Anti-Granulocyte–Macrophage Colony–Stimulating Factor Monoclonal Antibody Gimsilumab for COVID-19 Pneumonia: A Randomized, Double-Blind, Placebo-controlled Trial

RATIONALE: GM-CSF (granulocyte-macrophage colony-stimulating factor) has emerged as a promising target against the hyperactive host immune response associated with coronavirus disease (COVID-19). OBJECTIVES: We sought to investigate the efficacy and safety of gimsilumab, an anti-GM-CSF monoclonal antibody, for the treatment of hospitalized patients with elevated inflammatory markers and hypoxemia secondary to COVID-19. METHODS: We conducted a 24-week randomized, double-blind, placebo-controlled trial, BREATHE (Better Respiratory Education and Treatment Help Empower), at 21 locations in the United States. Patients were randomized 1:1 to receive two doses of intravenous gimsilumab or placebo 1 week apart. The primary endpoint was all-cause mortality rate at Day 43. Key secondary outcomes were ventilator-free survival rate, ventilator-free days, and time to hospital discharge. Enrollment was halted early for futility based on an interim analysis. MEASUREMENTS AND MAIN RESULTS: Of the planned 270 patients, 225 were randomized and dosed; 44.9% of patients were Hispanic or Latino. The gimsilumab and placebo groups experienced an all-cause mortality rate at Day 43 of 28.3% and 23.2%, respectively (adjusted difference = 5% vs. placebo; 95% confidence interval [26 to 17]; P = 0.377). Overall mortality rates at 24 weeks were similar across the treatment arms. The key secondary endpoints demonstrated no significant differences between groups. Despite the high background use of corticosteroids and anticoagulants, adverse events were generally balanced between treatment groups. CONCLUSIONS: Gimsilumab did not improve mortality or other key clinical outcomes in patients with COVID-19 pneumonia and evidence of systemic inflammation. The utility of anti-GM-CSF therapy for COVID-19 remains unclear. CLINICAL TRIAL registered with www.clinicaltrials.gov (NCT 04351243

Whole Earth Telescope observations of the DAV white dwarf G226-29

We observed G226-29 for 121 hr in 1992 February and confirm the presence of the three previously identified frequencies close to 109 s. We find no evidence of other pulsation periods down to our noise level of about 0.35 millimodulation amplitudes. The presence of only one triplet pulsation mode in G226-29 and its effective temperature near the blue edge of the instability strip identify the observed triplet of modes near 109 s as rotationally split components of the k = 1, l = 1 mode. With the mode identification, we derived a rotation period of 8.9 hr and an inclination of the pulsation axis of 70°-75° to our line of sight

Gender and the Organization of Sacred Space in Early Modern England c1580-1640

The relationship between gender and space has been a consistent theme in histories of women and of gender over many years, even if not always explicitly stated. One of the most influential master narratives about the status of women is a story of decline from the early modern to the Victorian age. Historians who support this theory argue that, with the advent of capitalism and the rise of a class society, the division between domestic space and work space became more distinct, the household became more sharply identified as private, domestic, and feminine, in opposition to the public and masculine spaces of work and politics, from which women were progressively excluded. The outcome of this sharpening of spatial and social distinctions, it is argued, was to produce a more rigidly hierarchical and patriarchal society.This ?separate spheres? model continues to have a very powerful influence on women?s and gender history, although there is now a mounting body of literature that challenges many of its assumptions. Work on masculinity has drawn attention to the ?private? and domestic aspects of the lives of men as well as women. The ?public? aspects of the family have been addressed in terms of its relationship to the community, to political institutions, public policy, and in terms of its economic role. Studies have also begun to stress continuity in the spheres and status of women