Edge Hill University

Haloxylon salicornicum is traditionally used for the treatment of several disorders associated with inflammation. Despite it is a defense response against tissue injury and infections, inflammation can become a chronic condition that can negatively impact the body. This study investigated the effect of H. salicornicum phytochemicals nuclear factor‐kappaB (NF‐κB), inducible nitric oxide synthase (iNOS) and cytokines release by lipopolysaccharide (LPS)‐challenged macrophages in vitro. The binding affinity of the tested phytochemical towards NF‐κB and iNOS was investigated using molecular docking. Ten compounds (four coumarins, three sterols and three flavonoids) were isolated from the ethanolic extract of H. salicornicum. Treatment of LPS‐challenged macrophages with the compounds resulted in remarkable decrease in NF‐κB p65 and iNOS mRNA abundance. All compounds suppressed the production of nitric oxide (NO) and the pro‐inflammatory cytokines (tumor necrosis factor (TNF)‐α and interleukin (IL)‐6) from macrophages challenged with LPS. Molecular docking revealed the ability of the isolated phytochemicals to bind NF‐κB p65 and iNOS. In conclusion, H. salicornicum is a rich source of phytochemicals with anti‐inflammatory properties. The anti‐inflammatory efficacy of H. salicornicum phytoconstituents is mediated via their ability to modulate NF‐κB and iNOS, and suppress the release of NO, TNF‐α, and IL‐6 from macrophages.

Background/Objectives: Dyslipidemia is frequently linked to various disorders, and its clinical relevance is now recognized. The role of inflammation and oxidative stress (OS) in dyslipidemia has been acknowledged. This study assessed the potential of arbutin (ARB) to prevent dyslipidemia and its associated OS and inflammation in rats with acute hyperlipidemia. Methods: Rats received ARB orally for 14 days and a single intraperitoneal injection of poloxamer-407 on day 15. Results: Poloxamer-407 elevated circulating cholesterol (CHOL), triglycerides (TG), very low-density lipoprotein (vLDL), and LDL, and reduced high-density lipoprotein (HDL)-C and lipoprotein lipase (LPL). ARB ameliorated the circulating lipids and LPL, and suppressed 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in rat liver and in vitro. Fatty acid synthase (FAS) in rat liver and its in vitro activity were suppressed by ARB, which also upregulated the LDL receptor (LDL-R) and ABCA1, and had no effect on ABCG5 and ABCG8 mRNA. ARB ameliorated liver malondialdehyde and nitric oxide and enhanced antioxidants in rats with dyslipidemia. Liver NF-κB p65 and blood inflammatory cytokines were increased in dyslipidemic rats, effects that were reversed by ARB. Moreover, ARB effectively suppressed lymphocyte E-NTPDase and E-ADA activities in dyslipidemic rats. The biochemical findings were supported by in silico data showing the affinity of ARB to bind LDL-R PCSK9 binding domain, HMGCR, FAS, and E-NTPDase. Conclusions: ARB possessed anti-dyslipidemia, anti-inflammatory, and antioxidant effects mediated via the modulation of CHOL and TG synthesis, LPL, lymphocyte E-NTPDase and E-ADA, and cytokine release in rats. Thus, ARB could be an effective agent to attenuate dyslipidemia and its associated OS and inflammation, pending further studies as well as clinical trials.

Aims The aim of this audit was to assess and improve the completeness and accuracy of the National Joint Registry (NJR) dataset for arthroplasty of the elbow. Methods It was performed in two phases. In Phase 1, the completeness was assessed by comparing the NJR elbow dataset with the NHS England Hospital Episode Statistics (HES) data between April 2012 and April 2020. In order to assess the accuracy of the data, the components of each arthroplasty recorded in the NJR were compared to the type of arthroplasty which was recorded. In Phase 2, a national collaborative audit was undertaken to evaluate the reasons for unmatched data, add missing arthroplasties, and evaluate the reasons for the recording of inaccurate arthroplasties and correct them. Results Phase 1 identified 5,539 arthroplasties in HES which did not match an arthroplasty on the NJR, and 448 inaccurate arthroplasties from 254 hospitals. Most mismatched procedures (3,960 procedures; 71%) were radial head arthroplasties (RHAs). In Phase 2, 142 NHS hospitals with 3,640 (66%) mismatched and 314 (69%) inaccurate arthroplasties volunteered to assess their records. A large proportion of the unmatched data (3,000 arthroplasties; 82%) were confirmed as being missing from the NJR. The overall rate of completeness of the NJR elbow dataset improved from 63% to 83% following phase 2, and the completeness of total elbow arthroplasty data improved to 93%. Missing RHAs had the biggest impact on the overall completeness, but through the audit the number of RHAs in the NJR nearly doubled and completeness increased from 35% to 70%. The accuracy of data was 94% and improved to 98% after correcting 212 of the 448 inaccurately recorded arthroplasties. Conclusion The rate of completeness of the NJR total elbow arthroplasty dataset is currently 93% and the accuracy is 98%. This audit identified challenges of data capture with regard to RHAs. Collaboration with a trauma and orthopaedic trainees through the British Orthopaedic Trainee Association improved the completeness and accuracy of the NJR elbow dataset, which will improve the validity of the reports and of the associated research. Cite this article: Bone Joint J 2024;106-B(12):1461–1468.

