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On December 5, 2022, an indirect drive fusion implosion on the National Ignition Facility (NIF) achieved a target gain G_{target} of 1.5. This is the first laboratory demonstration of exceeding "scientific breakeven" (or G_{target}>1) where 2.05 MJ of 351 nm laser light produced 3.1 MJ of total fusion yield, a result which significantly exceeds the Lawson criterion for fusion ignition as reported in a previous NIF implosion [H. Abu-Shawareb et al. (Indirect Drive ICF Collaboration), Phys. Rev. Lett. 129, 075001 (2022)PRLTAO0031-900710.1103/PhysRevLett.129.075001]. This achievement is the culmination of more than five decades of research and gives proof that laboratory fusion, based on fundamental physics principles, is possible. This Letter reports on the target, laser, design, and experimental advancements that led to this result.

Aims: The primary aim of this study was to assess the feasibility of recruiting and retaining patients to a patient-blinded randomized controlled trial comparing corticosteroid injection (CSI) to autologous protein solution (APS) injection for the treatment of subacromial shoulder pain in a community care setting. The study focused on recruitment rates and retention of participants throughout, and collected data on the interventions’ safety and efficacy. Methods: Participants were recruited from two community musculoskeletal treatment centres in the UK. Patients were eligible if aged 18 years or older, and had a clinical diagnosis of subacromial impingement syndrome which the treating clinician thought was suitable for treatment with a subacromial injection. Consenting patients were randomly allocated 1:1 to a patient-blinded subacromial injection of CSI (standard care) or APS. The primary outcome measures of this study relate to rates of recruitment, retention, and compliance with intervention and follow-up to determine feasibility. Secondary outcome measures relate to the safety and efficacy of the interventions. Results: A total of 53 patients were deemed eligible, and 50 patients (94%) recruited between April 2022 and October 2022. Overall, 49 patients (98%) complied with treatment. Outcome data were collected in 100% of participants at three months and 94% at six months. There were no significant adverse events. Both groups demonstrated improvement in patient-reported outcome measures over the six-month period. Conclusion: Our study shows that it is feasible to recruit to a patient-blinded randomized controlled trial comparing APS and CSI for subacromial pain in terms of clinical outcomes and health-resource use in the UK. Safety and efficacy data are presented. Cite this article: Bone Jt Open 2024;5(7):534–542.

The level structure of Er158 has been studied using the Gammasphere spectrometer via the Cd114(Ca48,4n) reaction at 215 MeV with both thin (self-supporting) and thick (backed) targets. The level scheme has been considerably extended with more than 200 new transitions and six new rotational structures, including two strongly coupled high-K bands. Configuration assignments for the new structures are based on their observed alignments, B(M1)/B(E2) ratios of reduced transition probabilities, excitation energies, and comparisons with neighboring nuclei and theoretical calculations. With increasing angular momentum, this nucleus exhibits Coriolis-induced alignments of both neutrons and protons before it then undergoes a rotation-induced transition from near-prolate collective rotation to a noncollective oblate configuration. This transition occurs via the mechanism of band termination around spin 45ħ in three rotational structures. Two distinct lifetime branches, consistent with the crossing of a collective "fast"rotational structure by an energetically favored "slow"terminating sequence, are confirmed for the positive-parity states, and similar behavior is established in the negative-parity states. Weak-intensity, high-energy transitions are observed to feed into the terminating states. At the highest spins, three collective bands with high dynamic moments of inertia and large quadrupole moments were identified. These bands are interpreted as triaxial strongly deformed structures and mark a return to collectivity at ultrahigh spin.

Aims: Ankle fractures are common, mainly affecting adults aged 50 years and over. To aid recovery, some patients are referred to physiotherapy, but referral patterns vary, likely due to uncertainty about the effectiveness of this supervised rehabilitation approach. To inform clinical practice, this study will evaluate the effectiveness of supervised versus self-directed rehabilitation in improving ankle function for older adults with ankle fractures. Methods: This will be a multicentre, parallel-group, individually randomized controlled superiority trial. We aim to recruit 344 participants aged 50 years and older with an ankle fracture treated surgically or non-surgically from at least 20 NHS hospitals. Participants will be randomized 1:1 using a web-based service to supervised rehabilitation (four to six one-to-one physiotherapy sessions of tailored advice and prescribed home exercise over three months), or self-directed rehabilitation (provision of advice and exercise materials that participants will use to manage their recovery independently). The primary outcome is participant-reported ankle-related symptoms and function six months after randomization, measured by the Olerud and Molander Ankle Score. Secondary outcomes at two, four, and six months measure health-related quality of life, pain, physical function, self-efficacy, exercise adherence, complications, and resource use. Due to the nature of the interventions, participants and intervention providers will be unblinded to treatment allocation. Conclusion: This study will assess whether supervised rehabilitation is more effective than self-directed rehabilitation for adults aged 50 years and older after ankle fracture. The results will provide evidence to guide clinical practice. At the time of submission, the trial is currently completing recruitment, and follow-up will be completed in 2024. Cite this article: Bone Jt Open 2024;5(6):499–513.

