Morin-type transition in 5C pyrrhotite

We report the discovery of a low temperature spin-flop transition in 5C pyrrhotite at ~155 K that is similar to those seen in hematite at 260 K and FeS (troilite) at 440 K. The 5C crystal was produced by annealing a 4C pyrrhotite crystal at 875 K, to produce a change in the vacancy-ordering scheme that developed during cooling. The 5C structure is confirmed by single crystal x-ray diffraction and the stoichiometry and homogeneity by electron microprobe and SEM BSE mapping. RUS, heat capacity and magnetisation measurements from room temperature down to 2 K are reported. The transition is marked by a steep change in elastic properties at the transition temperature, a peak in the heat capacity and weak anomalies in measurements of magnetisation. Magnetic hysteresis loops and comparison with the magnetic properties of 4C pyrrhotite suggest that the transition involves a change in orientation of moments between two different antiferromagnetic structures, perpendicular to the crystallographic c-axis at high temperatures and parallel to the crystallographic c-axis at low temperatures. The proposed structures are consistent with a group theoretical treatment that also predicts a first order transition between the magnetic structures.Leverhulme Trus

Progressive functional exercise versus best practice advice for adults aged 50 years or over after ankle fracture: protocol for a pilot randomised controlled trial in the UK - the Ankle Fracture Treatment: Enhancing Rehabilitation (AFTER) study

Introduction Ankle fractures result in significant morbidity in adults, with prognosis worsening with increasing age. Previous trials have not found evidence supporting supervised physiotherapy sessions, but these studies have not focused on older adults or tailored the exercise interventions to the complex needs of this patient group. The Ankle Fracture Treatment: Enhancing Rehabilitation study is a pilot randomised controlled trial to assess feasibility of a later definitive trial comparing best-practice advice with progressive functional exercise for adults aged 50 years and over after ankle fracture. The main objectives are to assess: (i) patient engagement with the trial, measured by the participation rate of those eligible; (ii) establish whether the interventions are acceptable to participants and therapists, assessed by intervention adherence levels, participant interviews and a therapist focus group; (iii) participant retention in the trial, measured by the proportion of participants providing outcome data at 6 months; (iv) acceptability of measuring outcomes at 3 and 6 month follow-up. Methods and analysis A multicentre pilot randomised controlled trial with an embedded qualitative study. At least 48 patients aged 50 years and over with an ankle fracture requiring surgical management, or non-operative management by immobilisation for at least 4 weeks, will be recruited from a minimum of three National Health Service hospitals in the UK. Participants will be allocated 1:1 via a central web-based randomisation system to: (i) best-practice advice (one session of face-to-face self-management advice delivered by a physiotherapist and up to two optional additional sessions) or (ii) progressive functional exercise (up to six sessions of individual face-to-face physiotherapy). An embedded qualitative study will include one-to-one interviews with up to 20 participants and a therapist focus group. Ethics and dissemination Hampshire B Research Ethics Committee (18/SC/0281) gave approval on 2nd July 2018. Trial registration number ISRCTN1661233

Platelet rich Plasma in Achilles Tendon Healing 2 (PATH-2) trial: protocol for a multicentre, participant and assessor-blinded, parallel-group randomised clinical trial comparing platelet-rich plasma (PRP) injection versus placebo injection for Achilles tendon rupture

