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Abstract Background Cancer navigation programs aim to support, educate, and empower patients and families, addressing barriers to diagnostics, treatment, and care. Navigators engage with people to ensure timely access to services and resources. While promising for older people with cancer, these programs are scarce in Europe, and research on their effectiveness and implementation is limited. We describe the protocol of the EU NAVIGATE randomized controlled trial, aimed to evaluate (1) effectiveness and cost-effectiveness of NavCare-EU, an intervention that aims to support older people with cancer throughout their illness trajectory, spanning the continuum of supportive, palliative, and end-of-life care, and (2) the intervention’s implementation processes and feasibility of its integration into different health care systems in Europe, contextual barriers and facilitators for effective and sustainable implementation, and mechanisms involved in reaching the outcomes. Methods We will conduct a multisite pragmatic fast-track randomized controlled trial with embedded convergent mixed-method process evaluation in Belgium, Ireland, Italy, Netherlands, Poland, and Portugal. The study targets people with cancer and declining health, 70 years or older, and their close family caregivers. The trial compares the NavCare-EU intervention plus standard care with standard care alone. We will perform a baseline measurement prior to randomization and follow-up measurements at 12 weeks, 24 weeks, and 48 weeks in intervention and control group, and an additional measurement at 72 weeks in the control group. Primary outcomes, measured at 24 weeks are (1) the older person’s global health status/quality of life, a 2-item subscale from EORTC-QLQ-C30 (revised) measuring health-related quality of life, (2) level of social support measured with Medical Outcomes Study Social Support Survey (MOS-SSS scale). The study will include at least 246 older persons with completed global health status/quality of life at 24 weeks. Discussion The EU NAVIGATE trial will cross-nationally test the effectiveness and cost-effectiveness of a navigation intervention for older people with cancer and their family caregivers, and its implementation in different health care systems in Europe. As continuity and access to health, social, and community care is a priority for patients and caregivers, the trial is timely and critically needed. Trial registration Clinicaltrials.gov: identifier NCT06110312 (2023/10/31).

Abstract Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant‐producing cells and lower surfactant‐protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12 mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term = 150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45 min before tissue collection. Lung function and structure were similar in control lambs (n = 16, 11 ewes) and lambs from asthma ewes (n = 14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n = 12, 8 ewes) compared to those from controls (P = 0.003) or asthma ewes (P = 0.008). Lung expression of surfactant protein genes SFTPA (P = 0.048) and SFTPB (P

Abstract Background Efficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines. Methods We applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool’s assessment to that of the genetic counselor who saw the patient. Patients’ histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool’s assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used. Results Of the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor’s assessment relied on details the tool was not programmed to collect since patients typically don’t have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient’s history met criteria for genetic testing. Conclusion We observed a high level of agreement with genetic counselor assessments, affirming the tool’s clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment.

Abstract Meditation, yoga, guided imagery, and progressive relaxation are promoted as complementary approaches for health and wellbeing in the United States, but their uptake by different sociodemographic groups is unclear. This study assessed the prevalence and 20 year trends in the use of these practices in US adults between 2002–2022. We examined practice use and associations with sociodemographic and health factors in a population-weighted analysis of n = 134,959 participants across 5 cycles of the National Health Interview Survey. The overall use of meditation (18.3%, 60.53 million), yoga (16.8%, 55.78 million) and guided imagery/progressive relaxation (6.7%, 22.22 million) increased significantly from 2002 to 2022. Growth was consistent across most sociodemographic and health strata, however users of ‘Other’ race (comprising 54% Indigenous Americans, Odds Ratios; ORs = 1.28–1.70) and users with moderate (ORs = 1.19–1.29) psychological distress were overrepresented across all practices, and those with severe psychological distress were overrepresented in meditation (OR = 1.33) and guided imagery/progressive relaxation (OR = 1.42). Meditation use has accelerated over time for 65 + year olds (OR = 4.22), people not accessing mental health care (OR = 1.39), and less educated (OR = 4.02) groups, potentially reflecting unmet health needs. Health professionals should consider the extensive use of complementary practices in service and treatment planning and consider their risks and benefits.

