20 research outputs found
The composition of a disrupted extrasolar planetesimal at SDSS J0845+2257 (Ton 345)
We present a detailed study of the metal-polluted DB white dwarf SDSS J0845+2257 (Ton 345). Using high-resolution Hubble Space Telescope/Cosmic Origins Spectrograph and Very Large Telescope spectroscopy, we have detected hydrogen and 11 metals in the atmosphere of the white dwarf. The origin of these metals is almost certainly the circumstellar disc of dusty and gaseous debris from a tidally disrupted planetesimal, accreting at a rate of 1.6 Ă 1010âgâsâ1. Studying the chemical abundances of the accreted material demonstrates that the planetesimal had a composition similar to the Earth, dominated by rocky silicates and metallic iron, with a low water content. The mass of metals within the convection zone of the white dwarf corresponds to an asteroid of at least âź130â170 km in diameter, although the presence of ongoing accretion from the debris disc implies that the planetesimal was probably larger than this. While a previous abundance study of the accreted material has shown an anomalously high mass fraction of carbon (15 per cent) compared to the bulk Earth, our independent analysis results in a carbon abundance of just 2.5 per cent. Enhanced abundances of core material (Fe, Ni) suggest that the accreted object may have lost a portion of its mantle, possibly due to stellar wind stripping in the asymptotic giant branch. Time series spectroscopy reveals variable emission from the orbiting gaseous disc, demonstrating that the evolved planetary system at SDSS J0845+2257 is dynamically active
Ustekinumab as Induction and Maintenance Therapy for Crohnâs Disease
BACKGROUND
Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and inter-leukin-23, was evaluated as an intravenous induction therapy in two populations with moderately to severely active Crohnâs disease. Ustekinumab was also evaluated as subcutaneous maintenance therapy.
METHODS
We randomly assigned patients to receive a single intravenous dose of ustekinumab (either 130 mg or approximately 6 mg per kilogram of body weight) or placebo in two induction trials. The UNITI-1 trial included 741 patients who met the criteria for primary or secondary nonresponse to tumor necrosis factor (TNF) antagonists or had unacceptable side effects. The UNITI-2 trial included 628 patients in whom conventional therapy failed or unacceptable side effects occurred. Patients who completed
these induction trials then participated in IM-UNITI, in which the 397 patients who had a response to ustekinumab were randomly assigned to receive subcutaneous maintenance injections of 90 mg of ustekinumab (either every 8 weeks or every 12 weeks) or placebo. The primary end point for the induction trials was a clinical response at week 6 (defined as a decrease from baseline in the Crohnâs Disease Activity Index [CDAI] score of âĽ100 points or a CDAI score <150). The primary end point for the maintenance trial was remission at week 44 (CDAI score <150).
RESULTS
The rates of response at week 6 among patients receiving intravenous ustekinumab at a dose of either 130 mg or approximately 6 mg per kilogram were significantly higher
than the rates among patients receiving placebo (in UNITI-1, 34.3%, 33.7%, and 21.5%, respectively, with Pâ¤0.003 for both comparisons with placebo; in UNITI-2, 51.7%, 55.5%, and 28.7%, respectively, with P<0.001 for both doses). In the groups receiving maintenance doses of ustekinumab every 8 weeks or every 12 weeks, 53.1% and 48.8%, respectively, were in remission at week 44, as compared with 35.9% of those receiving placebo (P = 0.005 and P = 0.04, respectively). Within each trial, adverse-event rates were similar among treatment groups.
CONCLUSIONS
Among patients with moderately to severely active Crohnâs disease, those receiving intravenous ustekinumab had a significantly higher rate of response than did those receiving placebo. Subcutaneous ustekinumab maintained remission in patients who had a clinical response to induction therapy. (Funded by Janssen Research and Development; ClinicalTrials.gov numbers, NCT01369329, NCT01369342, and NCT01369355.