Future Research Investment Research Articles

Knowledge co-production for identifying indicators and prioritising solutions for food and land system sustainability in Australia

Achieving sustainable Australian food and land systems requires the rapid implementation and scaling up of a broad suite of solutions to meet the Sustainable Development Goals (SDGs). Decision-making frameworks are needed to identify suitable indicators and prioritise solutions at national scales to inform sustainability transitions. Using a knowledge co-production framework, we convened 150 stakeholders from 100 + organisations to identify 18 nationally relevant indicators that aligned with critical SDGs describing a sustainable food and land system for Australia, in addition to 78 key solutions (supply- and demand-side) to enable progress against these indicators. We then asked subject matter experts to code the impact of each solution on each indicator using an adapted interaction mapping method accounting for uncertainty. The solution category ‘Protecting and restoring nature’, which included solutions targeting conservation and restoration, showed the highest potential for capturing synergies and avoiding trade-offs across multiple indicators. This category exhibited 34.6% of total major synergies, supporting the achievement of clean water and sanitation (SDG6), economic growth (SDG12), life under water (SDG14), and life on land (SDG15). The solution category ‘Carbon sequestration’, which included technological and biological carbon dioxide removal solutions, had the highest number of trade-offs with individual sustainability indicators (42.3%), particularly those relating to zero hunger (SDG2), wellbeing (SDG3), SDG6, SDG14, and SDG15. Our framework can be used to inform future research investment, support the prioritisation of solutions for quantitative modelling, and inform discussions with stakeholders and policymakers for transforming national-scale food and land systems in alignment with the SDGs.

The impact of a regionally based translational cancer research collaborative in Australia using the FAIT methodology

BackgroundTranslating research, achieving impact, and assessing impact are important aspirations for all research collaboratives but can prove challenging. The Hunter Cancer Research Alliance (HCRA) was funded from 2014 to 2021 to enhance capacity and productivity in cancer research in a regional centre in Australia. This study aimed to assess the impact and benefit of the HCRA to help inform future research investments of this type.MethodThe Framework to Assess the Impact from Translational health research (FAIT) was selected as the preferred methodology. FAIT incorporates three validated methodologies for assessing impact: 1) Modified Payback; 2) Economic Analysis; and 3) Narrative overview and case studies. All three FAIT methods are underpinned by a Program Logic Model. Data were collected from HCRA and the University of Newcastle administrative records, directly from HCRA members, and website searches.ResultsIn addition to advancing knowledge and providing capacity building support to members via grants, fellowships, scholarships, training, events and targeted translation support, key impacts of HCRA-member research teams included: (i) the establishment of a regional biobank that has distributed over 13,600 samples and became largely self-sustaining; (ii) conservatively leveraging $43.8 M (s.a.$20.5 M - $160.5 M) in funding and support from the initial $9.7 M investment; (iii) contributing to clinical practice guidelines and securing a patent for identification of stem cells for endometrial cell regeneration; (iv) shifting the treatment paradigm for all tumour types that rely on nerve cell innervation, (v) development and implementation of the world’s first real-time patient treatment verification system (Watchdog); (vi) inventing the effective ‘EAT’ psychological intervention to improve nutrition and outcomes in people experiencing radiotherapy for head and neck cancer; (vi) developing effective interventions to reduce smoking rates among priority groups, currently being rolled out to disadvantaged populations in NSW; and (vii) establishing a Consumer Advisory Panel and Consumer Engagement Committee to increase consumer involvement in research.ConclusionUsing FAIT methodology, we have demonstrated the significant impact and downstream benefits that can be achieved by the provision of infrastructure-type funding to regional and rural research collaboratives to help address inequities in research activity and health outcomes and demonstrates a positive return on investment.

