4MOST : the 4-metre multi-object spectroscopic telescope project in the assembly, integration, and test phase

4MOST is a new high-multiplex, wide-field spectroscopic survey facility under construction for ESO's 4m-VISTA telescope at Paranal, Chile. Its key specifications are: a large field of view of 4.4 square degrees, a high multiplex fibre positioner based on the tilting spine principle that positions 2436 science fibres in the focal surface of which 1624 fibres go to two low-resolution optical spectrographs (R = λ/Δλ ~ 6500) and 812 fibres transfer light to the high-resolution optical spectrograph (R ~ 20,000). Currently, almost all subsystems are completed and full testing in Europe will be finished in spring 2023, after which 4MOST will be shipped to Chile. An overview is given of instrument construction and capabilities, the planned science of the consortium and the recently selected community programmes, and the unique operational scheme of 4MOST

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Cannabinol (CBN; 30 and 300 mg) effects on sleep and next-day function in insomnia disorder (‘CUPID’ study): protocol for a randomised, double-blind, placebo-controlled, cross-over, three-arm, proof-of-concept trial

Objective Insomnia is the most prevalent sleep disorder, with few effective pharmacotherapies. Anecdotal reports and recent preclinical research suggest that cannabinol (CBN), a constituent of Cannabis sativa derived from delta-9-tetrahydrocannabinol, could be an effective treatment. Despite this, the isolated effects of CBN on sleep have yet to be systematically studied in humans.Methods The present protocol paper describes a randomised, double-blind, placebo-controlled, single-dose, three-arm, cross-over, proof-of-concept study which investigates the effects of CBN on sleep and next-day function in 20 participants with clinician-diagnosed insomnia disorder and an Insomnia Severity Index Score ≥15. Participants receive a single fixed oral liquid dose of 30 mg CBN, 300 mg CBN and matched placebo, in random order on three treatment nights; each separated by a 2-week wash-out period. Participants undergo overnight sleep assessment using in-laboratory polysomnography and next-day neurobehavioural function tests. The primary outcome is wake after sleep onset minutes. Secondary outcomes include changes to traditional sleep staging, sleep-onset latency and absolute spectral power during non-rapid eye movement (NREM) sleep. Tertiary outcomes include changes to sleep spindles during NREM sleep, arousal indices, absolute spectral power during REM sleep and subjective sleep quality. Safety-related and exploratory outcomes include changes to next-day simulated driving performance, subjective mood and drug effects, postural sway, alertness and reaction time, overnight memory consolidation, pre and post-sleep subjective and objective sleepiness; and plasma, urinary, and salivary cannabinoid concentrations. The study will provide novel preliminary data on CBN efficacy and safety in insomnia disorder, which will inform larger clinical trials.Ethics and dissemination Human Research Ethics Committee approval has been granted by Bellberry (2021-08-907). Study findings will be disseminated in a peer-reviewed journal and at academic conferences.Trial registration number NCT05344170

Measurements of the cosmological parameters omega and lambda from the first seven supernovae at z greater than or equal to 0.35

We have developed a technique to systematically discover and study high-redshift supernovae that can be used to measure the cosmological parameters. We report here results based on the initial seven of more than 28 supernovae discovered to date in the high-redshift supernova search of the Supernova Cosmology Project. We find an observational dispersion in peak magnitudes of σMB = 0.27; this dispersion narrows to σMB.corr = 0.19 after "correcting" the magnitudes using the light-curve "widthluminosity" relation found for nearby (z ≤ 0.1) Type la supernovae from the Calán/Tololo survey (Hamuy et al). Comparing light-curve width-corrected magnitudes as a function of redshift of our distant (z = 0.35-0.46) supernovae to those of nearby Type la supernovae yields a global measurement of the mass density, ΩM = 0.88-0.60+0.69 for a Λ = 0 cosmology. For a spatially flat universe (i.e., ΩM + ΩΛ = 1), we find ΩM = 0.94-0.28+0.34 or equivalently, a measurement of the cosmological constant, ΩΛ = 0.06-0.34+0.28 (<0.51 at the 95% confidence level). For the more general Friedmann-Lemaître cosmologies with independent ΩM and ΩΛ, the results are presented as a confidence region on the ΩM-ΩΛ plane. This region does not correspond to a unique value of the deceleration parameter q0. We present analyses and checks for statistical and systematic errors and also show that our results do not depend on the specifics of the width-luminosity correction. The results for ΩΛ-versus-ΩM are inconsistent with Λ-dominated, low-density, flat cosmologies that have been proposed to reconcile the ages of globular cluster stars with higher Hubble constant values