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Abstract The neuronal ceroid lipofuscinoses (NCLs) are a group of fatal, monogenic neurodegenerative disorders with an early onset in infancy or childhood. Despite identification of the genes disrupted in each form of the disease, their normal cellular role and how their deficits lead to disease pathology is not fully understood. Cln7, a major facilitator superfamily domain-containing protein, is affected in a late infantile-onset form of NCL. Cln7 is conserved across species suggesting a common function. Here we demonstrate that Cln7 is required for the normal growth of synapses at the Drosophila larval neuromuscular junction. In a Cln7 mutant, synapses fail to develop fully leading to reduced function and behavioral changes with dysregulation of TOR activity. Cln7 expression is restricted to the post-synaptic cell and the protein localizes to vesicles immediately adjacent to the post-synaptic membrane. Our data suggest an involvement for Cln7 in regulating trans-synaptic communication necessary for normal synapse development.

Objectives The psychological impact of the COVID-19 pandemic on doctors is a significant concern. Due to the emergence of multiple pandemic waves, longitudinal data on the impact of COVID-19 are vital to ensure an adequate psychological care response. The primary aim was to assess the prevalence and degree of psychological distress and trauma in frontline doctors during the acceleration, peak and deceleration of the COVID-19 first wave. Personal and professional factors associated with psychological distress are also reported.Design A prospective online three-part longitudinal survey.Setting Acute hospitals in the UK and Ireland.Participants Frontline doctors working in emergency medicine, anaesthetics and intensive care medicine during the first wave of the COVID-19 pandemic in March 2020.Primary outcome measures Psychological distress and trauma measured using the General Health Questionnaire-12 and the Impact of Events-Revised.Results The initial acceleration survey distributed across networks generated a sample of 5440 doctors. Peak and deceleration response rates from the original sample were 71.6% (n=3896) and 56.6% (n=3079), respectively. Prevalence of psychological distress was 44.7% (n=1334) during the acceleration, 36.9% (n=1098) at peak and 31.5% (n=918) at the deceleration phase. The prevalence of trauma was 23.7% (n=647) at peak and 17.7% (n=484) at deceleration. The prevalence of probable post-traumatic stress disorder was 12.6% (n=343) at peak and 10.1% (n=276) at deceleration. Worry of family infection due to clinical work was the factor most strongly associated with both distress (R2=0.06) and trauma (R2=0.10).Conclusion Findings reflect a pattern of elevated distress at acceleration and peak, with some natural recovery. It is essential that policymakers seek to prevent future adverse effects through (a) provision of vital equipment to mitigate physical and psychological harm, (b) increased awareness and recognition of signs of psychological distress and (c) the development of clear pathways to effective psychological care.Trial registration number ISRCTN10666798.

Abstract Introduction Barriers to recruitment for dementia studies are well documented. As part of the UK government's Dementia 2020 strategy, a nationally consistent system to increase public engagement and participation in research was launched in February 2015. Methods We describe the development of the “Join Dementia Research” registry, including evolution of policy, involvement of people with dementia in co‐production, data requirements, governance, technology, and the impact on study recruitment and what factors may have contributed to the services success. Results The UK‐wide online, telephone, and postal service has registered 47,071 volunteers, with 33,139 people (67.9% of all volunteers) taking part in 378 studies, with 49,954 total study enrolments. This has taken place across 295 research sites, involved 1522 researchers, and resulted in 134 peer‐reviewed publications. Discussion Public registries of individuals interested in research, with user‐provided data enabling basic phenotyping, are effective at increasing public engagement with research and removing barriers to study recruitment. Deeper pheno/genotyping could be undertaken to improve matching, but how and when that information is collected will be a key factor.