A Review of Critical Element Concentrations in High Enthalpy Geothermal Fluids in New Zealand

This review compiles publicly available datasets describing the chemical composition of geothermal fluids from eight wells in the Taupo Volcanic Zone (TVZ) and Ngāwhā, New Zealand. Our review allows previously reported geothermal reservoir water compositions at various locations around the TVZ (and Ngāwhā) to be assessed and compared for the first time. The combined data present a new perspective on potential critical elements of geothermal resources and will be a valuable tool for future research projects and investment opportunities. Composition data were used to estimate the annual flux of different elements in New Zealand geothermal systems. Several elements found in New Zealand geothermal fluids are currently considered ‘critical’ for the transition to a carbon-neutral economy and are present in economically extractable quantities. We estimate that each year, approximately 1100 tons of lithium pass as heat exchange fluids through Wairakei geothermal power station. An overview of the critical elemental capture and extractive potential from New Zealand’s geothermal fields is provided.

A Review of CRISPR Tools for Treating Usher Syndrome: Applicability, Safety, Efficiency, and In Vivo Delivery.

This review considers research into the treatment of Usher syndrome, a deaf-blindness syndrome inherited in an autosomal recessive manner. Usher syndrome mutations are markedly heterogeneous, involving many different genes, and research grants are limited due to minimal patient populations. Furthermore, gene augmentation therapies are impossible in all but three Usher syndromes as the cDNA sequence exceeds the 4.7 kb AAV packaging limit. It is, therefore, vital to focus research efforts on alternative tools with the broadest applicability. The CRISPR field took off in recent years following the discovery of the DNA editing activity of Cas9 in 2012. New generations of CRISPR tools have succeeded the original CRISPR/Cas9 model to enable more sophisticated genomic amendments such as epigenetic modification and precise sequence alterations. This review will evaluate the most popular CRISPR tools to date: CRISPR/Cas9, base editing, and prime editing. It will consider these tools in terms of applicability (in relation to the ten most prevalent USH2A mutations), safety, efficiency, and in vivo delivery potential with the intention of guiding future research investment.

Mental health service accessibility, development and research priority setting in Cambodia - a post-conflict nation

BackgroundThe limited health and social care infrastructure that existed in the 1970s in Cambodia was destroyed due to the Khmer Rouge. Mental Health service infrastructures have developed in Cambodia in the last twenty five years, however, they have been shaped significantly by very limited funding being made available for human resources, support services and research. The lack of research on Cambodia’s mental health systems and services is a significant barrier to the development of evidence-based mental health policies and practice. In order to address this barrier, effective research and development strategies are needed in Cambodia, which are based on locally well-informed research priorities. There are many possibilities for mental health research in LMIC countries such as Cambodia, therefore focused research priorities in these areas are needed to guide future research investment. This paper is the result of the development of international collaborative workshops, which focused on service mapping and research priority setting in the field of mental health in Cambodia. MethodsA nominal group technique was used to gather ideas and insights from a range of key mental health service stakeholders in Cambodia. Results: The key issues in service provisions for people with mental health issues and disorders, the interventions and programmes of support available, and currently needed, were identified. This paper also identifies five key mental health research priority areas which could form the basis for effective mental health research and development strategies in Cambodia. ConclusionThere is a clear need for the Cambodian government to devise a clear policy framework for health research. This framework could focus on the five research domains identified in this paper and could be incorporated within its National Health Strategic plans. The implementation of this approach would likely lead to the development of an evidence base which would allow the development of effective and sustainable strategies for mental health problem prevention and intervention. This would also contribute to promote the Cambodian government’s capacity to take the deliberate, concrete, and targeted steps necessary to address the complex mental health needs of its population.