BackgroundAchilles tendon injuries give rise to substantial long-lasting morbidity and pose considerable challenges for clinicians and patients during the lengthy healing period. Current treatment strategies struggle to curb the burden of this injury on health systems and society due to lengthy rehabilitation, work absence and reinjury risk. Platelet-rich plasma (PRP) is an autologous preparation that has been shown to improve the mechanobiological properties of tendons in laboratory and animal studies. The use of PRP in musculoskeletal injuries is on the increase despite the lack of adequately powered clinical studies.Methods and designThis is a multicentre randomised controlled trial to evaluate the efficacy and mechanism of PRP in patients with acute Achilles tendon rupture (ATR). All adults with acute ATR presenting within 12 days of the injury who are to be treated non-operatively are eligible. A total of 230 consenting patients will be randomly allocated via a remote web-based service to receive PRP injection or placebo injection to the site of the injury. All participants will be blinded to the intervention and will receive standardised rehabilitation to reduce efficacy interference.Participants will be followed up with blinded assessments of muscle–tendon function, quality of life, pain and overall patient’s functional goals at 4, 7, 13, 24 weeks and 24 months post-treatment. The primary outcome is the heel-rise endurance test (HRET), which will be supervised by a blinded assessor at 24 weeks. A subgroup of 16 participants in one centre will have needle biopsy under ultrasound guidance at 6 weeks. Blood and PRP will be analysed for cell count, platelet activation and growth factor concentrations.Ethics and disseminationThe protocol has been approved by the Oxfordshire Research Ethics Committee (Oxfordshire Research Ethics Committee A, reference no 14/SC/1333). The trial will be reported in accordance with the CONSORT statement and published in peer-reviewed scientific journals.Trial registration numberISRCTN: 54992179, assigned 12 January 2015. ClinicalTrials.gov:NCT02302664, received 18 November 2014. UK Clinical Research Network Study Portfolio Database: ID 17850.</jats:sec

Good Statistical Practice—development of tailored Good Clinical Practice training for statisticians

\ua9 The Author(s) 2024.Background: Statisticians are fundamental in ensuring clinical research, including clinical trials, are conducted with quality, transparency, reproducibility and integrity. Good Clinical Practice (GCP) is an international quality standard for the conduct of clinical trials research. Statisticians are required to undertake training on GCP but existing training is generic and, crucially, does not cover statistical activities. This results in statisticians undertaking training mostly unrelated to their role and variation in awareness and implementation of relevant regulatory requirements with regards to statistical conduct. The need for role-relevant training is recognised by the UK NHS Health Research Authority and the Medicines and Healthcare products Regulatory Agency (MHRA). Methods: The Good Statistical Practice (GCP for Statisticians) project was instigated by the UK Clinical Research Collaboration (UKCRC) Registered Clinical Trials Unit (CTU) Statisticians Operational Group and funded by the National Institute for Health and Care Research (NIHR), to develop materials to enable role-specific GCP training tailored to statisticians. Review of current GCP training was undertaken by survey. Development of training materials were based on MHRA GCP. Critical review and piloting was conducted with UKCRC CTU and NIHR researchers with comment from MHRA. Final review was conducted through the UKCRC CTU Statistics group. Results: The survey confirmed the need and desire for the development of dedicated GCP training for statisticians. An accessible, comprehensive, piloted training package was developed tailored to statisticians working in clinical research, particularly the clinical trials arena. The training materials cover legislation and guidance for best practice across all clinical trial processes with statistical involvement, including exercises and real-life scenarios to bridge the gap between theory and practice. Comprehensive feedback was incorporated. The training materials are freely available for national and international adoption. Conclusion: All research staff should have training in GCP yet the training undertaken by most academic statisticians does not cover activities related to their role. The Good Statistical Practice (GCP for Statisticians) project has developed and extensively piloted new, role-specific, comprehensive, accessible GCP training tailored to statisticians working in clinical research, particularly the clinical trials arena. This role-specific training will encourage best practice, leading to transparent and reproducible statistical activity, as required by regulatory authorities and funders

Platelet rich plasma injection for acute Achilles tendon rupture: PATH-2 randomised, placebo controlled, superiority trial