Abstract The physical river characteristics datasets described here provide spatially consistent information to support hydrological and inundation modelling at a 1 km × 1 km resolution across the United Kingdom, on the British National Grid. The datasets of physical river characteristics provide gridded datasets (outflow drainage directions, catchment areas, widths of bankfull rivers and depths of bankfull rivers) and a comma‐separated table of NRFA (National River Flow Archive) gauging station locations. These datasets are derived from a range of sources: outflow drainage directions, catchment area and bankfull river widths are derived from existing higher resolution datasets, whereas bankfull river depths were harder to source and instead are derived from sparse historical measurements. The new gridded datasets provide a derived value for each UK land cell on the British National Grid (BNG). The comma‐separated NRFA gauging station locations table provides the most appropriate locations of 1,499 river flow gauging stations on the 1 km resolution grids, together with the approximate error in the 1 km × 1 km gridded delineation of the upstream catchment area. This article explains how UK‐wide 1‐km grids of these variables were estimated, their format and how to use them. The data are available from the Environmental Information Data Centre (EIDC).

Background: Navigation interventions could support, educate and empower older people with cancer and/or their family caregivers by addressing barriers and ensuring timely access to needed services and resources throughout the continuum of supportive, palliative and end-of-life care. Objectives: European Union (EU) NAVIGATE is an interdisciplinary and cross-country Horizon Europe-funded project (2022–2027) aiming to evaluate the effectiveness, cost-effectiveness and implementation of a navigation intervention for older people with cancer and their family caregivers in Europe. EU NAVIGATE aims to advance the evidence on cancer patient navigation in Europe. Design: Adaptation, implementation and evaluation of a navigation intervention with an international pragmatic randomized controlled trial (RCT) and embedded mixed-method process evaluation at its core. A logic model guides dissemination and impact-generating strategies. EU NAVIGATE involves six experienced EU academic partners; one EU national cancer league with their affiliated academic partner; three EU dissemination partners; and a Canadian partner. Methods: We adapted the Canadian Navigation: Connecting, Advocating, Resourcing, and Engaging (Nav-CARE © ) volunteer programme to healthcare contexts in Belgium, Ireland, Italy, the Netherlands, Poland and Portugal following the new ADAPT guidance. Nav-CARE was developed over the past 15 years and supports people with declining health and their families to improve their quality of life and well-being, foster empowerment and facilitate timely and equitable access to healthcare and social services. In EU NAVIGATE, the navigation intervention is being provided by trained and mentored social workers in Poland and by trained and mentored volunteers in the other five countries. Via a pragmatic RCT with process evaluation, we implement and evaluate the navigation intervention to study its impact on older people with cancer and their family caregivers. We also aim to understand its cost-effectiveness, how to optimally implement it in different countries, and its differential effects in patient subgroups. We will also map existing cancer navigation interventions in Europe, the United States and Canada to position EU NAVIGATE within the field of navigation interventions worldwide. Conclusion: EU NAVIGATE aims to deliver high-quality evidence on a navigation intervention for older people with cancer in Europe and to develop practice and policy recommendations for sustainable implementation of navigation interventions in Europe and beyond.