Aims: Fractures of the humeral shaft represent 3% to 5% of all fractures. The most common treatment for isolated humeral diaphysis fractures in the UK is non-operative using functional bracing, which carries a low risk of complications, but is associated with a longer healing time and a greater risk of nonunion than surgery. There is an increasing trend to surgical treatment, which may lead to quicker functional recovery and lower rates of fracture nonunion than functional bracing. However, surgery carries inherent risk, including infection, bleeding, and nerve damage. The aim of this trial is to evaluate the clinical and cost-effectiveness of functional bracing compared to surgical fixation for the treatment of humeral shaft fractures. Methods: The HUmeral SHaft (HUSH) fracture study is a multicentre, prospective randomized superiority trial of surgical versus non-surgical interventions for humeral shaft fractures in adult patients. Participants will be randomized to receive either functional bracing or surgery. With 334 participants, the trial will have 90% power to detect a clinically important difference for the Disabilities of the Arm, Shoulder and Hand questionnaire score, assuming 20% loss to follow-up. Secondary outcomes will include function, pain, quality of life, complications, cost-effectiveness, time off work, and ability to drive. Discussion: The results of this trial will provide evidence regarding clinical and cost-effectiveness between surgical and non-surgical treatment of humeral shaft fractures. Ethical approval has been obtained from East of England – Cambridge Central Research Ethics Committee. Publication is anticipated to occur in 2024. Cite this article: Bone Jt Open 2024;5(4):343–349.

Abstract Background Explainer animations are a means to communicate aspects of clinical trials to participants in a more engaging and accessible way. Delivered well these have the potential to enhance recruitment and retention. The range of media technology used to deliver this material is expanding rapidly but is highly fragmented. Usage of explainer animations across the UK is unknown, the aim of this research was to determine current usage across the 52 registered UK Clinical Research Collaboration (UKCRC) Clinical Trials Units (CTUs) to understand the current landscape and any barriers that could be preventing wider uptake of this functionality. Methods A survey link was emailed to all UKCRC CTU Directors and Trial Management Leads to ascertain current usage of explainer animations within their CTU. The survey ran between 01 February 2023 and 07 March 2023. Results Responses were received from 35 CTUs—representing a response rate of 67%. 24 CTUs (69%) reported that they had created/used at least one explainer animation within their unit, although the usage, cost, length and production activities varied among the units. Conclusions The survey showed that a high proportion of the UKCRC CTUs have used explainer animations to provide information to participants about clinical studies. For those not using the technology yet, the most common reasons cited were a lack of expertise, lack of resources and costs to produce them. One of the desired outcomes of this project is the creation of a free-to-use library of animations to encourage wider uptake and avoid duplication.

Aims: The management of fractures of the medial epicondyle is one of the greatest controversies in paediatric fracture care, with uncertainty concerning the need for surgery. The British Society of Children’s Orthopaedic Surgery prioritized this as their most important research question in paediatric trauma. This is the protocol for a randomized controlled, multicentre, prospective superiority trial of operative fixation versus nonoperative treatment for displaced medial epicondyle fractures: the Surgery or Cast of the EpicoNdyle in Children’s Elbows (SCIENCE) trial. Methods: Children aged seven to 15 years old inclusive, who have sustained a displaced fracture of the medial epicondyle, are eligible to take part. Baseline function using the Patient-Reported Outcomes Measurement Information System (PROMIS) upper limb score, pain measured using the Wong Baker FACES pain scale, and quality of life (QoL) assessed with the EuroQol five-dimension questionnaire for younger patients (EQ-5D-Y) will be collected. Each patient will be randomly allocated (1:1, stratified using a minimization algorithm by centre and initial elbow dislocation status (i.e. dislocated or not-dislocated at presentation to the emergency department)) to either a regimen of the operative fixation or non-surgical treatment. Outcomes: At six weeks, and three, six, and 12 months, data on function, pain, sports/music participation, QoL, immobilization, and analgesia will be collected. These will also be repeated annually until the child reaches the age of 16 years. Four weeks after injury, the main outcomes plus data on complications, resource use, and school absence will be collected. The primary outcome is the PROMIS upper limb score at 12 months post-randomization. All data will be obtained through electronic questionnaires completed by the participants and/or parents/guardians. The NHS number of participants will be stored to enable future data linkage to sources of routinely collected data (i.e. Hospital Episode Statistics). Cite this article: Bone Jt Open 2024;5(1):69–77.

