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Abstract Aim Families from socioeconomically deprived backgrounds appear to have been greatly impacted and face worsening inequalities as a result of the COVID-19 pandemic. With more than half of children in Newham, East London, living in poverty, this study aimed to investigate the impact of the COVID-19 lockdowns on families with a child under 5 years-old in Newham and identify their immediate needs to inform recovery efforts. Subjects and methods This was a qualitative study. Semi-structured interviews were conducted with 13 participants (2 fathers; 11 mothers) exploring the impact of the COVID-19 lockdowns on family life, neighbourhood and community and important relationships in the child’s world. Results All parents experienced significant impacts on family life and well-being because of the pandemic. Families were placed under increased stress and were concerned about the impacts on child development. Low-income families were most disadvantaged, experiencing lack of professional support, community engagement and inadequate housing. Conclusion Families were placed under increasing pressure during the pandemic and recovery efforts need to target those most affected, such as families from low-income households. Recovery efforts should target child social and language development, family mental health, professional service engagement and community involvement.

Abstract Neural Crest cells (NC) are a multipotent cell population that give rise to a multitude of cell types including Schwann cells (SC) in the peripheral nervous system (PNS). Immature SC interact with neuronal axons via the neuregulin 1 (NRG1) ligand present on the neuronal surface and ultimately form the myelin sheath. Multiple attempts to derive functional SC from pluripotent stem cells have met challenges with respect to expression of mature markers and axonal sorting. Here, they hypothesized that sustained signaling from immobilized NRG1 (iNRG1) might enhance the differentiation of NC derived from glabrous neonatal epidermis towards a SC phenotype. Using this strategy, NC derived SC expressed mature markers to similar levels as compared to explanted rat sciatic SC. Signaling studies revealed that sustained NRG1 signaling led to yes‐associated protein 1 (YAP) activation and nuclear translocation. Furthermore, NC derived SC on iNRG1 exhibited mature SC function as they aligned with rat dorsal root ganglia (DRG) neurons in an in vitro coculture model; and most notably, aligned on neuronal axons upon implantation in a chick embryo model in vivo. Taken together their work demonstrated the importance of signaling dynamics in SC differentiation, aiming towards development of drug testing platforms for de‐myelinating disorders.

Low carbon management and policies should refer to local long-term inter-annual carbon uptake. However, most previous research has only focused on the quantity and spatial distribution of gross primary product (GPP) for the past 50 years because most satellite launches, the main GPP data source, were no earlier than 1980. We identified a close relationship between the tree-ring index (TRI) and vegetation carbon dioxide uptake (as measured by GPP) and then developed a nested TRI-GPP model to reconstruct spatially explicit GPP values since 1895 from seven tree-ring chronologies. The model performance in both phases was acceptable: We chose general regression neural network regression and random forest regression in Phase 1 (1895–1937) and Phase 2 (1938–1985). With the simulated and real GPP maps, we observed that the GPP for grassland and overall GPP were increasing. The GPP landscape patterns were stable, but in recent years, the GPP’s increasing rate surpassed any other period in the past 130 years. The main local climate driver was the Palmer Drought Severity Index (PDSI), and GPP had a significant positive correlation with PDSI in the growing season (June, July, and August). With the GPP maps derived from the nested TRI-GPP model, we can create fine-scale GPP maps to understand vegetation change and carbon uptake over the past century.

Diabetic bone disease (DBD) is a frequent complication in patients with type 2 diabetes mellitus (T2DM), characterised by altered bone mineral density (BMD) and bone turnover marker (BTMs) levels. The impact of different anti-diabetic medications on the skeleton remains unclear, and studies have reported conflicting results; thus, the need for a comprehensive systematic review is of paramount importance. A systematic search was conducted in PubMed and the Cochrane Library. The primary outcomes assessed were changes in BMD in relation to different anatomical sites and BTMs, including mainly P1NP and CTX as well as OPG, OCN, B-ALP and RANK-L. Risk of bias was evaluated using the JADAD score. The meta-analysis of 19 randomised controlled trials comprising 4914 patients showed that anti-diabetic medications overall increased BMD at the lumbar spine (SMD: 0.93, 95% CI [0.13, 1.73], p = 0.02), femoral neck (SMD: 1.10, 95% CI [0.47, 1.74], p = 0.0007) and in total hip (SMD: 0.33, 95% CI [−0.25, 0.92], p = 0.27) in comparison with placebo, but when compared with metformin, the overall effect favoured metformin over other treatments (SMD: −0.23, 95% CI [−0.39, −0.07], p = 0.004). GLP-1 receptor agonists and insulin analogues seem to improve BMD compared to placebo, while SGLT2 inhibitors and thiazolidinediones (TZDs) showed no significant effect, although studies’ number cannot lead to safe conclusions. For BTMs, TZDs significantly increased P1NP levels compared to placebo. However, no significant differences were observed for CTX, B-ALP, OCN, OPG, and RANK-L between anti-diabetic drugs and metformin or placebo. High heterogeneity and diverse follow-up durations among studies were evident, which obscures the validity of the results. This review highlights the variable effects of anti-diabetic drugs on DBD in T2DM patients, emphasising the need for long-term trials with robust designs to better understand these relationships and inform clinical decisions.

BackgroundDespite an increase in hospital-based deliveries, neonatal mortality remains high in low-resource settings. Due to limited laboratory diagnostics, there is significant reliance on clinical findings to inform diagnoses. Accurate, evidence-based identification and management of neonatal conditions could improve outcomes by standardizing care. This could be achieved through digital clinical decision support (CDS) tools. Neotree is a digital, quality improvement platform that incorporates CDS, aiming to improve neonatal care in low-resource health care facilities. Before this study, first-phase CDS development included developing and implementing neonatal resuscitation algorithms, creating initial versions of CDS to address a range of neonatal conditions, and a Delphi study to review key algorithms. ObjectiveThis second-phase study aims to codevelop and implement neonatal digital CDS algorithms in Malawi and Zimbabwe. MethodsOverall, 11 diagnosis-specific web-based workshops with Zimbabwean, Malawian, and UK neonatal experts were conducted (August 2021 to April 2022) encompassing the following: (1) review of available evidence, (2) review of country-specific guidelines (Essential Medicines List and Standard Treatment Guidelinesfor Zimbabwe and Care of the Infant and Newborn, Malawi), and (3) identification of uncertainties within the literature for future studies. After agreement of clinical content, the algorithms were programmed into a test script, tested with the respective hospital’s health care professionals (HCPs), and refined according to their feedback. Once finalized, the algorithms were programmed into the Neotree software and implemented at the tertiary-level implementation sites: Sally Mugabe Central Hospital in Zimbabwe and Kamuzu Central Hospital in Malawi, in December 2021 and May 2022, respectively. In Zimbabwe, usability was evaluated through 2 usability workshops and usability questionnaires: Post-Study System Usability Questionnaire (PSSUQ) and System Usability Scale (SUS). ResultsOverall, 11 evidence-based diagnostic and management algorithms were tailored to local resource availability. These refined algorithms were then integrated into Neotree. Where national management guidelines differed, country-specific guidelines were created. In total, 9 HCPs attended the usability workshops and completed the SUS, among whom 8 (89%) completed the PSSUQ. Both usability scores (SUS mean score 75.8 out of 100 [higher score is better]; PSSUQ overall score 2.28 out of 7 [lower score is better]) demonstrated high usability of the CDS function but highlighted issues around technical complexity, which continue to be addressed iteratively. ConclusionsThis study describes the successful development and implementation of the only known neonatal CDS system, incorporated within a bedside data capture system with the ability to deliver up-to-date management guidelines, tailored to local resource availability. This study highlighted the importance of collaborative participatory design. Further implementation evaluation is planned to guide and inform the development of health system and program strategies to support newborn HCPs, with the ultimate goal of reducing preventable neonatal morbidity and mortality in low-resource settings.