Objectives To determine the need for recovery (NFR) among emergency physicians and to identify demographic and occupational characteristics associated with higher NFR scores.Design Cross-sectional electronic survey.Setting Emergency departments (EDs) (n=112) in the UK and Ireland.Participants Emergency physicians, defined as any registered physician working principally within the ED, responding between June and July 2019.Main outcome measure NFR Scale, an 11-item self-administered questionnaire that assesses how work demands affect intershift recovery.Results The median NFR Score for all 4247 eligible, consented participants with a valid NFR Score was 70.0 (95% CI: 65.5 to 74.5), with an IQR of 45.5–90.0. A linear regression model indicated statistically significant associations between gender, health conditions, type of ED, clinical grade, access to annual and study leave, and time spent working out-of-hours. Groups including male physicians, consultants, general practitioners (GPs) within the ED, those working in paediatric EDs and those with no long-term health condition or disability had a lower NFR Score. After adjusting for these characteristics, the NFR Score increased by 3.7 (95% CI: 0.3 to 7.1) and 6.43 (95% CI: 2.0 to 10.8) for those with difficulty accessing annual and study leave, respectively. Increased percentage of out-of-hours work increased NFR Score almost linearly: 26%–50% out-of-hours work=5.7 (95% CI: 3.1 to 8.4); 51%–75% out-of-hours work=10.3 (95% CI: 7.6 to 13.0); 76%–100% out-of-hours work=14.5 (95% CI: 11.0 to 17.9).Conclusion Higher NFR scores were observed among emergency physicians than reported in any other profession or population to date. While out-of-hours working is unavoidable, the linear relationship observed suggests that any reduction may result in NFR improvement. Evidence-based strategies to improve well-being such as proportional out-of-hours working and improved access to annual and study leave should be carefully considered and implemented where feasible.

The neuronal ceroid lipofuscinoses are a group of recessively inherited, childhood-onset neurodegenerative conditions. Several forms are caused by mutations in genes encoding putative lysosomal membrane proteins. Studies of the cell biology underpinning these disorders are hampered by the poor antigenicity of the membrane proteins, which makes visualization of the endogenous proteins difficult. We have used Drosophila to generate knock-in YFP-fusions for two of the NCL membrane proteins: CLN7 and CLN3. The YFP-fusions are expressed at endogenous levels and the proteins can be visualized live without the need for overexpression. Unexpectedly, both CLN7 and CLN3 have restricted expression in the CNS of Drosophila larva and are predominantly expressed in the glia that form the insect blood-brain-barrier. CLN7 is also expressed in neurons in the developing visual system. Analogous with murine CLN3, Drosophila CLN3 is strongly expressed in the excretory and osmoregulatory Malpighian tubules, but the knock-in also reveals unexpected localization of the protein to the apical domain adjacent to the lumen. In addition, some CLN3 protein in the tubules is localized within mitochondria. Our in vivo imaging of CLN7 and CLN3 suggests new possibilities for function and promotes new ideas about the cell biology of the NCLs.

Objective: Bariatric anatomy and physiology present added clinical challenges to the provision of safe critical care and patient transport. LifeFlight Retrieval Medicine provides air medical retrieval services in Queensland, Australia, and performs over 6,000 retrieval missions annually using rotary wing, fixed wing, and ground ambulance platforms., Methods: Bariatric patient retrievals were identified from the LifeFlight Retrieval Medicine electronic patient database. These cases were interrogated to quantify and describe adverse events during patient transport., Results: Over the study period from July 2019 to December 2021 11,096 patient retrievals were completed. Of these patients, 816 (7.3%) had a body weight ≥ 120 kg (range, 120-246 kg; median = 146 kg). Bariatric patients were more likely to be male (70%) and to require critical care interventions than nonbariatric patients (25.9% vs. 19.9%). There was an absolute 1.5% increase of high-interest events during patient retrieval, corresponding to a 1.9-fold increased relative risk. Five hundred eleven of 11,096 patients were intubated by the retrieval team, and 61 of these weighed ≥ 120 kg. Bariatric patients undergoing intubation were of similar age and sex, weighed significantly more, had nonsignificant trends toward poorer airway visualization by Cormack-Lehane laryngoscopic grade, and tended toward reduced first-attempt success compared with nonbariatric patients. Rates of airway adverse events (AAEs) were significantly increased for the bariatric group (30/61, 49.2%) compared with the nonbariatric group (135/450, 30.0%) (χ 2 likelihood ratio, P = .004). Postintubation desaturation was the most common AAE and was the only criterion significantly increased when comparing bariatric (26%) versus nonbariatric (12%) patients (χ 2 likelihood ratio, P = .005). Using patient weight as a continuous variable, nominal logistic regression revealed a significant effect of increasing weight on AAEs (χ 2 = 12.9, P = .0003) with a threshold of 105 kg providing an optimal 88% sensitivity for predicting AAEs. The odds of AAEs were increased significantly for those weighing 105 to 119 kg versus those weighing < 105 kg (odds ratio [OR] = 3.4; 95% confidence interval [CI], 1.6-7.5) and for those weighing ≥ 120 kg versus those weighing < 105 kg (OR = 2.5; 95% CI, 1.4-4.3). There was no difference between those weighing ≥ 120 kg versus those weighing 105 to 119 kg (OR = 0.73; 95% CI, 0.3-1.8)., Conclusion: Air medical retrieval of bariatric patients is safe despite an increased risk of adverse events. Strategies to optimize emergency anesthesia should be used to maximize safe intubation in bariatric patients., Competing Interests: Declaration of Competing Interest The authors have no relevant disclosures. There was no grant funding or financial support for this manuscript., (Copyright © 2024 Air Medical Journal Associates. Published by Elsevier Inc. All rights reserved.)