Abstract Background The management of subacromial shoulder pain represents a significant challenge and is typically managed through either physiotherapy, joint injection or surgical intervention. Recent surgical trials have questioned the efficacy and there is a need to improve the evidence base for the non-surgical management of this condition. The study aims to provide evidence of the feasibility of conducting a randomised controlled trial to compare the efficacy of autologous protein solution (APS) against the current standard of care, corticosteroid injection (CSI) for subacromial shoulder pain. Autologous protein solution (APS) is a blood-derived biological injection which has been shown to have anti-inflammatory effects. Methods A parallel-group two-arm randomised control trial will be conducted, comparing APS and CSI for shoulder pain. Fifty patients will be recruited. Feasibility will be assessed by examination of the conversion rate of eligible participants to the total number of participants recruited, whether it is possible to collect the appropriate outcome measures and the levels of retention/data compliance at follow-up dates. Discussion CSI is the mainstay of conservative management of subacromial shoulder pain. Trials and systematic reviews have reported differing conclusions, but the consensus view is that any benefits seen from CSI use are most likely to be short-term and there remains a significant number of patients who go on to have surgical intervention despite CSI. Biological injections, such as APS are being increasingly used, in the anticipation they may offer improved longer lasting outcomes for shoulder pain. However, the evidence to demonstrate the comparative efficacy of CSI versus APS does not currently exist. If feasible, a fully powered study will offer clarity to the treatment pathway of thousands of patients each year with subacromial pain. Trial registration The study is funded by the National Institute for Health Research–Research for Patient Benefit, NIHR 201473, Trial Registration Number (ISRCTN12536844: SPiRIT. Shoulder pain: randomised trial of injectable treatments–date of Registration 15/9/2021). Protocol Version V1.0_30Jul2021. IRAS Project ID: 294,982.

For more than half a century, researchers around the world have been engaged in attempts to achieve fusion ignition as a proof of principle of various fusion concepts. Following the Lawson criterion, an ignited plasma is one where the fusion heating power is high enough to overcome all the physical processes that cool the fusion plasma, creating a positive thermodynamic feedback loop with rapidly increasing temperature. In inertially confined fusion, ignition is a state where the fusion plasma can begin "burn propagation" into surrounding cold fuel, enabling the possibility of high energy gain. While "scientific breakeven" (i.e., unity target gain) has not yet been achieved (here target gain is 0.72, 1.37 MJ of fusion for 1.92 MJ of laser energy), this Letter reports the first controlled fusion experiment, using laser indirect drive, on the National Ignition Facility to produce capsule gain (here 5.8) and reach ignition by nine different formulations of the Lawson criterion.

Abstract Background During the COVID-19 pandemic, in-person healthcare visits were reduced. Consequently, trial teams needed to consider implementing remote methods for conducting clinical trials, including e-Consent. Although some clinical trials may have implemented e-Consent prior to the pandemic, anecdotes of uptake for this method increased within academic-led trials. When the increased use of this process emerged, representatives from several large academic clinical trial groups within the UK collaborated to discuss ways in which trialists can learn from one another when implementing e-Consent. Methods A survey of UKCRC-registered Clinical Trials Units (CTUs) was undertaken in April–June 2021 to understand the implementation of and their views on the use of e-Consent and experiences from the perspectives of systems programmers and quality assurance staff on the use of e-Consent. CTUs not using e-Consent were asked to provide any reasons/barriers (including no suitable trials) and any plans for implementing it in the future. Two events for trialists and patient and public involvement (PPI) representatives were then held to disseminate findings, foster discussion, share experiences and aid in the identification of areas that the academic CTU community felt required more research. Results Thirty-four (64%) of 53 CTUs responded to the survey, with good geographical representation across the UK. Twenty-one (62%) of the responding CTUs had implemented e-Consent in at least one of their trials, across different types of trials, including CTIMPs (Clinical Trial of Investigational Medicinal Product), ATIMPs (Advanced Therapy Medicinal Products) and non-CTIMPs. One hundred ninety-seven participants attended the two workshops for wide-ranging discussions. Conclusion e-Consent is increasingly used in academic-led trials, yet uncertainties remain amongst trialists, patients and members of the public. Uncertainties include a lack of formal, practical guidance and a lack of evidence to demonstrate optimal or appropriate methods to use. We strongly encourage trialists to continue to share their own experiences of the implementation of e-Consent.