Aims We explored healthcare professionals' perceptions and understandings of the factors and considerations underlying inequities in technology access in children and young people (CYP) with type 1 diabetes. Methods We interviewed ( n = 29) healthcare professionals working in paediatric diabetes in England recruited from ( n = 15) purposively selected sites. We analysed data thematically. Results Interviewees highlighted multiple, often overlapping barriers to accessing technology faced by CYP with type 1 diabetes from deprived and/or ethnic minority backgrounds. They described the impacts of deprivation on technology uptake, together with the complex social, ethnic and cultural factors that could also reinforce disparities in technology access. Interviewees further highlighted staffing shortfalls as a significant barrier to supporting CYP to use technology, especially those from under‐represented groups who they perceived as requiring more staff time to be trained to use technology. While interviewees suggested that unconscious bias has become less prominent, they reported being less likely to recommend technology (especially pumps) to CYP/caregivers who they feared would not use it safely and effectively (e.g. those with low literacy levels). Interviewees also highlighted geographical variability in the technology commissioning process (a ‘postcode lottery’). Conclusions Our findings suggest that without targeted interventions, technology inequities may continue to persist amongst CYP from the most and least deprived areas and from white and ethnic minority groups in the United Kingdom. Additionally, our findings suggest that closing the technology gap will require large‐scale governmental and health policies aimed at fostering socioeconomic, ethnic and cultural equality alongside targeted measures to improve technology accessibility.

Geology and geomorphology link starkly in coastal environments, exemplifying the importance of Fookes' geo model approach to understanding site dynamics. Cliffs, and the shore platforms that front them, are subject to both marine and subaerial processes. Throughout his work, Fookes emphasises the role of climate as a weathering agent, influencing material properties and requiring consideration in engineering projects. Comparatively, more is known about the operation of rock weathering processes on shore platforms than on cliffs. Yet, with changing climate, it is becoming apparent that winter salt and frost weathering, and summer salt and wetting-drying weathering contribute to more frequent occurrences of coastal rockfalls. Increasing storm activity and rising sea levels are enhancing marine and subaerial processes. Rock coasts are amongst the most rapidly eroding coastlines in Europe. New applications of technologies, including seismometers, Lidar and InSAR, provide a fuller understanding of rock coast process-response geo model behaviour and the resilience of rock coasts on engineering timescales. Communicating scientific understanding of rock coast dynamics to policy-makers, planners and the public remains a challenge. Assessments of hazard, risk, resilience and vulnerability of rock coasts associated with climate change provide useful communication tools. Databases such as the British Geological Survey GeoCoast geohazard data product, and EMODnet Geology (European Marine Observation and Data Network) coastal behaviour data products integrate and visualise available data and information to communicate situational awareness to a broad audience.

An external focus of attention, enhanced expectancies, and autonomy support (i.e., OPTIMAL factors) are key factors to optimise motor performance and uncover latent movement capabilities. However, research on the combination of OPTIMAL factors, particularly in children's dynamic movement settings is limited. Therefore, this study examined the combined effects of OPTIMAL factors on children's performance on a dynamic movement assessment battery, hypothesising higher performance scores in the optimised version of the assessment battery versus standardised version of the assessment. Forty-nine children (15 boys, 34 girls; mean age 10.61 ± 1.38 years) completed the Dragon Challenge (DC) dynamic movement assessment battery. Performance was measured via a summation of movement process (technique), outcome, and time-to-completion scores (max score N = 54) with higher scores representing better performance. Participants completed a standardised and an optimised version of the DC in a counterbalanced fashion. For the latter, DC protocols were optimised via the provision of choice (autonomy support); external focus instructions augmented by simple knowledge statement, positive feedback and promotion of a growth mindset (Enhanced expectancies). Results indicate that motor performance (DC score) was better in the optimised (M = 31.08 ± 6.66) vs. standardised (M = 29.04 ± 5.88). The findings indicate that the combination of OPTIMAL factors can improve children's motor performance in dynamic movement settings and that standardised motor assessment may not reveal children's true movement capabilities.

