Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

Background: Future trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050. Methods: Using forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline. Findings: In the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]). Interpretation: Globally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions

Data Mining Model for Predicting Student Enrolment in STEM Courses in Higher Education Institutions

Educational data mining is the process of applying data mining tools and techniques to analyze data at educational institutions. In this paper, educational data mining was used to predict enrollment of students in Science, Technology, Engineering and Mathematics (STEM) courses in higher educational institutions. The study examined the extent to which individual, sociodemographic and school-level contextual factors help in pre-identifying successful and unsuccessful students in enrollment in STEM disciplines in Higher Education Institutions in Kenya. The Cross Industry Standard Process for Data Mining framework was applied to a dataset drawn from the first, second and third year undergraduate female students enrolled in STEM disciplines in one University in Kenya to model student enrollment. Feature selection was used to rank the predictor variables by their importance for further analysis. Various predictive algorithms were evaluated in predicting enrollment of students in STEM courses. Empirical results showed the following: (i) the most important factors separating successful from unsuccessful students are: High School final grade, teacher inspiration, career flexibility, pre-university awareness and mathematics grade. (ii) among classification algorithms for prediction, decision tree (CART) was the most successful classifier with an overall percentage of correct classification of 85.2%. This paper showcases the importance of Prediction and Classification based data mining algorithms in the field of education and also presents some promising future lines

A Novel Hybrid Deep Learning Model for Early Detection of Diabetic Retinopathy

Diabetic retinopathy is one of the most frightening complications of diabetes mellitus affecting the working-age population worldwide leading to irreversible blindness if left untreated. A major challenge is early detection, which is very important for treatment success. Presently, detecting diabetic retinopathy is a time-, effort-, and cost-consuming manual process where ophthalmologists identify diabetic retinopathy by the presence of lesions associated with the vascular abnormalities caused by the disease. However, the expertise and equipment needed are often lacking in places where the rate of diabetes in the populace is high and detection is most wanted. As the number of persons diagnosed with diabetes continues to increase, the infrastructure required to prevent diabetes-induced blindness will become even more important. The need for an automated approach to diabetic retinopathy screening has long been recognized, and several recent efforts have made good progress using image classification, pattern recognition, and machine learning. With color fundus photography as input, we proposes a novel approach to detection of diabetic retinopathy based on deep learning techniques ideally resulting in a model with realistic clinical potential. A hybrid configuration of a 2-dimensional Convolutional Neural Network (CNN) and Extreme Learning Machine (ELM) is proposed to leverage feature representation of CNN and fast classification learning of ELM. A publicly available benchmark dataset consisting of 35,126 retina scan images that are resized into 224x224 pixels are used to train, test and evaluate the proposed model. To measure the performance of the proposed model, the accuracy, precision, sensitivity, F1-score, and Cohen’s kappa score were determined. Model results reveal that the CNN-ELM approach achieved an accuracy of 94.72%, 92.71% precision, 0.7834 sensitivity, an F1-score of 0.8492 and an average Kappa-score of 0.6792 for the multi-class classification. These results demonstrate the proposed hybrid model’s ability to detect and classify diabetes retinopathy

Improving Student Enrollment Prediction Using Ensemble Classifiers

In the recent years, data mining has been utilized in education settings for extracting and manipulating data, and for establishing patterns in order to produce useful information for decision making. There is a growing need for higher education institutions to be more informed and knowledgeable about their students, and for them to understand some of the reasons behind students’ choice to enroll and pursue careers. One of the ways in which this can be done is for such institutions to obtain information and knowledge about their students by mining, processing and analyzing the data they accumulate about them. In this paper, we propose a general framework for mining student data enrolled in Science, Technology, Engineering and Mathematics (STEM) using performance weighted ensemble classifiers. We train an ensemble of classification models from enrollment data streams to improve the quality of student data by eliminating noisy instances, and hence improving predictive accuracy. We empirically compare our technique with single model based techniques and show that using ensemble models not only gives better predictive accuracies on student enrollment in STEM, but also provides better rules for understanding the factors that influence student enrollment in STEM disciplines

