The low-resolution version of HadGEM3 GC3.1: development and evaluation for global climate

A new climate model, HadGEM3 N96ORCA1, is presented that is part of the GC3.1 configuration of HadGEM3. N96ORCA1 has a horizontal resolution of ~135 km in the atmosphere and 1° in the ocean and requires an order of magnitude less computing power than its medium-resolution counterpart, N216ORCA025, while retaining a high degree of performance traceability. Scientific performance is compared both to observations and the N216ORCA025 model. N96ORCA1 reproduces observed climate mean and variability almost as well as N216ORCA025. Patterns of biases are similar across the two models. In the north-west Atlantic, N96ORCA1 shows a cold surface bias of up to 6K, typical of ocean models of this resolution. The strength of the Atlantic meridional overturning circulation (16 to 17 Sv) matches observations. In the Southern Ocean, a warm surface bias (up to 2K) is smaller than in N216ORCA025 and linked to improved ocean circulation. Model El Niño/Southern Oscillation and Atlantic Multidecadal Variability are close to observations. Both the cold bias in the Northern hemisphere (N96ORCA1) and the warm bias in the Southern hemisphere (N216ORCA025) develop in the first few decades of the simulations. As in many comparable climate models, simulated interhemispheric gradients of top-of-atmosphere radiation are larger than observations suggest, with contributions from both hemispheres. HadGEM3 GC3.1 N96ORCA1 constitutes the physical core of the UK Earth System Model (UKESM1) and will be used extensively in the Coupled Model Intercomparison Project 6 (CMIP6), both as part of UKESM1 and as a stand-alone coupled climate model

The mediating effect of changes in hand impairments on hand function in patients with rheumatoid arthritis: exploring the mechanisms of an effective exercise programme

Objective: To determine whether the effect of the ‘Strengthening And stretching for Rheumatoid Arthritis of the Hand’ (SARAH) exercise programme on hand function was mediated by changes in the proposed active ingredients: strength, dexterity, and/or range of motion. Methods: The SARAH intervention included exercises hypothesized to improve potential mediators of grip strength, pinch strength, wrist flexion, wrist extension, finger flexion, finger extension, thumb opposition, and dexterity, which would theoretically improve self-reported hand function. All variables were measured at baseline and at 4 and 12 months. Structural equation modelling was used to assess mediation on change in hand function via change in potential mediators. Results: Change in grip strength partially mediated change in hand function. Grip strength mediated 19.4% (95% confidence interval: 0.9% to 37.8%) of the treatment effect. Discussion: Improvements in grip strength at 4 months are likely to mediate improved hand function at 12 months. The role of joint mobility exercises is less clear and is likely influenced by the choice of measurement tools for both mobility and function outcomes. More robust measurements of wrist and hand mobility for patients with rheumatoid arthritis may be necessary to determine the relationship between this variable and self-reported hand function. Conclusion: Using a large trial dataset, we have demonstrated that techniques used to target grip strength are key active ingredients of the SARAH exercise programme and mediate its effect

Multifactorial and multiple component interventions for preventing falls in older people living in the community

This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects (benefits and harms) of multifactorial interventions and multiple component interventions for preventing falls in older people living in the community

Problems persist in reporting of methods and results for the WOMAC measure in hip and knee osteoarthritis trials

Purpose The Western Ontario and McMaster Universities Arthritis Index (WOMAC) is a commonly used outcome measure for osteoarthritis. There are different versions of the WOMAC (Likert, visual analogue or numeric scales). A previous review of trials published before 2010 found poor reporting and inconsistency in how the WOMAC was used. This review explores whether these problems persist. Methods This systematic review included randomised trials of hip and/or knee osteoarthritis published in 2016 that used the WOMAC. Data were extracted on the version used, score range, analysis and results of the WOMAC, and whether these details were clearly reported. Results This review included 62 trials and 41 reported the WOMAC total score. The version used and item range for the WOMAC total score were unclear in 44% (n = 18/41) and 24% (n = 10/41) of trials, respectively. The smallest total score range was 0–10 (calculated by averaging 24 items scored 0–10); the largest was 0–2400 (calculated by summing 24 items scored 0–100). All trials reported the statistical analysis methods but only 29% reported the between-group mean difference and 95% confidence interval. Conclusion Details on the use and scoring of the WOMAC were often not reported. We recommend that trials report the version of the WOMAC and the score range used. The between-group treatment effect and corresponding confidence interval should be reported. If all the items of the WOMAC are collected, the total score and individual subscale scores should be presented. Better reporting would facilitate the interpretation, comparison and synthesis of the WOMAC score in trials

First large-scale study of antimicrobial susceptibility data, and genetic resistance determinants, in Fusobacterium necrophorum highlighting the importance of continuing focused susceptibility trend surveillance

Objectives: The objective of the study was to explore antimicrobial resistance gene determinant, and phenotypic antibiotic susceptibility, data for Fusobacterium necrophorum from a collection of UK strains. In addition, antimicrobial resistance genes detected in publicly available assembled whole genome sequences were investigated for comparison.Methods: Three hundred and eighty five F. necrophorum strains (1982-2019) were revived from cryovials (Prolab). Subsequent to sequencing (Illumina) and quality checking, 374 whole genomes were available for analysis. These genomes, in addition to publicly available assembled F. necrophorum genetic data, were interrogated using BioNumerics (bioMérieux; v 8.1), for the presence of known antimicrobial resistance genes (ARGs). Agar dilution susceptibility results for 313 F. necrophorum isolates (2016-2021) were also examined.Results: The phenotypic antibiotic test data for the 313 contemporary strains demonstrated potential resistance to penicillin, without increased dosing, in only three isolates. Otherwise, all strains were susceptible to ceftriaxone, clindamycin, co-amoxiclav, meropenem, metronidazole, penicillin and piperacillin/tazobactam, using EUCAST (v 11.0) interpretive guidance. The tet(O), tet(M), tet(40), aph(3’)-III, ant(6)-la and blaOXA-85 ARGs were present in publicly available assembled genomes. tet(M), tet(32), erm(A) and erm(B) were found within the UK strains, with correspondingly raised clindamycin and tetracycline minimum inhibitory concentrations.Conclusions: Current antibiotics recommended for the treatment of infections caused by F. necrophorum, including Lemierre’s disease, are likely to be effective in most cases. However, with evidence of potential ARG transmission from oral bacteria, and the detection of a transposon-mediated beta-lactamase resistance determinant in F. necrophorum, surveillance of both phenotypic and genotypic antimicrobial susceptibility trends must continue, and increase.<br/