Whether curse or blessing: A counterintuitive perspective on global pest thrips infestation under climatic change with implications to agricultural economics

The improvement and application of pest models to predict yield losses is still a challenge for the scientific community. However, pest models were targeted chiefly towards scheduling scouting or pesticide applications to deal with pest infestation. Thysanoptera (thrips) significantly impact the productivity of many economically important crops worldwide. Until now, no comprehensive study is available on the global distribution of pest thrips, as well as on the extent of cropland vulnerability worldwide. Further, nothing is known about the climate change impacts on these insects. Thus the present study was designed to map the global distribution and quantify the extent of cropland vulnerability in the present and future climate scenarios using data of identified pest thrips within the genus, i.e., Thrips, Frankliniella, and Scirtothrips. Our found significant niche contraction under the climate change scenarios and thrips may reside primarily in their thermal tolerance thresholds. About 3,98,160 km2 of cropland globally was found to be affected in the present scenario. However, it may significantly reduce to 5530 Km2 by 2050 and 1990 km2 by 2070. Further, the thrips distribution mostly getting restricted to Eastern North America, the North-western of the Indian sub-continent, and the north of Europe. Among all realms, thrips may lose ground in the Indo-Malayan realm at the most and get restricted to only 27 out of 825 terrestrial ecoregions. The agrarian communities of the infested regions may get benefit if these pests get wiped out, but on the contrary, we may lose species diversity. Moreover, the vacated niche may attract other invasive species, which may seriously impact the species composition and agricultural productivity. The present study findings can be used in making informed decisions about prioritizing future economic and research investments on the thrips in light of anticipated climate change impacts.

Enhancing the On/Off Current Ratio in Single-Molecule FET via Destructive Quantum Interference

We investigate through atomistic calculation the electronic structure and transport properties of 3-phenylethynylene (OPE3), 7-phenylvynylene (OPV7), and [3, 3]paraCyclophane (pCp)-based molecules. We reveal and analyze the Destructive Quantum Interference (DQI) phenomenon for the pCp single-molecule junction. The provided explanation of DQI via the dominant concurrence of inter-orbital and intra-orbital interference may support DQI engineering through the chemical synthesis of ad hoc molecular channel. Furthermore, we propose a Back gate Biasing-based method for the ON/OFF CUrrent Ratio Enhancement of the single-molecule Field-Effect transistor via the control of DQI (BBB-CURE-DQI). As an important outcome of the proposed method, an ON/OFF current ratio of 103 is achieved for pCp single-molecule FET. This value is orders of magnitude larger than typical values presented in the literature. The benefit of the DQI and the effectiveness of the BBB-CURE-DQI method are finally demonstrated at the circuital level by SPICE simulations of digital inverters implemented with the investigated molecules. Our analysis and results motivate the importance of future research investment for DQI manipulation via chemical synthesis and successive control to enable single-molecule FET-based nanocomputing applications.

An ASBPA White Paper: U.S. community perspectives on coastal flooding

Coastal flooding, from both extreme events and sea level rise, is one of the top management challenges facing U.S. coastal stakeholders today. The intensity of coastal flooding is expected to increase with global sea level rise. This paper focuses on flooding challenges from the perspective of coastal communities. The myriad of flood mitigation strategies that have been implemented across the U.S. vary based on a multitude of factors including spatio-temporal scale of the coastal flooding hazard. ASBPA administered a survey of 106 coastal stakeholders from around the U.S. to assess specific community challenges and needs related to coastal flooding in late 2021. A majority of respondents indicated that their community includes an underserved population or neighborhood (54%) or nearby communities do (25%). While the vast majority of survey respondents indicated that flooding was a major challenge, only 24% of respondents’ communities have a coastal flooding adaptation plan. Improvements to drainage systems are the most commonly implemented gray infrastructure strategy in the Southeast and Gulf coast regions. Respondents from all regions noted that beach and dune restoration has been the most widely implemented nature-based flood mitigation strategy. Interest is now high in other nature-based solutions with application in low-lying, vulnerable coastal areas such as thin-layer placement on marshes, living shorelines, and hybrid projects on estuarine shorelines. This paper does not provide an exhaustive review of the science, forcings, or policies on coastal flooding in the U.S.; rather, it captures the perspectives of coastal communities and aims to inform and prioritize future research investments related to coastal flooding.

