We describe the procedure used to flux calibrate the three-band submillimetre photometer in the Spectral and Photometric Imaging Receiver instrument on the Herschel Space Observatory. This includes ...the equations describing the calibration scheme, a justification for using Neptune as the primary calibration source, a description of the observations and data processing procedures used to derive flux calibration parameters (for converting from voltage to flux density) for every bolometer in each array, an analysis of the error budget in the flux calibration for the individual bolometers and tests of the flux calibration on observations of primary and secondary calibrators. The procedure for deriving the flux calibration parameters is divided into two parts. In the first part, we use observations of astronomical sources in conjunction with the operation of the photometer internal calibration source to derive the unscaled derivatives of the flux calibration curves. To scale the calibration curves in Jy beam−1 V−1, we then use observations of Neptune in which the beam of each bolometer is mapped using a very fine scan pattern. The total instrumental uncertainties in the flux calibration for most individual bolometers is ∼0.5 per cent, although a few bolometers have uncertainties of ∼1-5 per cent because of issues with the Neptune observations. Based on application of the flux calibration parameters to Neptune observations performed using typical scan map observing modes, we determined that measurements from each array as a whole have instrumental uncertainties of 1.5 per cent. This is considerably less than the absolute calibration uncertainty associated with the model of Neptune, which is estimated at 4 per cent.
To test the hypothesis that atomoxetine does not significantly worsen tic severity relative to placebo in children and adolescents with attention deficit/hyperactivity disorder (ADHD) and comorbid ...tic disorders.
Study subjects were 7 to 17 years old, met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for ADHD, and had concurrent Tourette syndrome or chronic motor tic disorder. Patients were randomly assigned to double-blind treatment with placebo (n = 72) or atomoxetine (0.5 to 1.5 mg/kg/day, n = 76) for up to 18 weeks.
Atomoxetine treatment was associated with greater reduction of tic severity at endpoint relative to placebo, approaching significance on the Yale Global Tic Severity Scale total score (-5.5 +/- 6.9 vs -3.0 +/- 8.7, p = 0.063) and Tic Symptom Self-Report total score (-4.7 +/- 6.5 vs -2.9 +/- 5.2, p = 0.095) and achieving significance on the Clinical Global Impressions (CGI) tic/neurologic severity scale score (-0.7 +/- 1.2 vs -0.1 +/- 1.0, p = 0.002). Atomoxetine patients also showed greater improvement on the ADHD Rating Scale total score (-10.9 +/- 10.9 vs -4.9 +/- 10.3, p < 0.001) and CGI severity of ADHD/psychiatric symptoms scale score (-0.8 +/- 1.1 vs -0.3 +/- 1.0, p = 0.015). Discontinuation rates were not significantly different between treatment groups. Atomoxetine patients had greater increases in heart rate and decreases of body weight, and rates of treatment-emergent decreased appetite and nausea were higher. No other clinically relevant treatment differences were seen in any other vital sign, adverse event, or electrocardiographic or laboratory measures.
Atomoxetine did not exacerbate tic symptoms. Rather, there was some evidence of reduction in tic severity with a significant reduction of attention deficit/hyperactivity disorder symptoms. Atomoxetine treatment appeared safe and well tolerated.
The study of animal immune physiology and animal models of human disease have accelerated many aspects of translational research by allowing direct, definitive investigations. In particular, the use ...of mice has allowed genetic manipulation, adoptive transfer, immunization, and focused cell and tissue sampling, which would obviously be unthinkable for studies in humans. However, the disease relevance of some animal models may be uncertain and difficulties in interpretation may occur as a consequence of immunological differences between the two species. In this review, we will consider general differences in the structure and development of human and mouse mucosal lymphoid microenvironments and then discuss species differences in mucosal B- and T-cell biology that relate to the current concepts of intestinal immune function.