This is the final version. Available on open access from BMJ Publishing via the DOI in this record. Objective To determine whether an injection of platelet rich plasma improves outcomes after acute Achilles tendon rupture. Design Randomised, placebo controlled, two arm, parallel group, participant and assessor masked, superiority trial. Setting Secondary care trauma units across 19 hospitals in the United Kingdom's health service. Participants Recruitment commenced in July 2015 and follow-up was completed in March 2018. 230 adults aged 18 years and over were included, with acute Achilles tendon rupture presenting within 12 days of injury and managed with non-surgical treatment. Exclusions were injury at the insertion or musculotendinous junction, major leg injury or deformity, diabetes mellitus, platelet or haematological disorder, systemic corticosteroids, anticoagulation treatment, and other contraindicating conditions. Interventions Participants were randomised 1:1 to platelet rich plasma (n=114) or placebo (dry needle; n=116) injection. All participants received standard rehabilitation care (ankle immobilisation followed by physiotherapy). Main outcomes and measures Primary outcome was muscle tendon function at 24 weeks, measured objectively with the limb symmetry index (injured/uninjured×100) in maximal work done during the heel rise endurance test (an instrumented measure of repeated single leg heel rises until fatigue). Secondary outcomes included patient reported function (Achilles tendon rupture score), quality of life (short form 12 version 2®), pain (visual analogue scale), goal attainment (patient specific functional scale), and adverse events. A central laboratory analysed the quality and content of platelet rich plasma. Analyses were by modified intention to treat. Results Participants were 46 years old on average, and 57 (25%) of 230 were female. At 24 weeks, 202 (88%) participants completed the heel rise endurance test and 216 (94%) the patient reported outcomes. The platelet rich plasma was of good quality, with expected growth factor content. No difference was detected in muscle tendon function between participants receiving platelet rich plasma injections and those receiving placebo injections (limb symmetry index, mean 34.7% (standard deviation 17.7%) v 38.5% (22.8%); adjusted mean difference -3.9% (95% confidence interval -10.5% to 2.7%)) or in any secondary outcomes or adverse event rates. Complier average causal effect analyses gave similar findings. Conclusions There is no evidence to indicate that injections of platelet rich plasma can improve objective muscle tendon function, patient reported function, or quality of life after acute Achilles tendon rupture compared with placebo, or that they offer any patient benefit. Trial registration ISRCTN54992179.Efficacy and Mechanism Evaluation programme, a Medical Research Council (MRC) and National Institute for Health Research (NIHR) partnershi

Platelet-rich plasma injection for adults with acute Achilles tendon rupture: the PATH-2 RCT

BACKGROUND:Achilles tendon rupture (ATR) has a long healing period, which is challenging for patients and clinicians. Platelet-rich plasma (PRP) is an autologous concentration of platelets thought to improve tendon function recovery. Although preliminary research has indicated positive effects, there is, as yet, no evidence of clinical efficacy from adequately powered robust clinical trials. OBJECTIVES:The objectives were to determine the clinical efficacy of PRP in patients with acute ATR using an objective mechanical muscle–tendon function measure and patient-reported outcome measures (PROMs), and to determine which PRP components contribute to its mechanism. DESIGN:This was a multicentre, parallel-group, participant- and outcome assessor-blinded randomised controlled trial (RCT) comparing PRP with placebo. Two embedded substudies investigated the PRP’s quality and composition and its effects on healing tendon tissues. SETTING:This trial was set in trauma and orthopaedic surgery departments in 19 NHS hospitals in England and Wales. PARTICIPANTS:Adults with acute ATR presenting within 12 days of injury to be treated non-surgically were eligible. Patients with platelet dysfunction or leg functional deficiency were excluded. INTERVENTIONS:Participants were randomised 1 : 1 to the PRP injection group or the placebo group (dry needle in the rupture gap) by central computer-based randomisation using minimisation, stratified by centre and age. MAIN OUTCOME MEASURES:The primary outcome measure was the Limb Symmetry Index (LSI) of work during the heel-rise endurance test at 24 weeks. Secondary outcomes measures, collected at 4, 7, 13 and 24 weeks, were repetitions, maximum heel-rise height, Achilles tendon Total Rupture Score (ATRS), quality of life (as measured using the Short Form questionnaire-12 items version 2), pain and participant goal attainment. Needle biopsies of the affected tendon zone were taken under ultrasound guidance at 6 weeks from 16 participants from one centre. Whole blood was analysed for cell count. PRP was analysed for cell count, platelet activation and growth factor concentration. The primary analysis was intention to treat. RESULTS:A total of 230 participants were randomised: 114 to the PRP group (103 treated) and 116 to the placebo group (all treated). One participant withdrew after randomisation but before the intervention. At 24 weeks, 201 out of 230 participants (87.4%) completed the primary outcome and 216 out of 230 participants (93.9%) completed the PROMs. The treatment groups had similar participant characteristics. At 24 weeks, there was no difference in work LSI (mean difference –3.872; 95% confidence interval –10.454 to 2.710; p = 0.231), ATRS, pain or goal attainment between PRP- and placebo-injected participants. There were no differences between the groups in any PROM at any time point or in complication rates, including re-rupture and deep-vein thrombosis. There was no correlation between work LSI and platelet activation in PRP, or erythrocyte, leucocyte or platelet counts in whole blood or PRP. Biopsies showed similar cellularity and vascularity between groups. CONCLUSIONS:This trial design and standardised PRP preparation gives the first robust RCT evidence about PRP’s role in managing ATR, which suggests that PRP offers no patient benefit. Equally robust evidence to investigate PRP application in tendon and soft tissue injuries is required. The 24-month follow-up will be completed in April 2020. TRIAL REGISTRATION:Current Controlled Trials ISRCTN54992179. FUNDING:This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research (NIHR) partnership. The trial was supported by the NIHR Biomedical Research Centre, Oxford, and the NIHR Fellowship programme