Empirical Evaluation of Adaptive Optimization on the Generalization Performance of Convolutional Neural Networks

Recently, deep learning based techniques have garnered significant interest and popularity in a variety of fields of research due to their effectiveness in search for an optimal solution given a finite amount of data. However, the optimization of these networks has become more challenging as neural networks become deeper and datasets growing larger. The choice of the algorithm to optimize a neural network is one of the most important steps in model design and training in order to obtain a model that will generalize well on new, previously unseen data. In deep learning, adaptive gradient optimization methods are mostly preferred for supervised and unsupervised tasks. First, they accelerate the training of neural networks and since mini batches are selected randomly and are independent, an unbiased estimate of the expected gradient can be computed. This paper examined six state-of-the-art adaptive gradient optimization algorithms, namely, AdaMax, AdaGrad, AdaDelta, RMSProp, Nadam, and Adam on the generalization performance of convolutional neural networks (CNN) architecture that are extensively used in computer vision tasks. Experiments were conducted giving comparative analysis on the behaviour of these algorithms during model training on three large image datasets, namely, Fashion-MNIST, Kaggle Flowers Recognition and Scene classification. The results show that Adam, Adadelta and Nadam finds the global minimum faster in the experiments, have a better convergence curve, and higher test set accuracy in experiments using the three datasets. These optimization approaches adaptively tune the learning rate based only on the recent gradients; thus, controlling the reliance of the update on the past few gradients

Network Intrusion Detection Systems: A Systematic Literature Review of Hybrid Deep Learning Approaches

Network Intrusion Detection Systems (NIDSs) have become standard security solutions that endeavours to discover unauthorized access to an organizational computer network by scrutinizing incoming and outgoing network traffic for signs of malicious activity. In recent years, deep learning based NIDSs have emerged as an active area of research in cybersecurity and several surveys have been done on these systems. Although a plethora of surveys exists covering this burgeoning body of research, there lacks in the literature an empirical analysis of the different hybrid deep learning models. This paper presents a review of hybrid deep learning models for network intrusion detection and pinpoints their characteristics which researchers and practitioners are exploiting to develop modern NIDSs. The paper first elucidates the concept of network intrusion detection systems. Secondly, the taxonomy of hybrid deep learning techniques employed in designing NIDSs is presented. Lastly, a survey of the hybrid deep learning based NIDS is presented. The study adopted the systematic literature review methodology, a formal and systematic procedure by conducting bibliographic review, while defining explicit protocols for obtaining information. The survey results suggest that hybrid deep learning-based models yield desirable performance compared to other deep learning algorithms. The results also indicate that optimization, empirical risk minimization and model complexity control are the most important characteristics in the design of hybrid deep learning-based models. Lastly, key issues in the literature exposed in the research survey are discussed and then propose several potential future directions for researchers and practitioners in the design of deep learning methods for network intrusion detectio

Evaluating Linear and Non-linear Dimensionality Reduction Approaches for Deep Learning-based Network Intrusion Detection Systems

Dimensionality reduction is an essential ingredient of machine learning modelling that seeks to improve the performance of such models by extracting better quality features from data while removing irrelevant and redundant ones. The technique aids reduce computational load, avoiding data over-fitting, and increasing model interpretability. Recent studies have revealed that dimensionality reduction can benefit from labeled information, through joint approximation of predictors and target variables from a low-rank representation. A multiplicity of linear and non-linear dimensionality reduction techniques are proposed in the literature contingent on the nature of the domain of interest. This paper presents an evaluation of the performance of a hybrid deep learning model using feature extraction techniques while being applied to a benchmark network intrusion detection dataset. We compare the performance of linear and non-linear feature extraction methods namely, the Principal Component Analysis and Isometric Feature Mapping respectively. The Principal Component Analysis is a non-parametric classical method normally used to extract a smaller representative dataset from high-dimensional data and classifies data that is linear in nature while preserving spatial characteristics. In contrast, Isometric Feature Mapping is a representative method in manifold learning that maps high-dimensional information into a lower feature space while endeavouring to maintain the neighborhood for each data point as well as the geodesic distances present among all pairs of data points. These two approaches were applied to the CICIDS 2017 network intrusion detection benchmark dataset to extract features. The extracted features were then utilized in the training of a hybrid deep learning-based intrusion detection model based on convolutional and a bidirection long short term memory architecture and the model performance results were compared. The empirical results demonstrated the dominance of the Principal Component Analysis as compared to Isometric Feature Mapping in improving the performance of the hybrid deep learning model in classifying network intrusions. The suggested model attained 96.97% and 96.81% in overall accuracy and F1-score, respectively, when the PCA method was used for dimensionality reduction. The hybrid model further achieved a detection rate of 97.91% whereas the false alarm rate was reduced to 0.012 with the discriminative features reduced to 48. Thus the model based on the principal component analysis extracted salient features that improved detection rate and reduced the false alarm rate