Aims: The aim of this study was to describe the current pathways of care for patients with a fracture of the hip in five low- and middle-income countries (LMIC) in South Asia (Nepal and Sri Lanka) and Southeast Asia (Malaysia, Thailand, and the Philippines). Methods: The World Health Organization Service Availability and Readiness Assessment tool was used to collect data on the care of hip fractures in Malaysia, Thailand, the Philippines, Sri Lanka, and Nepal. Respondents were asked to provide details about the current pathway of care for patients with hip fracture, including pre-hospital transport, time to admission, time to surgery, and time to weightbearing, along with healthcare professionals involved at different stages of care, information on discharge, and patient follow-up. Results: Responses were received from 98 representative hospitals across the five countries. Most hospitals were publicly funded. There was consistency in clinical pathways of care within country, but considerable variation between countries. Patients mostly travel to hospital via ambulance (both publicly- and privately-funded) or private transport, with only half arriving at hospital within 12 hours of their injury. Access to surgery was variable and time to surgery ranged between one day and more than five days. The majority of hospitals mobilized patients on the first or second day after surgery, but there was notable variation in postoperative weightbearing protocols. Senior medical input was variable and specialist orthogeriatric expertise was unavailable in most hospitals. Conclusion: This study provides the first step in mapping care pathways for patients with hip fracture in LMIC in South Asia. The previous lack of data in these countries hampers efforts to identify quality standards (key performance indicators) that are relevant to each different healthcare system. Cite this article: Bone Jt Open 2023;4(9):676–681.

Abstract Background Patellar dislocations mainly affect adolescents and young adults. After this injury, patients are usually referred to physiotherapy for exercise-based rehabilitation. Currently, limited high-quality evidence exists to guide rehabilitation practice and treatment outcomes vary. A full-scale trial comparing different rehabilitation approaches would provide high-quality evidence to inform rehabilitation practice. Whether this full-scale trial is feasible is uncertain: the only previous trial that compared exercise-based programmes in this patient population had high loss to follow-up. This study aims to assess the feasibility of conducting a future full-scale trial comparing the clinical and cost-effectiveness of two different rehabilitation approaches for people with an acute patellar dislocation. Methods Two-arm parallel external pilot randomised controlled trial and qualitative study. We aim to recruit at least 50 participants aged ≥ 14 years with an acute first-time or recurrent patellar dislocation from at least three English National Health Service hospitals. Participants will be randomised 1:1 to supervised rehabilitation (four to six, one-to-one, physiotherapy sessions of advice and prescription of tailored progressive home exercise over a maximum of 6 months) or self-managed rehabilitation (one physiotherapy session of self-management advice, exercise, and provision of self-management materials). Pilot objectives are (1) willingness to be randomised, (2) recruitment rate, (3) retention, (4) intervention adherence, and (5) intervention and follow-up method acceptability to participants assessed through one-to-one semi-structured interviews (maximum 20 participants). Follow-up data will be collected 3, 6, and 9 months after randomisation. Quantitative pilot and clinical outcomes will be numerically summarised, with 95% confidence intervals generated for the pilot outcomes using Wilson’s and exact Poisson methods as appropriate. Discussion This study will assess the feasibility of conducting a full-scale trial comparing supervised versus self-managed rehabilitation for people after acute first-time or recurrent patellar dislocation. This full-scale trial’s results would provide high-quality evidence to guide rehabilitation provision for patients with this injury. Trial registration ISRCTN registry ISRCTN14235231 . Registered on 09 August 2022.

