Search

Introduction: Kinematic analyses have recently revealed a strong potential to contribute to the assessment of neurological diseases. However, the validation of home-based kinematic assessments using consumer-grade video technology has yet to be performed. In line with best practices for digital biomarker development, we sought to validate webcam-based kinematic assessment against established, laboratory-based recording gold standards. We hypothesized that webcam-based kinematics would possess psychometric properties comparable to those obtained using the laboratory-based gold standards. Methods: We collected data from 21 healthy participants who repeated the phrase “buy Bobby a puppy” (BBP) at four different combinations of speaking rate and volume: Slow, Normal, Loud, and Fast. We recorded these samples twice back-to-back, simultaneously using (1) an electromagnetic articulography (“EMA”; NDI Wave) system, (2) a 3D camera (Intel RealSense), and (3) a 2D webcam for video recording via an in-house developed app. We focused on the extraction of kinematic features in this study, given their demonstrated value in detecting neurological impairments. We specifically extracted measures of speed/acceleration, range of motion (ROM), variability, and symmetry using the movements of the center of the lower lip during these tasks. Using these kinematic features, we derived measures of (1) agreement between recording methods, (2) test-retest reliability of each method, and (3) the validity of webcam recordings to capture expected changes in kinematics as a result of different speech conditions. Results: Kinematics measured using the webcam demonstrated good agreement with both the RealSense and EMA (ICC-A values often ≥0.70). Test-retest reliability, measured using the absolute agreement (2,1) formulation of the intraclass correlation coefficient (i.e., ICC-A), was often “moderate” to “strong” (i.e., ≥0.70) and similar between the webcam and EMA-based kinematic features. Finally, the webcam kinematics were typically as sensitive to differences in speech tasks as EMA and the 3D camera gold standards. Discussion and Conclusions: Our results suggested that webcam recordings display good psychometric properties, comparable to laboratory-based gold standards. This work paves the way for a large-scale clinical validation to continue the development of these promising technologies for the assessment of neurological diseases via home-based methods.

When described in 2014, Maotoweta virescens was believed to be one of New Zealand’s rarest cave wētā (Rhaphidophoridae). Here, we present new information about the distribution, ecology, and life history of the species. M. virescens has now been recorded from indigenous forest sites throughout the length of the western South Island, where it can occur in relatively high abundance. M. virescens shows a close association with arboreal mosses, particularly Weymouthia mollis, roosting within them during the day and feeding on them at night. The wētā has also been documented feeding on lichens and dead insects. The species is hypothesized to have a lifecycle of approximately one year, closely linked to season. Eggs are thought to hatch out relatively quickly after being laid in summer and early autumn, with the species overwintering as nymphs and maturing the following late spring through to early-autumn. Further work is required to fully understand its biology. A comparison was made between active night searching and vegetation beating as two different methods for the detection and monitoring of M. virescens. Beating of W. mollis and other suitable M. virescens microhabitats was found to be significantly more effective than night searching. Our results show that M. virescens is widespread and can occur at relatively high densities within South Island temperate forests, with the species’ perceived rarity to date largely owing to a lack of survey effort and the past use of ineffective sampling methods.

Introduction Pre-registration interprofessional rural immersion programmes provide students with first-hand insight into challenges faced in rural clinical practice and can influence future practice intentions. The impact of short rural and hauora Māori interdisciplinary placements on early healthcare careers is unknown. Aim Explore whether a 5-week rural interprofessional education programme influenced graduates’ choices to work in primary care, rurally, and with Māori patients. Methods We conducted a survey-based, non-randomised trial of graduates from eight healthcare disciplines who did (n = 132) and did not (n = 479) attend the Tairāwhiti interprofessional education rural programme with hauora Māori placements. Participants were surveyed at 1-, 2-, and 3-years’ post-registration. Self-reported practice location and vocation were analysed with mixed-model logistic regression. Free-text comments were analysed with Template Analysis. Results We did not identify any measurable impact on rural or community workforce participation at 3-years’ post-registration. Free-text analysis indicated that a short rural interprofessional immersion placement had long-term self-perceived impacts on desire and skills to work in rural locations, and on desire and ability to work with Māori and embrace Māori models of health. Discussion Our study suggests that short rural immersion placements do not increase rural workforce participation during early healthcare careers. Three-years’ post-graduation may be too early to determine whether rural placements help to address rural health workforce needs. Reports from rural placement participants of increased ability to care for people from rural backgrounds, even when encountered in a city, suggest that assessment of practice location may not adequately capture the benefits of rural placement programmes.