Appropriate adaptation planning is contingent upon information about the potential future impacts of climate change, and hydrological impact assessments are of particular importance. The UKSCAPE-G2G datasets were produced, as part of the Natural Environment Research Council (NERC) UK-SCAPE (UK Status, Change and Projections of the Environment) programme, to contribute to this information requirement. They use the Grid-to-Grid (G2G) national-scale hydrological model configured for both Great Britain and Northern Ireland (and the parts of the Republic of Ireland that drain to rivers in NI). Six separate datasets are provided, for two sets of driving data – one observation-based (1980–2011) and one climate-projection-based (1980–2080) – for both river flows and soil moisture on 1 km × 1 km grids across Great Britain and Northern Ireland. The river flow datasets include grids of monthly mean flow, annual maxima of daily mean flow, and annual minima of 7 d mean flow (m3 s−1). The soil moisture datasets are grids of monthly mean soil moisture content (m water / m soil), which should be interpreted as depth-integrated values for the whole soil column. The climate-projection-based datasets are produced using data from the 12-member 12 km regional climate model ensemble of the latest UK climate projections (UKCP18), which uses RCP8.5 emissions. The production of the datasets is described, along with details of the file format and how the data should be used. Example maps are provided, as well as simple UK-wide analyses of the various outputs. These suggest potential future decreases in summer flows, annual minimum 7 d flows, and summer/autumn soil moisture, along with possible future increases in winter flows and annual maximum flows. References are given for published papers providing more detailed spatial analyses, and some further potential uses of the data are suggested. The datasets are listed in Table 1.

Data are presented from intercomparisons between two research aircraft, the FAAM BAe-146 and the NASA Lockheed P3, and between the BAe-146 and the surface-based DOE (Department of Energy) ARM (Atmospheric Radiation Measurement) Mobile Facility at Ascension Island (8∘ S, 14.5∘ W; a remote island in the mid-Atlantic). These took place from 17 August to 5 September 2017, during the African biomass burning (BB) season. The primary motivation was to give confidence in the use of data from multiple platforms with which to evaluate numerical climate models. The three platforms were involved in the CLouds–Aerosol–Radiation Interaction and Forcing for Year 2017 (CLARIFY-2017), ObseRvations of Aerosols above CLouds and their intEractionS (ORACLES), and Layered Atlantic Smoke and Interactions with Clouds (LASIC) field experiments. Comparisons from flight segments on 6 d where the BAe-146 flew alongside the ARM facility on Ascension Island are presented, along with comparisons from the wing-tip-to-wing-tip flight of the P3 and BAe-146 on 18 August 2017. The intercomparison flight sampled a relatively clean atmosphere overlying a moderately polluted boundary layer, while the six fly-bys of the ARM site sampled both clean and polluted conditions 2–4 km upwind. We compare and validate characterisations of aerosol physical, chemical and optical properties as well as atmospheric radiation and cloud microphysics between platforms. We assess the performance of measurement instrumentation in the field, under conditions where sampling conditions are not as tightly controlled as in laboratory measurements where calibrations are performed. Solar radiation measurements compared well enough to permit radiative closure studies. Optical absorption coefficient measurements from all three platforms were within uncertainty limits, although absolute magnitudes were too low ( Mm−1) to fully support a comparison of the absorption Ångström exponents. Aerosol optical absorption measurements from airborne platforms were more comparable than aircraft-to-ground observations. Scattering coefficient observations compared adequately between airborne platforms, but agreement with ground-based measurements was worse, potentially caused by small differences in sampling conditions or actual aerosol population differences over land. Chemical composition measurements followed a similar pattern, with better comparisons between the airborne platforms. Thermodynamics, aerosol and cloud microphysical properties generally agreed given uncertainties.

Presbyopia occurs when the physiologically normal age-related reduction in the eyes focusing range reaches a point, when optimally corrected for distance vision, that the clarity of vision at near is insufficient to satisfy an individual’s requirements. Hence, it is more about the impact it has on an individual’s visual ability to function in their environment to maintain their lifestyle than a measured loss of focusing ability. Presbyopia has a significant impact on an individual’s quality of life and emotional state. While a range of amelioration strategies exist, they are often difficult to access in the developing world and prescribing is generally not optimal even in developed countries. This review identified the need for a standardised definition of presbyopia to be adopted. An appropriate battery of tests should be applied in evaluating presbyopic management options and the results of clinical trials should be published (even if unsuccessful) to accelerate the provision of better outcomes for presbyopes.