Background Systematic annual screening for sight-threatening diabetic retinopathy is established in several countries but is resource intensive. Personalised (individualised) medicine offers the opportunity to extend screening intervals for people at low risk of progression and to target high-risk groups. However, significant concern exists among all stakeholders around the safety of changing programmes. Evidence to guide decisions is limited, with, to the best of our knowledge, no randomised controlled trials to date. Objectives To develop an individualised approach to screening for sight-threatening diabetic retinopathy and test its acceptability, safety, efficacy and cost-effectiveness. To estimate the changing incidence of patient-centred outcomes. Design A risk calculation engine; a randomised controlled trial, including a within-trial cost-effectiveness study; a qualitative acceptability study; and an observational epidemiological cohort study were developed. A patient and public group was involved in design and interpretation. Setting A screening programme in an English health district of around 450,000 people. Participants People with diabetes aged ≥ 12 years registered with primary care practices in Liverpool. Interventions The risk calculation engine estimated each participant’s risk at each visit of progression to screen-positive diabetic retinopathy (individualised intervention group) and allocated their next appointment at 6, 12 or 24 months (high, medium or low risk, respectively). Main outcome measures The randomised controlled trial primary outcome was attendance at first follow-up assessing the safety of individualised compared with usual screening. Secondary outcomes were overall attendance, rates of screen-positive and sight-threatening diabetic retinopathy, and measures of visual impairment. Cost-effectiveness outcomes were cost/quality-adjusted life year and incremental cost savings. Cohort study outcomes were rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy. Data sources Local screening programme (retinopathy), primary care (demographic, clinical) and hospital outcomes. Methods A seven-person patient and public involvement group was recruited. Data were linked into a purpose-built dynamic data warehouse. In the risk assessment, the risk calculation engine used patient-embedded covariate data, a continuous Markov model, 5-year historical local population data, and most recent individual demographic, retina and clinical data to predict risk of future progression to screen-positive. The randomised controlled trial was a masked, two-arm, parallel assignment, equivalence randomised controlled trial, with an independent trials unit and 1 : 1 allocation to individualised screening (6, 12 or 24 months, determined by risk calculation engine at each visit) or annual screening (control). Cost-effectiveness was assessed using a within-trial analysis over a 2-year time horizon, including NHS and societal perspectives and costs directly observed within the randomised controlled trial. Acceptability was assessed by purposive sampling of 60 people with diabetes and 21 healthcare professionals with semistructured interviews analysed thematically; this was a constant comparative method until saturation. The cohort was an 11-year retrospective/prospective screening population data set. Results In the randomised controlled trial, 4534 participants were randomised: 2097 out of 2265 in the individualised arm (92.6%) and 2224 out of 2269 in the control arm (98.0%) remained after withdrawals. Attendance rates at first follow-up were equivalent (individualised 83.6%, control 84.7%) (difference –1.0%, 95% confidence interval –3.2% to 1.2%). Sight-threatening diabetic retinopathy detection rates were non-inferior: individualised 1.4%, control 1.7% (difference –0.3%, 95% confidence interval –1.1% to 0.5%). In the cost-effectiveness analysis, the mean differences in complete-case quality-adjusted life years (EuroQol-5 Dimensions, five-level version, and Health Utilities Index Mark 3) did not significantly differ from zero. Incremental cost savings per person not including treatment costs were from the NHS perspective £17.34 (confidence interval £17.02 to £17.67) and the societal perspective £23.11 (confidence interval £22.73 to £23.53). In the individualised arm, 43.2% fewer screening appointments were required. In terms of acceptability, changing to variable intervals was acceptable for the majority of people with diabetes and health-care professionals. Annual screening was perceived as unsustainable and an inefficient use of resources. Many people with diabetes and healthcare professionals expressed concerns that 2-year screening intervals may detect referable eye disease too late and might have a negative effect on perceptions about the importance of attendance and diabetes care. The 6-month interval was perceived positively. Among people with dementia, there was considerable misunderstanding about eye-related appointments and care. In the cohort study, the numbers of participants (total 28,384) rose over the 11 years (2006/7, n = 6637; 2016/17, n = 14,864). Annual incidences ranged as follows: screen-positive 4.4–10.6%, due to diabetic retinopathy 2.3–4.6% and sight-threatening diabetic retinopathy 1.3–2.2%. The proportions of screen-positive fell steadily but sight-threatening diabetic retinopathy rates remained stable. Limitations Our findings apply to a single city-wide established English screening programme of mostly white people with diabetes. The cost-effectiveness analysis was over a short timeline for a long-standing disease; the study, however, was designed to test the safety and effectiveness of the screening regimen, not the cost-effectiveness of screening compared with no screening. Cohort data collection was partly retrospective: data were unavailable on people who had developed sight-threatening diabetic retinopathy or died prior to 2013. Conclusions Our randomised controlled trial can reassure stakeholders involved in diabetes care that extended intervals and personalised screening is feasible, where data linkage is possible, and can be safely introduced in established screening programmes with potential cost savings compared with annual screening. Rates of screen-positive diabetic retinopathy and sight-threatening diabetic retinopathy are low and show consistent falls over time. Involvement of patients in research is crucial to success. Future work Future work could include external validation with other programmes followed by scale-up of individualised screening outside a research setting and economic modelling beyond the 2-year time horizon. Trial registration This trial is registered as ISRCTN87561257. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 11, No. 6. See the NIHR Journals Library website for further project information. Plain language summary Diabetic retinopathy remains a leading cause of vision loss for people with diabetes. Annual photographic screening allows early detection and prompt treatment in many countries. A new approach is to vary how often this is undertaken at each visit, after calculating each person’s risk of progression; we have called this ‘individualised’ screening. We tested this variable-interval risk-based approach against annual screening in a randomised controlled trial of 4534 people in Liverpool. Six-, 12- or 24-month intervals represented high, medium and low risks, respectively, of becoming screen-positive by the next appointment. With our patient and public involvement group, we designed a computer-based risk-calculation system using personal information from screening, general practitioners and hospitals. Attendance rates at the next screening appointment were similar in the individualised (84%) and annual (control) (85%) groups. Similar amounts of sight-threatening diabetic retinopathy were detected in the two arms (1.4% individualised, 1.7% control), with 43% fewer visits. In this study in a single geographical region, savings estimated to accrue to the NHS per person over 2 years were £17.34 and £23.11 for wider society, but estimates did not include treatment costs. During interviews, 60 people with diabetes and 21 healthcare professionals said that individualised screening would be acceptable because of increasing rates of diabetes and the chance to target high-risk people. Patients had anxieties about the reliability of the risk-calculation and restricting access, requesting opportunities for earlier screening if risks changed. Varying screening intervals based on a person’s own risk of progression appears feasible and safe. Low-risk people would be spared unnecessary appointments. Introducing an individualised approach could now move to wider testing and validation in other UK and international settings. The trial only ran for 2 years and was in a long-established programme with low rates of disease, so monitoring of attendance and retinopathy rates should be included as part of wider testing. Scientific summary Background Diabetic retinopathy remains the most common cause of visual impairment in working populations worldwide. Systematic annual screening to detect and treat sight-threatening diabetic retinopathy (STDR) is established in several countries including the United Kingdom (UK) and has greatly improved the detection of treatable disease. With the rapid increase in the prevalence of diabetes, new approaches to screening are required. Risk stratification, personalised (individualised) medicine, and clinical bioinformatics offer opportunities to extend the screening interval for people at low risk of progression and to target those at high risk. However there is significant concern among people with diabetes, healthcare professionals and health commissioners in the UK around the safety and acceptability of changing an established and successful programme. To ensure that health care is available for all it is imperative that it is not only efficacious but cost-efficient, that is, it delivers care at an affordable cost for commissioners. Evidence to guide these decisions is very limited and there are no randomised controlled trials (RCTs). Much of the data on prevalence and incidence of diabetic retinopathy and progression to more severe stages of disease come from the 1980s to 1990s and before the introduction of systematic screening and improvements in diabetes and blood pressure control. Data on the current progression rates in screening populations are limited and are reported variably. We conducted a programme of quantitative and qualitative research to develop and test the acceptability, safety, efficacy and cost-effectiveness of an individualised approach to screening for STDR. To provide data for future planning of early detection programmes and the design of future research studies we designed a longitudinal observational cohort study of the population of people with diabetes in Liverpool. We aimed to investigate the prevalence and incidence of the stages in the natural history of diabetic retinopathy, namely screen-positive, sight-threatening and treatable disease, and visual impairment, all key patient-centred outcomes in the disease. Changes to the programme and their implications A number of changes to the programme occurred in the early years. A systematic review was published at around the time of the programme start. We used these data to design aspects of the study and conducted a literature review instead. Data for the cohort study proved not to be available on people who had died prior to programme start. We adopted a mixed retrospective and prospective analysis but this added some difficulty in interpreting the findings. In 2016 resources were repurposed from the cohort study to support recruitment of the RCT, which was behind schedule. The scope of the cohort study was narrowed to focus only on the data available from the screening programme, meaning that we were unable to complete data collection on the patient-centred outcomes after sight-threatening retinopathy had been confirmed, namely treatment and visual impairment. Recruitment of non-attenders proved beyond the resources available and was abandoned. Further research is needed to address these unanswered questions. Methods The programme included the development of a bespoke data warehouse, the development of a risk-calculation engine, a RCT, a within-trial cost-effectiveness study, a qualitative study of acceptability, and an observational cohort study. We recruited and fully embedded a seven-person patient and public involvement group which was maintained throughout the programme. The setting was the screening programme of a single English health district (clinical commissioning group). All people with diabetes aged 12 years and over registered with general practices in the Liverpool city area were invited by letter to participate in the research programme. Consent was through an opt-out process. A purpose-built dynamic data warehouse was developed to support all aspects of the programme including bespoke processes addressing inconsistency in routinely collected data, multiple data platforms and lack of technical manuals. Data on eligible participants were sourced from primary care (demographic, clinical), Liverpool Diabetes Eye Screening Programme (retinopathy) and hospital outcomes (true screen-positive, STDR). Data were cross referenced against opt-out records before further use within the programme. A risk-calculation engine was developed for the assessment of individual risk of progressing to screen-positive using patient-focused covariate selection, a continuous-time Markov model, 5-year historical local population data, and the most recent individual demographic, retina and clinical data. The risk-calculation engine was linked to the data warehouse. The Patient and Public Involvement group determined the risk criterion of