Economic costs, health-related quality of life outcomes and cost-utility of a physical and psychological group intervention targeted at older adults with neurogenic claudication

This is the final version. Available from BMC via the DOI in this record. The datasets analysed during the current study are available from the corresponding author upon reasonable request.BACKGROUND: Emerging evidence suggests that structured and progressive exercise underpinned by a cognitive behavioural approach can improve functional outcomes in patients with neurogenic claudication (NC). However, evidence surrounding its economic benefits is lacking. OBJECTIVES: To estimate the economic costs, health-related quality of life outcomes and cost-effectiveness of a physical and psychological group intervention (BOOST programme) versus best practice advice (BPA) in older adults with NC. METHODS: An economic evaluation was conducted based on data from a pragmatic, multicentre, superiority, randomised controlled trial. The base-case economic evaluation took the form of an intention-to-treat analysis conducted from a UK National Health Service (NHS) and personal social services (PSS) perspective and separately from a societal perspective. Costs (£ 2018-2019 prices) were collected prospectively over a 12 month follow-up period. A bivariate regression of costs and quality-adjusted life-years (QALYs), with multiple imputation of missing data, was conducted to estimate the incremental cost per QALY gained and the incremental net monetary benefit (INMB) of the BOOST programme in comparison to BPA. Sensitivity and pre-specified subgroup analyses explored uncertainty and heterogeneity in cost-effectiveness estimates. RESULTS: Participants (N = 435) were randomised to the BOOST programme (n = 292) or BPA (n = 143). Mean (standard error [SE]) NHS and PSS costs over 12 months were £1,974 (£118) in the BOOST arm versus £1,827 (£169) in the BPA arm (p = 0.474). Mean (SE) QALY estimates were 0.620 (0.009) versus 0.599 (0.006), respectively (p = 0.093). The probability that the BOOST programme is cost-effective ranged between 67 and 83% (NHS and PSS perspective) and 79-89% (societal perspective) at cost-effectiveness thresholds between £15,000 and £30,000 per QALY gained. INMBs ranged between £145 and £464 at similar cost-effectiveness thresholds. The cost-effectiveness results remained robust to sensitivity analyses. CONCLUSIONS: The BOOST programme resulted in modest QALY gains over the 12 month follow-up period. Future studies with longer intervention and follow-up periods are needed to address uncertainty around the health-related quality of life impacts and cost-effectiveness of such programmes. Trial registration This study has been registered in the International Standard Randomised Controlled Trial Number registry, reference number ISRCTN12698674. Registered on 10 November 2015.National Institute for Health Research (NIHR

Statistical analysis plan for a pragmatic phase III randomised controlled trial examining behaviour change physiotherapy intervention to increase physical activity following hip and knee replacements: the PEP-TALK trial.