The Herschel Spectral and Photometric REceiver (SPIRE) instrument consists of an imaging photometric camera and an imaging Fourier Transform Spectrometer (FTS), both operating over a frequency range ...of ∼450–1550 GHz. In this paper, we briefly review the FTS design, operation, and data reduction, and describe in detail the approach taken to relative calibration (removal of instrument signatures) and absolute calibration against standard astronomical sources. The calibration scheme assumes a spatially extended source and uses the Herschel telescope as primary calibrator. Conversion from extended to point-source calibration is carried out using observations of the planet Uranus. The model of the telescope emission is shown to be accurate to within 6 per cent and repeatable to better than 0.06 per cent and, by comparison with models of Mars and Neptune, the Uranus model is shown to be accurate to within 3 per cent. Multiple observations of a number of point-like sources show that the repeatability of the calibration is better than 1 per cent, if the effects of the satellite absolute pointing error (APE) are corrected. The satellite APE leads to a decrement in the derived flux, which can be up to ∼10 per cent (1 σ) at the high-frequency end of the SPIRE range in the first part of the mission, and ∼4 per cent after Herschel operational day 1011. The lower frequency range of the SPIRE band is unaffected by this pointing error due to the larger beam size. Overall, for well-pointed, point-like sources, the absolute flux calibration is better than 6 per cent, and for extended sources where mapping is required it is better than 7 per cent.
We present a power spectrum analysis of the Herschel-SPIRE observations of the Polaris flare, a high Galactic latitude cirrus cloud midway between the diffuse and molecular phases. The SPIRE images ...of the Polaris flare reveal for the first time the structure of the diffuse interstellar medium down to 0.01 parsec over a 10 square degrees region. These exceptional observations highlight the highly filamentary and clumpy structure of the interstellar medium even in diffuse regions of the map. The power spectrum analysis shows that the structure of the interstellar medium is well described by a single power law with an exponent of -2.7±0.1 at all scales from 30” to 8°. That the power spectrum slope of the dust emission is constant down to the SPIRE angular resolution is an indication that the inertial range of turbulence extends down to the 0.01 pc scale. The power spectrum analysis also allows the identification of a Poissonian component at sub-arcminute scales in agreement with predictions of the cosmic infrared background level at SPIRE wavelengths. Finally, the comparison of the SPIRE and IRAS 100 μm data of the Polaris flare clearly assesses the capability of SPIRE in maping diffuse emission over large areas.
Abstract Diffuse ionized gas pervades the disk of the Milky Way. We detect extremely faint emission from this Galactic warm ionized medium (WIM) using the Green Bank Telescope to make radio ...recombination line (RRL) observations toward two Milky Way sight lines: G20, ( ℓ , b ) = (20°, 0°), and G45, ( ℓ , b ) = (45°, 0°). We stack 18 consecutive Hn α transitions between 4.3 and 7.1 GHz to derive 〈Hn α 〉 spectra that are sensitive to RRL emission from plasmas with emission measures EM ≳ 10 cm −6 pc. Each sight line has two Gaussian-shaped spectral components with emission measures that range between ∼100 and ∼300 cm −6 pc. Because there is no detectable RRL emission at negative LSR velocities, the emitting plasma must be located interior to the solar orbit. The G20 and G45 emission measures imply rms densities of 0.15 and 0.18 cm −3 , respectively, if these sight lines are filled with homogeneous plasma. The observed 〈Hn β 〉/〈Hn α 〉 line ratios are consistent with LTE excitation for the strongest components. The high-velocity component of G20 has a narrow line width, 13.5 km s −1 , that sets an upper limit of ≲4000 K for the plasma electron temperature. This is inconsistent with the ansatz of a canonically pervasive, low-density, ∼10,000 K WIM plasma.
A systematic programme of calibration observations was carried out to monitor the performance of the Spectral and Photometric Imaging REceiver (SPIRE) Fourier Transform Spectrometer (FTS) instrument ...on board the Herschel Space Observatory. Observations of planets (including the prime point-source calibrator, Uranus), asteroids, line sources, dark sky and cross-calibration sources were made in order to monitor repeatability and sensitivity, and to improve FTS calibration. We present a complete analysis of the full set of calibration observations and use them to assess the performance of the FTS. Particular care is taken to understand and separate out the effect of pointing uncertainties, including the position of the internal beam steering mirror for sparse observations in the early part of the mission. The repeatability of spectral-line centre positions is <5 km s−1, for lines with signal-to-noise ratios >40, corresponding to <0.5–2.0 per cent of a resolution element. For spectral-line flux, the repeatability is better than 6 per cent, which improves to 1–2 per cent for spectra corrected for pointing offsets. The continuum repeatability is 4.4 per cent for the SPIRE Long Wavelength spectrometer (SLW) band and 13.6 per cent for the SPIRE Short Wavelength spectrometer (SSW) band, which reduces to ∼1 per cent once the data have been corrected for pointing offsets. Observations of dark sky were used to assess the sensitivity and the systematic offset in the continuum, both of which were found to be consistent across the FTS-detector arrays. The average point-source calibrated sensitivity for the centre detectors is 0.20 and 0.21 Jy 1σ; 1 h, for SLW and SSW. The average continuum offset is 0.40 Jy for the SLW band and 0.28 Jy for the SSW band.