Abstract BackgroundTwo-thirds of the 2.4 million newborn deaths that occurred in 2020 within the first 28 days of life might have been avoided by implementing existing low-cost evidence-based interventions for all sick and small newborns. An open-source digital quality improvement tool (Neotree) combining data capture with education and clinical decision support is a promising solution for this implementation gap. ObjectiveWe present results from a cost analysis of a pilot implementation of Neotree in 3 hospitals in Malawi and Zimbabwe. MethodsWe combined activity-based costing and expenditure approaches to estimate the development and implementation cost of a Neotree pilot in 1 hospital in Malawi, Kamuzu Central Hospital (KCH), and 2 hospitals in Zimbabwe, Sally Mugabe Central Hospital (SMCH) and Chinhoyi Provincial Hospital (CPH). We estimated the costs from a provider perspective over 12 months. Data were collected through expenditure reports, monthly staff time-use surveys, and project staff interviews. Sensitivity and scenario analyses were conducted to assess the impact of uncertainties on the results or estimate potential costs at scale. A pilot time-motion survey was conducted at KCH and a comparable hospital where Neotree was not implemented. ResultsTotal cost of pilot implementation of Neotree at KCH, SMCH, and CPH was US $37,748, US $52,331, and US $41,764, respectively. Average monthly cost per admitted child was US $15, US $15, and US $58, respectively. Staff costs were the main cost component (average 73% of total costs, ranging from 63% to 79%). The results from the sensitivity analysis showed that uncertainty around the number of admissions had a significant impact on the costs in all hospitals. In Malawi, replacing monthly web hosting with a server also had a significant impact on the costs. Under routine (nonresearch) conditions and at scale, total costs are estimated to fall substantially, up to 76%, reducing cost per admitted child to as low as US $5 in KCH, US $4 in SMCH, and US $14 in CPH. Median time to admit a baby was 27 (IQR 20-40) minutes using Neotree (n=250) compared to 26 (IQR 21-30) minutes using paper-based systems (n=34), and the median time to discharge a baby was 9 (IQR 7-13) minutes for Neotree (n=246) compared to 3 (IQR 2-4) minutes for paper-based systems (n=50). ConclusionNeotree is a time- and cost-efficient tool, comparable with the results from limited similar mHealth decision-support tools in low- and middle-income countries. Implementation costs of Neotree varied substantially between the hospitals, mainly due to hospital size. The implementation costs could be substantially reduced at scale due to economies of scale because of integration to the health systems and reductions in cost items such as staff and overhead. More studies assessing the impact and cost-effectiveness of large-scale mHealth decision-support tools are needed.

Although scholars started investigating self-objectification more than twenty years ago, only a few studies focused on men and even fewer have taken into account the cross-cultural dimension. Our study focused on the antecedents of self-objectification paying attention to the role of biological and sociodemographic variables (gender, BMI), psychological characteristics (self-esteem, perfectionism) together with social and cultural factors (internalization of media standards, influence of family and friends). Self-objectification was operationalized as Body Shame and Body Surveillance. A self-reported questionnaire was administered to 2165 adults living in four European countries (UK, Italy, Poland and Romania) and Iran. Ten regression models were performed (2 per country) to analyse the correlates of self-objectification. Overall, self-objectification emerged as a process affected by factors entrenched in psychological, biological, social and cultural domains, partially different for Body Shame and Body Surveillance. Findings showed the key role of self-esteem as a protective factor against Body Shame across countries. On the other hand, the internalization of media standards emerged as risk factor for both Body Shame and Body Surveillance in the five countries. Taken together, these results underline the complexity of self-objectification and the need to deepen research on this topic among non-Western countries.

Background The recent World Health Organization (WHO) blueprint for dementia research and Lancet Commission on ending stigma and discrimination in mental health has identified a gap around dementia-related measures of stigma and discrimination that can be used in different cultural, language and regional contexts. Aims We aimed to characterise experiences of discrimination, and report initial psychometric properties of a new tool to capture these experiences, among a global sample of people living with dementia. Method We analysed data from 704 people living with dementia who took part in a global survey from 33 different countries and territories. Psychometric properties were examined, including internal consistency and construct validity. Results A total of 83% of participants reported discrimination in one or more areas of life, and this was similar across WHO Regions. The exploratory factor analysis factor loadings and scree plot supported a unidimensional structure for the Discrimination and Stigma Scale Ultra Short for People Living with Dementia (DISCUS-Dementia). The instrument demonstrated excellent internal consistency, with most of the construct validity hypotheses being confirmed and qualitative responses demonstrating face validity. Conclusions Our analyses suggest that the DISCUS-Dementia performs well with a global sample of people living with dementia. This scale can be integrated into large-scale studies to understand factors associated with stigma and discrimination. It can also provide an opportunity for a structured discussion around stigma and discrimination experiences important to people living with dementia, as well as planning psychosocial services and initiatives to reduce stigma and discrimination.

