Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. Gates Foundation.
For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. Gates Foundation and Bloomberg Philanthropies.
We provide a reconstruction of Kant's empirical-pragmatic account of science, focusing on psychological, social, and historical conditions that 'pragmatically' promote or hinder the advancement of science. Our novel reconstruction offers a realistic portrayal of Kant's view. Part 1 claims that he presents a differentiated and dynamic account of research. Part 2 looks at psychological conditions, beginning with Kant's analysis of cognitive faculties (2.1), and the distinction between higher and lower faculties (2.2). Then, we turn to layers of scientific cognition: (2.3) observation, (2.4) imagination, (2.5) 'methodical meditation', and (2.6) 'sagacity', the talent for scientific discovery. Part 3 addresses biological, political, and historical conditions that hinder the development of science: mortality, lack of liberty, and 'barbarism'. We explain how Kant conceptualizes science as a collective historical process promoting human flourishing (3.1). To cope with individual limits, Kant demands to divide scientific labour between (3.2) kinds of minds and (3.3) disciplines. Section (3.4) treats his views on truth and testimony as crucial for science. In our conclusion, part 4, we show how Kant thinks the history of science ought to be studied, how his pragmatic approach relates to his claims about reason's role in scientific progress, and what research questions emerge next.
Historians of science and religion have occasionally resorted to stereotypes, rejecting harmonious accounts without clear justifications. This article chronicles the creation and reception history of Religion and the Rise of Modern Science (1972), written by one so-called harmony promoting historian, Reijer Hooykaas (1906-1994). Over the decades, the book has received substantial criticism and praise. Based on our research on publications and archival materials - primarily comprising correspondence between Hooykaas, friends, colleagues, and publishers - we show that the multifaceted creation history of Religion and the Rise of Modern Science (RRMS) has significantly impacted its reception. We argue that the book, and, by extension, Hooykaas's scholarship on science and religion, has been too easily discarded as Protestant apologetics at worst and as an attempt to harmonize science and religion at best. Painting a picture of the dynamics of the science and religion field during its formative years from the 1960s onwards, this article is a call to take the complexity principle seriously when conducting historiography in the science and religion field instead of merely framing previous research as a counterpoint.
In the context of the 150th anniversary of Hermann Graßmann's death, the results of 50 years of recent Graßmann research, starting with Lewis's dissertation and his contribution to the Annals of Science, are reflected upon. The unexpected revision initiated by Schubring in 1996 of the research findings on the sources of Graßmann's mathematical creativity, which have been available since Friedrich Engel, is rejected as unfounded. New insights into the introduction of the negative in geometry and the significance of the concept of multiplication for Graßmann are presented. Biographical information about Graßmann's work receives a stronger contextualization, and a simplistic handling of material hermeneutics in the historiography of mathematics is criticized. As shown by the influence of Pestalozzi on mathematics education in Prussia in the first half of the nineteenth century, in the case of Justus and Hermann Graßmann, there are 'causally effective societal factors in the development of mathematics' [Hans Wußing, 'Externalismus - Internalismus', N.T.M., 15 (2007), [284-88]], which were historically intertwined with the inner-mathematical development potentials of their time.