Climate change is the number one threat to child health according to the World Health Organisation. It increases existing inequalities, and lower-income countries are disproportionately affected. This is unjust. Higher-income countries have contributed and continue to contribute more to climate change than lower-income countries. This has been recognised by the United Nations Committee on the Rights of the Child, which has ruled that states can be held responsible if their carbon emissions harm child rights both within and outside their jurisdiction. Nevertheless, there are few analyses of the bilateral relationship between higher- and lower-income countries concerning climate change. This article uses the UK and Malawi as a case study to illustrate higher-income countries' impact on child health in lower-income countries. It aims to assist higher-income countries in developing more targeted policies. Children in Malawi can expect more food insecurity and reduced access to clean water, sanitation, and education. They will be more exposed to heat stress, droughts, floods, air pollution and life-threatening diseases, such as malaria. In 2019, 5,000 Malawian children died from air pollution (17% of under-five deaths). The UK needs to pay its 'fair share' of climate finance and ensure adaptation is prioritised for lower-income countries. It can advocate for more equitable and transparent allocation of climate finance to support the most vulnerable countries. Additionally, the UK can act domestically to curtail revenue losses in Malawi and other lower-income countries, which would free up resources for adaptation. In terms of mitigation, the UK must increase its nationally determined commitments by 58% to reach net zero and include overseas emissions. Land use, heating systems and renewable energy must be reviewed. It must mandate comprehensive scope three emission reporting for companies to include impacts along their value chain, and support businesses, multinational corporations, and banks to reach net zero., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hannah et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Nearly all countries have ratified the United Nations Convention on the Rights of the Child and, therefore, support children having access to their rights. However, only a small minority of children worldwide have access to their environmental, economic, and social rights. The most recent global effort to address these deficits came in 2015, when the United Nations General Assembly agreed to a plan for a fairer and more sustainable future by 2030 and outlined the Sustainable Development Goals (SDGs). One remediable cause is the lack of revenue in many countries, which affects all SDGs. However, illicit financial flows from low-income to high-income countries, including international tax abuse, continue unabated., Methods: Using the most recent estimates of tax abuse perpetuated by multinational companies and tax evasion through offshore wealth, and precise econometric modelling, we illustrate the potential regarding child rights (or progress towards the SDGs) if there was an increase in revenue equivalent to tax abuse in Malawi, a low-income country particularly vulnerable to climate change. The Government Revenue and Development Estimations model provides realistic estimates of government revenue changes in developmental outcomes. Using panel data on government revenue per capita, it models the impact of increased revenue on governance and SDG progress., Results: If cross-border tax abuse and tax evasion were curtailed, the equivalent increase in government revenue in one country, Malawi, would be associated with 12,000 and 20,000 people having access to basic water and sanitation respectively each year. Each year, an additional 5000 children would attend school, 150 additional children would survive, and 10 mothers would survive childbirth., Conclusions: More children would access their economic and social rights if actions were taken to close the gap in global governance regarding taxation. We discuss the responsibility of duty bearers, the need for a global body to arbitrate and monitor international tax matters, and how the Government of Malawi could take further domestic action to mitigate the gaps in global governance and protect itself against illicit financial flows, including tax abuse., (© 2023. The Author(s).)