Abstract Transport of active species (i.e., ions) leaching from pigment particles incorporated in a polymer matrix is the main mechanism behind the anticorrosive performance of protective coatings. Understanding this mechanism is necessary for the effective design of the systems utilizing pigments less toxic than the most efficient chromate salts. It was demonstrated that anticorrosive pigment particles can themselves facilitate the transport of active species via the pathways formed after pigment leaching from a coating. It was also suggested that other paint components, e.g., certain additives, pigments, and fillers can be involved in the formation of transport pathways. Investigation of the possible influence of inert pigment (TiO2) on creating the pathways for chromate ion transport in polymer coatings was the primary objective of this work. In an experiment mimicking the transport of pigment species (i.e., chromate ions), a model epoxy coating containing particles of a single pigment (TiO2) was exposed to a chromate solution (aqueous, or with the addition of acetone as a polymer swelling agent). It was shown that the chromate ions can be transported in the epoxy film preferentially via the TiO2 particles/polymer matrix interface.

The representations of clouds, aerosols, and cloud–aerosol–radiation impacts remain some of the largest uncertainties in climate change, limiting our ability to accurately reconstruct past climate and predict future climate. The south-east Atlantic is a region where high atmospheric aerosol loadings and semi-permanent stratocumulus clouds are co-located, providing an optimum region for studying the full range of aerosol–radiation and aerosol–cloud interactions and their perturbations of the Earth's radiation budget. While satellite measurements have provided some useful insights into aerosol–radiation and aerosol–cloud interactions over the region, these observations do not have the spatial and temporal resolution, nor the required level of precision to allow for a process-level assessment. Detailed measurements from high spatial and temporal resolution airborne atmospheric measurements in the region are very sparse, limiting their use in assessing the performance of aerosol modelling in numerical weather prediction and climate models. CLARIFY-2017 was a major consortium programme consisting of five principal UK universities with project partners from the UK Met Office and European- and USA-based universities and research centres involved in the complementary ORACLES, LASIC, and AEROCLO-sA projects. The aims of CLARIFY-2017 were fourfold: (1) to improve the representation and reduce uncertainty in model estimates of the direct, semi-direct, and indirect radiative effect of absorbing biomass burning aerosols; (2) to improve our knowledge and representation of the processes determining stratocumulus cloud microphysical and radiative properties and their transition to cumulus regimes; (3) to challenge, validate, and improve satellite retrievals of cloud and aerosol properties and their radiative impacts; (4) to improve the impacts of aerosols in weather and climate numerical models. This paper describes the modelling and measurement strategies central to the CLARIFY-2017 deployment of the FAAM BAe146 instrumented aircraft campaign, summarizes the flight objectives and flight patterns, and highlights some key results from our initial analyses.

Skewing of X chromosome inactivation (XCI) occurs when the silencing of one parental X chromosome is non-random. Here, Zito et al. report XCI patterns in lymphoblastoid cell lines, blood, subcutaneous adipose tissue samples and skin samples of monozygotic and dizygotic twins and find XCI skew to associate with tissue and age.

Abstract Objective The addition of residual oils such as palm fibre oil (PFO) and sludge palm oil (SPO) to crude palm oil (CPO) can be problematic within supply chains. PFO is thought to aggravate the accumulation of monochloropropanediols (MCPDs) in CPO, whilst SPO is an acidic by-product of CPO milling and is not fit for human consumption. Traditional targeted techniques to detect such additives are costly, time-consuming and require highly trained operators. Therefore, we seek to assess the use of gas chromatography–ion mobility spectrometry (GC–IMS) for rapid, cost-effective screening of CPO for the presence of characteristic PFO and SPO volatile organic compound (VOC) fingerprints. Results Lab-pressed CPO and commercial dispatch tank (DT) CPO were spiked with PFO and SPO, respectively. Both additives were detectable at concentrations of 1% and 10% (w/w) in spiked lab-pressed CPO, via seven PFO-associated VOCs and 21 SPO-associated VOCs. DT controls could not be distinguished from PFO-spiked DT CPO, suggesting these samples may have already contained low levels of PFO. DT controls were free of SPO. SPO was detected in all SPO-spiked dispatch tank samples by all 21 of the previously distinguished VOCs and had a significant fingerprint consisting of four spectral regions.

