Rolling out the red carpet: Non-offending partners and affected family members as allies in disruption.

BACKGROUND: In Australia, there is a lack of research on the impacts on law enforcement officers (LEO) and agencies (LEA) working with families impacted by child sexual abuse. PartnerSPEAK is the only Australian specialist not-for-profit, peer-led agency advocating for the secondary victims or non-offending partners and affected family members (NOP/AFM) of those who engage in the online sexual exploitation of children (OSEC). OBJECTIVE: This research explores the interactions between Australian specialised OSEC LEO and the perpetrators of NOP/AFM in OSEC and how these impact well-being and investigative efficacy. SETTING AND PARTICIPANTS: This research surveyed 48 Australian OSEC specialist investigators online from within the Australian Federal Police, Border Force, and local law enforcement agencies. DESIGN: This study employed a mixed-method design, including quantitative scaled responses and qualitative open-ended questions through an online survey. RESULTS: The results showed investigators reported responding to families as more distressing than viewing OSEC. Additionally, positive relationships with NOP/AFM enhanced well-being and justice outcomes. However, given the research design, methods, and sample size, we could not determine statistical significance from the findings. CONCLUSIONS: Responding to non-offending family members is not an adjunct to the investigator's role but is an integral part of OSEC investigations. Therefore, we recommend that law enforcement leadership prioritise improving the procedures and well-being of investigators and non-offending family members impacted by OSEC investigations. This study provides the first evidence in examining this topic and, as such, has meaningful practice implications for law enforcement and opportunities to build on these findings.

Classifying High-Risk Patients for Persistent Opioid Use After Major Spine Surgery: A Machine-Learning Approach.

BACKGROUND: Persistent opioid use is a common occurrence after surgery and prolonged exposure to opioids may result in escalation and dependence. The objective of this study was to develop machine-learning-based predictive models for persistent opioid use after major spine surgery. METHODS: Five classification models were evaluated to predict persistent opioid use: logistic regression, random forest, neural network, balanced random forest, and balanced bagging. Synthetic Minority Oversampling Technique was used to improve class balance. The primary outcome was persistent opioid use, defined as patient reporting to use opioids after 3 months postoperatively. The data were split into a training and test set. Performance metrics were evaluated on the test set and included the F1 score and the area under the receiver operating characteristics curve (AUC). Feature importance was ranked based on SHapley Additive exPlanations (SHAP). RESULTS: After exclusion (patients with missing follow-up data), 2611 patients were included in the analysis, of which 1209 (46.3%) continued to use opioids 3 months after surgery. The balanced random forest classifiers had the highest AUC (0.877, 95% confidence interval [CI], 0.834-0.894) compared to neural networks (0.729, 95% CI, 0.672-0.787), logistic regression (0.709, 95% CI, 0.652-0.767), balanced bagging classifier (0.859, 95% CI, 0.814-0.905), and random forest classifier (0.855, 95% CI, 0.813-0.897). The balanced random forest classifier had the highest F1 (0.758, 95% CI, 0.677-0.839). Furthermore, the specificity, sensitivity, precision, and accuracy were 0.883, 0.700, 0.836, and 0.780, respectively. The features based on SHAP analysis with the highest impact on model performance were age, preoperative opioid use, preoperative pain scores, and body mass index. CONCLUSIONS: The balanced random forest classifier was found to be the most effective model for identifying persistent opioid use after spine surgery.

Perception is reality: qualitative insights into how consumers perceive alcohol warning labels.

