A High Angular Resolution Survey of Massive Stars in Cygnus OB2: Results from the Hubble Space Telescope Fine Guidance Sensors

We present results of a high angular resolution survey of massive OB stars in the Cygnus OB2 association that we conducted with the Fine Guidance Sensor 1R (FGS1r) on the Hubble Space Telescope. FGS1r is able to resolve binary systems with a magnitude difference delta-V < 4 down to separations as small as 0.01 arcsec. The sample includes 58 of the brighter members of Cyg OB2, one of the closest examples of an environment containing a large number of very young and massive stars. We resolved binary companions for 12 targets and confirmed the triple nature of one other target, and we offer evidence of marginally resolved companions for two additional stars. We confirm the binary nature of 11 of these systems from complementary adaptive optics imaging observations. The overall binary frequency in our study is 22% to 26% corresponding to orbital periods ranging from 20 - 20,000 years. When combined with the known short-period spectroscopic binaries, the results supports the hypothesis that the binary fraction among massive stars is > 60%. One of the new discoveries is a companion to the hypergiant star MT 304 = Cyg OB2-12, and future measurements of orbital motion should provide mass estimates for this very luminous star.Comment: accepted for AJ, 84 pages, 61 figure

Efficacy and safety of epratuzumab in patients with moderate/severe active systemic lupus erythematosus: results from EMBLEM, a phase IIb, randomised, double-blind, placebo-controlled, multicentre study

Objective: To identify a suitable dosing regimen of the CD22-targeted monoclonal antibody epratuzumab in adults with moderately to severely active systemic lupus erythematosus (SLE). Methods: A phase IIb, multicentre, randomised controlled study (NCT00624351) was conducted with 227 patients (37–39 per arm) receiving either: placebo, epratuzumab 200 mg cumulative dose (cd) (100 mg every other week (EOW)), 800 mg cd (400 mg EOW), 2400 mg cd (600 mg weekly), 2400 mg cd (1200 mg EOW), or 3600 mg cd (1800 mg EOW). The primary endpoint (not powered for significance) was the week 12 responder rate measured using a novel composite endpoint, the British Isles Lupus Assessment Group (BILAG)-based Combined Lupus Assessment (BICLA). Results: Proportion of responders was higher in all epratuzumab groups than with placebo (overall treatment effect test p=0.148). Exploratory pairwise analysis demonstrated clinical improvement in patients receiving a cd of 2400 mg epratuzumab (OR for 600 mg weekly vs placebo: 3.2 (95% CI 1.1 to 8.8), nominal p=0.03; OR for 1200 mg EOW vs placebo: 2.6 (0.9 to 7.1), nominal p=0.07). Post-hoc comparison of all 2400 mg cd patients versus placebo found an overall treatment effect (OR=2.9 (1.2 to 7.1), nominal p=0.02). Incidence of adverse events (AEs), serious AEs and infusion reactions was similar between epratuzumab and placebo groups, without decreases in immunoglobulin levels and only partial reduction in B-cell levels. Conclusions: Treatment with epratuzumab 2400 mg cd was well tolerated in patients with moderately to severely active SLE, and associated with improvements in disease activity. Phase III studies are ongoing

Determining the Genetic Architecture of Reproductive Stage Drought Tolerance in Wheat Using a Correlated Trait and Correlated Marker Effect Model

Water stress during reproductive growth is a major yield constraint for wheat (Triticum aestivum L). We previously established a controlled environment drought tolerance phenotyping method targeting the young microspore stage of pollen development. This method eliminates stress avoidance based on flowering time. We substituted soil drought treatments by a reproducible osmotic stress treatment using hydroponics and NaCl as osmolyte. Salt exclusion in hexaploid wheat avoids salt toxicity, causing osmotic stress. A Cranbrook x Halberd doubled haploid (DH) population was phenotyped by scoring spike grain numbers of unstressed (SGNCon) and osmotically stressed (SGNTrt) plants. Grain number data were analyzed using a linear mixed model (LMM) that included genetic correlations between the SGNCon and SGNTrt traits. Viewing this as a genetic regression of SGNTrt on SGNCon allowed derivation of a stress tolerance trait (SGNTol). Importantly, and by definition of the trait, the genetic effects for SGNTol are statistically independent of those for SGNCon. Thus they represent non-pleiotropic effects associated with the stress treatment that are independent of the control treatment. QTL mapping was conducted using a whole genome approach in which the LMM included all traits and all markers simultaneously. The marker effects within chromosomes were assumed to follow a spatial correlation model. This resulted in smooth marker profiles that could be used to identify positions of putative QTL. The most influential QTL were located on chromosome 5A for SGNTol (126cM; contributed by Halberd), 5A for SGNCon (141cM; Cranbrook) and 2A for SGNTrt (116cM; Cranbrook). Sensitive and tolerant population tail lines all showed matching soil drought tolerance phenotypes, confirming that osmotic stress is a valid surrogate screening method