Abstract Background Distal radius fractures represent about 1 in 5 of all fractures treated in UK hospitals. Most distal radius fractures occur in women aged 50 years or over after a fall. Distal radius fractures are managed using splints or casting, some are also treated with surgical fixation. Patients often experience long-term muscle weakness of the hand and arm that may impact their ability to do daily activities such as personal hygiene, routine household chores and food preparation. We propose a structured and tailored flexibility and resistance exercise programme for the hand and arm supplemented with behaviour change strategies to help perform daily exercise. The main aim of our study is to assess the feasibility of conducting a definitive randomised controlled trial. Methods This study is a multicentre, parallel-group individually randomised feasibility trial. We will recruit a minimum of 72 adults aged 50 years or over with distal radius fracture treated surgically or non-surgically from at least three UK National Health Service (NHS) hospitals. They will be randomised 1:1:1 to receive usual care, usual care and independent exercise with a single therapy session or usual care and supervised exercise with three therapy sessions over 12 weeks. Our primary feasibility objectives are (1) patient engagement assessed by recruitment, (2) acceptability of the interventions assessed by adherence and patient and clinician experience and (3) retention of participants in the trial. Outcome measures will be assessed at baseline, 3 months and at 6 months after randomisation. A qualitative sub-study will explore the experiences of the trial participants and therapists delivering the exercises. Discussion A definitive trial will be considered feasible without major modifications if our progression criteria are met. If successful, the findings will inform the design of a future definitive RCT to evaluate the clinical and cost-effectiveness of the WISE exercise programme. Trial registration ISRCTN12290145 .