Objective Interpersonal violence (IV) in sport is challenging to define, prevent and remedy due to its subjectivity and complexity. The 2024 International Olympic Committee Consensus on Interpersonal Violence and Safeguarding aimed to synthesise evidence on IV and safeguarding in sport, introduce a new conceptual model of IV in sport and offer more accessible safeguarding guidance to all within the sports ecosystem by merging evidence with insights from Olympic athletes. Methods A 15-member expert panel performed a scoping review following Joanna Briggs Institute methodologies. A seminal works-driven approach was used to identify relevant grey literature. Four writing groups were established focusing on: definitions/ epidemiology, individual/interpersonal determinants, contextual determinants and solutions. Writing groups developed referenced scientific summaries related to their respective topics, which were discussed by all members at the consensus meeting. Recommendations were then developed by each group, presented as voting statements and circulated for confidential voting following a Delphi protocol with ≥80% agreement defined a priori as reaching consensus. Results Of 48 voting statements, 21 reached consensus during first-round voting. Second-round and third-round voting saw 22 statements reach consensus, 5 statements get discontinued and 2 statements receive minority dissension after failing to reach agreement. A total of 43 statements reached consensus, presented as overarching (n=5) and topical (n=33) consensus recommendations, and actionable consensus guidelines (n=5). Conclusion This evidence review and consensus process elucidated the characterisation and complexity of IV and safeguarding in sport and demonstrates that a whole-of-system approach is needed to fully comprehend and prevent IV. Sport settings that emphasise mutual care, are athlete centred, promote healthy relationships, embed trauma and violence- informed care principles, integrate diverse perspectives and measure IV prevention and response effectiveness willexemplifysafesport.Asharedresponsibilitybetween all within the sports ecosystem is required to advance effective safeguarding through future research, policy and practice.

Background High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children (‘step-up’ RCT) and extubated children (‘step-down’ RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT. This study evaluates the cost-effectiveness of HFNC versus CPAP. Methods All-cause mortality, health-related Quality of Life (HrQoL), and costs up to six months were reported using FIRST-ABC RCTs data. HrQoL was measured with the age-appropriate Paediatric Quality of Life Generic Core Scales questionnaire and mapped onto the Child Health Utility 9D index score at six months. Quality-Adjusted Life Years (QALYs) were estimated by combining HrQoL with mortality. Costs at six months were calculated by measuring and valuing healthcare resources used in paediatric critical care units, general medical wards and wider health service. The cost-effectiveness analysis used regression methods to report the cost-effectiveness of HFNC versus CPAP at six months and summarised the uncertainties around the incremental cost-effectiveness results. Results In both RCTs, the incremental QALYs at six months were similar between the randomised groups. The estimated incremental cost at six months was − £4565 (95% CI − £11,499 to £2368) and − £5702 (95% CI − £11,328 to − £75) for step-down and step-up RCT, respectively. The incremental net benefits of HFNC versus CPAP in step-down RCT and step-up RCT were £4388 (95% CI − £2551 to £11,327) and £5628 (95% CI − £8 to £11,264) respectively. The cost-effectiveness results were surrounded by considerable uncertainties. The results were similar across most pre-specified subgroups, and the base case results were robust to alternative assumptions. Conclusions HFNC compared to CPAP as non-invasive respiratory support for critically-ill children in paediatric critical care units reduces mean costs and is relatively cost-effective overall and for key subgroups, although there is considerable statistical uncertainty surrounding this result.

The paper outlines the history of the different uses of ‘quality’ in higher education. Emphasis is given to the United Kingdom, but consideration is also given to a range of international contexts. Three different uses of ‘academic quality’ are identified (the state‐driven, sector‐derived, and the traditional academic uses) and their relationship to fundamentally different priorities, values, criteria, purposes and practices is established. The notion of a concept as it applies in the paper is then explained before four alternatives to the thought that there is more than one concept of academic quality are evaluated and ultimately rejected. It is argued that those different uses of ‘academic quality’ are not minor changes in emphasis, but fundamentally different uses of the words rooted in different concepts of academic quality with different implications for measurement and/or evaluation. The identification of those three concepts of academic quality is then put to use in critically analysing the current situation in relation to quality in higher education, involving discussion of the implications of the operation of different concepts of academic quality and reflection on how we might revise our approach to thinking about academic quality as a result.