Rhodopseudomonas palustris CGA009 is a versatile model purple nonsulfur bacterium used for both fundamental and applied research. Here, we present a new genome sequence for the derivative strain CGA0092. We further present an improved CGA009 genome assembly that differs from the original CGA009 sequence at three positions.

There is growing recognition that primary care provision plays a pivotal role in improving health outcomes for LGBTQIA+ (rainbow) youth, but few studies have centered on youth experiences of primary care in Aotearoa New Zealand. This study aimed to explore the experiences and perspectives of rainbow youth when engaging with primary care. Two focus groups were held in 2021 with eleven rainbow young people aged 13–23 years recruited with assistance from local rainbow support organizations in Aotearoa NZ. Groups were audio-recorded, transcribed and analyzed using thematic analysis. Four main themes were identified: (i) anticipated and enacted discrimination, (ii) building trust, (iii) confidentiality and (iv) healthcare provider knowledge and competence. Participants spoke of some positive experiences but perceived these to be lucky or surprising, with most also having encountered less supportive interactions and heteronormative views. Visual indicators of rainbow-friendliness in clinic settings were appreciated only if affirmed by inclusive and accepting practice. Frustrations were expressed about gaps in provider knowledge and the sense of having to educate clinicians about rainbow-specific health issues. Primary care providers can facilitate positive consultations with rainbow young people by using clear communication to build trusting relationships, and by being accepting, non-judgmental and transparent about confidentiality.

Many women experience pelvic floor disorders which may require medical intervention such as transvaginal mesh implant surgeries (TVM; the abdominal or vaginal insertion of woven netting to support pelvic tissue). We examined women's perceptions of communication with their health professionals concerning TVM.We analysed 153 women's written submissions to an Australian Government Inquiry regarding their experiences of transvaginal mesh surgery to explore their perceptions of TVM-related doctor-patient communication. Data were analysed using deductive and inductive reflexive thematic analysis.Women expressed several challenges in their communication with their health professionals. Three themes regarding communication were generated: Insufficient information was abundant; Normalisation and minimisation of the procedure and risks; and, Desired communication interactions.According to women's accounts, doctor-patient communication was poor. Health professionals must be knowledgeable about medical procedures and their potential complications and provide their patients with adequate, accurate information to make informed choices about their health. Health professionals should also document informed consent.Health professionals should be well-informed about TVM, including best-practice treatments for pelvic floor disorders, indications for TVM, the risks, outcomes and potential complications from various forms of TVM, and ways to adequately communicate sufficient information to women.

BackgroundSignificant morbidity and mortality can be associated with gastrostomy insertion, likely influenced by patient selection, indication and aftercare. We aimed to establish what current variation in practice exists and how this has improved by comparison to our previously published British Society of Gastroenterology survey of 2010.MethodsWe approached all National Health Service (NHS) hospitals in England (n=198). Email and web-based questionnaires were circulated. These data were correlated with the National Endoscopy Database (NED).ResultsThe response rate was 69% (n=136/198). Estimated Percutaneous Endoscopic Gastrostomy (PEG) placements in the UK are currently 6500 vs 17 000 in 2010 (pConclusionThis national survey, validated by the results from NED, demonstrates a reduction of over 60% for PEG insertion rates compared with previous estimates. There has also been an increase in consultant involvement, MDT discussion and aftercare provision. However, two-third of responders described ‘pressure’ to insert a gastrostomy. Perhaps further efforts are needed to include and educate other specialty teams, patients and next of kin.

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for “orientation scanning” (the dynamic process of acquiring the final view) and for “block view” (which visualizes the block site and is maintained for needle insertion/injection). A “strong recommendation” was made if ≥75% of participants rated any structure as “definitely include” in any round. A “weak recommendation” was made if >50% of participants rated it as “definitely include” or “probably include” for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a “strong recommendation” was made for 60 structures on orientation scanning and 44 on the block view. A “weak recommendation” was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice.