AIMS: This study explores perspectives of on-pack alcohol warning labels, and how they might influence alcohol purchase and/or consumption behavior to inform culturally appropriate label design for effective behavior change. METHODS: New Zealand participants ≥18 years, who reported having purchased and consumed alcoholic beverages in the last month were recruited via a market research panel and grouped into 10 focus groups (n = 53) by ethnicity (general population, Maori, and Pacific peoples), age group, and level of alcohol consumption. Participants were shown six potential alcohol health warning labels, with design informed by relevant literature, label framework, and stakeholder feedback. Interviews were transcribed and analyzed via qualitative (directed) content analysis. RESULTS: Effective alcohol labels should be prominent, featuring large red and/or black text with a red border, combining text with visuals, and words like "WARNING" in capitals. Labels should contrast with bottle color, be easily understood, and avoid excessive text and confusing imagery. Participants preferred specific health outcomes, such as heart disease and cancer, increasing message urgency and relevance. Anticipated behavior change included reduced drinking and increased awareness of harms, but some may attempt to mitigate warnings by covering or removing labels. Contextual factors, including consistent design and targeted labels for different beverages and populations, are crucial. There was a strong emphasis on collective health impacts, particularly among Maori and Pacific participants. CONCLUSIONS: Our findings indicate that implementing alcohol warning labels, combined with comprehensive strategies like retail and social marketing campaigns, could effectively inform and influence the behavior of New Zealand's varied drinkers.

MNK-driven eIF4E phosphorylation regulates the fibrogenic transformation of mesenchymal cells and chronic lung allograft dysfunction.

Tissue fibrosis remains unamenable to meaningful therapeutic interventions and is the primary cause of chronic graft failure after organ transplantation. Eukaryotic translation initiation factor (eIF4E), a key translational regulator, serves as convergent target of multiple upstream profibrotic signaling pathways that contribute to mesenchymal cell (MC) activation. Here, we investigate the role of MAP kinase-interacting serine/threonine kinase-induced (MNK-induced) direct phosphorylation of eIF4E at serine 209 (Ser209) in maintaining fibrotic transformation of MCs and determine the contribution of the MNK/eIF4E pathway to the pathogenesis of chronic lung allograft dysfunction (CLAD). MCs from patients with CLAD demonstrated constitutively higher eIF4E phosphorylation at Ser209, and eIF4E phospho-Ser209 was found to be critical in regulating key fibrogenic protein autotaxin, leading to sustained ß-catenin activation and profibrotic functions of CLAD MCs. MNK1 signaling was upregulated in CLAD MCs, and genetic or pharmacologic targeting of MNK1 activity inhibited eIF4E phospho-Ser209 and profibrotic functions of CLAD MCs in vitro. Treatment with an MNK1/2 inhibitor (eFT-508) abrogated allograft fibrosis in an orthotopic murine lung-transplant model. Together these studies identify what we believe is a previously unrecognized MNK/eIF4E/ATX/ß-catenin signaling pathway of fibrotic transformation of MCs and present the first evidence, to our knowledge, for the utility of MNK inhibitors in fibrosis.

A qualitative study of using nicotine products for smoking cessation after discharge from residential drug and alcohol treatment in Australia.

INTRODUCTION: Tobacco smoking is highly prevalent among alcohol and other drugs (AOD) service clients and, despite interest in quitting, abstinence is rarely sustained. Nicotine products may assist after discharge from residential treatment services, but little is known about client receptivity to them. This study examined AOD withdrawal service clients' experiences of two types of nicotine products for smoking cessation post-discharge, combination nicotine replacement therapy (cNRT) and nicotine vaping products (NVP). METHODS: We held semi-structured telephone interviews with 31 Australian AOD service clients in a clinical trial of a 12-week smoking cessation intervention using Quitline support plus cNRT or NVP delivered post-discharge from a smoke-free residential service. We asked about health and social factors, nicotine cravings, Quitline experience, and barriers and facilitators to cNRT or NVP, then thematically analysed data. RESULTS: cNRT and NVP were described by participants as feasible and acceptable for smoking cessation. For most participants, cost limited cNRT access post study, as did difficulty navigating NVP prescription access. Quitline support was valued, but not consistently used, with participants noting low assistance with NVP-facilitated cessation. Participants considered both cessation methods acceptable and socially supported, and sought information on decreasing nicotine use via NVP. DISCUSSION AND CONCLUSIONS: AOD service clients highly valued receiving cNRT or NVP with behavioural support for smoking reduction or abstinence. Both interventions were acceptable to service clients. Findings suggest a potential need to examine both whether NVP use should be permitted in this context, and guidance on the individual suitability of cNRT or NVP.

MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution.

Fibrosis following tissue injury is distinguished from normal repair by the accumulation of pathogenic and apoptosis-resistant myofibroblasts (MFs), which arise primarily by differentiation from resident fibroblasts. Endogenous molecular brakes that promote MF dedifferentiation and clearance during spontaneous resolution of experimental lung fibrosis may provide insights that could inform and improve the treatment of progressive pulmonary fibrosis in patients. MAPK phosphatase 1 (MKP1) influences the cellular phenotype and fate through precise and timely regulation of MAPK activity within various cell types and tissues, yet its role in lung fibroblasts and pulmonary fibrosis has not been explored. Using gain- and loss-of-function studies, we found that MKP1 promoted lung MF dedifferentiation and restored the sensitivity of these cells to apoptosis - effects determined to be mainly dependent on MKP1's dephosphorylation of p38α MAPK (p38α). Fibroblast-specific deletion of MKP1 following peak bleomycin-induced lung fibrosis largely abrogated its subsequent spontaneous resolution. Such resolution was restored by treating these transgenic mice with the p38α inhibitor VX-702. We conclude that MKP1 is a critical antifibrotic brake whose inhibition of pathogenic p38α in lung fibroblasts is necessary for fibrosis resolution following lung injury.

The Lung Microbiome Predicts Mortality and Response to Azithromycin in Lung Transplant Recipients with Chronic Rejection.

Rationale: Chronic lung allograft dysfunction (CLAD) is the leading cause of death after lung transplant, and azithromycin has variable efficacy in CLAD. The lung microbiome is a risk factor for developing CLAD, but the relationship between lung dysbiosis, pulmonary inflammation, and allograft dysfunction remains poorly understood. Whether lung microbiota predict outcomes or modify treatment response after CLAD is unknown. Objectives: To determine whether lung microbiota predict post-CLAD outcomes and clinical response to azithromycin. Methods: Retrospective cohort study using acellular BAL fluid prospectively collected from recipients of lung transplant within 90 days of CLAD onset. Lung microbiota were characterized using 16S rRNA gene sequencing and droplet digital PCR. In two additional cohorts, causal relationships of dysbiosis and inflammation were evaluated by comparing lung microbiota with CLAD-associated cytokines and measuring ex vivo P. aeruginosa growth in sterilized BAL fluid. Measurements and Main Results: Patients with higher bacterial burden had shorter post-CLAD survival, independent of CLAD phenotype, azithromycin treatment, and relevant covariates. Azithromycin treatment improved survival in patients with high bacterial burden but had negligible impact on patients with low or moderate burden. Lung bacterial burden was positively associated with CLAD-associated cytokines, and ex vivo growth of P. aeruginosa was augmented in BAL fluid from transplant recipients with CLAD. Conclusions: In recipients of lung transplants with chronic rejection, increased lung bacterial burden is an independent risk factor for mortality and predicts clinical response to azithromycin. Lung bacterial dysbiosis is associated with alveolar inflammation and may be promoted by underlying lung allograft dysfunction.

GTP Signaling Links Metabolism, DNA Repair, and Responses to Genotoxic Stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a guanine nucleotide-binding protein, which promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes nonhomologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard-of-care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in nonmalignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment. SIGNIFICANCE: A newly described GTP-dependent signaling axis is an unexpected link between nucleotide metabolism and DNA repair. Disrupting this pathway can overcome cancer resistance to genotoxic therapy while augmenting it can mitigate genotoxic injury of normal tissues. This article is featured in Selected Articles from This Issue, p. 5.

Genetic deficiency of the transcription factor NFAT1 confers protection against fibrogenic responses independent of immune influx.