Objectives: Information professionals have supported medical providers, administrators and decision-makers, and guideline creators in the COVID-19 response. Searching COVID-19 literature presented new challenges, including the volume and heterogeneity of literature and the proliferation of new information sources, and exposed existing issues in metadata and publishing. An expert panel developed best practices, including recommendations, elaborations, and examples, for searching during public health emergencies. Methods: Project directors and advisors developed core elements from experience and literature. Experts, identified by affiliation with evidence synthesis groups, COVID-19 search experience, and nomination, responded to an online survey to reach consensus on core elements. Expert participants provided written responses to guiding questions. A synthesis of responses provided the foundation for focus group discussions. A writing group then drafted the best practices into a statement. Experts reviewed the statement prior to dissemination. Results: Twelve information professionals contributed to best practice recommendations on six elements: core resources, search strategies, publication types, transparency and reproducibility, collaboration, and conducting research. Underlying principles across recommendations include timeliness, openness, balance, preparedness, and responsiveness. Conclusions: The authors and experts anticipate the recommendations for searching for evidence during public health emergencies will help information specialists, librarians, evidence synthesis groups, researchers, and decision-makers respond to future public health emergencies, including but not limited to disease outbreaks. The recommendations complement existing guidance by addressing concerns specific to emergency response. The statement is intended as a living document. Future revisions should solicit input from a broader community and reflect conclusions of meta-research on COVID-19 and health emergencies.

# Background Despite increasing rates of facility-based deliveries, neonatal mortality rates remain persistently high in low-resource settings (LRS). This has catalysed international focus on understanding and enabling quality newborn care. We aimed to understand persistent barriers to Quality of Care (QoC) and to identify quality improvement priorities from the perspective of a panel of neonatal experts with first-hand experience of delivering newborn care in low-resource settings (LRS). # Methods We conducted 13 semi-structured interviews with neonatal health experts via Skype. All interviews were recorded and transcribed verbatim. We adopted an inductive thematic analytical approach. Ethical approvals were not required. # Results Twenty-two experts were invited to participate, of whom 16 responded and 13 agreed to take part (five neonatologists, six paediatricians and two advanced neonatal nurse practitioners). Participants had a mean of 13 (±7 SD) years working in LRS. Lack of physical resources including basic equipment and infrastructure such as running water, combined with limited human resources, education and specialist neonatal training were cited as key barriers to delivering quality care. In addition, weak leadership at the community, local and national level were thought to hinder progress. Poor communication within clinical teams, limited documentation and lack of standardised and locally appropriate guidelines were also identified as challenges. Digital technologies were perceived to have potential for data capture and enabling standardised care. However, some highlighted that unreliable internet access and possible stigma may hinder implementation. # Conclusions With less than 10 years to reach the Sustainable Development Goals (SDGs), it is critical to ensure access to quality care for all sick and vulnerable newborns admitted to health facilities. Clinical leaders in low resource settings need to be empowered to define local agendas and advocate for critical resources in order to close the gap between local and global quality of care priorities.

Cholesteatoma is a rare progressive disease of the middle ear. Most cases are sporadic, but some patients report a positive family history. Identifying functionally important gene variants associated with this disease has the potential to uncover the molecular basis of cholesteatoma pathology with implications for disease prevention, surveillance, or management. We performed an observational WES study of 21 individuals treated for cholesteatoma who were recruited from ten multiply affected families. These family studies were complemented with gene-level mutational burden analysis. We also applied functional enrichment analyses to identify shared properties and pathways for candidate genes and their products. Filtered data collected from pairs and trios of participants within the ten families revealed 398 rare, loss of function (LOF) variants co-segregating with cholesteatoma in 389 genes. We identified six genes DENND2C, DNAH7, NBEAL1, NEB, PRRC2C, and SHC2, for which we found LOF variants in two or more families. The parallel gene-level analysis of mutation burden identified a significant mutation burden for the genes in the DNAH gene family, which encode products involved in ciliary structure. Functional enrichment analyses identified common pathways for the candidate genes which included GTPase regulator activity, calcium ion binding, and degradation of the extracellular matrix. The number of candidate genes identified and the locus heterogeneity that we describe within and between multiply affected families suggest that the genetic architecture for familial cholesteatoma is complex.

Abstract Introduction Improving peri‐ and postnatal facility‐based care in low‐resource settings (LRS) could save over 6000 babies' lives per day. Most of the annual 2.4 million neonatal deaths and 2 million stillbirths occur in healthcare facilities in LRS and are preventable through the implementation of cost‐effective, simple, evidence‐based interventions. However, their implementation is challenging in healthcare systems where one in four babies admitted to neonatal units die. In high‐resource settings healthcare systems strengthening is increasingly delivered via learning healthcare systems to optimise care quality, but this approach is rare in LRS. Methods Since 2014 we have worked in Bangladesh, Malawi, Zimbabwe, and the UK to co‐develop and pilot the Neotree system: an android application with accompanying data visualisation, linkage, and export. Its low‐cost hardware and state‐of‐the‐art software are used to support healthcare professionals to improve postnatal care at the bedside and to provide insights into population health trends. Here we summarise the formative conceptualisation, development, and preliminary implementation experience of the Neotree. Results Data thus far from ~18 000 babies, 400 healthcare professionals in four hospitals (two in Zimbabwe, two in Malawi) show high acceptability, feasibility, usability, and improvements in healthcare professionals' ability to deliver newborn care. The data also highlight gaps in knowledge in newborn care and quality improvement. Implementation has been resilient and informative during external crises, for example, coronavirus disease 2019 (COVID‐19) pandemic. We have demonstrated evidence of improvements in clinical care and use of data for Quality Improvement (QI) projects. Conclusion Human‐centred digital development of a QI system for newborn care has demonstrated the potential of a sustainable learning healthcare system to improve newborn care and outcomes in LRS. Pilot implementation evaluation is ongoing in three of the four aforementioned hospitals (two in Zimbabwe and one in Malawi) and a larger scale clinical cost effectiveness trial is planned.

The global priority of improving neonatal survival could be tackled through the universal implementation of cost-effective maternal and newborn health interventions. Despite 90% of neonatal deaths occurring in low-resource settings, very few evidence-based digital health interventions exist to assist healthcare professionals in clinical decision-making in these settings. To bridge this gap, Neotree was co-developed through an iterative, user-centered design approach in collaboration with healthcare professionals in the UK, Bangladesh, Malawi, and Zimbabwe. It addresses a broad range of neonatal clinical diagnoses and healthcare indicators as opposed to being limited to specific conditions and follows national and international guidelines for newborn care. This digital health intervention includes a mobile application (app) which is designed to be used by healthcare professionals at the bedside. The app enables real-time data capture and provides education in newborn care and clinical decision support via integrated clinical management algorithms. Comprehensive routine patient data are prospectively collected regarding each newborn, as well as maternal data and blood test results, which are used to inform clinical decision making at the bedside. Data dashboards provide healthcare professionals and hospital management a near real-time overview of patient statistics that can be used for healthcare quality improvement purposes. To enable this workflow, the Neotree web editor allows fine-grained customization of the mobile app. The data pipeline manages data flow from the app to secure databases and then to the dashboard. Implemented in three hospitals in two countries so far, Neotree has captured routine data and supported the care of over 21,000 babies and has been used by over 450 healthcare professionals. All code and documentation are open source, allowing adoption and adaptation by clinicians, researchers, and developers.