Feasibility of a best-worst scaling exercise to set priorities for autism research.

BackgroundThe preferences of autism stakeholders regarding the top priorities for future autism research are largely unknown.ObjectiveThis study had two objectives: First, to examine what autism stakeholders think new research investments should be and the attributes of investment that they consider important, and second, to explore the feasibility, acceptability and outcomes of two prioritization exercises among autism stakeholders regarding their priorities for future research in autism.DesignThis was a prospective stakeholder‐engaged iterative study consisting of best–worst scaling (BWS) and direct prioritization exercise.Setting and ParticipantsA national snowball sample of 219 stakeholders was included: adults with autism, caregivers, service providers and researchers.Main Outcome MeasuresThe main outcomes measures were attributes that participants value in future research investments, and priority research investments for future research.ResultsTwo hundred and nineteen participants completed the exercises, of whom 11% were adults with autism, 58% were parents/family members, 37% were service providers and 21% were researchers. Among stakeholders, the BWS exercises were easier to understand than the direct prioritization, less frequently skipped and yielded more consistent results. The proportion of children with autism affected by the research was the most important attribute for all types of stakeholders. The top three priorities among future research investments were (1) evidence on which child, family and intervention characteristics lead to the best/worst outcomes; (2) evidence on how changes in one area of a child's life are related to changes in other areas; and (3) evidence on dietary interventions. Priorities were similar for all stakeholder types.ConclusionsThe values and priorities examined here provide a road map for investigators and funders to pursue autism research that matters to stakeholders.Patient or Public ContributionStakeholders completed a BWS and direct prioritization exercise to inform us about their priorities for future autism research.

Pre-pregnancy and pregnancy cohorts: a scoping review protocol

Introduction: Recent research in life course epidemiology has demonstrated the importance of evaluating how pre-pregnancy and pregnancy exposures affect later life developmental outcomes. While the fields of nutrition, non-communicable disease, and social epidemiology have examined a diversity of birth- and longer-term outcomes related to different exposures during pregnancy, little information exists on other types of exposures, including infectious, medication, and vaccine-related exposures. In this review, we describe completed or ongoing pregnancy and pre-pregnancy cohorts to assess gaps in the exposures and outcomes measured in these initiatives to inform future research investments. Methods and analysis: We will apply the Arskey and O’Malley scoping review methodology and use the National Institutes of Health quality assessment tool for cohort studies. The systematic search strategy was developed and tailored for Ovid Medline and Embase, LILACs, and Web of Science with the assistance of an information scientist. We selected a scoping review rather than a systematic review methodology because this review is meant to provide a comprehensive overview of pregnancy and pre-pregnancy cohorts, rather than to focus on the findings from related research. The title-abstract and full text screening and data charting will be conducted independently by two reviewers. Discrepancies will be resolved by a third reviewer and results will be summarised in narrative form. Ethics and dissemination: This scoping review summarizes findings from existing publications in peer reviewed journals and does not require ethics review. Findings will be disseminated through an open access publication.

Bronchiectasis-Could Immunonutrition Have a Role to Play in Future Management?

Bronchiectasis is a chronic condition in which areas of the bronchial tubes become permanently widened predisposing the lungs to infection. Bronchiectasis is an age-associated disease with the highest prevalence in people older than 75 years. While the prevalence of bronchiectasis is higher in males, disease is more severe in females who have a poorer prognosis. The overall prevalence of the disease is thought to be rising. Its aetiology is multi-faceted, but a compromised immune system is now thought to play a central role in the pathology of this disease. Research has begun to study the role of malnutrition and certain nutrients—vitamin D and zinc—along with the role of the lung microbiome in relation to the management of bronchiectasis. Given this, the present mini review sets out to provide an overview of the state-of-the-art within the field, identify research gaps and pave the way for future developments and research investment within this field.