SSH-Brute Force Attack Detection Model based on Deep Learning

The rising number of malicious threats on computer networks and Internet services owing to a large number of attacks makes the network security be at incessant risk. One of the predominant network attacks that poses distressing threats to networks security are the brute force attacks. A brute force attack uses a trial and error algorithm to decode encrypted data such as passwords or Data Encryption Standard keys, through exhaustive effort (using brute force) rather than using intellectual strategies. Brute force attacks resemble legitimate network traffic, making it difficult to defend an organization that rely mainly on perimeter-based security solutions a major challenge. For stopping the occurrence of such attacks, several curable steps must be taken. This paper proposes an efficient mechanism for SSH-Brute force network attacks detection based on a supervised deep learning algorithm, Convolutional Neural Network. The model performance was compared with experimental results from 5 classical machine learning algorithms including Naive Bayes, Logistic Regression, Decision Tree, k-Nearest Neighbour, and Support Vector Machine. Four standard metrics namely, Accuracy, Precision, Recall, and the F-measure were used. Results show that the CNN-based model is superior to the traditional machine learning methods with 94.3% accuracy, a precision rate of 92.5%, recall rate of 97.8% and F1-score of 91.8% in terms of the ability to detect SSH-Brute force attacks.

Burden of disease scenarios for 204 countries and territories, 2022–2050: a forecasting analysis for the Global Burden of Disease Study 2021