[Background] Unpaid caregivers have faced and dealt with additional challenges during the COVID-19 pandemic. Understanding the psychological processes associated with their resilience is warranted. The objective of this study was to examine the associations between resilience with mental distress, emotion regulation strategies (i.e., reappraisal and suppression) and interpretation bias in adult caregivers. [Method] Participants were living in the UK, aged 18+, and consisted of 182 unpaid caregivers of an adult aged 18+ living with a long-term health condition, and 120 non-caregivers. Data were collected in an online study during the first national UK COVID-19 lockdown (May and September 2020). Hierarchical multiple regression analyses explored whether emotion regulation strategies and interpretation bias explained unique variance in levels of resilience in caregivers whilst controlling for anxiety and depression. [Results] Compared to non-caregivers, caregivers reported higher levels of anxiety, depression, negative interpretation bias and lower levels of resilience. Emotion regulation strategies did not differ between groups. Within caregivers, greater resilience was associated with lower mood disturbance, a positive interpretation bias, and greater use of cognitive reappraisal and lower use of suppression strategies to regulate emotions. Emotion regulation and interpretation bias together predicted an additional 15% of variance in current levels of resilience. [Conclusion] Our findings indicate that psychological mechanisms such as emotion regulation strategies, particularly reappraisal, and interpretation bias are associated with resilience in caregivers. Although preliminary, our findings speak to exciting clinical possibilities that could form the target of interventions to improve resilience and lower mental distress in unpaid caregivers.

BackgroundDementia misconceptions on Twitter can have detrimental or harmful effects. Machine learning (ML) models codeveloped with carers provide a method to identify these and help in evaluating awareness campaigns. ObjectiveThis study aimed to develop an ML model to distinguish between misconceptions and neutral tweets and to develop, deploy, and evaluate an awareness campaign to tackle dementia misconceptions. MethodsTaking 1414 tweets rated by carers from our previous work, we built 4 ML models. Using a 5-fold cross-validation, we evaluated them and performed a further blind validation with carers for the best 2 ML models; from this blind validation, we selected the best model overall. We codeveloped an awareness campaign and collected pre-post campaign tweets (N=4880), classifying them with our model as misconceptions or not. We analyzed dementia tweets from the United Kingdom across the campaign period (N=7124) to investigate how current events influenced misconception prevalence during this time. ResultsA random forest model best identified misconceptions with an accuracy of 82% from blind validation and found that 37% of the UK tweets (N=7124) about dementia across the campaign period were misconceptions. From this, we could track how the prevalence of misconceptions changed in response to top news stories in the United Kingdom. Misconceptions significantly rose around political topics and were highest (22/28, 79% of the dementia tweets) when there was controversy over the UK government allowing to continue hunting during the COVID-19 pandemic. After our campaign, there was no significant change in the prevalence of misconceptions. ConclusionsThrough codevelopment with carers, we developed an accurate ML model to predict misconceptions in dementia tweets. Our awareness campaign was ineffective, but similar campaigns could be enhanced through ML to respond to current events that affect misconceptions in real time.

Introduction Self-harm and suicide are major public health concerns among children and adolescents. Many risk and protective factors for suicide and self-harm have been identified and reported in the literature. However, the capacity of these identified risk and protective factors to guide assessment and management is limited due to their great number. This protocol describes an ongoing systematic review and meta-analysis which aims to examine longitudinal studies of risk factors for self-harm and suicide in children and adolescents, to provide a comparison of the strengths of association of the various risk factors for self-harm and suicide and to shed light on those that require further investigation.Methods and analysis We perform a systematic search of the literature using the databases EMBASE, PsycINFO, Medline, CINAHL and HMIC from inception up to 28 October 2020, and the search will be updated before the systematic review publication. Additionally, we will contact experts in the field, including principal investigators whose peer-reviewed publications are included in our systematic review as well as investigators from our extensive research network, and we will search the reference lists of relevant reviews to retrieve any articles that were not identified in our search. We will extract relevant data and present a narrative synthesis and combine the results in meta-analyses where there are sufficient data. We will assess the risk of bias for each study using the Newcastle–Ottawa Scale and present a summary of the quantity and the quality of the evidence for each risk or protective factor.Ethics and dissemination Ethical approval will not be sought as this is a systematic review of the literature. Results will be published in mental health journals and presented at conferences focused on suicide prevention.PROSPERO registration number CRD42021228212.

BackgroundCommunication via technology is regarded as an effective way of maintaining social connection and helping individuals to cope with the psychological impact of social distancing measures during a pandemic. However, there is little information about which factors have influenced increased use of technology to communicate with others during lockdowns and whether this has changed over time. ObjectiveThe aim of this study is to explore which psychosocial factors (eg, mental health and employment) and pandemic-related factors (eg, shielding and time) influenced an increase in communication via technology during the first lockdown in the United Kingdom. MethodsA cross-sectional, web-based survey was conducted between April and July 2020, examining thoughts, feelings, and behaviors associated with the pandemic, including communicating more using technology (eg, via messaging, phone, or video). We collected sociodemographic information, employment status, mental health service user status, and depression symptoms. We used hierarchical logistic regression to test which factors were associated with communicating more using technology during the lockdown. ResultsParticipants (N=1464) were on average 41.07 (SD 14.61) years old, and mostly women (n=1141; 77.9%), White (n=1265; 86.4%), and employed (n=1030; 70.4%). Participants reported a mild level of depression (mean 9.43, SD 7.02), and were communicating more using technology (n=1164; 79.5%). The hierarchical regression indicated that people who were employed and experiencing lower levels of depression were more likely to report increased communication using technology during a lockdown period of the COVID-19 pandemic, and over time, men communicated more using technology. Increased use of technology to communicate was related to greater communication and the inability to see others due to the social distancing measures enacted during the lockdown. It was not related to a general increase in technology use during the lockdown. ConclusionsAlthough most participants reported increased use of technology to communicate during a lockdown period of the COVID-19 pandemic, this was more apparent in the employed and those experiencing low levels of depression. Moving forward, we should continue to monitor groups who may have been excluded from the benefits of support and communication using technology.