Research Questions that Matter to Us: priorities of young people with chronic illnesses and their caregivers.

The rising number of children carrying chronic disease with them into adulthood presents the research community with an obligation to address their unique needs. Authentic involvement of individuals and communities directly affected by the condition being studied ensures that research answers the questions of those most affected. Our aim was to identify the highest priority research questions of young people living with chronic illness and their caregivers. We conducted a qualitative study using the Research Prioritization by Affected Communities (RPAC) method. Participants were recruited from two hospitals and two community organizations to participate in focus groups. Twenty three participants developed and prioritized 300 potentially researchable questions. Thematic analysis of the priority research topics revealed three health dimensions of chronic illness (physical health, social-emotional health and navigating the health care system) and two cross-cutting dimensions (living with a chronic illness and future with a chronic illness). Young people experiencing different chronic conditions were able to achieve consensus on the same set of condition-agnostic research priorities, age and role influenced research priorities. We report these research priorities to inform and influence local and national research agendas and funding priorities. Patients and caregivers affected by different chronic illnesses were able to achieve consensus on condition-agnostic research priorities. Age and role influenced research priorities. Questions posed by young people experiencing different chronic conditions fell under three themes (physical, social-emotional and health care system) and two cross-cutting dimensions (living with a chronic illness and future with a chronic illness). Use of the Research Prioritization byAffected Communities (RPAC) method, which begins with the patient's lived experiences, provided nuanced insights into the complexity of living with a chronic illness and surfaced under-studied research topics to guide future research investment.

Global research priorities for social, behavioural and community engagement interventions for maternal, newborn and child health

BackgroundSocial, behavioural and community engagement (SBCE) interventions are essential for global maternal, newborn and child health (MNCH) strategies. Past efforts to synthesise research on SBCE interventions identified a need for clear priorities to guide future research. WHO led an exercise to identify global research priorities for SBCE interventions to improve MNCH.MethodsWe adapted the Child Health and Nutrition Research Initiative method and combined quantitative and qualitative methods to determine MNCH SBCE intervention research priorities applicable across different contexts. Using online surveys and meetings, researchers and programme experts proposed up to three research priorities and scored the compiled priorities against four criteria – health and social impact, equity, feasibility, and overall importance. Priorities were then ranked by score. A group of 29 experts finalised the top 10 research priorities for each of maternal, newborn or child health and a cross-cutting area.ResultsA total of 310 experts proposed 867 research priorities, which were consolidated into 444 priorities and scored by 280 experts. Top maternal and newborn health priorities focused on research to improve the delivery of SBCE interventions that strengthen self-care/family care practices and care-seeking behaviour. Child health priorities focused on the delivery of SBCE interventions, emphasising determinants of service utilisation and breastfeeding and nutrition practices. Cross-cutting MNCH priorities highlighted the need for better integration of SBCE into facility-based and community-based health services.ConclusionsAchieving global targets for MNCH requires increased investment in SBCE interventions that build capacities of individuals, families and communities as agents of their own health. Findings from this exercise provide guidance to prioritise investments and ensure that they are best directed to achieve global objectives. Stakeholders are encouraged to use these priorities to guide future research investments and to adapt them for country programmes by engaging with national level stakeholders.

Surveillance Strategies for Tracking Sepsis Incidence and Outcomes.