Cancer is a leading cause of death globally. Accurate cancer burden information is crucial for policy planning, but many countries do not have up-to-date cancer surveillance data. To inform global cancer-control efforts, we used the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 framework to generate and analyse estimates of cancer burden for 47 cancer types or groupings by age, sex, and 204 countries and territories from 1990 to 2023, cancer burden attributable to selected risk factors from 1990 to 2023, and forecasted cancer burden up to 2050. Cancer estimation in GBD 2023 used data from population-based cancer registration systems, vital registration systems, and verbal autopsies. Cancer mortality was estimated using ensemble models, with incidence informed by mortality estimates and mortality-to-incidence ratios (MIRs). Prevalence estimates were generated from modelled survival estimates, then multiplied by disability weights to estimate years lived with disability (YLDs). Years of life lost (YLLs) were estimated by multiplying age-specific cancer deaths by the GBD standard life expectancy at the age of death. Disability-adjusted life-years (DALYs) were calculated as the sum of YLLs and YLDs. We used the GBD 2023 comparative risk assessment framework to estimate cancer burden attributable to 44 behavioural, environmental and occupational, and metabolic risk factors. To forecast cancer burden from 2024 to 2050, we used the GBD 2023 forecasting framework, which included forecasts of relevant risk factor exposures and used Socio-demographic Index as a covariate for forecasting the proportion of each cancer not affected by these risk factors. Progress towards the UN Sustainable Development Goal (SDG) target 3.4 aim to reduce non-communicable disease mortality by a third between 2015 and 2030 was estimated for cancer. In 2023, excluding non-melanoma skin cancers, there were 18·5 million (95% uncertainty interval 16·4 to 20·7) incident cases of cancer and 10·4 million (9·65 to 10·9) deaths, contributing to 271 million (255 to 285) DALYs globally. Of these, 57·9% (56·1 to 59·8) of incident cases and 65·8% (64·3 to 67·6) of cancer deaths occurred in low-income to upper-middle-income countries based on World Bank income group classifications. Cancer was the second leading cause of deaths globally in 2023 after cardiovascular diseases. There were 4·33 million (3·85 to 4·78) risk-attributable cancer deaths globally in 2023, comprising 41·7% (37·8 to 45·4) of all cancer deaths. Risk-attributable cancer deaths increased by 72·3% (57·1 to 86·8) from 1990 to 2023, whereas overall global cancer deaths increased by 74·3% (62·2 to 86·2) over the same period. The reference forecasts (the most likely future) estimate that in 2050 there will be 30·5 million (22·9 to 38·9) cases and 18·6 million (15·6 to 21·5) deaths from cancer globally, 60·7% (41·9 to 80·6) and 74·5% (50·1 to 104·2) increases from 2024, respectively. These forecasted increases in deaths are greater in low-income and middle-income countries (90·6% [61·0 to 127·0]) compared with high-income countries (42·8% [28·3 to 58·6]). Most of these increases are likely due to demographic changes, as age-standardised death rates are forecast to change by -5·6% (-12·8 to 4·6) between 2024 and 2050 globally. Between 2015 and 2030, the probability of dying due to cancer between the ages of 30 years and 70 years was forecasted to have a relative decrease of 6·5% (3·2 to 10·3). Cancer is a major contributor to global disease burden, with increasing numbers of cases and deaths forecasted up to 2050 and a disproportionate growth in burden in countries with scarce resources. The decline in age-standardised mortality rates from cancer is encouraging but insufficient to meet the SDG target set for 2030. Effectively and sustainably addressing cancer burden globally will require comprehensive national and international efforts that consider health systems and context in the development and implementation of cancer-control strategies across the continuum of prevention, diagnosis, and treatment. Gates Foundation, St Jude Children's Research Hospital, and St Baldrick's Foundation.
Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with more readily available all-age vital registration (VR) data. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) is an ongoing research effort that quantifies human health by estimating a range of epidemiological quantities of interest across time, age, sex, location, cause, and risk. This study-part of the latest GBD release, GBD 2023-aims to provide new and updated estimates of all-cause mortality and life expectancy for 1950 to 2023 using a novel statistical model that accounts for complex correlation structures in demographic data across age and time. We used 24 025 data sources from VR, sample registration, surveys, censuses, and other sources to estimate all-cause mortality for males, females, and all sexes combined across 25 age groups in 204 countries and territories as well as 660 subnational units in 20 countries and territories, for the years 1950-2023. For the first time, we used complete birth history data for ages 5-14 years, age-specific sibling history data for ages 15-49 years, and age-specific mortality data from Health and Demographic Surveillance Systems. We developed a single statistical model that incorporates both parametric and non-parametric methods, referred to as OneMod, to produce estimates of all-cause mortality for each age-sex-location group. OneMod includes two main steps: a detailed regression analysis with a generalised linear modelling tool that accounts for age-specific covariate effects such as the Socio-demographic Index (SDI) and a population attributable fraction (PAF) for all risk factors combined; and a non-parametric analysis of residuals using a multivariate kernel regression model that smooths across age and time to adaptably follow trends in the data without overfitting. We calibrated asymptotic uncertainty estimates using Pearson residuals to produce 95% uncertainty intervals (UIs) and corresponding 1000 draws. Life expectancy was calculated from age-specific mortality rates with standard demographic methods. For each measure, 95% UIs were calculated with the 25th and 975th ordered values from a 1000-draw posterior distribution. In 2023, 60·1 million (95% UI 59·0-61·1) deaths occurred globally, of which 4·67 million (4·59-4·75) were in children younger than 5 years. Due to considerable population growth and ageing since 1950, the number of annual deaths globally increased by 35·2% (32·2-38·4) over the 1950-2023 study period, during which the global age-standardised all-cause mortality rate declined by 66·6% (65·8-67·3). Trends in age-specific mortality rates between 2011 and 2023 varied by age group and location, with the largest decline in under-5 mortality occurring in east Asia (67·7% decrease); the largest increases in mortality for those aged 5-14 years, 25-29 years, and 30-39 years occurring in high-income North America (11·5%, 31·7%, and 49·9%, respectively); and the largest increases in mortality for those aged 15-19 years and 20-24 years occurring in Eastern Europe (53·9% and 40·1%, respectively). We also identified higher than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 5-14 years (87·3% higher in GBD 2023 than GBD 2021 on average across countries and territories over the 1950-2021 period) and for females aged 15-29 years (61·2% higher), as well as lower than previously estimated mortality rates in sub-Saharan Africa for all sexes combined aged 50 years and older (13·2% lower), reflecting advances in our modelling approach. Global life expectancy followed three distinct trends over the study period. First, between 1950 and 2019, there were considerable improvements, from 51·2 (50·6-51·7) years for females and 47·9 (47·4-48·4) years for males in 1950 to 76·3 (76·2-76·4) years for females and 71·4 (71·3-71·5) years for males in 2019. Second, this period was followed by a decrease in life expectancy during the COVID-19 pandemic, to 74·7 (74·6-74·8) years for females and 69·3 (69·2-69·4) years for males in 2021. Finally, the world experienced a period of post-pandemic recovery in 2022 and 2023, wherein life expectancy generally returned to pre-pandemic (2019) levels in 2023 (76·3 [76·0-76·6] years for females and 71·5 [71·2-71·8] years for males). 194 (95·1%) of 204 countries and territories experienced at least partial post-pandemic recovery in age-standardised mortality rates by 2023, with 61·8% (126 of 204) recovering to or falling below pre-pandemic levels. There were several mortality trajectories during and following the pandemic across countries and territories. Long-term mortality trends also varied considerably between age groups and locations, demonstrating the diverse landscape of health outcomes globally. This analysis identified several key differences in mortality trends from previous estimates, including higher rates of adolescent mortality, higher rates of young adult mortality in females, and lower rates of mortality in older age groups in much of sub-Saharan Africa. The findings also highlight stark differences across countries and territories in the timing and scale of changes in all-cause mortality trends during and following the COVID-19 pandemic (2020-23). Our estimates of evolving trends in mortality and life expectancy across locations, ages, sexes, and SDI levels in recent years as well as over the entire 1950-2023 study period provide crucial information for governments, policy makers, and the public to ensure that health-care systems, economies, and societies are prepared to address the world's health needs, particularly in populations with higher rates of mortality than previously known. The estimates from this study provide a robust framework for GBD and a valuable foundation for policy development, implementation, and evaluation around the world. Gates Foundation.