Introduction Every year 2.4 million deaths occur worldwide in babies younger than 28 days. Approximately 70% of these deaths occur in low-resource settings because of failure to implement evidence-based interventions. Digital health technologies may offer an implementation solution. Since 2014, we have worked in Bangladesh, Malawi, Zimbabwe and the UK to develop and pilot Neotree: an android app with accompanying data visualisation, linkage and export. Its low-cost hardware and state-of-the-art software are used to improve bedside postnatal care and to provide insights into population health trends, to impact wider policy and practice.Methods and analysis This is a mixed methods (1) intervention codevelopment and optimisation and (2) pilot implementation evaluation (including economic evaluation) study. Neotree will be implemented in two hospitals in Zimbabwe, and one in Malawi. Over the 2-year study period clinical and demographic newborn data will be collected via Neotree, in addition to behavioural science informed qualitative and quantitative implementation evaluation and measures of cost, newborn care quality and usability. Neotree clinical decision support algorithms will be optimised according to best available evidence and clinical validation studies.Ethics and dissemination This is a Wellcome Trust funded project (215742_Z_19_Z). Research ethics approvals have been obtained: Malawi College of Medicine Research and Ethics Committee (P.01/20/2909; P.02/19/2613); UCL (17123/001, 6681/001, 5019/004); Medical Research Council Zimbabwe (MRCZ/A/2570), BRTI and JREC institutional review boards (AP155/2020; JREC/327/19), Sally Mugabe Hospital Ethics Committee (071119/64; 250418/48). Results will be disseminated via academic publications and public and policy engagement activities. In this study, the care for an estimated 15 000 babies across three sites will be impacted.Trial registration number NCT0512707; Pre-results

BackgroundThere is increasing interest in the potential uses of mobile health (mHealth) technologies, such as wearable biosensors, as supplements for the care of people with neurological conditions. However, adherence is low, especially over long periods. If people are to benefit from these resources, we need a better long-term understanding of what influences patient engagement. Previous research suggests that engagement is moderated by several barriers and facilitators, but their relative importance is unknown. ObjectiveTo determine preferences and the relative importance of user-generated factors influencing engagement with mHealth technologies for 2 common neurological conditions with a relapsing-remitting course: multiple sclerosis (MS) and epilepsy. MethodsIn a discrete choice experiment, people with a diagnosis of MS (n=141) or epilepsy (n=175) were asked to select their preferred technology from a series of 8 vignettes with 4 characteristics: privacy, clinical support, established benefit, and device accuracy; each of these characteristics was greater or lower in each vignette. These characteristics had previously been emphasized by people with MS and or epilepsy as influencing engagement with technology. Mixed multinomial logistic regression models were used to establish which characteristics were most likely to affect engagement. Subgroup analyses explored the effects of demographic factors (such as age, gender, and education), acceptance of and familiarity with mobile technology, neurological diagnosis (MS or epilepsy), and symptoms that could influence motivation (such as depression). ResultsAnalysis of the responses to the discrete choice experiment validated previous qualitative findings that a higher level of privacy, greater clinical support, increased perceived benefit, and better device accuracy are important to people with a neurological condition. Accuracy was perceived as the most important factor, followed by privacy. Clinical support was the least valued of the attributes. People were prepared to trade a modest amount of accuracy to achieve an improvement in privacy, but less likely to make this compromise for other factors. The type of neurological condition (epilepsy or MS) did not influence these preferences, nor did the age, gender, or mental health status of the participants. Those who were less accepting of technology were the most concerned about privacy and those with a lower level of education were prepared to trade accuracy for more clinical support. ConclusionsFor people with neurological conditions such as epilepsy and MS, accuracy (ie, the ability to detect symptoms) is of the greatest interest. However, there are individual differences, and people who are less accepting of technology may need far greater reassurance about data privacy. People with lower levels of education value greater clinician involvement. These patient preferences should be considered when designing mHealth technologies.

The Hollywood Reporter feature on Gianfranco Rosi’s Fire at Sea (Fuocoammare, 2016) reads: “Where journalism leaves off, Fire at Sea begins”. The director spent months living alone on Lampedusa looking for ways to film the current refugee tragedy in the Mediterranean. The poetic film that he made (and that won the Golden Bear at Berlin) is an indirect reckoning with its subject, and, I argue no less political for this. Referring to the work of Adriana Cavarero, Christina Sharpe, Anne Dufourmantelle and Judith Butler, this article explores the uses of recorded telephone calls and other transmitted voices and songs in the film. These calls and voices offer forms of appeal and aural, non-visual, but bodily, affective traces. The film emphasises the political importance of listening, and of attending to these calls and voices, envisaging a mesh of connectedness, of threads of human attachment.

Background Patient and public involvement can improve study outcomes, but little data have been collected on why this might be. We investigated the impact of the Feasibility and Support to Timely Recruitment for Research (FAST-R) service, made up of trained patients and carers who review research documents at the beginning of the research pipeline. Aims To investigate the impact of the FAST-R service, and to provide researchers with guidelines to improve study documents. Method A mixed-methods design assessing changes and suggestions in documents submitted to the FAST-R service from 2011 to 2020. Quantitative measures were readability, word count, jargon words before and after review, the effects over time and if changes were implemented. We also asked eight reviewers to blindly select a pre- or post-review participant information sheet as their preferred version. Reviewers’ comments were analysed qualitatively via thematic analysis. Results After review, documents were longer and contained less jargon, but did not improve readability. Jargon and the number of suggested changes increased over time. Participant information sheets had the most suggested changes. Reviewers wanted clarity, better presentation and felt that documents lacked key information such as remuneration, risks involved and data management. Six out of eight reviewers preferred the post-review participant information sheet. FAST-R reviewers provided jargon words and phrases with alternatives for researchers to use. Conclusions Longer documents are acceptable if they are clear, with jargon explained or substituted. The highlighted barriers to true informed consent are not decreasing, although this study has suggestions for improving research document accessibility.

There are increasing numbers of scientific articles dedicated to developments in the field of redox flow batteries. To date it is most common to provide efficiency values as a measure of performance. However, there are no agreed standard experimental conditions for these measurements, and so their merit as a tool for comparing different innovations among research groups is put into question. In the following manuscript, various experimental precautions are outlined to reduce experimental artefacts. Original experimental measurements on vanadium flow cells, together with data from the literature, are examined to explore efficiencies and two alternative benchmarking metrics: resistivity and self-discharge current density. The sensitivity of these parameters to current density, temperature, flow rate and state-of-charge range are examined, from which it is concluded that resistivity and self-discharge current density exhibit superior properties to efficiencies for quantifying flow battery improvements.