Sepsis is a leading cause of death and the target of intense efforts to improve recognition, management and outcomes. Accurate sepsis surveillance is essential to properly interpreting the impact of quality improvement initiatives, making meaningful comparisons across hospitals and geographic regions, and guiding future research and resource investments. However, it is challenging to reliably track sepsis incidence and outcomes because sepsis is a heterogeneous clinical syndrome without a pathologic reference standard, allowing for subjectivity and broad discretion in assigning diagnoses. Most epidemiologic studies of sepsis to date have used hospital discharge codes and have suggested dramatic increases in sepsis incidence and decreases in mortality rates over time. However, diagnosis and coding practices vary widely between hospitals and are changing over time, complicating the interpretation of absolute rates and trends. Other surveillance approaches include death records, prospective clinical registries, retrospective medical record reviews, and analyses of the usual care arms of randomized controlled trials. Each of these strategies, however, has substantial limitations. Recently, the US Centers for Disease Control and Prevention released an "Adult Sepsis Event" definition that uses objective clinical indicators of infection and organ dysfunction that can be extracted from most hospitals' electronic health record systems. Emerging data suggest that electronic health record-based clinical surveillance, such as surveillance of Adult Sepsis Event, is accurate, can be applied uniformly across diverse hospitals, and generates more credible estimates of sepsis trends than administrative data. In this review, we discuss the advantages and limitations of different sepsis surveillance strategies and consider future directions.

Wheat straw biorefinery for agricultural waste valorisation

This study justifies strategies for a new concept of agricultural waste management prior to biorefinery, based on comprehensive materials science investigations. Efficient pretreatments for the extraction, separation and fractionation of agricultural waste in conjunction with understanding of the details of its microstructure and properties can be essential for high-efficiency biorefinery. The information in this study will serve as a valuable and fundamental basis for researchers and industries in the sector of straw biomass biorefinery. In order to achieve the maximum efficiency possible in agricultural waste valorisation, it is crucial to understand that not all parts of the straw are equally valuable and can be treated in the same biorefinery process. In this study, the wheat straw stem, which is composed of nodes and internodes, has been shown to have distinct properties and characteristics. Separation of these anatomical parts before the biorefinery process presents a unique area for future research investment, as it can lead to higher performance of the intended product. For example, the node has higher extractives and ash content, which prove to be a diminishing factor for biocomposite or bioenergy production.

Eremotherium (Xenarthra, Mammalia) materials from the collections of Laboratório de Paleontologia e Evolução and Laboratório de Geologia of Universidade Federal de Goiás

This study presents the first survey of fossil mammal specimens housed at the collections of the Federal University of Goiás. Here, we describe a set of associated femur and vertebrae fragments, one fragment of tibia, and two left and right maxillary fragments, identified as Eremotherium. Despite its fragmentary condition, the size and morphological aspect of the materials show diagnostic characteristics that suggest their relationship with Eremotherium. These new specimens described here contribute to the paleontology of the Goiás State, which may provide future research investments in collections not yet known, which may increase the knowledge on Pleistocene mammals of Central Brazil.

2019 US Forest Service National Silviculture Workshop: Forest Management and Research Partnerships

The 27th US Forest Service National Silviculture Workshop was held May 21–23, 2019 in Bemidji, MN. The theme of the workshop was Forest Management–Research Partnerships. The workshop series began in 1973 and was held annually until 1979, when it went on a biennial schedule. The main purpose of the workshop has been to provide a forum for US Forest Service managers and scientists to come together to share knowledge, approaches, and insights on practical issues facing the National Forests. The workshop location has been near a National Forest to facilitate a field day to review regional management practices, problems, and research on the National Forests. It has been held in 19 states over the years. Beginning in 2007, a concerted effort has been made to invite silviculture professors from university forestry programs across the nation to join in the workshop, as they also are important partners of Forest Service management and research. The objectives of the workshop were to: • Provide a forum to showcase successful partnerships and shared stewardship between forest managers and researchers. • Enhance forest management and research relationships within the US Forest Service and with external partners to meet shared goals and objectives. • Build on the US Forest Service strategic objectives to improve the condition of forests through innovative silviculture and active forest management. • Identify emerging forest-management needs to guide future research investment.