Introduction: Adherence to Antiretroviral Treatment (ART) in children and adolescents living with HIV in low-resource settings is not extensively studied in large cohort studies including both adults and pediatric patients. We compared rates of virological suppression, adherence and defaulting among children, adolescents and adults attending a family ART clinic at Queen Elizabeth Central Hospital; a tertiary hospital situated in the southern region of Malawi., Methods: The study was longitudinal and made use of routinely collected data for all 27,229 clinic attendees. Clinical information obtained at routine clinical visits entered electronically since 2008 was extracted in February 2017. This data was used to ascertain differences across the different age groups. Logistic regression and Cox regression models were fitted to compare rates of Virological Suppression (VS), adherence, and defaulting, respectively., Results: Younger and older adolescents (ages 10-14 years and 15-19 years respectively) were less likely to achieve VS compared to adults in the final model AOR 0.4 (0.2-0.9, 95% CI) and AOR 0.2 (0.1-0.4, 95% CI) respectively. Young children (ages 0-4 years), older children (ages 5-9 years) and younger adolescents were less adherent to ART compared to adults AOR 0.1 (0.1-0.2, 95% CI), AOR 0.2 (0.1-0.3, 95% CI), and AOR 0.4 (0.3-0.5, 95% CI) respectively. Young adults and younger children had an increased likelihood of defaulting compared to adults., Conclusion: Poor performance on ART of children and adolescents highlights unaddressed challenges to adherence. Ongoing research to explore these potential barriers and possible interventions needs to be carried out. The adherence assessment methods used and strategies for improving it among children and adolescents need to be revised at the clinic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chakakala-Chaziya, Patson, Samuel, Mbotwa, Buonsenso, Chisale, Phiri and O’Hare.)

Background: The COVID-19 pandemic and the climate emergency threaten progress in reaching many of the Sustainable Development Goal (SDG) targets by 2030. The under-5 mortality and maternal mortality rates are well below the targets, and if we progress at the current pace, there is a high risk of not meeting the 2030 goals. Furthermore, the initial progress in the decline in child and maternal mortality since 1990 is likely to be eroded. Much of this progress has resulted from increased sanitation, drinking water, education, and health service coverage. The adequate provision of public services is possible if there is sufficient government funding. When governments have more income, they spend more on public services, which increases access to fundamental economic and social rights and, thus, contributes to the SDGs. One of the key drivers of government financing, taxation, constitutes 70% of government revenue in low- and lower-middle-income countries. Corporate income tax constitutes 18.8% of tax revenue in African countries compared to 10% of tax revenue in OECD countries. Therefore, it plays a critical role in SDG progress. This paper aims to quantify the contribution of one large taxpayer, that publishes their tax payments, (Vodafone Group Plc) on progress towards SDGs in six African countries. We use econometric modelling to estimate the impact of an increase in government revenue equivalent to Vodafone's average tax paid between 2007-2017., Results: We find that government revenue equivalent to Vodafone's taxes made a significant contribution to progress in attaining selected SDGs. We found that the revenue equivalent to Vodafone's taxes allowed 966,188 people to access clean water and 1,371,972 people to access basic sanitation each year. Over the time period studied, 858,054 children spent an extra year in school and 54,275 children under five years and 3,655 mothers survived. In just one of these countries, Tanzania, the revenue equivalent to Vodafone's tax contribution allowed 174,121 people to access clean water and 223,586 to access sanitation each year. Over the time studied 187,023 children spent an additional year at school, 6,569 additional children under five and 625 additional mothers survived., Conclusions: These findings demonstrate that the reported contributions from a single multinational corporation drive SDG progress. Furthermore, it highlights the importance of transparent taxes and explores the responsibilities of global institutions, governments, investors, and multinational corporations., (© 2023. The Author(s).)

Competing Interests: Competing interests: None declared.