Since its inception in 1974, the Essential Programme on Immunization (EPI) has achieved remarkable success, averting the deaths of an estimated 154 million children worldwide through routine childhood vaccination. However, more recent decades have seen persistent coverage inequities and stagnating progress, which have been further amplified by the COVID-19 pandemic. In 2019, WHO set ambitious goals for improving vaccine coverage globally through the Immunization Agenda 2030 (IA2030). Now halfway through the decade, understanding past and recent coverage trends can help inform and reorient strategies for approaching these aims in the next 5 years. Based on the Global Burden of Diseases, Injuries, and Risk Factors Study 2023, this study provides updated global, regional, and national estimates of routine childhood vaccine coverage from 1980 to 2023 for 204 countries and territories for 11 vaccine-dose combinations recommended by WHO for all children globally. Employing advanced modelling techniques, this analysis accounts for data biases and heterogeneity and integrates new methodologies to model vaccine scale-up and COVID-19 pandemic-related disruptions. To contextualise historic coverage trends and gains still needed to achieve the IA2030 coverage targets, we supplement these results with several secondary analyses: (1) we assess the effect of the COVID-19 pandemic on vaccine coverage; (2) we forecast coverage of select life-course vaccines up to 2030; and (3) we analyse progress needed to reduce the number of zero-dose children by half between 2023 and 2030. Overall, global coverage for the original EPI vaccines against diphtheria, tetanus, and pertussis (first dose [DTP1] and third dose [DTP3]), measles (MCV1), polio (Pol3), and tuberculosis (BCG) nearly doubled from 1980 to 2023. However, this long-term trend masks recent challenges. Coverage gains slowed between 2010 and 2019 in many countries and territories, including declines in 21 of 36 high-income countries and territories for at least one of these vaccine doses (excluding BCG, which has been removed from routine immunisation schedules in some countries and territories). The COVID-19 pandemic exacerbated these challenges, with global rates for these vaccines declining sharply since 2020, and still not returning to pre-COVID-19 pandemic levels as of 2023. Coverage for newer vaccines developed and introduced in more recent years, such as immunisations against pneumococcal disease (PCV3) and rotavirus (complete series; RotaC) and a second dose of the measles vaccine (MCV2), saw continued increases globally during the COVID-19 pandemic due to ongoing introductions and scale-ups, but at slower rates than expected in the absence of the pandemic. Forecasts to 2030 for DTP3, PCV3, and MCV2 suggest that only DTP3 would reach the IA2030 target of 90% global coverage, and only under an optimistic scenario. The number of zero-dose children, proxied as children younger than 1 year who do not receive DTP1, decreased by 74·9% (95% uncertainty interval 72·1-77·3) globally between 1980 and 2019, with most of those declines reached during the 1980s and the 2000s. After 2019, counts of zero-dose children rose to a COVID 19-era peak of 18·6 million (17·6-20·0) in 2021. Most zero-dose children remain concentrated in conflict-affected regions and those with various constraints on resources available to put towards vaccination services, particularly sub-Saharan Africa. As of 2023, more than 50% of the 15·7 million (14·6-17·0) global zero-dose children resided in just eight countries (Nigeria, India, Democratic Republic of the Congo, Ethiopia, Somalia, Sudan, Indonesia, and Brazil), emphasising persistent inequities. Our estimates of current vaccine coverage and forecasts to 2030 suggest that achieving IA2030 targets, such as halving zero-dose children compared with 2019 levels and reaching 90% global coverage for life-course vaccines DTP3, PCV3, and MCV2, will require accelerated progress. Substantial increases in coverage are necessary in many countries and territories, with those in sub-Saharan Africa and south Asia facing the greatest challenges. Recent declines will need to be reversed to restore previous coverage levels in Latin America and the Caribbean, especially for DTP1, DTP3, and Pol3. These findings underscore the crucial need for targeted, equitable immunisation strategies. Strengthening primary health-care systems, addressing vaccine misinformation and hesitancy, and adapting to local contexts are essential to advancing coverage. COVID-19 pandemic recovery efforts, such as WHO's Big Catch-Up, as well as efforts to bolster routine services must prioritise reaching marginalised populations and target subnational geographies to regain lost ground and achieve global immunisation goals. The Bill & Melinda Gates Foundation and Gavi, the Vaccine Alliance.