Early Childhood Education and Care (ECEC) in Australia is facing a workforce crisis. A knowledge gap around educators studying to pursue a career in ECEC, particularly in long day care (LDC), has prompted research with Australian educators who engage in further education and training while working in LDC services. The paper examines 32 biographical interviews from an Australian Research Council Linkage project Identifying Effective Strategies to Grow and Sustain a Professional Early Years Workforce. Research reported here applies a social constructivist framework to investigate the personal and structural characteristics of educators studying at Certificate III, Diploma, Bachelor and Master levels of Australia’s regulated qualifications and training system. An important finding is that the legislative provisions of Australia’s National Quality Framework is a key driver for educator engagement in education and training. The paper highlights the importance of clear qualification pathways in raising the professionalism of the ECEC workforce in Australia.

Abstract Background Early onset fetal growth restriction secondary to placental insufficiency can lead to severe maternal and neonatal morbidity and mortality. Pre-clinical studies and a few small randomised clinical trials have suggested that phosphodiesterase type 5 (PDE-5) inhibitors may have protective effects against placental insufficiency in this context; however, robust evidence is lacking. The STRIDER Consortium conducted four randomised trials to investigate the use of a PDE-5 inhibitor, sildenafil, for the treatment of early onset fetal growth restriction. We present a protocol for the pre-planned systematic review with individual participant data meta-analysis, aggregate meta-analysis, and trial sequential analysis of these and other eligible trials. The main objective of this study will be to evaluate the effects of PDE-5 inhibitors on neonatal morbidity compared with placebo or no intervention among pregnancies with fetal growth restriction. Methods We will search the following electronic databases with no language or date restrictions: OVID MEDLINE, OVID EMBASE, the Cochrane Controlled Register of Trials (CENTRAL), and the clinical trial registers Clinicaltrials.gov and World Health Organisation International Clinical Trials Registry Platform (ICTRP). We will identify randomised trials of PDE-5 inhibitors in singleton pregnancies with growth restriction. Two reviewers will independently screen all citations, full-text articles, and abstract data. Our primary outcome will be infant survival without evidence of serious adverse neonatal outcome. Secondary outcomes will include gestational age at birth and birth weight z-scores. We will assess bias using the Cochrane Risk of Bias 2 tool. We will conduct aggregate meta-analysis using fixed and random effects models, Trial Sequential Analysis, and individual participant data meta-analysis using one- and two-stage approaches. The certainty of evidence will be assessed with GRADE. Discussion This pre-defined protocol will minimise bias during analysis and interpretation of results, toward the goal of providing robust evidence regarding the use of PDE-5 inhibitors for the treatment of early onset fetal growth restriction. Systematic review registration PROSPERO (CRD42017069688).

Background Bronchopulmonary dysplasia (BPD), an inflammatory-mediated chronic lung disease, is common in extremely preterm infants born before 28 weeks’ gestation and is associated with an increased risk of adverse neurodevelopmental and respiratory outcomes in childhood. Effective and safe prophylactic therapies for BPD are urgently required. Systemic corticosteroids reduce rates of BPD in the short-term but are associated with poorer neurodevelopmental outcomes if given to ventilated infants in the first week after birth. Intratracheal administration of corticosteroid admixed with exogenous surfactant could overcome these concerns by minimizing systemic sequelae. Several small, randomized trials have found intratracheal budesonide in a surfactant vehicle to be a promising therapy to increase survival free of BPD. Methods An international, multicenter, double-blinded, randomized trial of intratracheal budesonide (a corticosteroid) mixed with surfactant for extremely preterm infants to increase survival free of BPD at 36 weeks’ postmenstrual age (PMA; primary outcome). Extremely preterm infants aged Discussion Combining budesonide with surfactant for intratracheal administration is a simple intervention that may reduce BPD in extremely preterm infants and translate into health benefits in later childhood. The PLUSS trial is powered for the primary outcome and will address gaps in the evidence due to its pragmatic and inclusive design, targeting all extremely preterm infants regardless of their initial mode of respiratory support. Should intratracheal budesonide mixed with surfactant increase survival free of BPD, without severe adverse effects, this readily available intervention could be introduced immediately into clinical practice. Trial registration Australian New Zealand Clinical Trials Registry (https://www.anzctr.org.au), ACTRN12617000322336. First registered on 28th February 2017.