Abstract Background Unstable ankle fractures represent a substantial burden of disease, accounting for a mean hospital stay of nine days, a mean cost of £4,491 per patient and 20,000 operations per year. There is variation in UK practice around weight-bearing instructions after operatively managed ankle fracture. Early weight-bearing may reduce reliance on health services, time off work, and improve functional outcomes. However, concerns remain about the potential for complications such as implant failure. This is the protocol of a multicentre randomised non-inferiority clinical trial of weight-bearing following operatively treated ankle fracture. Methods Adults aged 18 years and over who have been managed operatively for ankle fracture will be assessed for eligibility. Baseline function (Olerud and Molander Ankle Score [OMAS]), health-related quality of life (EQ-5D-5L), and complications will be collected after informed consent has been obtained. A randomisation sequence has been prepared by a trial statistician to allow for 1:1 allocation to receive either instruction to weight-bear as pain allows from the point of randomisation, two weeks after the time of surgery (‘early weight-bearing’ group) or to not weight-bear for a further four weeks (‘delayed weight -bearing’ group). All other treatment will be as per the guidance of the treating clinician. Participants will be asked about their weight-bearing status weekly until four weeks post-randomisation. At four weeks post-randomisation complications will be collected. At six weeks, four months, and 12 months post-randomisation, the OMAS, EQ-5D-5L, complications, physiotherapy input, and resource use will be collected. The primary outcome measure is ankle function (OMAS) at four months post-randomisation. A minimum of 436 participants will be recruited to obtain 80% power to detect a non-inferiority margin of -6 points on the OMAS 4 months post-randomisation. A within-trial health economic evaluation will be conducted to estimate the cost-effectiveness of the treatment options. Discussion The results of this study will inform national guidance with regards to the most clinically and cost-effective strategy for weight-bearing after surgery for unstable ankle fractures. Trial registration ISRCTN12883981 , Registered 02 December 2019.