Enhanced buffering capacity following sodium citrate (SC) ingestion may be optimized when subsequent exercise commences at individual time-to-peak (TTP) alkalosis (blood pH or bicarbonate concentration [HCO 3 ⁻ ]). While accounting for considerable interindividual variation in TTP (188–300 min), a reliable blood alkalotic response is required for practical use. This study evaluated the reliability of blood pH, HCO 3 ⁻ , and sodium (Na ⁺ ) following acute SC ingestion. Fourteen recreationally active males ingested 0.4 or 0.5 g/kg body mass (BM) of SC on two occasions each and 0.07 g/kg BM of sodium chloride (control) once. Blood pH and HCO 3 ⁻ were measured for 4 hr postingestion. Blood pH and HCO 3 ⁻ displayed good reliability following 0.5 g/kg BM SC ( r = .819, p = .002, standardized technical error [sTE] = 0.67 and r = .840, p < .001, sTE = 0.63, respectively). Following 0.4 g/kg BM SC, blood HCO 3 ⁻ retained good reliability ( r = .771, p = .006, sTE = 0.78) versus moderate for blood pH ( r = .520, p = .099, sTE = 1.36). TTP pH was moderately reliable following 0.5 ( r = .676, p = .026, sTE = 1.05) and 0.4 g/kg BM SC ( r = .679, p = .025, sTE = 0.91) versus poor for HCO 3 ⁻ following 0.5 ( r = .183, p = .361, sTE = 5.38) and 0.4 g/kg BM SC ( r = .290, p = .273, sTE = 2.50). Although the magnitude of (and displacement in) blood alkalosis, particularly HCO 3 ⁻ , appears reliable following potentially ergogenic doses of SC, strategies based on individual TTP cannot be recommended.

Objective To report 52‐week safety and efficacy of ianalumab from phase 2b dose‐finding study in patients with Sjögren's disease (SjD). Methods Patients randomly received (1:1:1:1) ianalumab (5, 50, or 300 mg) or placebo subcutaneously every 4 weeks till week 24 (treatment period [TP]1). At week 24, patients on 300 mg were re‐randomized to continue 300 mg or receive placebo till week 52 (TP2), patients on placebo were switched to ianalumab 150 mg, while patients on 5 and 50 mg directly entered post treatment safety follow‐up. Patients who discontinued treatment early or completed treatment entered safety follow‐up (≥20 weeks). Results During TP1, 190 patients were randomized (placebo=49, 5 mg=47, 50 mg=47, 300 mg=47). Of these 190 patients, 90 (47.4 %; 43 continued 300 mg and 47 received placebo) entered TP2, and 81/90 (90.0%) completed the study treatment. By week 52, efficacy was sustained in patients who continued 300 mg in TP2 (ESSDAI, ESSPRI, PaGA, PhGA change from week 24: −1.45, −0.46, −4.69, −6.86, respectively). Stimulated salivary flow rates and autoantibody levels numerically improved in the 300 mg group. Treatment‐emergent adverse events were not dose‐dependent, except for injection‐site reactions. Cases of decreased neutrophil counts (CTCAE v4.03 grade 3 according to laboratory listings) were observed in 3 patients during the post‐treatment follow‐up, occurring at 3.5, 5.5, and 3 months, after the last ianalumab administration. None were associated with infection except one incidental finding of asymptomatic cytomegalovirus infection (IgM+). Conclusion In patients with SjD, ianalumab 300 mg demonstrated sustained efficacy through week 52 and a favorable safety profile up to two years of follow‐up.

Background Health care staff should be given the opportunity to participate in research, but recruiting clinicians via their employing organisation is not always straightforward or quick in the UK. Unlike many countries outside the UK, very low-risk survey, interview or focus group studies can be subject to some of the same governance approval procedures as interventional studies. An exemplar study carried out by the NIHR funded Palliative Care Research Partnership North West Coast is used to highlight the challenges still faced by researchers and health care organisations when setting up a low-risk staff study across multiple NHS and non-NHS sites. Methods A study database was created and information was collected on the first point of contact with the clinical site, Health Research Authority (HRA) and local organisational approval times, time from trust or hospice agreement to the first survey participant recruited and overall site survey recruitment numbers. Descriptive statistics (median, range) were used to analyse these data. Results Across participating NHS trusts, it took a median of 147.5 days (range 99–195) from initial contact with the local collaborator to recruitment of the first survey participant and hospice sites mirrored these lengthy timescales (median 142 days, range 110–202). The lengthiest delays in the HRA approval process were the period between asking NHS trusts to assess whether they had capacity and capability to support the research and them granting local agreement. Local approval times varied between trusts and settings which may indicate organisations are applying national complex guidance differently. Conclusions There is the potential for HRA processes to use more NHS resources than the research study itself when recruiting to a low-risk staff study across multiple organisations. There is a need to reduce unnecessary administrative burden and bureaucracy to give clinicians and research staff more opportunities to participate in research, and to free up NHS R&D departments, research nurses and clinicians to focus on more demanding and patient focused research studies. Hospices need standardised guidance on how to assess the risk of being involved in low-risk research without adopting the unnecessarily complex systems that are currently used within the NHS.