BACKGROUND: Total hip (THR) and total knee replacements (TKR) are two highly successful orthopaedic procedures that reduce pain for people with osteoarthritis. Previous evidence suggests that physical activity, at best, remains the same pre- to post-operatively, and in some instances declines. The PEP-TALK trial evaluates the effects of a group-based, behaviour change intervention on physical activity following a THR or TKR. METHODS: PEP-TALK is an open, phase III, pragmatic, multi-centre, parallel, two-arm, two-way superiority randomised controlled trial investigating the effectiveness of usual care plus a behaviour change therapy compared with usual care alone following primary THR or TKR. The primary outcome is the UCLA Activity Score at 12 months post-randomisation which will be analysed using a linear mixed effects model. Secondary outcomes measured at 6 months and 12 months after randomisation include the UCLA Activity Score, Lower Extremity Functional Scale, Oxford Hip/Knee Score, Numerical Rating Scale for Pain, Generalised Self-Efficacy Scale, Tampa Scale for Kinesiophobia, Hospital Anxiety and Depression Scale, EuroQoL EQ-5D-5L index and EQ-VAS and complications or adverse events. Full details of the planned analysis approaches for the primary and secondary outcomes, as well as the planned sensitivity analyses to be undertaken due to the COVID-19 pandemic, are described here. The PEP-TALK study protocol has been published previously. DISCUSSION: This paper provides details of the planned statistical analyses for the PEP-TALK trial. This is aimed to reduce the risk of outcome reporting bias and enhance transparency in reporting. TRIAL REGISTRATION: International Standard Randomised Controlled Trials database, ISRCTN Number: 29770908 . Registered on October 2018

Twenty years of geomagnetic field observations at Mario Zucchelli Station (Antarctica)

During the 1986-87 austral summer a geomagnetic observatory was installed at Terra Nova Bay. During the first years both geomagnetic field time variation monitoring and absolute measurements were carried out only during summer. Since 1991 variometer measurements are automatically performed during the whole year, while absolute measurements are still performed only during summer. In spite of this, interesting observations were obtained during the life (quite long for Antarctica) of the geomagnetic observatory. In particular in this paper some of the most relevant results are briefly presented: studies about secular variation, daily variation (and its dependence from solar cycle and seasons) and geomagnetic higher frequency variations, such as geomagnetic pulsations

Platelet-rich plasma injection for acute Achilles tendon rupture : two-year follow-up of the PATH-2 randomized, placebo-controlled, superiority trial

This is the final version. Available on open access from the British Editorial Society of Bone and Joint Surgery via the DOI in this recordAIMS: To determine whether platelet-rich plasma (PRP) injection improves outcomes two years after acute Achilles tendon rupture. METHODS: A randomized multicentre two-arm parallel-group, participant- and assessor-blinded superiority trial was undertaken. Recruitment commenced on 28 July 2015 and two-year follow-up was completed in 21 October 2019. Participants were 230 adults aged 18 years and over, with acute Achilles tendon rupture managed with non-surgical treatment from 19 UK hospitals. Exclusions were insertion or musculotendinous junction injuries, major leg injury or deformity, diabetes, platelet or haematological disorder, medication with systemic corticosteroids, anticoagulation therapy treatment, and other contraindicating conditions. Participants were randomized via a central online system 1:1 to PRP or placebo injection. The main outcome measure was Achilles Tendon Rupture Score (ATRS) at two years via postal questionnaire. Other outcomes were pain, recovery goal attainment, and quality of life. Analysis was by intention-to-treat. RESULTS: A total of 230 participants were randomized, 114 to PRP and 116 to placebo. Two-year questionnaires were sent to 216 participants who completed a six-month questionnaire. Overall, 182/216 participants (84%) completed the two-year questionnaire. Participants were aged a mean of 46 years (SD 13.0) and 25% were female (57/230). The majority of participants received the allocated intervention (219/229, 96%). Mean ATRS scores at two years were 82.2 (SD 18.3) in the PRP group (n = 85) and 83.8 (SD 16.0) in the placebo group (n = 92). There was no evidence of a difference in the ATRS at two years (adjusted mean difference -0.752, 95% confidence interval -5.523 to 4.020; p = 0.757) or in other secondary outcomes, and there were no re-ruptures between 24 weeks and two years. CONCLUSION: PRP injection did not improve patient-reported function or quality of life two years after acute Achilles tendon rupture compared with placebo. The evidence from this study indicates that PRP offers no patient benefit in the longer term for patients with acute Achilles tendon rupture.Medical Research Council (MRC)National Institute for Health and Care Research (NIHR)Scar Free Foundatio