Feasibility study and pilot cluster randomised controlled trial of the GoActive Intervention aiming to promote physical activity among adolescents: outcomes and lessons learnt

$\textbf{Objectives:}$ Assess the feasibility of implementing the GoActive intervention in secondary schools, to identify improvements, test study procedures, determine preliminary effectiveness to increase moderate-to-vigorous physical activity (MVPA), and inform power calculations to establish programme effectiveness. $\textbf{Setting:}$ Feasibility study (1 school) and pilot CRCT (2 intervention;1 control school(s)) $\textbf{Participants:}$ 460 participants (46.6% female; 13.2(0.4) years-old). $\textbf{Interventions:}$ 8-week intervention (2013) involved: classes choosing weekly activities encouraged by Mentors (older adolescents) and in-class peer-leaders. Students gain points for trying activities which are entered into an intra-mural competition. $\textbf{Primary and secondary outcome measures:}$ Planned quantitative (questionnaire) and qualitative (focus groups) process evaluation addressed enjoyment, confidence, participation, suggested improvements. Outcomes were assessed at baseline and follow-up (week 8) in pilot CRCT and included: accelerometer-assessed MVPA; adolescent-reported activity type, wellbeing, peer-support, shyness, sociability. ANCOVA was used to assess preliminary effectiveness as change in MVPA adjusted for baseline. $\textbf{Results:}$ All Year 9 students in intervention schools were exposed to the intervention; over all schools 77% of eligible students were measured. 71% boys and 74% girls found GoActive ‘fun’; 38% boys and 32% girls said it increased confidence and 64% boys and 59% girls said they would continue with a GoActive activity. Suggested improvements included more Mentorship; improved training; streamlined points recording. Pilot results indicated potential effectiveness ((adjusted mean difference (95%CI)p-value) (MVPA mins) 5.1(1.1,9.2)p=0.014)) and suggest recruitment of 16 schools (2400 adolescents) for a full trial. Compared to control, intervention students reported greater peer support 0.5(0.1,0.9)p=0.03, wellbeing 1.8(0.1, 3.4)p=0.04 but no difference in shyness/sociability. Participation in activity types approached significance (intervention group 2.3(-0.2,4.7)p=0.07 more activity types). $\textbf{Conclusions:}$ Results suggest feasibility and indicate potential effectiveness of GoActive to increase MVPA and support a fully-powered evaluation of effectiveness and cost-effectiveness. Process evaluation data was used to refine GoActive prior to a full trial. $\textbf{Trial Registration:}$ ISRCTN registry ISRCTN31583496.Funding for this study and the work of all authors was supported, wholly or in part, by the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence (RES-590-28-0002). Funding from the British Heart Foundation, Department of Health, Economic and Social Research Council, Medical Research Council, and the Wellcome Trust, under the auspices of the UK Clinical Research Collaboration, is gratefully acknowledged. The work of Kirsten Corder, Helen Brown and Esther M F van Sluijs was supported by the Medical Research Council (MC_UU_12015/7)

The application of a management procedure to regulate the directed and bycatch fishery of South African sardine sardinops sagax

The South African sardine Sardinops sagax resource is subjected to both directed fishing that targets adult fish, and bycatch of both juvenile and adult fish taken in the directed fisheries for anchovy Engraulis capensisand round herring Etrumeus whiteheadi. Two separate TACs (Total Allowable Catch) for sardine are calculated in the management procedures considered. The first is a directed TAC linked to sardine abundance, and the second is a bycatch TAC with an “anchovy” component coupled to the anchovy population dynamics as a proportion of the anchovy TAC, plus a “round herring” component reflecting a fixed tonnage independent of round herring abundance. Requirements from the pelagic industry, such as a minimum economically viable annual directed catch and a maximum percentage decrease in the directed TAC that could be tolerated from year to year are also incorporated. The selection of a single management procedure for implementation is based on the comparison of performance statistics such as risk of severe depletion and average annual catch, which incorporate the consequences of random error in survey estimates of abundance and random fluctuations in recruitment from year to year. Sensitivity tests are carried out to ensure robustness over a range of alternative assumptions concerning resource dynamics. A description is given of the development of the management procedure for sardine thatwas implemented in 1994, and the rationale for its selection. A wide range of variants to this procedure, including those that consider alternative approaches for handling bycatch, are investigated. Performance of the management procedures considered demonstrates extreme sensitivity to the choice of the proportion of the anchovy TAC used in the sardine bycatch TAC calculation. A lack of robustness of the selected management procedure to possible bias in estimates of spawner biomass from hydroacoustic surveys, and poor precision of recruit survey estimatesare argued as justification for adopting a conservative approach for managing sardine