Idiopathic pulmonary fibrosis (IPF) is marked by unremitting matrix deposition and architectural distortion. Multiple profibrotic pathways contribute to the persistent activation of mesenchymal cells (MCs) in fibrosis, highlighting the need to identify and target common signaling pathways. The transcription factor nuclear factor of activated T cells 1 (NFAT1) lies downstream of second messenger calcium signaling and has been recently shown to regulate key profibrotic mediator autotaxin (ATX) in lung MCs. Herein, we investigate the role of NFAT1 in regulating fibroproliferative responses during the development of lung fibrosis. Nfat1-/--deficient mice subjected to bleomycin injury demonstrated improved survival and protection from lung fibrosis and collagen deposition as compared with bleomycin-injured wild-type (WT) mice. Chimera mice, generated by reconstituting bone marrow cells from WT or Nfat1-/- mice into irradiated WT mice (WT→WT and Nfat1-/-→WT), demonstrated no difference in bleomycin-induced fibrosis, suggesting immune influx-independent fibroprotection in Nfat1-/- mice. Examination of lung tissue and flow sorted lineageneg/platelet-derived growth factor receptor alpha (PDGFRα)pos MCs demonstrated decreased MC numbers, proliferation [↓ cyclin D1 and 5-ethynyl-2'-deoxyuridine (EdU) incorporation], myofibroblast differentiation [↓ α-smooth muscle actin (α-SMA)], and survival (↓ Birc5) in Nfat1-/- mice. Nfat1 deficiency abrogated ATX expression in response to bleomycin in vivo and MCs derived from Nfat1-/- mice demonstrated decreased ATX expression and migration in vitro. Human IPF MCs demonstrated constitutive NFAT1 activation, and regulation of ATX in these cells by NFAT1 was confirmed using pharmacological and genetic inhibition. Our findings identify NFAT1 as a critical mediator of profibrotic processes, contributing to dysregulated lung remodeling and suggest its targeting in MCs as a potential therapeutic strategy in IPF.NEW & NOTEWORTHY Idiopathic pulmonary fibrosis (IPF) is a fatal disease with hallmarks of fibroblastic foci and exuberant matrix deposition, unknown etiology, and ineffective therapies. Several profibrotic/proinflammatory pathways are implicated in accelerating tissue remodeling toward a honeycombed end-stage disease. NFAT1 is a transcriptional factor activated in IPF tissues. Nfat1-deficient mice subjected to chronic injury are protected against fibrosis independent of immune influxes, with suppression of profibrotic mesenchymal phenotypes including proliferation, differentiation, resistance to apoptosis, and autotaxin-related migration.

Effectiveness of nicotine salt vapes, cytisine, and a combination of these products, for smoking cessation in New Zealand: protocol for a three-arm, pragmatic, community-based randomised controlled trial.

BACKGROUND: Combining short-acting nicotine replacement therapy with varenicline increases smoking cessation rates compared with varenicline alone, but not all people tolerate these medications or find them helpful. We aim to investigate the therapeutic potential of an analogous combination, by evaluating the effectiveness, safety, and acceptability of combining nicotine salt e-cigarettes with cytisine, compared to nicotine salt e-cigarettes or cytisine only, on smoking abstinence at six months. METHODS: A pragmatic, community-based, investigator-blinded, randomised superiority trial design will be utilised. Eligible participants will be people who smoke daily (N = 800, 90% power) from throughout New Zealand, who are: aged ≥ 18 years, motivated to quit in the next two weeks, able to provide online consent, willing to use e-cigarettes and/or cytisine, and have daily access to a mobile phone. Recruitment will utilise multi-media advertising. Participants will be randomised (3:3:2 ratio) to 12 weeks of: 1) e-cigarettes (closed pod system, 3% nicotine salt, tobacco flavour) plus cytisine; 2) e-cigarettes alone, or 3) cytisine alone. All groups will receive a six-month, text-message-based behavioural support programme. The primary outcome is self-reported, biochemically verified, continuous abstinence at six months post-quit date. Secondary outcomes, measured at quit date, then one, three, six, and 12 months post-quit date, include self-reported continuous abstinence, 7-day point prevalence abstinence, cigarettes smoked per day, withdrawal and urge to smoke, time to (re)lapse, treatment use and compliance, treatment crossover, dual-use, use of other cessation products, change in e-cigarette products, continuation of product use, acceptability, change in health state, health-related quality of life, change in body mass index, adverse events, and cost per quitter. DISCUSSION: Pragmatic trials are of particular value as they reflect the 'real world' impact of interventions. The trial will provide some of the first evidence on the effectiveness of combining nicotine salt e-cigarettes with cytisine for smoking cessation, in a country with strong tobacco control policy. Findings will be incorporated into relevant systematic reviews, informing practice and policy. TRIAL REGISTRATION: NCT05311085 ClinicalTrials.gov. Registered 5th April, 2022.