Inertial confinement fusion (ICF) experiments create a unique laboratory environment in which thermonuclear fusion reactions occur within a plasma, with conditions comparable to stellar cores and the early universe. In contrast, accelerator-based measurements must compete with bound electron screening effects and beam stopping when measuring fusion cross sections at nucleosynthesis-relevant energies. Therefore, ICF experiments are a natural place to study nuclear reactions relevant to nuclear astrophysics. However, analysis of ICF-based measurements must address its own set of complicating factors. These include: the inherent range of reaction energies, spatial and temporal thermal temperature variation, and kinetic effects such as species separation. In this work we examine these phenomena and develop an analysis to quantify and, when possible, compensate for their effects on our inference. Error propagation in the analyses are studied using synthetic data combined with Markov Chain Monte Carlo (MCMC) machine learning. The novel inference techniques will aid in the extraction of valuable and accurate data from ICF-based nuclear astrophysics experiments.

Background: Torus (buckle) fractures of the wrist are the most common fractures in children involving the distal radius and/or ulna. It is unclear if children require rigid immobilisation and follow-up or would recover equally as well by being discharged without any immobilisation or a bandage. Given the large number of these injuries, identifying the optimal treatment strategy could have important effects on the child, the number of days of school absence and NHS costs. Objectives: To establish whether or not treating children with a distal radius torus fracture with the offer of a soft bandage and immediate discharge (i.e. offer of a bandage) provides the same recovery, in terms of pain, function, complications, acceptability, school absence and resource use, as treatment with rigid immobilisation and follow-up as per usual practice (i.e. rigid immobilisation). Design: A pragmatic, multicentre, randomised controlled equivalence trial. Setting: Twenty-three UK emergency departments. Participants: A total of 965 children (aged 4–15 years) with a distal radius torus fracture were randomised from January 2019 to July 2020 using a secure, centralised, online-encrypted randomisation service. Exclusion criteria included presentation > 36 hours after injury, multiple injuries and an inability to complete follow-up. Interventions: A bandage was offered to 489 participants and applied to 458, and rigid immobilisation was carried out in 476 participants. Participants and clinicians were not blinded to the treatment allocation. Main outcome measures: The pain at 3 days post randomisation was measured using the Wong–Baker FACES Pain Rating Scale. Secondary outcomes were the patient-reported outcomes measurement system upper extremity limb score for children, health-related quality of life, complications, school absence, analgesia use and resource use collected up to 6 weeks post randomisation. Results: A total of 94% of participants provided primary outcome data. At 3 days, the primary outcome of pain was equivalent in both groups. With reference to the prespecified equivalence margin of 1.0, the adjusted difference in the intention-to-treat population was –0.10 (95% confidence interval –0.37 to 0.17) and the per-protocol population was –0.06 (95% confidence interval –0.34 to 0.21). There was equivalence of pain in both age subgroups (i.e. 4–7 years and 8–15 years). There was no difference in the rate of complications, with five complications (1.0%) in the offer of a bandage group and three complications (0.6%) in the rigid immobilisation group. There were no differences between treatment groups in functional recovery, quality of life or school absence at any point during the follow-up. Analgesia use was marginally higher at day 1 in the offer of a bandage group than it was in the rigid immobilisation group (83% vs. 78% of participants), but there was no difference at other time points. The offer of a bandage significantly reduced the cost of treatment and had a high probability of cost-effectiveness at a willingness-to-pay threshold of £30,000 per quality-adjusted life-year. Limitations: Families had a strong pre-existing preference for the rigid immobilisation treatment. Given this, and the inability to blind families to the treatment allocation, observer bias was a concern. However, there was clear evidence of equivalence. Conclusions: The study findings support the offer of a bandage in children with a distal radius torus fracture. Future work: A clinical decision tool to determine which children require radiography is an important next step to prevent overtreatment of minor wrist fractures. There is also a need to rationalise interventions for other common childhood injuries (e.g. ‘toddler’s fractures’ of the tibia). Trial registration: This trial is registered as ISRCTN13955395 and UKCRN Portfolio 39678. Funding: This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 33. See the NIHR Journals Library website for further project information.