Introduction The coronavirus pandemic (COVID-19) has affected the functioning and capacity of healthcare systems worldwide. COVID-19 has also disproportionately affected older adults, including those living with dementia. In the context of COVID-19, decision-making surrounding place of care and place of death in this population involves significant new challenges. Objectives To explore key factors that influence place of care and place of death decisions in older adults. A secondary aim was to investigate key factors that influence the process and outcome of these decisions in older adults. To apply findings from current evidence to the context of COVID-19. Methods Rapid review of reviews, undertaken using WHO guidance for rapid reviews. Ten papers were included for full data extraction. These papers were published between 2005-2020. Data extracted was synthesised using narrative synthesis, with thematic analysis and tabulation. Results Papers included discussed actual place of death, as well as preferred. Results were divided into papers that explored the process of decision-making, and those that explored decision-making outcomes. Factors such as caregiver capacity, the availability of multidisciplinary teams, cultural appropriateness of care packages and advanced care planning were found to be key. Conclusions The process and outcomes of decision-making for older people are affected by many factors – all of which have the potential to influence both patients and caregivers experience of illness and dying. Within the context of COVID-19, such decisions may have to be made rapidly and be reflexive to changing needs of systems and of families and patients.

Introduction COVID-19 as a pandemic has disproportionately affected older adults, including those with dementia. The effects on health and social care systems has necessitated a rapid-response approach to care planning and decision-making in this population, with reflexivity and responsiveness to changing individual and system needs at its core. In light of this, a decision-making tool to help families of persons with dementia was developed using a combination of qualitative data and evidence synthesis. Objectives To develop a decision-aid using a combination of assessment and evidence-gathering methods for families of persons with dementia. Methods Semi-structured interviews with helpline staff from national end-of-life and supportive care organisations formed the basis of the tool design. Co-design with people living with dementia, current and former carers and experts in general practice and social care shaped the next stage. Simultaneously, a rapid review of current evidence on making decisions with older people at the end of life was undertaken. Results Output from interviews covered many topics, including trust, agency and confusion in making decisions in the context of COVID-19. The rapid review of existing evidence highlighted the need to consider both process and outcome elements of decision-making. Conclusions Combining different sources and forms of evidence was efficient and valuable in creating a novel decision-making tool for persons with dementia and their families within the context of COVID-19. The decision-aid covered care planning, caregiver support systems, access to information and contingency considerations. Upon publication, the tool was adopted by NHS England and other leading healthcare organisations. Disclosure No significant relationships.

Increasing sea surface temperature and extreme heat events pose the greatest threat to coral reefs globally, with trends exceeding previous norms. The resultant mass bleaching events, such as those evidenced on the Great Barrier Reef in 2016, 2017, and 2020 have substantial ecological costs in addition to economic and social costs. Advancing remote (nanosatellites, rapid revisit traditional satellites) and in-field (drones) technological capabilities, cloud data processing, and analysis, coupled with existing infrastructure and in-field monitoring programs, have the potential to provide cost-effective and timely information to managers allowing them to better understand changes on reefs and apply effective remediation. Within a risk management framework for monitoring coral bleaching, we present an overview of how remote sensing can be used throughout the whole risk management cycle and highlight the role technological advancement has in earth observations of coral reefs for bleaching events.

There is a growing emphasis on formally recognizing the connection to the marine environment of Indigenous peoples and the traditional ecological knowledge (TEK) these strong connections cultivate. The potential for TEK to significantly enrich the scientific comprehension of the marine environment, whilst also celebrating the rich bio-cultural knowledge in its own right, is indisputable. Here, we present a scientifically robust and culturally appropriate participatory mapping methodology for the marine environment which can effectively achieve genuine cross-cultural ecological knowledge transfer between scientists and Indigenous Peoples. Through a case study working with the Anindilyakwa people of the Groote Eylandt Archipelago, we mapped the TEK of benthic habitats off Australia’s poorly surveyed northern coast. Representatives from 14 Anindilyakwa clan groups participated in the marine mapping (n = 53), resulting in 22 individual maps. Eleven broad-scale habitat classifications, predominately in the intertidal and nearshore marine environment, were described in both Anindilyakwa and English. The information gathered was then used to develop benthic habitat maps covering a combined area of ∼1800 km2 and was assessed for accuracy against in situ observations. We found that despite the difficulties in working across two different world views, through the application of this carefully refined methodology, scientists can effectively document the rich TEK of the marine environment in a manner suitable for conservation and management planning while also supporting the prioritization of Indigenous values within the decision-making process.