Invitation methods for Indigenous New Zealand Maori in lung cancer screening: Protocol for a pragmatic cluster randomized controlled trial.

Lung cancer screening can significantly reduce mortality from lung cancer. Further evidence about how to optimize lung cancer screening for specific populations, including Aotearoa New Zealand (NZ)'s Indigenous Maori (who experience disproportionately higher rates of lung cancer), is needed to ensure it is equitable. This community-based, pragmatic cluster randomized trial aims to determine whether a lung cancer screening invitation from a patient's primary care physician, compared to from a centralized screening service, will optimize screening uptake for Maori. Participating primary care practices (clinics) in Auckland, Aotearoa NZ will be randomized to either the primary care-led or centralized service for delivery of the screening invitation. Clinic patients who meet the following criteria will be eligible: Maori; aged 55-74 years; enrolled in participating clinics in the region; ever-smokers; and have at least a 2% risk of developing lung cancer within six years (determined using the PLCOM2012 risk prediction model). Eligible patients who respond positively to the invitation will undertake shared decision-making with a nurse about undergoing a low dose CT scan (LDCT) and an assessment for Chronic Obstructive Pulmonary Disease (COPD). The primary outcomes are: 1) the proportion of eligible population who complete a risk assessment and 2) the proportion of people eligible for a CT scan who complete the CT scan. Secondary outcomes include evaluating the contextual factors needed to inform the screening process, such as including assessment for Chronic Obstructive Pulmonary Disease (COPD). We will also use the RE-AIM framework to evaluate specific implementation factors. This study is a world-first, Indigenous-led lung cancer screening trial for Maori participants. The study will provide policy-relevant information on a key policy parameter, invitation method. In addition, the trial includes a nested analysis of COPD in the screened Indigenous population, and it provides baseline (T0 screen round) data using RE-AIM implementation outcomes.

GTP signaling links metabolism, DNA repair, and responses to genotoxic stress.

How cell metabolism regulates DNA repair is incompletely understood. Here, we define a GTP-mediated signaling cascade that links metabolism to DNA repair and has significant therapeutic implications. GTP, but not other nucleotides, regulates the activity of Rac1, a G protein, that promotes the dephosphorylation of serine 323 on Abl-interactor 1 (Abi-1) by protein phosphatase 5 (PP5). Dephosphorylated Abi-1, a protein previously not known to activate DNA repair, promotes non-homologous end joining. In patients and mouse models of glioblastoma, Rac1 and dephosphorylated Abi-1 mediate DNA repair and resistance to standard of care genotoxic treatments. The GTP-Rac1-PP5-Abi-1 signaling axis is not limited to brain cancer, as GTP supplementation promotes DNA repair and Abi-1-S323 dephosphorylation in non-malignant cells and protects mouse tissues from genotoxic insult. This unexpected ability of GTP to regulate DNA repair independently of deoxynucleotide pools has important implications for normal physiology and cancer treatment.