Background In Aotearoa/New Zealand (NZ) general practices diagnose and manage pre-diabetes. This work is important as it has the potential to delay or prevent the onset of Type 2 Diabetes (T2DM), reduce NZ’s health inequities, and the burden that T2DM places on health care services. However, no study has previously examined how this work routinely occurs in NZ. Methods Two case studies of practices serving ethnically and socio-economically diverse populations, followed by cross-case analysis. Results The NZ health care context including funding mechanisms, reporting targets, and the disease centred focus of care, acted together to dis-incentivise and de-prioritise pre-diabetes care in general practices. The social determinants of health differentially influenced patients’ ability to engage with and respond to pre-diabetes care, significantly impacting this work. Differing perspectives about the significance of pre-diabetes and gaps in systematic screening practices were identified. Interventions used were inconsistent and lacked comprehensive ongoing support. Conclusions Complex multi-layered factors impact on pre-diabetes care, and many of the barriers cannot be addressed at the general practice level. The practice serving the most disadvantaged population who concurrently have higher rates of pre-diabetes/T2DM were more adversely affected by the barriers identified.

ObjectiveIn a highly vaccinated Australian population we aimed to compare ongoing symptoms and functional impairment 12 weeks after PCR-confirmed COVID-19 infection with PCR-confirmed influenza infection.Methods and AnalysisThe study commenced upon a positive PCR test for either COVID-19 or influenza in June 2022 during concurrent waves of both viruses. Participants were followed up 12 weeks later in September 2022 and self-reported ongoing symptoms and functional impairment. We conducted a multivariate logistic regression analysis, controlling for age, sex, First Nations status, vaccination status, and socio-economic profile.ResultsThere were 2 195 and 951 participants in the COVID-19 and influenza-positive cohorts respectively. After controlling for potential predictor variables, we found no evidence to suggest adults with COVID-19 were more likely to have ongoing symptoms (21.4% vs 23.0%, aOR 1.18; 95% CI 0.92-1.50) or moderate to severe functional impairment (4.1% vs 4.4%, OR 0.81; 95% CI 0.55-1.20) at 12 weeks after their diagnosis than adults who had influenza.ConclusionsIn a highly vaccinated population exposed to the SARS-CoV-2 omicron variant, long COVID may manifest as a post-viral syndrome of no greater severity than seasonal influenza but differing in terms of the volume of people affected and the potential impact on health systems. This study underscores the importance of long COVID research featuring an appropriate comparator group.What is already known on this subject?Post-acute infection syndromes are associated with a range of illnesses, including COVID-19 and influenza. “Long COVID” may pose a risk to health systems.What are the new findings?In a highly vaccinated population whose primary exposure has been to the Omicron variant, the rates of ongoing symptoms and moderate to severe functional impairment at 12 weeks after COVID-19 are no different to influenza.How might these results change the focus of research or clinical practice?The public health impact arising from long COVID may not stem from severity, but from volume. We do not dismiss the validity of long COVID but recommend an appropriate comparator group when researching this condition.

The acquisition of apoptosis resistance is a fundamental event in cancer development. Among the mechanisms used by cancer cells to evade apoptosis is the dysregulation of inhibitor of apoptosis (IAP) proteins. The activity of the IAPs is regulated by endogenous IAP antagonists such as SMAC (also termed DIABLO). Antagonism of IAP proteins by SMAC occurs via binding of the N-terminal tetrapeptide (AVPI) of SMAC to selected BIR domains of the IAPs. Small molecule compounds that mimic the AVPI motif of SMAC have been designed to overcome IAP-mediated apoptosis resistance of cancer cells. Here, we report the preclinical characterization of birinapant (TL32711), a bivalent SMAC-mimetic compound currently in clinical trials for the treatment of cancer. Birinapant bound to the BIR3 domains of cIAP1, cIAP2, XIAP, and the BIR domain of ML-IAP in vitro and induced the autoubiquitylation and proteasomal degradation of cIAP1 and cIAP2 in intact cells, which resulted in formation of a RIPK1:caspase-8 complex, caspase-8 activation, and induction of tumor cell death. Birinapant preferentially targeted the TRAF2-associated cIAP1 and cIAP2 with subsequent inhibition of TNF-induced NF-κB activation. The activity of a variety of chemotherapeutic cancer drugs was potentiated by birinapant both in a TNF-dependent or TNF-independent manner. Tumor growth in multiple primary patient–derived xenotransplant models was inhibited by birinapant at well-tolerated doses. These results support the therapeutic combination of birinapant with multiple chemotherapies, in particular, those therapies that can induce TNF secretion. Mol Cancer Ther; 13(4); 867–79. ©2014 AACR.