BackgroundFuture trends in disease burden and drivers of health are of great interest to policy makers and the public at large. This information can be used for policy and long-term health investment, planning, and prioritisation. We have expanded and improved upon previous forecasts produced as part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) and provide a reference forecast (the most likely future), and alternative scenarios assessing disease burden trajectories if selected sets of risk factors were eliminated from current levels by 2050.MethodsUsing forecasts of major drivers of health such as the Socio-demographic Index (SDI; a composite measure of lag-distributed income per capita, mean years of education, and total fertility under 25 years of age) and the full set of risk factor exposures captured by GBD, we provide cause-specific forecasts of mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) by age and sex from 2022 to 2050 for 204 countries and territories, 21 GBD regions, seven super-regions, and the world. All analyses were done at the cause-specific level so that only risk factors deemed causal by the GBD comparative risk assessment influenced future trajectories of mortality for each disease. Cause-specific mortality was modelled using mixed-effects models with SDI and time as the main covariates, and the combined impact of causal risk factors as an offset in the model. At the all-cause mortality level, we captured unexplained variation by modelling residuals with an autoregressive integrated moving average model with drift attenuation. These all-cause forecasts constrained the cause-specific forecasts at successively deeper levels of the GBD cause hierarchy using cascading mortality models, thus ensuring a robust estimate of cause-specific mortality. For non-fatal measures (eg, low back pain), incidence and prevalence were forecasted from mixed-effects models with SDI as the main covariate, and YLDs were computed from the resulting prevalence forecasts and average disability weights from GBD. Alternative future scenarios were constructed by replacing appropriate reference trajectories for risk factors with hypothetical trajectories of gradual elimination of risk factor exposure from current levels to 2050. The scenarios were constructed from various sets of risk factors: environmental risks (Safer Environment scenario), risks associated with communicable, maternal, neonatal, and nutritional diseases (CMNNs; Improved Childhood Nutrition and Vaccination scenario), risks associated with major non-communicable diseases (NCDs; Improved Behavioural and Metabolic Risks scenario), and the combined effects of these three scenarios. Using the Shared Socioeconomic Pathways climate scenarios SSP2-4.5 as reference and SSP1-1.9 as an optimistic alternative in the Safer Environment scenario, we accounted for climate change impact on health by using the most recent Intergovernmental Panel on Climate Change temperature forecasts and published trajectories of ambient air pollution for the same two scenarios. Life expectancy and healthy life expectancy were computed using standard methods. The forecasting framework includes computing the age-sex-specific future population for each location and separately for each scenario. 95% uncertainty intervals (UIs) for each individual future estimate were derived from the 2·5th and 97·5th percentiles of distributions generated from propagating 500 draws through the multistage computational pipeline.FindingsIn the reference scenario forecast, global and super-regional life expectancy increased from 2022 to 2050, but improvement was at a slower pace than in the three decades preceding the COVID-19 pandemic (beginning in 2020). Gains in future life expectancy were forecasted to be greatest in super-regions with comparatively low life expectancies (such as sub-Saharan Africa) compared with super-regions with higher life expectancies (such as the high-income super-region), leading to a trend towards convergence in life expectancy across locations between now and 2050. At the super-region level, forecasted healthy life expectancy patterns were similar to those of life expectancies. Forecasts for the reference scenario found that health will improve in the coming decades, with all-cause age-standardised DALY rates decreasing in every GBD super-region. The total DALY burden measured in counts, however, will increase in every super-region, largely a function of population ageing and growth. We also forecasted that both DALY counts and age-standardised DALY rates will continue to shift from CMNNs to NCDs, with the most pronounced shifts occurring in sub-Saharan Africa (60·1% [95% UI 56·8–63·1] of DALYs were from CMNNs in 2022 compared with 35·8% [31·0–45·0] in 2050) and south Asia (31·7% [29·2–34·1] to 15·5% [13·7–17·5]). This shift is reflected in the leading global causes of DALYs, with the top four causes in 2050 being ischaemic heart disease, stroke, diabetes, and chronic obstructive pulmonary disease, compared with 2022, with ischaemic heart disease, neonatal disorders, stroke, and lower respiratory infections at the top. The global proportion of DALYs due to YLDs likewise increased from 33·8% (27·4–40·3) to 41·1% (33·9–48·1) from 2022 to 2050, demonstrating an important shift in overall disease burden towards morbidity and away from premature death. The largest shift of this kind was forecasted for sub-Saharan Africa, from 20·1% (15·6–25·3) of DALYs due to YLDs in 2022 to 35·6% (26·5–43·0) in 2050. In the assessment of alternative future scenarios, the combined effects of the scenarios (Safer Environment, Improved Childhood Nutrition and Vaccination, and Improved Behavioural and Metabolic Risks scenarios) demonstrated an important decrease in the global burden of DALYs in 2050 of 15·4% (13·5–17·5) compared with the reference scenario, with decreases across super-regions ranging from 10·4% (9·7–11·3) in the high-income super-region to 23·9% (20·7–27·3) in north Africa and the Middle East. The Safer Environment scenario had its largest decrease in sub-Saharan Africa (5·2% [3·5–6·8]), the Improved Behavioural and Metabolic Risks scenario in north Africa and the Middle East (23·2% [20·2–26·5]), and the Improved Nutrition and Vaccination scenario in sub-Saharan Africa (2·0% [–0·6 to 3·6]).InterpretationGlobally, life expectancy and age-standardised disease burden were forecasted to improve between 2022 and 2050, with the majority of the burden continuing to shift from CMNNs to NCDs. That said, continued progress on reducing the CMNN disease burden will be dependent on maintaining investment in and policy emphasis on CMNN disease prevention and treatment. Mostly due to growth and ageing of populations, the number of deaths and DALYs due to all causes combined will generally increase. By constructing alternative future scenarios wherein certain risk exposures are eliminated by 2050, we have shown that opportunities exist to substantially improve health outcomes in the future through concerted efforts to prevent exposure to well established risk factors and to expand access to key health interventions.FundingBill & Melinda Gates Foundation.</p