'It's somewhere here, isn't it'? The provision of information and health warnings for alcoholic beverages sold online in New Zealand and the United Kingdom.

INTRODUCTION: Alcohol beverages in many countries are required to display health information and warnings on all product packaging, given the individual and societal harm caused by alcohol. It is unclear whether consumers purchasing alcohol online are able to easily view such information. This study examines the presence, type and location of mandatory and voluntary health information and warnings consumers are exposed to when entering online alcohol retail shopping environments in the United Kingdom (UK) and New Zealand (NZ). METHODS: Using an observational study design, 1407 randomly sampled alcoholic beverages from 14 online alcohol retailers (7 per country) were reviewed to ascertain the visual presence or absence of mandatory and voluntary health information and warnings. RESULTS: UK online alcohol retailers were more compliant than NZ retailers in showing mandatory health information (e.g., alcohol by volume percentage was visible on 92% of alcoholic beverages sold online in the UK, compared to 31% in NZ, p < 0.001). A similar pattern was noted for voluntary health warnings. Online retailers in both countries had a low proportion of alcohol products with the viewable mandatory information, and voluntary health warnings were rarely present and/or viewable. DISCUSSION AND CONCLUSIONS: Mandatory health information and warnings for alcoholic beverages are not fully adhered to within the UK and NZ online retail environments, impacting the ability of consumers to make informed purchase decisions. In both countries, alcohol policy needs to stipulate that mandatory health information and warnings should be clearly viewable on the product page and product imagery of online alcohol retailers.

The mitigating effect of exogenous carbon monoxide on chronic allograft rejection and fibrosis post-lung transplantation.

BACKGROUND: Small airway inflammation and fibrosis or bronchiolitis obliterans (BO) is the predominant presentation of chronic lung allograft dysfunction (CLAD) post-lung transplantation. Carbon monoxide (CO) is a critical endogenous signaling transducer with known anti-inflammatory and anti-fibrotic effects but its therapeutic potential in CLAD remains to be fully elucidated. METHODS: Here we investigate the effect of inhaled CO in modulating chronic lung allograft rejection pathology in a murine orthotopic lung transplant model of BO (B6D2F1/J→DBA/2J). Additionally, the effects of CO on the activated phenotype of mesenchymal cells isolated from human lung transplant recipients with CLAD were studied. RESULTS: Murine lung allografts treated with CO (250 ppm × 30 minutes twice daily from days 7 to 40 post-transplantation) demonstrated decreased immune cell infiltration, fibrosis, and airway obliteration by flow cytometry, trichrome staining, and morphometric analysis, respectively. Decreased total collagen, with levels comparable to isografts, was noted in CO-treated allografts by quantitative hydroxyproline assay. In vitro, CO (250 ppm × 16h) was effective in reversing the fibrotic phenotype of human CLAD mesenchymal cells with decreased collagen I and ß-catenin expression as well as an inhibitory effect on ERK1/2 MAPK, and mTORC1/2 signaling. Sildenafil, a phosphodiesterase 5 inhibitor, partially mimicked the effects of CO on CLAD mesenchymal cells and was partially effective in decreasing collagen deposition in murine allografts, suggesting the contribution of cGMP-dependent and -independent mechanisms in mediating the effect of CO. CONCLUSION: These results suggest a potential role for CO in alleviating allograft fibrosis and mitigating chronic rejection pathology post-lung transplant.

Vitamin D supplementation in children and young adults with persistent proteinuria secondary to glomerular disease.