This paper presents an all-sky model of dust emission from the Planck 353, 545, and 857 GHz, and IRAS 100 μm data. Using a modified blackbody fit to the data we present all-sky maps of the dust ...optical depth, temperature, and spectral index over the 353–3000 GHz range. This model is a good representation of the IRAS and Planck data at 5′ between 353 and 3000 GHz (850 and 100 μm). It shows variations of the order of 30% compared with the widely-used model of Finkbeiner, Davis, and Schlegel. The Planck data allow us to estimate the dust temperature uniformly over the whole sky, down to an angular resolution of 5′, providing an improved estimate of the dust optical depth compared to previous all-sky dust model, especially in high-contrast molecular regions where the dust temperature varies strongly at small scales in response to dust evolution, extinction, and/or local production of heating photons. An increase of the dust opacity at 353 GHz, τ353/NH, from the diffuse to the denser interstellar medium (ISM) is reported. It is associated with a decrease in the observed dust temperature, Tobs, that could be due at least in part to the increased dust opacity. We also report an excess of dust emission at H i column densities lower than 1020 cm-2 that could be the signature of dust in the warm ionized medium. In the diffuse ISM at high Galactic latitude, we report an anticorrelation between τ353/NH and Tobs while the dust specific luminosity, i.e., the total dust emission integrated over frequency (the radiance) per hydrogen atom, stays about constant, confirming one of the Planck Early Results obtained on selected fields. This effect is compatible with the view that, in the diffuse ISM, Tobs responds to spatial variations of the dust opacity, due to variations of dust properties, in addition to (small) variations of the radiation field strength. The implication is that in the diffuse high-latitude ISM τ353 is not as reliable a tracer of dust column density as we conclude it is in molecular clouds where the correlation of τ353 with dust extinction estimated using colour excess measurements on stars is strong. To estimate Galactic E(B − V) in extragalactic fields at high latitude we develop a new method based on the thermal dust radiance, instead of the dust optical depth, calibrated to E(B − V) using reddening measurements of quasars deduced from Sloan Digital Sky Survey data.
: Idiopathic pulmonary fibrosis is a fatal and progressive disease with limited treatment options.
To assess the efficacy and safety of CC-90001, an oral inhibitor of c-Jun N-terminal kinase 1, in ...patients with idiopathic pulmonary fibrosis.
NCT03142191 was a phase 2, randomized (1:1:1), double-blind, placebo-controlled study in which patients received CC-90001 (200 or 400 mg) or placebo once daily for 24 weeks. Background antifibrotic treatment (pirfenidone) was allowed. The primary endpoint was change in percentage of predicted forced vital capacity (ppFVC) from baseline to Week 24; secondary endpoints included safety.
In total, 112 patients received ≥1 dose of study drug. The study was terminated early due to a strategic decision made by the sponsor. Ninety-one patients (81%) completed the study. The least-squares mean changes from baseline in ppFVC at Week 24 were -3.1% (placebo), -2.1% (200 mg), and -1.0% (400 mg); the differences compared with placebo were 1.1% (200 mg; 95% CI: -2.1, 4.3;
=.50) and 2.2% (400 mg; 95% CI: -1.1, 5.4; P=.19). Adverse event frequency was similar in patients in the combined CC-90001 arms versus placebo. The most common adverse events were nausea, diarrhea, and vomiting, which were more frequent in patients in CC-90001 arms versus placebo. Fewer patients in the CC-90001 than in the placebo arm experienced cough and dyspnea.
Treatment with CC-90001 over 24 weeks led to numerical improvements in ppFVC in patients with idiopathic pulmonary fibrosis compared to placebo. CC-90001 was generally well tolerated, consistent with previous studies. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT03142191.
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