Background: Mental health services are turning to technology to ease the resource burden, but privacy policies are hard to understand potentially compromising consent for people with mental health problems. The FDA recommends a reading grade of 8. Objective: To investigate and improve the accessibility and acceptability of mental health depression app privacy policies. Methods: A mixed methods study using quantitative and qualitative data to improve the accessibility of app privacy policies. Service users completed assessments and focus groups to provide information on ways to improve privacy policy accessibility, including identifying and rewording jargon. This was supplemented by comparisons of mental health depression apps with social media, music and finance apps using readability analyses and examining whether GDPR affected accessibility. Results: Service users provided a detailed framework for increasing accessibility that emphasised having critical information for consent. Quantitatively, most app privacy policies were too long and complicated for ensuring informed consent (mental health apps mean reading grade = 13.1 (SD = 2.44)). Their reading grades were no different to those for other services. Only 3 mental health apps had a grade 8 or less and 99% contained service user identified jargon. Mental health app privacy policies produced for GDPR weren't more readable and were longer. Conclusions: Apps specifically aimed at people with mental health difficulties are not accessible and even those that fulfilled the FDA's recommendation for reading grade contained jargon words. Developers and designers can increase accessibility by following a few rules and should, before launching, check whether the privacy policy can be understood.

Objectives: Little is known about sex workers’ experiences of cervical cryotherapy. We sought to understand sex workers’ perspectives of ‘screen and treat’ programmes and their management of the World Health Organization post-treatment guidance to abstain from sex or use condoms consistently for 4 weeks. We explored contraceptive preferences and use of menstrual regulation services. Methods: We conducted semi-structured interviews with 16 sex workers and six brothel leaders in an urban brothel complex in Bangladesh between October and November 2018. All had undergone cryotherapy. We conducted a thematic analysis using deductive coding, informed by a priori themes, and inductive data-driven coding. Results: Most sex workers could not abstain from sex during the healing period. Consistent condom use was challenging due to economic incentives attached to condomless sex and coercive behaviours of clients. The implications of non-adherence among high-risk groups such as sex workers are not known. Use of short-acting methods of contraception was common, and discontinuation was high due to side effects and other perceived health concerns. The majority of sex workers and brothel leaders had utilized menstrual regulation services. Barriers to accessing timely menstrual regulation and other sexual and reproductive health services included limited mobility, economic costs, and discriminatory attitudes of health care workers. Conclusion: Service innovations are required to enable sex workers to abstain or use condoms consistently in the post-cryotherapy healing phase and to address sex workers’ broader sexual and reproductive health needs. Further research is required to assess the risk of HIV and other sexually transmitted infection transmission following cryotherapy among high-risk groups.

Background: Vascular services is changing rapidly, having emerged as a new specialty with its own training and specialised techniques. This has resulted in the need for reconfiguration of services to provide adequate specialist provision and accessible and equitable services. Objectives: To identify the effects of service configuration on practice, resource use and outcomes. To model potential changes in configuration. To identify and/or develop electronic data collection tools for collecting patient-reported outcome measures and other clinical information. To evaluate patient preferences for aspects of services other than health-related quality of life. Design: This was a multiple methods study comprising multiple systematic literature reviews; the development of a new outcome measure for users of vascular services (the electronic Personal Assessment Questionnaire – Vascular) based on the reviews, qualitative studies and psychometric evaluation; a trade-off exercise to measure process utilities; Hospital Episode Statistics analysis; and the development of individual disease models and a metamodel of service configuration. Setting: Specialist vascular inpatient services in England. Data sources: Modelling and Hospital Episode Statistics analysis for all vascular inpatients in England from 2006 to 2018. Qualitative studies and electronic Personal Assessment Questionnaire – Vascular evaluation with vascular patients from the Sheffield area. The trade-off studies were based on a societal sample from across England. Interventions: The data analysis, preference studies and modelling explored the effect of different potential arrangements for service provision on the resource use, workload and outcomes for all interventions in the three main areas of inpatient vascular treatment: peripheral arterial disease, abdominal aortic aneurysm and carotid artery disease. The electronic Personal Assessment Questionnaire – Vascular was evaluated as a potential tool for clinical data collection and outcome monitoring. Main outcome measures: Systematic reviews assessed quality and psychometric properties of published outcome measures for vascular disease and the relationship between volume and outcome in vascular services. The electronic Personal Assessment Questionnaire – Vascular development considered face and construct validity, test–retest reliability and responsiveness. Models were validated using case studies from previous reconfigurations and comparisons with Hospital Episode Statistics data. Preference studies resulted in estimates of process utilities for aneurysm treatment and for travelling distances to access services. Results: Systematic reviews provided evidence of an association between increasing volume of activity and improved outcomes for peripheral arterial disease, abdominal aortic aneurysm and carotid artery disease. Reviews of existing patient-reported outcome measures did not identify suitable condition-specific tools for incorporation in the electronic Personal Assessment Questionnaire – Vascular. Reviews of qualitative evidence, primary qualitative studies and a Delphi exercise identified the issues to be incorporated into the electronic Personal Assessment Questionnaire – Vascular, resulting in a questionnaire with one generic and three disease-specific domains. After initial item reduction, the final version has 55 items in eight scales and has acceptable psychometric properties. The preference studies showed strong preference for endovascular abdominal aortic aneurysm treatment (willingness to trade up to 0.135 quality-adjusted life-years) and for local services (up to 0.631 quality-adjusted life-years). A simulation model with a web-based interface was developed, incorporating disease-specific models for abdominal aortic aneurysm, peripheral arterial disease and carotid artery disease. This predicts the effects of specified reconfigurations on workload, resource use, outcomes and cost-effectiveness. Initial exploration suggested that further reconfiguration of services in England to accomplish high-volume centres would result in improved outcomes, within the bounds of cost-effectiveness usually considered acceptable in the NHS. Limitations: The major source of evidence to populate the models was Hospital Episode Statistics data, which have limitations owing to the complexity of the data, deficiencies in the coding systems and variations in coding practice. The studies were not able to address all of the potential barriers to change where vascular services are not compliant with current NHS recommendations. Conclusions: There is evidence of potential for improvement in the clinical effectiveness and cost-effectiveness of vascular services through further centralisation of sites where major vascular procedures are undertaken. Preferences for local services are strong, and this may be addressed through more integrated services, with a range of services being provided more locally. The use of a web-based tool for the collection of clinical data and patient-reported outcome measures is feasible and can provide outcome data for clinical use and service evaluation. Future work: Further evaluation of the economic models in real-world situations where local vascular service reconfiguration is under consideration and of the barriers to change where vascular services do not meet NHS recommendations for service configuration is needed. Further work on the electronic Personal Assessment Questionnaire – Vascular is required to assess its acceptability and usefulness in clinical practice and to develop appropriate report formats for clinical use and service evaluation. Further studies to assess the implications of including non-health-related preferences for care processes, and location of services, in calculations of cost-effectiveness are required. Study registration: This study is registered as PROSPERO CRD42016042570, CRD42016042573, CRD42016042574, CRD42016042576, CRD42016042575, CRD42014014850, CRD42015023877 and CRD42015024820. Funding: This project was funded by the National Institute for Health Research (NIHR) Programme Grants for Applied Research programme and will be published in full in Programme Grants for Applied Research; Vol. 9, No. 5. See the NIHR Journals Library website for further project information.