BACKGROUND: Vitamin D deficiency is common in glomerular disease. Supplementation may be ineffective due to ongoing urinary losses of vitamin D binding protein. We sought to determine if daily cholecalciferol supplementation would increase vitamin D concentrations in children with glomerular disease and persistent proteinuria, without adverse effects. METHODS: Eighteen participants at least 5 years of age with primary glomerular disease and urine protein:creatinine ratio ≥ 0.5 were enrolled from four pediatric nephrology practices to receive cholecalciferol supplementation: 4,000 IU or 2,000 IU per day for serum 25 hydroxyvitamin vitamin D (25OHD) concentrations < 20 ng/mL and 20 ng/mL to < 30 ng/mL, respectively. Measures of vitamin D and mineral metabolism were obtained at baseline and weeks 6 and 12. Multivariable generalized estimating equation (GEE) regression estimated mean percent changes in serum 25OHD concentration. RESULTS: Median baseline 25OHD was 12.8 ng/mL (IQR 9.3, 18.9) and increased to 27.8 ng/mL (20.5, 36.0) at week 6 (p < 0.001) without further significant increase at week 12. A total of 31% of participants had a level ≥ 30 ng/mL at week 12. Supplementation was stopped in two participants at week 6 for mildly elevated calcium and phosphorus, respectively, with subsequent declines in 25OHD of > 20 ng/mL. In the adjusted GEE model, 25OHD was 102% (95% CI: 64, 141) and 96% (95% CI: 51, 140) higher versus baseline at weeks 6 and 12, respectively (p < 0.001). CONCLUSION: Cholecalciferol supplementation in vitamin D deficient children with glomerular disease and persistent proteinuria safely increases 25OHD concentration. Ideal dosing to fully replete 25OHD concentrations in this population remains unknown. CLINICAL TRIAL: NCT01835639. A higher resolution version of the Graphical abstract is available as Supplementary information.

Incentivised physical activity intervention promoting daily steps among university employees in the workplace through a team-based competition.

Introduction: The benefits of walking on health and well-being is well established and regarded as the most accessible form of physical activity (PA) that most individuals can incorporate into their lives. Despite the benefits, the impact of a competitive walking intervention combined with a prize incentive in the workplace is yet to be established. The aim of this intervention was to promote PA among university employees through teams-based competition with a prize incentive targeted towards the recommended 10,000 steps per day. Methods: A total of 49 employees participated and formed eight departmental teams ranging from Senior Admin management, Educational & Social work, Nursing & Midwifery, Sport & Exercise, Health Sciences, Admin Assistant, Library, and IT to compete in a walking intervention. Each team was handed an ActiGraph wGT3X-BT from Monday to Friday to record their walking steps. Steps. Post intervention participants completed an open-ended survey to provide their views about the intervention. Results: The ActiGraph findings determined that steps increased by 4,799 per day from daily baseline of 5,959 to 10,758 throughout this intervention. The themes from qualitative data showed that the prize incentive and competitive nature of this intervention has motivated staff to walk more, changed their behaviour, enjoyed the team-based competition, and improved perceived productivity in the workplace. Discussion and conclusion: This intervention increased employees' daily steps by 4,799 and met the 10,000 steps guideline. The 'Health Sciences' team recorded the highest steps 531,342 followed by the 'Education and Social Work' accumulating 498,045 steps throughout this intervention. This intervention with prize incentive demonstrated a positive impact on employees personal and work-based outcomes as well as contributed to the workplace PA, health, and wellbeing literature, and more specifically, to the scarce research focused on university settings.

Examination of national survey data regarding academic foundation training during the COVID-19 pandemic second wave.

Aim: We aimed to examine the effect of the second wave of the COVID-19 pandemic on Academic Foundation Programme (AFP) trainees. Methods: A voluntary, anonymous questionnaire was circulated to all UK AFP doctors. Data were collected from February 2021 to April 2021 then analysed. Results: Of a possible 1,096 trainees, 149 responded to the survey: 48% of respondents were at least partially redeployed, 31% lost academic time and 47% had projects cancelled or postponed. In free-text responses, despite some research opportunities, frustration at lost research time and opportunities were common themes. Trainees also highlighted communication and wellbeing issues. Conclusion: These results demonstrate that the overall effect of COVID-19 on this cohort cannot be underestimated. We propose that a series of measures are implemented to protect and support academic trainees. We hope that these measures would encourage high-quality academic output and help secure the development of the academic clinical workforce.