT Gould Belt Survey: evidence for radiative heating in Serpens MWC 297 and its influence on local star formation

We present SCUBA-2 450 and 850 μm observations of the Serpens MWC 297 region, part of the James Clerk Maxwell Telescope (JCMT) Gould Belt Survey of nearby star-forming regions. Simulations suggest that radiative feedback influences the star formation process and we investigate observational evidence for this by constructing temperature maps. Maps are derived from the ratio of SCUBA-2 fluxes and a two-component model of the JCMT beam for a fixed dust opacity spectral index of β = 1.8. Within 40 arcsec of the B1.5Ve Herbig star MWC 297, the submillimetre fluxes are contaminated by free-free emission with a spectral index of 1.03 ± 0.02, consistent with an ultracompact H II region and polar winds/jets. Contamination accounts for 73 ± 5 per cent and 82 ± 4 per cent of peak flux at 450 μm and 850 μm, respectively. The residual thermal disc of the star is almost undetectable at these wavelengths. Young stellar objects (YSOs) are confirmed where SCUBA-2 850 μm clumps identified by the FELLWALKER algorithm coincide with Spitzer Gould Belt Survey detections. We identify 23 objects and use Tbol to classify nine YSOs with masses 0.09 to 5.1 M⊙. We find two Class 0, one Class 0/I, three Class I and three Class II sources. The mean temperature is 15 ± 2 K for the nine YSOs and 32 ± 4 K for the 14 starless clumps. We observe a starless clump with an abnormally high mean temperature of 46 ± 2 K and conclude that it is radiatively heated by the star MWC 297. Jeans stability provides evidence that radiative heating by the star MWC 297 may be suppressing clump collapse

Magnetic Fields toward Ophiuchus-B Derived from SCUBA-2 Polarization Measurements

We present the results of dust emission polarization measurements of Ophiuchus-B (Oph-B) carried out using the Submillimetre Common-User Bolometer Array 2 (SCUBA-2) camera with its associated polarimeter (POL-2) on the James Clerk Maxwell Telescope in Hawaii. This work is part of the B-fields in Star-forming Region Observations survey initiated to understand the role of magnetic fields in star formation for nearby star-forming molecular clouds. We present a first look at the geometry and strength of magnetic fields in Oph-B. The field geometry is traced over ~0.2 pc, with clear detection of both of the sub-clumps of Oph-B. The field pattern appears significantly disordered in sub-clump Oph-B1. The field geometry in Oph-B2 is more ordered, with a tendency to be along the major axis of the clump, parallel to the filamentary structure within which it lies. The degree of polarization decreases systematically toward the dense core material in the two sub-clumps. The field lines in the lower density material along the periphery are smoothly joined to the large-scale magnetic fields probed by NIR polarization observations. We estimated a magnetic field strength of 630 ± 410 μG in the Oph-B2 sub-clump using a Davis–Chandrasekhar–Fermi analysis. With this magnetic field strength, we find a mass-to-flux ratio λ = 1.6 ± 1.1, which suggests that the Oph-B2 clump is slightly magnetically supercritical

The TOP-SCOPE Survey of Planck Galactic Cold Clumps : Survey Overview and Results of an Exemplar Source, PGCC G26.53+0.17

The low dust temperatures (<14 K) of Planck Galactic cold clumps (PGCCs) make them ideal targets to probe the initial conditions and very early phase of star formation. "TOP-SCOPE" is a joint survey program targeting similar to 2000 PGCCs in J = 1-0 transitions of CO isotopologues and similar to 1000 PGCCs in 850 mu m continuum emission. The objective of the "TOP-SCOPE" survey and the joint surveys (SMT 10 m, KVN 21 m, and NRO 45 m) is to statistically study the initial conditions occurring during star formation and the evolution of molecular clouds, across a wide range of environments. The observations, data analysis, and example science cases for these surveys are introduced with an exemplar source, PGCC G26.53+0.17 (G26), which is a filamentary infrared dark cloud (IRDC). The total mass, length, and mean line mass (M/L) of the G26 filament are similar to 6200 M-circle dot, similar to 12 pc, and similar to 500 M-circle dot pc(-1), respectively. Ten massive clumps, including eight starless ones, are found along the filament. The most massive clump as a whole may still be in global collapse, while its denser part seems to be undergoing expansion owing to outflow feedback. The fragmentation in the G26 filament from cloud scale to clump scale is in agreement with gravitational fragmentation of an isothermal, nonmagnetized, and turbulent supported cylinder. A bimodal behavior in dust emissivity spectral index (beta) distribution is found in G26, suggesting grain growth along the filament. The G26 filament may be formed owing to large-scale compression flows evidenced by the temperature and velocity gradients across its natal cloud.Peer reviewe