Purpose: To investigate non-cycloplegic changes in refractive error prior to the onset of presbyopia. Methods: The Aston Longitudinal Assessment of Presbyopia (ALAP) study is a prospective 2.5 year longitudinal study, measuring objective refractive error using a binocular open-field WAM-5500 autorefractor at 6-month intervals in participants aged between 33 and 45 years. Results: From the 58 participants recruited, 51 participants (88%) completed the final visit. At baseline, 21 participants were myopic (MSE -3.25 ± 2.28 DS; baseline age 38.6 ± 3.1 years) and 30 were emmetropic (MSE −0.17 ± 0.32 DS; baseline age 39.0 ± 2.9 years). After 2.5 years, 10% of the myopic group experienced a hypermetropic shift (≥0.50 D), 5% a myopic shift (≥0.50 D) and 85% had no significant change in refraction (

Skilful winter seasonal predictions for the North Atlantic circulation and northern Europe have now been demonstrated and the potential for seasonal hydrological forecasting in the UK is now being explored. One of the techniques being used combines seasonal rainfall forecasts provided by operational weather forecast systems with hydrological modelling tools to provide estimates of seasonal mean river flows up to a few months ahead. The work presented here shows how spatial information contained in a distributed hydrological model typically requiring high-resolution (daily or better) rainfall data can be used to provide an initial condition for a much simpler forecast model tailored to use low-resolution monthly rainfall forecasts. Rainfall forecasts (hindcasts) from the GloSea5 model (1996 to 2009) are used to provide the first assessment of skill in these national-scale flow forecasts. The skill in the combined modelling system is assessed for different seasons and regions of Britain, and compared to what might be achieved using other approaches such as use of an ensemble of historical rainfall in a hydrological model, or a simple flow persistence forecast. The analysis indicates that only limited forecast skill is achievable for Spring and Summer seasonal hydrological forecasts; however, Autumn and Winter flows can be reasonably well forecast using (ensemble mean) rainfall forecasts based on either GloSea5 forecasts or historical rainfall (the preferred type of forecast depends on the region). Flow forecasts using ensemble mean GloSea5 rainfall perform most consistently well across Britain, and provide the most skilful forecasts overall at the 3-month lead time. Much of the skill (64 %) in the 1-month ahead seasonal flow forecasts can be attributed to the hydrological initial condition (particularly in regions with a significant groundwater contribution to flows), whereas for the 3-month ahead lead time, GloSea5 forecasts account for ∼ 70 % of the forecast skill (mostly in areas of high rainfall to the north and west) and only 30 % of the skill arises from hydrological memory (typically groundwater-dominated areas). Given the high spatial heterogeneity in typical patterns of UK rainfall and evaporation, future development of skilful spatially distributed seasonal forecasts could lead to substantial improvements in seasonal flow forecast capability, potentially benefitting practitioners interested in predicting hydrological extremes, not only in the UK but also across Europe.

Abstract Background DNA methylation is an important epigenetic mechanism involved in gene regulation, with alterations in DNA methylation in the nuclear genome being linked to numerous complex diseases. Mitochondrial DNA methylation is a phenomenon that is receiving ever-increasing interest, particularly in diseases characterized by mitochondrial dysfunction; however, most studies have been limited to the investigation of specific target regions. Analyses spanning the entire mitochondrial genome have been limited, potentially due to the amount of input DNA required. Further, mitochondrial genetic studies have been previously confounded by nuclear-mitochondrial pseudogenes. Methylated DNA Immunoprecipitation Sequencing is a technique widely used to profile DNA methylation across the nuclear genome; however, reads mapped to mitochondrial DNA are often discarded. Here, we have developed an approach to control for nuclear-mitochondrial pseudogenes within Methylated DNA Immunoprecipitation Sequencing data. We highlight the utility of this approach in identifying differences in mitochondrial DNA methylation across regions of the human brain and pre-mortem blood. Results We were able to correlate mitochondrial DNA methylation patterns between the cortex, cerebellum and blood. We identified 74 nominally significant differentially methylated regions (p