PDF file - 1384KB, Supplemental Figure 1. Structure of biotinylated birinapant Supplemental Figure 2. Concentration-dependent degradation of GFP-cIAP1/2 by birinapant Supplemental Figure 3. Representative examples of data analysis from 111 cell line panel of birinapant in combination with TRAIL analyzed using the MacSynergy II program. Supplemental Figure 4. Cells which are sensitive to birinapant as a single agent produce TNF in response to birinapant treatment Supplemental Figure 5. Birinapant induces cell death as a single agent in a TNF-dependent manner Supplemental Figure 6. Preferential degradation of TRAF2-associated cIAP1 and cIAP2 by birinapant Supplemental Figure 7. Birinapant inhibits the degradation of IkappaBalpha in cells stimulated with TNF; Supplemental Table 1: Kd values of birinapant and Smac-AVPI peptide for IAP BIR domains.

PDF file - 73KB

XLS file - 45KB, Sensitivity of a 111 cell line panel to birinapant as a single agent and in combination with TNF or TRAIL.

The COVID-19 pandemic has led to greater societal divides based on alignment with vaccine mandates and social distancing requirements. This paper briefly lays out the experiences of individuals in Aotearoa New Zealand related to public health messaging.Adults in Aotearoa New Zealand participated in a mixed-methods study involving a survey (n=1,010 analysed results) and then semi-structured interviews with a subset of surveyed participants (38 participants). Results were thematically analysed.Participants highlighted two key areas related to public health messaging, these related to message consistency and the impact of messaging on wellbeing. Conclusions and public health implications: As the COVID-19 pandemic continues and further disrupts health service delivery and normal societal functioning, forward planning is needed to deliver more targeted messaging.

Companion animals can both protect against, and increase risk for, coercive control and abuse, yet have not been considered in existing UK COVID-19 reports of domestic abuse (DA). This study aimed to explore the nature and frequency of animal-related calls received by UK domestic abuse helpline (DAH) staff during the COVID-19 pandemic, examine any lockdown-related changes, identify potential commonalities across helpline organisations, and explore perspectives about ongoing animal-related issues in the context of DA. Semi-structured virtual interviews were conducted with 11 DAH staff workers during the COVID-19 pandemic. Data were subjected to thematic analysis. The analysis revealed four overarching themes. Theme (1) lockdown-related changes in the frequency and nature of animal-related calls received. Theme (2) animals as tools for abuse during lockdown, with subthemes (a) manipulating the family-animal bond, and (b) fears over animal safety. Theme (3) animals as barriers to refuge during lockdown, with subthemes, (a) lack of animal-friendly accommodation, (b) lack of social support systems, and (c) animals as coping mechanisms. Theme (4) helpline staffs’ awareness of and links to animal-friendly accommodation and fostering services. The findings can inform decision making regarding appropriate long-term support needs for multi-species families with complex needs, both during and post-pandemic.

Introduction Prediabetes is the asymptomatic precursor to type two diabetes mellitus, a significant and growing public health problem in New Zealand (NZ). Little is known about how general practitioners (GPs) and nurses view prediabetes care, and similarly little is known about how people with prediabetes view their condition and care. Aim This study aimed to investigate the views of NZ GPs and nurses, and people with prediabetes about prediabetes and its management. Methods This was a mixed qualitative methods study that is part of a randomised control trial of a prediabetes intervention. Results Three key themes emerged from the health professional data (GPs and nurses) and another three themes emerged from people with prediabetes data. GPs and nurses were uncertain about the progression of prediabetes; they felt prediabetes was not a priority and they were unsure about what to advise. People with prediabetes were uncertain about the diagnosis and information given to them; they were unsure about what to do about prediabetes and they found lifestyle change hard. Discussion GPs, nurses and people with prediabetes, expressed much uncertainty, but also some certainty about prediabetes. All were certain that prediabetes is common and increasing and that sustained lifestyle change was very difficult. But uncertainty prevailed about whether, in reality, prediabetes could be stopped, who would be most likely to benefit from lifestyle interventions and how best to achieve these. Older Māori and Pacific women were keen to promote lifestyle change and this appeared best done through Māori and Pacific peoples’ organisations by means of co-designed interventions.