Working with Chronic Musculoskeletal Disorders : Good Practice Advice Report

This report takes an in-depth look at working with chronic musculoskeletal disorders (MSDs) and makes a clear case for the benefits of enabling those with chronic conditions to remain in work. It highlights the importance of designing inclusive workplaces and sets out principles for managing chronic MSDs, with prevention, early intervention, and effective, participative rehabilitation and return-to-work planning being identified as key. Good practice examples detail a wide range of workplace adjustments made to accommodate individuals with MSDs, from offering flexitime to providing the right tools and ergonomic equipment. This comprehensive practical advice is complemented by broader recommendations for policy-makers

Painted flowers: Eluta generates pigment patterning in Antirrhinum

*In the early 1900s, Erwin Baur established Antirrhinum majus as a model system, identifying and characterising numerous flower colour variants. This included Picturatum /Eluta, which restricts the accumulation of magenta anthocyanin pigments, forming bullseye markings on the flower face. *We identified the gene underlying the Eluta locus by transposon-tagging, using an Antirrhinum line that spontaneously lost the non-suppressive el phenotype. A candidate MYB repressor gene at this locus contained a CACTA transposable element. We subsequently identified plants where this element excised, reverting to a suppressive Eluta phenotype. El alleles inhibit expression of anthocyanin biosynthetic genes, confirming it to be a regulatory locus. The modes of action of Eluta were investigated by generating stable transgenic tobacco lines, biolistic transformation of Antirrhinum petals and by promoter activation/repression assays. *Eluta competes with MYB activators for promoter cis-elements, and also by titrating essential co-factors (bHLH proteins) to reduce transcription of target genes. Eluta restricts the pigmentation established by the R2R3-MYB factors, Rosea and Venosa, with greatest repression on those parts of the petals where Eluta is most highly expressed. *Baur questioned the origin of heredity units determining flower colour variation in cultivated A. majus. Our findings support introgression from wild species into cultivated varieties. <br/

Physiotherapist-delivered cognitive behavioural interventions are effective for low back pain, but can they be replicated in clinical practice? A systematic review

Purpose: To determine if physiotherapist-led cognitive-behavioural (CB) interventions are effective for low back pain (LBP) and described sufficiently for replication. Method: RCTs of patients with LBP treated by physiotherapists using a CB intervention were included. Outcomes of disability, pain and quality of life were assessed using the GRADE approach. Intervention reporting was assessed using the Template for Intervention Description and Replication. Results: Of 1898 titles, 5 RCTs (n=1,390) were identified. Compared to education and/or exercise interventions, we found high quality evidence that CB had a greater effect (SMD; 95% CI) on reducing disability (-0.19; -0.32, -0.07), pain (- 0.21; -0.33, -0.09); and moderate quality evidence of little difference in quality of life (-0.06; -0.18 to 0.07). Sufficient information was provided on dose, setting and provider; but not content and procedural information. Studies tended to report the type of CB component used (e.g. challenging unhelpful thoughts) with little detail on how it was operationalised. Moreover, access to treatment manuals, patient materials and provider training was lacking. Conclusions: With additional training, physiotherapists can deliver effective CB interventions. However, without training or resources, successful translation and implementation remains unlikely. Researchers should improve reporting of procedural information, provide relevant materials and offer accessible provider training

Study protocol: a multi-centre, double blind, randomised, placebo-controlled, parallel group, phase II trial (RIDD) to determine the efficacy of intra-nodular injection of anti-TNF to control disease progression in early Dupuytren's disease, with an embedded dose response study.

Dupuytren’s disease is a common fibrotic condition of the hand affecting 4% of the population and causes the fingers to curl irreversibly into the palm. It has a strong familial tendency, there is no approved treatment for early stage disease, and patients with established digital contractures are most commonly treated by surgery. This is associated with prolonged recovery, and less invasive techniques have high recurrence rates.The myofibroblasts, the cells responsible for the excessive matrix deposition and contraction, are aggregated in nodules. Using excised diseased and control human tissue, we found that immune cells interspersed amongst the myofibroblasts secrete cytokines. Of these, only tumour necrosis factor (TNF) promoted the development of myofibroblasts. The clinically approved anti-TNF agents led to inhibition of the myofibroblast phenotype in vitro. This clinical trial is designed to assess the efficacy of the anti-TNF agent adalimumab on participants with early disease. The first part is a dose-ranging study where nodules of participants already scheduled for surgery will be injected with either placebo (saline) or varying doses of adalimumab. The excised tissue will then be analysed for markers of myofibroblast activity.The second part of the study will recruit participants with early stage disease. They will be randomised 1: 1 to receive either adalimumab or placebo at 3 month intervals over 1 year and will then be followed for a further 6 months. Outcome measures will include nodule hardness, size and disease progression. The trial will also determine the cost-effectiveness of adalimumb treatment for this group of participants