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Background Symptomatic hand osteoarthritis is more common in women than in men, and its incidence increases around the age of menopause, implicating oestrogen deficiency. No randomised controlled trials of hormone replacement therapy (HRT) have been done in people with hand osteoarthritis. We aimed to determine the feasibility and acceptability of a form of HRT (conjugated oestrogens plus bazedoxifene) in post-menopausal women with painful hand osteoarthritis. Methods The HOPE-e feasibility study was a randomised, double-blind, placebo-controlled trial, for which we recruited women aged 40–65 years, for whom 1–10 years had passed after their final menstrual period, with definite hand osteoarthritis and at least two painful hand joints. Participants were recruited across three primary or secondary care sites and from the community and were randomly assigned (1:1) to receive conjugated oestrogens plus bazedoxifene or placebo, orally once every day for 24 weeks, before weaning for 4 weeks until the end of the study. The primary feasibility outcomes were rates of identification, recruitment, randomisation, retention, and compliance of eligible participants, and the likelihood of unmasking. The secondary objective was to generate proof-of-concept quantitative and qualitative data on the acceptability of proposed clinical outcomes for a full trial and adverse events. We used an intention-to-treat analysis, and criteria for progression to a full trial were pre-defined as recruitment of at least 30 participants across all sites in 18 months; a dropout rate of less than or equal to 30% of randomised individuals; and acceptability to the majority of participants, including acceptable rates of adverse events. Due to the COVID-19 pandemic, the recruitment window was reduced to 12–15 months. A proportionately reduced minimum sample size of 22 was judged to be sufficient to test feasibility. This trial was registered at ISRCTN, ISRCTN12196200. Findings From May 9, 2019 to Dec 31, 2020, 434 enquiries or referrals were received. We did 96 telephone pre-screens; of the 35 eligible participants, seven were excluded as ineligible at the telephone or face-to-face screening and 28 (80% [95% CI 63–92]) were randomly assigned. Of the 406 who were not randomly assigned, 250 (62%) were ineligible (with contraindicated medications accounting for 50 [20%] of these), 101 (25%) did not respond to further enquiries, and 55 (14%) chose not to proceed (with the most common reason being not wanting to take a hormone-based drug). All 28 randomised participants completed all follow-up assessments with high compliance and outcome measure completeness. All three adverse event-related treatment withdrawals were in the placebo group. No serious adverse events were reported. Participants and investigators were successfully masked (participant Bang's blinding index placebo group 0·50 [95% CI 0·25–0·75]). The trial met the prespecified criteria for progression to a full trial. Interpretation This first-ever feasibility study of a randomised controlled trial of HRT for post-menopausal women with painful hand osteoarthritis met its progression criteria, although it was not powered to detect a clinical effect. This outcome indicates that a full trial of an HRT in this population is feasible and acceptable and identifies potential refinements with regard to the design of such a trial. Funding Research for Patient Benefit programme, National Institute for Health Research.

We report on the first measurement of the average mass and mass-to-light ratio of galaxy groups by analyzing the weak-lensing signal induced by these systems. The groups, which have velocity dispersions of 50-400 km s(-1), have been selected from the Canadian Network for Observational Cosmology Field Galaxy Redshift Survey (CNOC2). This survey allows the identification of a large number of groups with redshifts ranging from z = 0.12 to 0.55, ideal for a weak-lensing analysis of their mass distribution. For our analysis we use a sample of 50 groups that are selected on the basis of a careful dynamical analysis of group candidates. We detect a signal at the 99% confidence limit. The best-fit singular isothermal sphere model yields an Einstein radius. r(E) = 0".72 +/- 0".29. This corresponds to a velocity dispersion of [sigma (2)](1/2) = 274(-59)(+48) km s(-1) (using photometric redshift distributions for the source galaxies), which is in good agreement with the dynamical estimate. Under the assumption that the light traces the mass, we find an average mass-to-light ratio of 191 +/- 83 h (M)./L-B. in the rest-frame B band. Unlike dynamical estimates, this result is insensitive to problems associated with determining group membership. After correction of the observed mass-to-light ratio for luminosity evolution to z = 0, we find 254 +/- 110 h M./L-B., lower than what is found for rich clusters. We use the observed mass-to-light ratio to estimate the matter density of the universe, for which we find Omega (m) = 0.19 +/- 0.10 (Omega (Lambda) = 0), in good agreement with other recent estimates. For a closed universe (Omega (m) + Omega (Lambda) = 1), we obtain Omega (m) = 0.13 +/- 0.07.

An 8 month monitoring campaign on the Seyfert 1 galaxy Fairall 9 has been conducted with the International Ultraviolet Explorer in an attempt to obtain reliable estimates of continuum-continuum and continuum-emission-line delays for a high-luminosity active galactic nucleus (AGN). While the results of this campaign are more ambiguous than those of previous monitoring campaigns on lower luminosity sources, we find general agreement with the earlier results: (1) there is no measurable lag between ultraviolet continuum bands, and (2) the measured emission-line time lags are very short. It is especially notable that the Lyα + N v emission-line lag is about 1 order of magnitude smaller than determined from a previous campaign by Clavel, Wamsteker, & Glass (1989) when Fairall 9 was in a more luminous state. In other well-monitored sources, specifically NGC 5548 and NGC 3783, the highest ionization lines are found to respond to continuum variations more rapidly than the lower ionization lines, which suggests a radially ionization-stratified broad-line region. In this case, the results are less certain, since none of the emission-line lags are very well determined. The best-determined emission line lag is Lyα + N v, for which we find that the centroid of the continuum-emission-line cross-correlation function is τcent ≈ 14-20 days. We measure a lag τcent ≲ 4 days for He II λ1640; this result is consistent with the ionization-stratification pattern seen in lower luminosity sources, but the relatively large uncertainties in the emission-line lags measured here cannot rule out similar lags for Lyα + N v and He II λ1640 at a high level of significance. We are unable to determine a reliable lag for C IV λ1550, but we note that the profiles of the variable parts of Lyα and C IV λ1550 are not the same, which does not support the hypothesis that the strongest variations in these two lines arise in the same region.

We examine the relationship between galaxies and the intergalactic medium at z < 1 using a group of three closely spaced background quasi-stellar objects (QSOs) with zem ≈ 1 observed with the Hubble Space Telescope. Using a new grouping algorithm, we identify groups of galaxies and absorbers across the three QSO sightlines that may be physically linked. There is an excess number of such groups compared to the number we expect from a random distribution of absorbers at a confidence level of 99.9 per cent. The same search is performed with mock spectra generated using a hydrodynamical simulation, and we find that the vast majority of such groups arise in dense regions of the simulation.We find that atz

This paper presents a progress report on a major extension of the Einstein Observatory Medium Sensitivity Survey (MSS). The results obtained from the survey are briefly summarized, particular emphasis is given to the Active Galactic Nuclei (AGN) and BL Lac objects of the MSS. The basic properties of these classes of extragalactic objects are presented and discussed.