Development of a Highly Differentiated Human Primary Proximal Tubule MPS Model (aProximate MPS Flow)

\ua9 2023 by the authors.The kidney proximal tubule (PT) mediates renal drug elimination in vivo and is a major site of drug-induced toxicity. To reliably assess drug efficacy, it is crucial to construct a model in which PT functions are replicated. Current animal studies have proven poorly predictive of human outcome. To address this, we developed a physiologically relevant micro-physiological system (MPS) model of the human PT, the aProximate MPS Flow platform (Patent No: G001336.GB). In this model, primary human PT cells (hPTCs) are subjected to fluidic media flow and a shear stress of 0.01–0.2 Pa. We observe that these cells replicate the polarity of hPTCs and exhibit a higher expression of all the key transporters of SLC22A6 (OAT1), SLC22A8 (OAT3), SLC22A2 (OCT2), SLC47A1 (MATE1), SLC22A12 (URAT1), SLC2A9 (GLUT9), ABCB1 (MDR1), ABCC2 (MRP2), LRP2 (megalin), CUBN (cubilin), compared with cells grown under static conditions. Immunofluorescence microscopy confirmed an increase in OAT1, OAT3, and cilia protein expression. Increased sensitivity to nephrotoxic protein cisplatin was observed; creatinine and FITC-albumin uptake was significantly increased under fluidic shear stress conditions. Taken together, these data suggest that growing human PT cells under media flow significantly improves the phenotype and function of hPTC monolayers and has benefits to the utility and near-physiology of the model

Radiation-induced root surface caries restored with glass-ionomer cement placed in conventional and ART cavity preparations: Results at two years

The document attached has been archived with permission from the Australian Dental Association (8th Jan 2008). An external link to the publisher’s copy is included.Background: There are no published studies comparing the clinical performances of more-viscous glass-ionomer cement (GIC) restorations when placed using conventional and atraumatic restorative treatment (ART) cavity preparation methods to restore root surface caries. Methods: One dentist used encapsulated Fuji IX GP and Ketac-Molar to restore 72 conventional and 74 ART cavity preparations for 15 patients who had received cervicofacial radiation therapy. Two assessors evaluated the restorations at six, 12, and 24 months for retention, marginal defects and surface wear, and recurrent caries. Results: After two years, the cumulative restoration successes were 65.2 per cent for the conventional and 66.2 per cent for the ART cavity preparations, without statistical or clinical significance (P>0.50). Restoration dislodgement accounted for 82.8 per cent and marginal defects for 17.2 per cent of all failures. There were no instances of unsatisfactory restoration wear or recurrent caries observed. Teeth with three or more restored cervical surfaces accounted for 79.3 per cent of all failures (P<0.0001). Conclusions: For root surface caries restored with GIC, the use of hand instruments only with the ART method was an equally effective alternative to conventional rotary instrumentation for cavity preparation. Larger restorations had higher failures, usually from dislodgement.JY Hu, XC Chen, YQ Li, RJ Smales and KH Yi

Signs of deterioration in infants discharged home following congenital heart surgery in the first year of life: a qualitative study

AIMS: To describe the ways in which parents recognise and make decisions about their child's symptoms following discharge home after congenital heart interventions in the first year of life and their experiences of seeking help. METHODS: This was a qualitative study involving semistructured interviews with parents. Twenty-one parents were recruited to the study. Parents all had a child who had congenital heart surgery in their first year of life between September 2009 and October 2013 at one of three UK cardiac centres; the children had either died or were readmitted as an emergency following initial discharge. RESULTS: Some parents were unable to identify any early warning signs. Others described symptoms of deterioration including changes in feeding and appearance, respiratory distress and subtle behavioural changes that may not be routinely highlighted to parents at discharge. Several barriers to accessing prompt medical assistance were identified including parents feeling that their concerns were not taken seriously, long wait times and lack of protocols at A&E. CONCLUSIONS: Our study highlights behavioural symptoms as being a potentially underemphasised sign of deterioration and identifies a number of barriers to parents accessing support when they are concerned. It is important that parents are encouraged to seek advice at the earliest opportunity and that those health professionals at the front line have access to the information they need in order to respond in an appropriate and timely way. A role for home monitoring was also noted as potentially useful in identifying at risk children who appear clinically well

Integrin-mediated interactions with extracellular matrix proteins for nucleus pulposus cells of the human intervertebral disc.