Background Ketamine is a new and promising treatment for depression but comes with challenges to implement because of its potential for abuse. Aims We sought the views of patients to inform policy and practical decisions about the clinical use of ketamine before large-scale roll-out is considered. Method This qualitative study used three focus groups and three validation sessions from 14 patients with prior diagnoses of depression but no experience of ketamine treatment. Focus groups explored their views about clinical use of ketamine and the best way for ketamine to be administered and monitored. The qualitative data were analysed by three service-user researchers using thematic analysis. Results Five themes were generated: changing public perceptions, risks, monitoring, privacy and data protection, and practical aspects. Participants were conscious of the stigma attached to ketamine as a street drug and wanted better public education, and evidence on the safety of ketamine after long-term use. They felt that monitoring was required to provide evidence for ketamine's safe use and administration, but there were concerns about the misuse of this information. Practical aspects included discussions about treatment duration, administration and accessibility (for example who would receive it, under what criteria and how). Conclusions Patients are enthusiastic about ketamine treatment but need more information before national roll-out. The wider societal impact of ketamine treatment also needs to be considered and patients need to be part of any future roll-out to ensure its success.

People with eating disorders display a negative interpretation bias towards ambiguous social stimuli. This bias may be particularly relevant to young people with the illness due to the developmental salience of social acceptance and rejection. The overall aim of this study was to systematically develop and validate stimuli for a cognitive bias modification training to reduce a social rejection-related negative interpretation bias in young people with eating disorders. A mixed-methods design was used to achieve this aim. A review of the literature was conducted using EMBASE, MEDLINE, PsycINFO, Web of Science, and PubMed. Six studies were included in the review. Focus groups were held with patients with eating disorders, carers and healthcare professionals. Content analysis was used to identify key themes from the qualitative data. Based on these themes, a total of 339 scenarios were generated by the researchers. Salient themes identified from the focus group data included virtual rejection/exclusion, rejection associated with an aspect of the eating disorder, rejection triggered by ambiguous/benign comments or behaviors of others and rejection perceived when confiding in others. Patients rated these scenarios in terms of their age-relevance and emotional salience and 301 scenarios were included in the final stimulus set. These materials may be used by researchers conducting future experimental research into the potential benefits of interpretation bias training for young people with eating disorders.

Hurricane Charley made landfall on the Gulf Coast of Florida on 13 August 2004 as a category 4 hurricane, devastating North Captiva Island. The hurricane caused a breach to occur to the southern end of the island, which naturally healed itself over the course of three years. By 2008, the cut was completely repaired geomorphologically. LiDAR data analysis shows the northern half of the island has been subjected to persistent erosion from 1998–2018, while the southern half experienced accretion since 2004, including the complete closure of the “Charley cut”. The maximum volume of sediment erosion in the northern sector of the island (R71–R73) from 2004–2018 was −85,710.1 m3, which was the source of southern accretion. The breached area of the island (R78b–R79a) obtained 500,163.9 m3 of sediments from 2004–2018 to heal the cut made by Hurricane Charley. Along with LiDAR data analysis, Google Earth Pro historical imageries and SANDS volumetric analysis confirmed the longshore transport of sediments from the northern to the southern end of the island. Winter storms are mainly responsible for this southerly longshore transport and are hypothesized to be the main factor driving the coastal dynamics that restored the breach and helps in widening the southern end of North Captiva Island.

Corporate social responsibility (CSR) is promoted and critiqued by many players involved in or opposed to petroleum exploration and extraction, although a common understanding of CSR's theoretical and practical meanings rarely exists. This paper uses Arctic petroleum in the Barents region (Norway and Russia) to investigate local perceptions of CSR. We conducted open-ended, semi-structured interviews in four locations: Hammerfest, Murmansk, Komi Republic, and Nenets Autonomous Okrug (NAO). Interviewees included the local population, regional and local authorities, non-governmental organisations (NGOs), and petroleum company representatives. The field research suggests that those who gain directly from the petroleum industry and do not directly experience negative impacts were more inclined to be positive about the industry, although overall, general support for petroleum activity was high. In some cases, positive economic benefits resulted in greater tolerance of environmental risk. Sometimes, the industry and government were criticised by locals for failing to support a more equitable distribution of broader economic benefits. Rather than splitting along for-profit/NGO or indigenous/non-indigenous lines, our analysis suggests that those who are closer to the petroleum industry or its benefits, termed ‘insiders’, tend to be more positive than ‘outsiders’. This study is perhaps the first of its kind in its focus on local perceptions of CSR for Arctic petroleum across the Barents region. The findings of this study not only match with that of the previous literature on Arctic petroleum but also provide further practical and theoretical insights by indicating subtleties and nuances within the localities examined.

Umbilical cord mesenchymal stromal cells (UCMSCs) have shown an ability to modulate the immune system through the secretion of paracrine mediators, such as extracellular vesicles (EVs). However, the culture conditions that UCMSCs are grown in can alter their secretome and thereby affect their immunomodulatory potential. UCMSCs are commonly cultured at 21% O2 in vitro, but recent research is exploring their growth at lower oxygen conditions to emulate circulating oxygen levels in vivo. Additionally, a pro-inflammatory culture environment is known to enhance UCMSC anti-inflammatory potential. Therefore, this paper examined EVs from UCMSCs grown in normal oxygen (21% O2), low oxygen (5% O2) and pro-inflammatory conditions to see the impact of culture conditions on the EV profile. EVs were isolated from UCMSC conditioned media and characterised based on size, morphology and surface marker expression. EV protein cargo was analysed using a proximity-based extension assay. Results showed that EVs had a similar size and morphology. Differences were found in EV protein cargo, with pro-inflammatory primed EVs showing an increase in proteins associated with chemotaxis and angiogenesis. This showed that the UCMSC culture environment could alter the EV protein profile and might have downstream implications for their functions in immunomodulation.