Background. Ninety percent of the world’s HIV-positive pregnant women live in 22 countries. These 22 countries, including South Africa (SA) have prioritised the elimination of mother-to-child transmission of HIV (EMTCT). Since 2016 all 22 countries recommend lifelong antiretroviral treatment for all HIV-positive pregnant and lactating women. To measure South African national, provincial and district-level progress towards attaining EMTCT, we analysed the number of in utero (IU) paedatric HIV infections per 100 000 live births (IU case rate), and synthesised factors hindering the monitoring of EMTCT progress and attainment from the viewpoint of provincial and district-level healthcare managers and implementers. We highlight potential innovations to strengthen health systems and improve EMTCT programme delivery. Methods. We reviewed national-, provincial- and district-level birth HIV testing data from routine National Health Laboratory Services (NHLS) records between April 2016 and March 2017. To obtain a qualitative perspective from healthcare managers and implementers, we synthesised information from the nine 2016 provincial-level EMTCT stock-taking workshops. These workshops involve key provincial and district-level staff, mentors and supporting partners. Lastly, we highlight potential innovations presented at these workshops to overcome operational challenges. Results. The national IU mother-to-child transmission (MTCT) rate was 0.9%, which translated to an IU case rate of 245 HIV-positive neonates per 100 000 live births. Provincial IU percent MTCT risk ranged from 0.6% to 1.3%, with IU case rates ranging between 168 and 325 cases per 100 000 live births. District-level IU percent MTCT risk ranged from 0.4% to 1.9%. Potential game changers include: pre-conception counselling to optimise maternal-partner health, weekly dissemination of HIV polymerase chain reaction (PCR) and viral load reports from the NHLS to specific individuals who trace mothers and infants needing care, use of ward-based outreach teams and community caregivers to trace HIV-infected mothers and their infants to link them into care, inclusion of a unique identifier in patient-held infant Road to Health booklets to facilitate infant tracing and continuous quality improvement (CQI) processes within facilities and districts and implementation of an HIV-positive baby tool to understand the characteristics and risks of HIV-positive infants. On an ecological level, provinces and districts using community-based approaches and CQI methodology seemed to have lower MTCT and IU case rates. Conclusions. More quantitative analyses are needed to understand what proportion of the success can be attributed to community-based and CQI approaches and the impact of the potential game changers on progress towards EMTCT.

Lysine acetylation (AcK), a posttranslational modification wherein a two-carbon acetyl group binds covalently to a lysine residue, occurs prominently on mitochondrial proteins and has been linked to metabolic dysfunction. An emergent theory suggests mitochondrial AcK occurs via mass action rather than targeted catalysis. To test this hypothesis, we performed mass spectrometry-based acetylproteomic analyses of quadriceps muscles from mice with skeletal muscle-specific deficiency of carnitine acetyltransferase (CrAT), an enzyme that buffers the mitochondrial acetyl-CoA pool by converting short-chain acyl-CoAs to their membrane permeant acylcarnitine counterparts. CrAT deficiency increased tissue acetyl-CoA levels and susceptibility to diet-induced AcK of broad-ranging mitochondrial proteins, coincident with diminished whole body glucose control. Sub-compartment acetylproteome analyses of muscles from obese mice and humans showed remarkable overrepresentation of mitochondrial matrix proteins. These findings reveal roles for CrAT and L-carnitine in modulating the muscle acetylproteome and provide strong experimental evidence favoring the nonenzymatic carbon pressure model of mitochondrial AcK.