To complement Zack Taylor’s paper on Regionalism from Above: Metro Governance in Canada, the journal commissioned four short ‘perspectives’ from Commonwealth countries grappling with similar issues – Australia, England, New Zealand and South Africa. The purpose was not in any way to ‘review’ Taylor’s work, but rather to establish a broader picture of issues and trends in metropolitan governance, and to identify common threads. The perspectives from Australia, England and South Africa focus on recent developments and governance issues in particular metropolitan areas. These are respectively the fast-growing outer metropolitan sub-region of Western Sydney; the long-established conurbation of Greater Manchester; and the vast, emerging ‘multi-nodal sprawl’ of South Africa’s Gauteng City Region, centred on Johannesburg. The New Zealand perspective takes a different approach, exploring the implications of shifts in national policy towards a focus on wellbeing and the quality of life in communities, with significant implications for the future of local government and the way metropolitan areas are governed. Nevertheless, all four perspectives reveal similar underlying concerns that metropolitan governance frameworks and practices often struggle to keep pace with global trends, urban growth, community needs and national priorities. Effective inter-government relations are crucial, but local governments may not be at the table, or their views may be largely ignored. The governance of metropolitan regions becomes increasingly fraught, a battleground between the forces of devolution and centralisation. How can meaningful and effective collaborative governance be realised? Who should take the lead and do we have the right tools and skills? In such a complex and fluid environment, can we realistically expect anything more than brief periods of clarity and consensus that at least enable agreement on the next few steps?

Desmopressin (DDAVP) is a proven therapy for bleeding disorders; however, the therapeutic efficacy of different parenteral formulations has never been systematically analyzed. This study investigated whether subcutaneous (SC) DDAVP provides equivalent hemostatic efficacy to intravenous (IV) desmopressin, particularly in patients with mild to moderate bleeding tendencies from hemophilia A (HA) or von Willebrand disease (vWD).We searched PubMed, EMBASE, MEDLINE, Cochrane, and CINAHL databases for observational studies and randomized controlled trials which compared the hemostatic efficacy of parenteral formulations of DDAVP in healthy patients and those with bleeding disorders. Two reviewers independently performed screening and data extraction. Extracted data included Factor VIII (FVIII) levels, von Willebrand factor (vWF) antigen levels, and vWF activity.The search strategy yielded a total of 5519 studies. Twelve studies met the inclusion criteria and were included in the review. Seven out of eight studies conducted in patients with bleeding disorders and all four studies conducted in healthy subjects found no difference in hemostatic efficacy between parenteral formulations. A meta-analysis was not performed due to disparities between study design and outcomes of interest.Our study showed that IV and SC administration of DDAVP appeared to result in near equivalent hemostatic efficacy; however, the strength of these findings is limited by the small number and lack of comparability in the primary studies. A sizable contemporary study powered to detect differences in coagulation factor levels would be required to confirm our findings.

ObjectivesWhen followed, there is evidence that social distancing measures play a major role in reducing the transmission of viruses such as COVID-19. However, not all individuals follow the guidance. This study aimed to explore barriers and facilitators to compliance with United Kingdom social distancing guidelines during the COVID-19 pandemic.MethodSemi-structured interviews with 116 adults. Data were analysed using reflexive thematic analysis and themes mapped to domains of the Capability, Opportunity and Motivation Model of Behaviour (COM-B).Main Outcome MeasuresWe identified 12 themes affecting compliance to UK social distancing guidelines.ResultsBarriers to compliance included inconsistent rules, caring responsibilities, fatigue, unintended consequences of control measures, and the need for emotional support. Facilitators were informational support and social responsibility. Six themes acted both as a barrier or facilitator: lived environment and shared spaces, beliefs about consequences of non-compliance, influence of others, practical social support, and trust in government. Conclusions Participants experienced a range of barriers and facilitators to compliance, often dependent on individual circumstances. Reflective motivation, psychological capability and social opportunity were important drivers for compliance. Measures that enable social support alongside strategies that help maintain motivation to comply, provide clear guidance and optimise social cohesion should be promoted.

During a period of intensified exercise (e.g. training/identification camps), often undertaken by competitive youth athletes, the maintenance of muscle function and peak performance can become challenging due to an accumulation of fatigue. The provision of post-exercise dairy protein in adults has been previously shown to accelerate recovery; however, its efficacy in youth athletes is currently unknown. Therefore, the purpose of this study was to examine the effects of increased dairy protein consumption with plain Greek yogurt (GY) on performance and recovery indices during an intensified soccer training camp in adolescent female soccer players.Thirteen players (14.3 ± 1.3 years) participated in a randomized, double blinded, crossover design study where they received 3 servings/day of either GY (~115 kcal, 17 g protein, ~11.5 g carbohydrates) or an isoenergetic carbohydrate control (CHO, ~115 kcal, 0.04 g protein, ~28.6 g carbohydrates) during two 5-day soccer-specific training camps. Performance was assessed before and after each training camp. Fasted, morning, creatine kinase (CK), insulin-like growth factor-1 (IGF-1), C-reactive protein (CRP), interleukin 6 (IL6), interleukin 10 (IL10) and tumor necrosis factor-α (TNFα) were measured in plasma pre- and post-training.Training led to decrements in counter-movement jump (These results demonstrate that consumption of GY did not offer any added recovery benefit with respect to measures of performance and in the attenuation of exercise-induced muscle damage above that achieved with energy-matched carbohydrate in this group of young female soccer players. However, regular consumption of GY may assist with the acute anti-inflammatory response during periods of intensified training in adolescent athletes.