A study on how startups approach sustainable development through intellectual property

AbstractSustainability is an important concept in various fields, from public policy to detailed principles associated with society, the economy, and the environment. Therefore, revealing the dynamic patterns of the sustainability sector is important for understanding how startups have used the sustainability concept. This study analyzes a sample dataset consisting of patents associated with sustainability and registered by startups. The results are as follows. First, the sustainability sector exhibits diversified patterns, which indicates the growth potential of the sector, measured as the number of International Patent Classification classes, Herfindahl–Hirschman index, and Shannon entropy for the robustness. Second, the corresponding technologies can be classified into three groups: The recent sustainability trend in terms of startups involves consumer‐focused technologies, whereas basis and traditional technologies have diminished in focus. Thus, the environmental government agency should consider this discrepancy when deciding future research and development investments and provide subsidies to startups effectively.

A compendium of ecological knowledge for restoration of freshwater fishes in Australia

Many freshwater fishes are imperilled globally, and there is a need for easily accessible, contemporary ecological knowledge to guide management. This compendium contains knowledge collated from over 600 publications and 27 expert workshops to support the restoration of 9 priority native freshwater fish species, representative of the range of life-history strategies and values in south-eastern Australia’s Murray–Darling Basin. To help prioritise future research investment and restoration actions, ecological knowledge and threats were assessed for each species and life stage. There is considerable new knowledge (80% of publications used were from the past 20 years), but this varied among species and life stages, with most known about adults, then egg, juvenile and larval stages (in that order). The biggest knowledge gaps concerned early life stage requirements, survival, recruitment, growth rates, condition and movements. Key threats include reduced longitudinal and lateral connectivity, altered flows, loss of refugia, reductions in both flowing (lotic) and slackwater riverine habitats, degradation of wetland habitats, alien species interactions and loss of aquatic vegetation. Examples and case studies illustrating the application of this knowledge to underpin effective restoration management are provided. This extensive ecological evidence base for multiple species is presented in a tabular format to assist a range of readers.

Estimates of the global population of children who are HIV-exposed and uninfected, 2000–18: a modelling study

Children who are HIV-exposed uninfected (HEU) have higher morbidity and mortality than children who are HIV-unexposed and uninfected despite safer breastfeeding and improved maternal health with maternal antiretroviral therapy. We present the first global estimates of the population of children who are HEU (aged 0-14 years) and the geographical and temporal trends in HIV high-burden countries between 2000 and 2018. The Spectrum AIDS Impact Module developed by Avenir Health, UNAIDS, and partners is used to estimate key HIV epidemic indicators from mathematical models. We used 2019 UNAIDS global estimates of children (aged 0-14 years) who are HEU generated by Spectrum and 2017 UN Population Division estimates of the number of all children in each region or country to estimate the regional or national prevalence of children who were HEU, the regional or national contribution of children who were HEU to the global population of children who were HEU, and the proportion of children who were HEU and exposed to antiretrovirals for six UNAIDS regions and 21 HIV high-burden countries in 2018. We also estimated the percentage change in the global population of children who were HEU between 2000 and 2018. In 2018, there were an estimated 14·8 million (lower estimate 11·1-upper estimate 18·3) children who were HEU, 13·2 million (9·8-16·3; 90%) of whom resided in sub-Saharan Africa and 760 000 (640 000-970 000; 5%) of whom resided in the Asia and Pacific region. Five countries accounted for 50% of all 14·8 million children who were HEU globally: South Africa (3·5 million [23·8%]), Uganda (1·1 million [7·5%]), Mozambique (1·0 million [6·6%]), Tanzania (910 000 [6·1%]); and Nigeria (880 000 [6·0%]). In five southern African countries, the prevalence of children who were HEU exceeded 15% of the general child population: eSwatini (32·4%), Botswana (27·4%), South Africa (21·6%), Lesotho (21·1%), and Namibia (16·4%). The global population of children who are HEU is substantial, requiring a coordinated strategy to reduce HIV exposure in children and ensure optimal health and wellbeing of children who are HEU and their families. Future research and programmatic funding investments must be aligned with the geographical distribution of children who are HEU. National Institutes of Health, International AIDS Society.