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense (NH 10 22 2 ~ –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores

The JCMT BISTRO Survey: Revealing the Diverse Magnetic Field Morphologies in Taurus Dense Cores with Sensitive Submillimeter Polarimetry

Abstract: We have obtained sensitive dust continuum polarization observations at 850 μm in the B213 region of Taurus using POL-2 on SCUBA-2 at the James Clerk Maxwell Telescope as part of the B-fields in STar-forming Region Observations (BISTRO) survey. These observations allow us to probe magnetic field (B-field) at high spatial resolution (∼2000 au or ∼0.01 pc at 140 pc) in two protostellar cores (K04166 and K04169) and one prestellar core (Miz-8b) that lie within the B213 filament. Using the Davis–Chandrasekhar–Fermi method, we estimate the B-field strengths in K04166, K04169, and Miz-8b to be 38 ± 14, 44 ± 16, and 12 ± 5 μG, respectively. These cores show distinct mean B-field orientations. The B-field in K04166 is well ordered and aligned parallel to the orientations of the core minor axis, outflows, core rotation axis, and large-scale uniform B-field, in accordance with magnetically regulated star formation via ambipolar diffusion taking place in K04166. The B-field in K04169 is found to be ordered but oriented nearly perpendicular to the core minor axis and large-scale B-field and not well correlated with other axes. In contrast, Miz-8b exhibits a disordered B-field that shows no preferred alignment with the core minor axis or large-scale field. We found that only one core, K04166, retains a memory of the large-scale uniform B-field. The other two cores, K04169 and Miz-8b, are decoupled from the large-scale field. Such a complex B-field configuration could be caused by gas inflow onto the filament, even in the presence of a substantial magnetic flux

The JCMT BISTRO Survey: An 850/450 μ m Polarization Study of NGC 2071IR in Orion B

Abstract: We present the results of simultaneous 450 μm and 850 μm polarization observations toward the massive star-forming region NGC 2071IR, a target of the BISTRO (B-fields in STar-forming Region Observations) Survey, using the POL-2 polarimeter and SCUBA-2 camera mounted on the James Clerk Maxwell Telescope. We find a pinched magnetic field morphology in the central dense core region, which could be due to a rotating toroidal disklike structure and a bipolar outflow originating from the central young stellar object IRS 3. Using the modified Davis–Chandrasekhar–Fermi method, we obtain a plane-of-sky magnetic field strength of 563 ± 421 μG in the central ∼0.12 pc region from 850 μm polarization data. The corresponding magnetic energy density of 2.04 × 10−8 erg cm−3 is comparable to the turbulent and gravitational energy densities in the region. We find that the magnetic field direction is very well aligned with the whole of the IRS 3 bipolar outflow structure. We find that the median value of polarization fractions is 3.0% at 450 μm in the central 3′ region, which is larger than the median value of 1.2% at 850 μm. The trend could be due to the better alignment of warmer dust in the strong radiation environment. We also find that polarization fractions decrease with intensity at both wavelengths, with slopes, determined by fitting a Rician noise model of 0.59 ± 0.03 at 450 μm and 0.36 ± 0.04 at 850 μm, respectively. We think that the shallow slope at 850 μm is due to grain alignment at the center being assisted by strong radiation from the central young stellar objects

The JCMT BISTRO Survey: Studying the Complex Magnetic Field of L43

We present observations of polarized dust emission at 850 μm from the L43 molecular cloud, which sits in the Ophiuchus cloud complex. The data were taken using SCUBA-2/POL-2 on the James Clerk Maxwell Telescope as a part of the BISTRO large program. L43 is a dense ( NH2∼1022 –1023 cm−2) complex molecular cloud with a submillimeter-bright starless core and two protostellar sources. There appears to be an evolutionary gradient along the isolated filament that L43 is embedded within, with the most evolved source closest to the Sco OB2 association. One of the protostars drives a CO outflow that has created a cavity to the southeast. We see a magnetic field that appears to be aligned with the cavity walls of the outflow, suggesting interaction with the outflow. We also find a magnetic field strength of up to ∼160 ± 30 μG in the main starless core and up to ∼90 ± 40 μG in the more diffuse, extended region. These field strengths give magnetically super- and subcritical values, respectively, and both are found to be roughly trans-Alfvénic. We also present a new method of data reduction for these denser but fainter objects like starless cores