Introduction: Glucagon is often used in neonatal hypoglycaemia, but its effects have not been systematically assessed. We undertook a systematic review to determine the efficacy and safety of glucagon treatment for neonatal hypoglycaemia. Methods: We searched MEDLINE, CINAHL, EMBASE, and CENTRAL from inception until May 2021. We included studies that reported one or more prespecified outcomes and compared glucagon with placebo or no glucagon. Studies were excluded if the majority (>70%) of participants were >1 month of age. Two authors independently extracted data. We used ROB-2/modified ROBINS-I to assess risk of bias, GRADE for certainty of evidence, and RevMan for meta-analysis. Results: 100 studies were screened, 37 reviewed in full, and seven single-arm non-randomised intervention studies, involving 348 infants, were included (no trials). Data were insufficient to undertake meta-analysis of the critical outcomes (time to blood glucose normalization, recurrent hypoglycaemia, neurocognitive impairment). In 3 studies, ≥80% of neonates achieved normoglycaemia within 4 h of glucagon administration. However, recurrent hypoglycaemia was common (up to 55%). Glucagon increased blood glucose concentration at 1–2 h by 2.3 mmol/L (95% CI 2.1, 2.5) (low certainty evidence, 6 studies, N = 323). There were few data for other important clinical outcomes. Conclusion: There is a paucity of evidence about the efficacy and safety of glucagon for treatment of neonatal hypoglycaemia. Low certainty evidence suggests that glucagon may increase blood glucose by ∼2.3 mmol/L but recurrent hypoglycaemia appears common. High-quality, randomized controlled trials are required to determine the role of glucagon in managing neonatal hypoglycaemia.

PDF file - 121 KB, Seventeen human melanoma cell lines representing major mutational subgroups of cutaneous melanoma were treated with TNF-� at concentrations up to 50ng/ml.

OX40L, CD80 and CD86 mRNA-CART treatment increased the expression of CD80, CD86 and OX40L protein on tumor infiltrating cells

PDF file - 110 KB, Immunoblot showing a cohort of birinapant in combination with TNF- � resistant cell lines.

Localized expression of effector molecules can initiate antitumor responses through engagement of specific receptors on target cells in the tumor microenvironment. These locally induced responses may also have a systemic effect, clearing additional tumors throughout the body. In this study, to evoke systemic antitumor responses, we utilized charge-altering releasable transporters (CART) for local intratumoral delivery of mRNA coding for costimulatory and immune-modulating factors. Intratumoral injection of the CART–mRNA complexes resulted in mRNA expression at the site of administration, transfecting a substantial proportion of tumor-infiltrating dendritic cells, macrophages, and T cells in addition to the tumor cells, resulting in a local antitumor effect. Using a two-tumor model, we further show that mRNA therapy locally administered to one tumor stimulated a systemic antitumor response, curing both tumors. The combination of Ox40l-, Cd80-, and Cd86-encoding mRNA resulted in the local upregulation of proinflammatory cytokines, robust local T-cell activation, and migration of immune cells to local draining lymph node or to an anatomically distant tumor. This approach delayed tumor growth, facilitated tumor regression, and cured tumors in both A20 and CT26 tumor models. These results highlight mRNA-CART therapy as a viable approach to induce systemic antitumor immunity from a single localized injection.Significance:The mRNA-CART system is a highly effective delivery platform for delivering immunostimulatory genes into the tumor microenvironment for potential therapeutic development.

PDF file - 57 KB, Mutation profile of cell lines treated with birinapant.

PDF file - 89 KB, TNF-� as a single agent has no effect on cell line proliferation.

PDF file - 79 KB, Levels of TNF-� in cell culture supernatant.