The extracellular matrix (ECM) of the human intervertebral disc is rich in molecules that interact with cells through integrin-mediated attachments. Porcine nucleus pulposus (NP) cells have been shown to interact with laminin (LM) isoforms LM-111 and LM-511 through select integrins that regulate biosynthesis and cell attachment. Since human NP cells lose many phenotypic characteristics with age, attachment and interaction with the ECM may be altered. Expression of LM-binding integrins was quantified for human NP cells using flow cytometry. The cell-ECM attachment mechanism was determined by quantifying cell attachment to LM-111, LM-511, or type II collagen after functionally blocking specific integrin subunits. Human NP cells express integrins β1, α3, and α5, with over 70% of cells positive for each subunit. Blocking subunit β1 inhibited NP cell attachment to all substrates. Blocking subunits α1, α2, α3, and α5 simultaneously, but not individually, inhibits NP cell attachment to laminins. While integrin α6β1 mediated porcine NP cell attachment to LM-111, we found integrins α3, α5, and β1 instead contributed to human NP cell attachment. These findings identify integrin subunits that may mediate interactions with the ECM for human NP cells and could be used to promote cell attachment, survival, and biosynthesis in cell-based therapeutics

Identifying improvements to complex pathways: evidence synthesis and stakeholder engagement in infant congenital heart disease

OBJECTIVES: Many infants die in the year following discharge from hospital after surgical or catheter intervention for congenital heart disease (3–5% of discharged infants). There is considerable variability in the provision of care and support in this period, and some families experience barriers to care. We aimed to identify ways to improve discharge and postdischarge care for this patient group. DESIGN: A systematic evidence synthesis aligned with a process of eliciting the perspectives of families and professionals from community, primary, secondary and tertiary care. SETTING: UK. RESULTS: A set of evidence-informed recommendations for improving the discharge and postdischarge care of infants following intervention for congenital heart disease was produced. These address known challenges with current care processes and, recognising current resource constraints, are targeted at patient groups based on the number of patients affected and the level and nature of their risk of adverse 1-year outcome. The recommendations include: structured discharge documentation, discharging certain high-risk patients via their local hospital, enhanced surveillance for patients with certain (high-risk) cardiac diagnoses and an early warning tool for parents and community health professionals. CONCLUSIONS: Our recommendations set out a comprehensive, system-wide approach for improving discharge and postdischarge services. This approach could be used to address challenges in delivering care for other patient populations that can fall through gaps between sectors and organisations

A tool for routine monitoring and feedback of morbidities following paediatric cardiac surgery

Short-term survival after paediatric cardiac surgery has improved significantly over the past 20 years and increasing attention is being given to measuring and reducing incidence of morbidities following surgery. How to best use routinely collected data to share morbidity information constitutes a challenge for clinical teams interested in analysing their outcomes for quality improvement. We aimed to develop a tool facilitating this process in the context of monitoring morbidities following paediatric cardiac surgery, as part of a prospective multi-centre research study in the United Kingdom. We developed a prototype software tool to analyse and present data about morbidities associated with cardiac surgery in children. We used an iterative process, involving engagement with potential users, tool design and implementation, and feedback collection. Graphical data displays were based on the use of icons and graphs designed in collaboration with clinicians. Our tool enables automatic creation of graphical summaries, displayed as a Microsoft PowerPoint presentation, from a spreadsheet containing patient-level data about specified cardiac surgery morbidities. Data summaries include numbers/percentages of cases with morbidities reported, co-occurrences of different morbidities, and time series of each complication over a time window. Our work was characterised by a very high level of interaction with potential users of the tool, enabling us to promptly account for feedback and suggestions from clinicians and data managers. The United Kingdom centres involved in the project received the tool positively, and several expressed their interest in using it as part of their routine practice