Indigenous marine governance is increasingly recognized as having a crucial role in marine management and conservation, yet most examples are from the tropical Pacific and Oceania. We showcase strong and ongoing marine governance by the Kitasoo/Xai'xais people of British Columbia, Canada. In partnership with the Kitasoo/Xai'xais Stewardship Authority, we synthesized information about marine governance by the Kitasoo/Xai'xais people as collated in their Heritage Database, a compilation of interviews and recordings with knowledge holders, traditional stories, and historical documents, e.g., journals of explorers and anthropologists. We found that Kitasoo/Xai'xais marine governance underpinned sustainable resource use and has remained strong despite colonial efforts to undermine it. Kitasoo/Xai'xais marine governance flows from the underlying principles of their indigenous law that guide all actions in the traditional territory. The social institutions of the Kitasoo/Xai'xais people are the mechanism for implementing marine governance: Importantly, hereditary chiefs hold key responsibilities regarding management of the oceans, embedded in ownership of specific places, passed on through names and stories. Kitasoo/Xai'xais protocols exist for respecting their territories, those of other nations, and the plants and animals being harvested. There are natural and spiritual consequences for not accessing and sharing marine resources in a way that follows Kitasoo/Xai'xais underlying principles, including loss of access. Contemporary examples of marine governance include the work of Kitasoo/Xai'xais Stewardship Authority, the Food Fish Committee guided by hereditary chiefs and elders, and everyone's actions to defend their territory from external threats. Given global efforts to recognize indigenous rights, an opportunity exists to change ocean management to fully recognize indigenous marine governance and leadership.

BackgroundInternet-accessed sexually transmitted infection testing (e-STI testing) is increasingly available as an alternative to testing in clinics. Typically this testing modality enables users to order a test kit from a virtual service (via a website or app), collect their own samples, return test samples to a laboratory, and be notified of their results by short message service (SMS) or telephone. e-STI testing is assumed to increase access to testing in comparison with face-to-face services, but the evidence is unclear. We conducted a randomised controlled trial to assess the effectiveness of an e-STI testing and results service (chlamydia, gonorrhoea, HIV, and syphilis) on STI testing uptake and STI cases diagnosed.Methods and findingsThe study took place in the London boroughs of Lambeth and Southwark. Between 24 November 2014 and 31 August 2015, we recruited 2,072 participants, aged 16-30 years, who were resident in these boroughs, had at least 1 sexual partner in the last 12 months, stated willingness to take an STI test, and had access to the internet. Those unable to provide consent and unable to read English were excluded. Participants were randomly allocated to receive 1 text message with the web link of an e-STI testing and results service (intervention group) or to receive 1 text message with the web link of a bespoke website listing the locations, contact details, and websites of 7 local sexual health clinics (control group). Participants were free to use any other services or interventions during the study period. The primary outcomes were self-reported STI testing at 6 weeks, verified by patient record checks, and self-reported STI diagnosis at 6 weeks, verified by patient record checks. Secondary outcomes were the proportion of participants prescribed treatment for an STI, time from randomisation to completion of an STI test, and time from randomisation to treatment of an STI. Participants were sent a £10 cash incentive on submission of self-reported data. We completed all follow-up, including patient record checks, by 17 June 2016. Uptake of STI testing was increased in the intervention group at 6 weeks (50.0% versus 26.6%, relative risk [RR] 1.87, 95% CI 1.63 to 2.15, P < 0.001). The proportion of participants diagnosed was 2.8% in the intervention group versus 1.4% in the control group (RR 2.10, 95% CI 0.94 to 4.70, P = 0.079). No evidence of heterogeneity was observed for any of the pre-specified subgroup analyses. The proportion of participants treated was 1.1% in the intervention group versus 0.7% in the control group (RR 1.72, 95% CI 0.71 to 4.16, P = 0.231). Time to test, was shorter in the intervention group compared to the control group (28.8 days versus 36.5 days, P < 0.001, test for difference in restricted mean survival time [RMST]), but no differences were observed for time to treatment (83.2 days versus 83.5 days, P = 0.51, test for difference in RMST). We were unable to recruit the planned 3,000 participants and therefore lacked power for the analyses of STI diagnoses and STI cases treated.ConclusionsThe e-STI testing service increased uptake of STI testing for all groups including high-risk groups. The intervention required people to attend clinic for treatment and did not reduce time to treatment. Service innovations to improve treatment rates for those diagnosed online are required and could include e-treatment and postal treatment services. e-STI testing services require long-term monitoring and evaluation.Trial registrationISRCTN Registry ISRCTN13354298.

International standards refer to Indigenous peoples’ right to benefit from resource development, participate in decision-making and determine priorities in development planning that directly affects them. While good practice exists in benefit sharing, Indigenous peoples still lack opportunities for a meaningful role in strategic planning. In his role as UN Special Rapporteur on the Rights of Indigenous Peoples, James Anaya identified a ‘preferred model’ of resource development in which Indigenous peoples have greater control over planning decisions and project implementation, and consequently a more meaningful share of the benefits of resource development. This paper explores the requirements of international standards and guidance alongside different models of benefit sharing in practice by extractive industries in Arctic and sub-Arctic contexts. It is based primarily on desk-based analysis of international hard and soft law and industry standards, while also drawing on ethnographic field research in Russia and Norway. It highlights good practice within mainstream development scenarios and identifies models of benefit sharing that represent a greater degree of Indigenous participation and control. It concludes that there is a need to consider benefit sharing within an overall paradigm that allows greater space for Indigenous voices in decision making, including at the strategic planning stage.

Mutations in PINK1, a mitochondrially targeted serine/threonine kinase, cause autosomal recessive Parkinson's disease (PD). Substantial evidence indicates that PINK1 acts with another PD gene, parkin, to regulate mitochondrial morphology and mitophagy. However, loss of PINK1 also causes complex I (CI) deficiency, and has recently been suggested to regulate CI through phosphorylation of NDUFA10/ND42 subunit. To further explore the mechanisms by which PINK1 and Parkin influence mitochondrial integrity, we conducted a screen in Drosophila cells for genes that either phenocopy or suppress mitochondrial hyperfusion caused by pink1 RNAi. Among the genes recovered from this screen was ND42. In Drosophila pink1 mutants, transgenic overexpression of ND42 or its co-chaperone sicily was sufficient to restore CI activity and partially rescue several phenotypes including flight and climbing deficits and mitochondrial disruption in flight muscles. Here, the restoration of CI activity and partial rescue of locomotion does not appear to have a specific requirement for phosphorylation of ND42 at Ser-250. In contrast to pink1 mutants, overexpression of ND42 or sicily failed to rescue any Drosophila parkin mutant phenotypes. We also find that knockdown of the human homologue, NDUFA10, only minimally affecting CCCP-induced mitophagy, and overexpression of NDUFA10 fails to restore Parkin mitochondrial-translocation upon PINK1 loss. These results indicate that the in vivo rescue is due to restoring CI activity rather than promoting mitophagy. Our findings support the emerging view that PINK1 plays a role in regulating CI activity separate from its role with Parkin in mitophagy.

Chitinases are chitin-degrading enzymes. Chitinases play essential roles in combating chitin-containing pathogens as well as established roles in asthmatic inflammation. This assay is designed to detect chitinase activity in macrophage cell lysates. The chitin substrate is labeled with 4-methylumbelliferone. Hydrolysis of chitin releases 4-methylumbelliferone, and is measured fluorometrically to determine chitinase activity.