Modelling the X-ray spectra of high velocity outflows from quasars

High velocity outflows from supermassive black holes have been invoked to explain the recent identification of strong absorption features in the hard X-ray spectra of several quasars. Here, Monte Carlo radiative transfer calculations are performed to synthesise X-ray spectra from models of such flows. It is found that simple, parametric bi-conical outflow models with plausible choices for the wind parameters predict spectra that are in good qualitative agreement with observations in the 2 - 10 keV band. The influence on the spectrum of both the mass-loss rate and opening angle of the flow are considered: the latter is important since photon leakage plays a significant role in establishing an ionization gradient within the flow, a useful discriminant between spherical and conical outflow for this and other applications. Particular attention is given to the bright quasar PG1211+143 for which constraints on the outflow geometry and mass-loss rate are discussed subject to the limitations of the currently available observational data.Comment: 15 pages, 8 figures. Accepted for publication by MNRA

Cost-effectiveness of two online interventions supporting self-care for eczema for parents/carers and young people

Objective: To estimate the cost-effectiveness of online behavioral interventions (EczemaCareOnline.org.uk) designed to support eczema self-care management for parents/carers and young people from an NHS perspective. Methods: Two within-trial economic evaluations, using regression-based approaches, adjusting for baseline and pre-specified confounder variables, were undertaken alongside two independent, pragmatic, parallel group, unmasked randomized controlled trials, recruiting through primary care. Trial 1 recruited 340 parents/carers of children aged 0–12years and Trial 2 337 young people aged 13–25years with eczema scored ≥ 5 on Patient-Oriented Eczema Measure (POEM). Participants were randomized (1:1) to online intervention plus usual care or usual care alone. Resource use, collected via medical notes review, was valued using published unit costs in UK £Sterling 2021. Quality-of-life was elicited using proxy CHU-9D in Trial 1 and self-report EQ-5D-5L in Trial 2. Results: The intervention was dominant (cost saving and more effective) with a high probability of cost-effectiveness (> 68%) in most analyses. The exception was the complete case cost–utility analysis for Trial 1 (omitting participants with children aged < 2), with adjusted incremental cost savings of -£34.15 (95% CI – 104.54 to 36.24) and incremental QALYs of – 0.003 (95% CI – 0.021 to 0.015) producing an incremental cost per QALY of £12,466. In the secondary combined (Trials 1 and 2) cost-effectiveness analysis, the adjusted incremental cost was -£20.35 (95% CI – 55.41 to 14.70) with incremental success (≥ 2-point change on POEM) of 10.3% (95% CI 2.3–18.1%). Conclusion: The free at point of use online eczema self-management intervention was low cost to run and cost-effective. Trial registration: This trial was registered prospectively with the ISRCTN registry (ISRCTN79282252). URL www.EczemaCareOnline.org.uk

Supporting self-care for eczema: protocol for two randomised controlled trials of ECO (Eczema Care Online) interventions for young people and parents/carers

Introduction Eczema care requires management of triggers and various treatments. We developed two online behavioural interventions to support eczema care called ECO (Eczema Care Online) for young people and ECO for families. This protocol describes two randomised controlled trials aimed to evaluate clinical and cost effectiveness of the two interventions. Methods and analysis Design: Two independent, pragmatic, unmasked, parallel group randomised controlled trials with internal pilots and nested health economic and process evaluation studies. Setting: Participants will be recruited from GP practices in England. Participants: young people aged 13-25 years with eczema and parents / carers of children aged 0-12 years with eczema, excluding inactive or very mild eczema (5 or less on Patient-Oriented Eczema Measure (POEM)). Interventions: Participants will be randomised to online intervention plus usual care or to usual eczema care alone. Outcome measures: Primary outcome is eczema severity over 24 weeks measured by POEM. Secondary outcomes include: POEM 4-weekly for 52 weeks, quality of life, eczema control, itch intensity (young people only), patient enablement, health service and treatment use. Process measures include treatment adherence, barriers to adherence, and intervention usage. Our sample sizes of 303 participants per trial are powered to detect a group difference of 2.5 (SD 6.5) in monthly POEM scores over 24 weeks (significance 0.05, power 0.9), allowing for 20% loss to follow-up. Cost effectiveness analysis will be from an NHS and personal social service perspective. Qualitative and quantitative process evaluation will help understand mechanisms of action and participant experiences and inform implementation. Ethics and dissemination The study has been approved by South Central Oxford A Research Ethics Committee (19/SC/0351). Recruitment is ongoing, and follow-up will be completed by mid-2022. Findings will be disseminated to participants, the public, dermatology and primary care journals, and policymakers

Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial

Background Phenytoin is the recommended second-line intravenous anticonvulsant for treatment of paediatric convulsive status epilepticus in the UK; however, some evidence suggests that levetiracetam could be an effective and safer alternative. This trial compared the efficacy and safety of phenytoin and levetiracetam for second-line management of paediatric convulsive status epilepticus.Methods This open-label, randomised clinical trial was undertaken at 30 UK emergency departments at secondary and tertiary care centres. Participants aged 6 months to under 18 years, with convulsive status epilepticus requiring second-line treatment, were randomly assigned (1:1) using a computer-generated randomisation schedule to receive levetiracetam (40 mg/kg over 5 min) or phenytoin (20 mg/kg over at least 20 min), stratified by centre. The primary outcome was time from randomisation to cessation of convulsive status epilepticus, analysed in the modified intention-to-treat population (excluding those who did not require second-line treatment after randomisation and those who did not provide consent). This trial is registered with ISRCTN, number ISRCTN22567894.Findings Between July 17, 2015, and April 7, 2018, 1432 patients were assessed for eligibility. After exclusion of ineligible patients, 404 patients were randomly assigned. After exclusion of those who did not require second-line treatment and those who did not consent, 286 randomised participants were treated and had available data: 152 allocated to levetiracetam, and 134 to phenytoin. Convulsive status epilepticus was terminated in 106 (70%) children in the levetiracetam group and in 86 (64%) in the phenytoin group. Median time from randomisation to cessation of convulsive status epilepticus was 35 min (IQR 20 to not assessable) in the levetiracetam group and 45 min (24 to not assessable) in the phenytoin group (hazard ratio 1·20, 95% CI 0·91–1·60; p=0·20). One participant who received levetiracetam followed by phenytoin died as a result of catastrophic cerebral oedema unrelated to either treatment. One participant who received phenytoin had serious adverse reactions related to study treatment (hypotension considered to be immediately life-threatening [a serious adverse reaction] and increased focal seizures and decreased consciousness considered to be medically significant [a suspected unexpected serious adverse reaction]). Interpretation Although levetiracetam was not significantly superior to phenytoin, the results, together with previously reported safety profiles and comparative ease of administration of levetiracetam, suggest it could be an appropriate alternative to phenytoin as the first-choice, second-line anticonvulsant in the treatment of paediatric convulsive status epilepticus

Structural plasticity of SARS-CoV-2 3CL Mpro active site cavity revealed by room temperature X-ray crystallography

The SARS-CoV-2 3CL main protease (3CL Mpro) is a chymotrypsin-like protease that facilitates the production of non-structural proteins, which are essential for viral replication and is therefore of great interest as a drug target. Here, the authors present the 2.30 Å room temperature crystal structure of ligand-free 3CL Mpro and compare it with the earlier determined low-temperature ligand-free and inhibitor-bound crystal structures

Impact of Patient Body Mass Index on Post-Operative Recovery from Robotic-Assisted Hysterectomy

A longitudinal, descriptive, prospective, and prolective study of individuals with endometrial or cervical cancer/pre-cancer diagnoses and high BMI (over 35 kg/m2) undergoing RH was conducted. Of the 53 participants recruited, 3 (6%) were converted to open surgery. The 50 RH participants had median BMI 42 kg/m2 (range 35 to 60): the range 35–39.9 kg/m2 had 17 cases; the range 40–44.9 kg/m2 had 15 cases; 45–49.9 kg/m2 8 cases; and those ≥50 kg/m2 comprised 10 cases. The mean RH operating time was 128.1 min (SD 25.3) and the median length of hospital stay was 2 days (range 1–14 days). Increased BMI was associated with small, but statistically significant, increases in operating time and anaesthetic time, 65 additional seconds and 37 seconds, respectively, for each unit increase in BMI. The median self-reported time for individuals who underwent RH to return to their pre-operative activity levels was 4 weeks (range 2 to >12 weeks). There was a significant improvement in pain and physical independence scores over time (p = 0.001 and p < 0.001, respectively) and no significant difference in scores for overall QOL, pain, or physical independence scores was found between the BMI groups. Patient-reported recovery and quality of life following RH is high in individuals with high BMI (over 35 kg/m2) and does not appear to be impacted by the severity of obesity