Introduction A major challenge is retention of complex clinical skills. Spacing training and testing have been demonstrated to increase knowledge and skill retention but the combination has not been previously investigated in complex clinical skills. The aim of our study was to compare the effectiveness of combined spacing and testing for Basic Life Support (BLS) and Advance Life Support (ALS) simulation training in one group (intervention group), with combined spacing and testing, and another group (control) that received simulation training in a single-session simulation training without testing. Methods A quasi-experimental study. Results Thirteen nursing students were in the intervention group and 18 in the control group. After three months, there was no significant reduction in retention of BLS knowledge (p > 0.05) or BLS skills (p < 0.05) in the intervention group, but there was a significant reduction in both (p < 0.05) in the control group. We found no significant reduction in retention of ALS knowledge in the control group (p > 0.05), but there was a significant reduction in the intervention group (p < 0.05). There was no significant decay of ALS skills in both groups (p < 0.05). Discussion This is the first study to demonstrate that combined spacing and testing could be highly effective for complex skills simulation training to increase retention after three months.

Background We examined the influence of text and reader characteristics on sixth graders' inference generation. Methods Eleven‐ to 12‐year‐old US monolingual English speakers ( N = 71) and Spanish‐English bilinguals ( N = 81) read narrative and informational expository texts requiring an inference and answered an inference‐tapping question after each text. We examined the influence of language status, word reading ability, knowledge (background knowledge and vocabulary), and reading strategy awareness and use on question accuracy, question‐answering times and sentence reading times. Results Linear mixed effects models predicting response accuracy indicated an advantage for narrative texts, in general, and for participants with higher knowledge. When examining variation across the whole sample, rather than contrasting language groups, faster question‐answering and sentence processing times were associated with higher knowledge. Conclusions Adolescent readers are better able to generate inferences from narrative than informational expository texts, and knowledge has a critical influence on both the process and product of inference generation and may explain reading comprehension performance differences between monolingual and bilingual students.

This study adopts an integrative approach, combining quantitative and quantitative analysis based on Court judgements to uncover trends, dynamics and projections in the illegal drug trade. A quantitative analysis offers insight into drug specialisations. A Computer-Assisted Qualitative Document Analysis Software unveils socio-economic changes in a newly pivotal Italian region for international drug trade. The analysis highlights the intricate complexities of this underground activity and assesses the role of organised crime groups, shifts in criminal activities, and the emergence of complementary profitable crimes. The study offers a novel understanding of the multi-faceted nature of the drug trade, its impact on society, and its connection with other types of crimes, empowering policymakers to make evidence-based decisions on prevention and treatment policies.

It is estimated that disruptions to life caused by the COVID-19 pandemic have led to an increase in the number of children and young people suffering from mental health issues globally. In England one in four children experienced poor mental health in 2022. Social prescribing is gaining traction as a systems-based approach, which builds upon person-centered methods, to refer children and young people with non-clinical mental health issues to appropriate community assets. Recognition of social prescribing benefits for children’s mental health is increasing, yet evidence is limited. Inconsistent terminology and variation of terms used to describe social prescribing practices across the literature hinders understanding and assessment of social prescribing’s impact on children’s mental health. This scoping review thus aims to systematically identify and analyse the various terms, concepts and language used to describe social prescribing with children and young people across the wider health and social care literature base. The scoping review will be undertaken using a six-stage framework which includes: identifying the research question, identifying relevant studies, study selection, charting the data, collating, summarising and reporting the results, and consultation. Electronic databases (MEDLINE, Embase, Cumulative Index to Nursing and Allied Health, PsychInfo, Social Policy Practice, Scopus, Science Direct, Cochrane library and Joanna Briggs), alongside evidence from grey literature, hand search, citation tracking, and use of expert correspondence will be included in the review to ensure published and unpublished literature is captured. Data extraction will be carried out by two reviewers using a predefined form to capture study characteristics, intervention descriptions, outcomes, and key terms used to report social prescribing for children and young people. No formal quality appraisal or risk of bias evaluation will be performed, as this scoping review aims to map and describe the literature. Data will be stored and managed using the Rayaan.ai platform and a critical narrative of the common themes found will be included.