The following paper was inspired by editorial work on some of early precritical writings for the new Academy Edition of Immanuel Kant which can be characterized as more or (more often) less coherent compositions of traditional rational cosmology and physical cosmology of his time, the further transformation of which gave rise to some investigations how basic concepts changed in the period from around 1746-1768. The aim of the paper is twofold: Firstly - and for the first time, as far as I can see - to give a concise account of the most important conceptual developments of Kant's precretical cosmology, especially of his precitical theory of matter. Secondly, to show how innovations in his later pre-critical writings in particular influenced the cosmology of his critical phase, mainly presented in the Critique of Pure Reason and the Metaphysical Foundations of Natural Science. Although the paper in no way plays down the philosophical significance of Kant's transcendental turn, it intends to show the extent to which argumentative patterns of the precritical period have found their way into his critical philosophy and others have become obsolete as a result of this turn.
Chagas disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, primarily transmitted by infected bugs, but also through contaminated food, transfusions, congenital transmission, and organ transplantation. Chagas disease has acute and chronic phases; the chronic phase can occur decades after infection, leading to complications such as heart failure, arrhythmias, and megaviscera. Accurate mortality and morbidity estimates are hindered by under-reporting and misclassification. Comprehensive and updated estimates are needed to improve global assessments of Chagas disease burden. We aim to provide a comprehensive description of global and regional burden of Chagas disease and its trends from 1990 to 2023. In this systematic analysis for the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023, we produced estimates of Chagas disease deaths, years of life lost (YLLs), prevalence, incidence, years lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 204 countries and territories from 1990 to 2023 by age and sex. The GBD 2023 estimates supersede previous estimates for all years. For mortality estimates, we fit a cause of death ensemble model to vital registration data. For non-fatal estimates in endemic locations, we did a systematic review of seroprevalence data, defining a confirmed case as a confirmed diagnosis of T cruzi infection by two different positive tests (or a single ELISA or immunochromatographic test). After adjustment for the population at risk, we used a Bayesian compartmental model (DisMod-MR) to produce estimates. For non-endemic locations, we estimated prevalence on the basis of migration patterns and estimated prevalence from endemic countries. Prevalence of acute and chronic sequelae and corresponding disability weights were used to calculate YLDs. We estimated 10·5 million (95% uncertainty interval 9·4-11·7) Chagas disease prevalent cases in 2023 globally, a 16·1% (12·6-19·2) decrease compared with 1990. The global age-standardised Chagas disease prevalence rate declined by 55·0% (53·8-56·1) from 1990 to 2023, with rates decreasing across all endemic regions. The highest age-standardised Chagas disease prevalence rates in 2023 were in southern Latin America (2485·9 [2249·6-2707·7] per 100 000) and Andean Latin America (2313·8 [2093·7-2570·1] per 100 000). Non-endemic regions experienced notable increases in prevalence due to migration from endemic countries. The age distribution of cases shifted over time, peaking at older ages in 2023 (between age 45 years and 65 years) compared with 1990 (30-45 years). In 2023, there were 352 000 (308 000-398 000) new cases of Chagas disease globally, with the age-standardised rate decreasing by 55·1% (53·4-56·6) since 1990. There were 8420 (7480-9360) deaths globally in 2023. Age-standardised mortality decreased by 72·5% (68·9-75·4) globally from 1990 to 2023. In 2023, the highest age-standardised mortality rates were in tropical Latin America (2·2 [1·9-2·4] per 100 000) and Andean Latin America (0·92 [0·70-1·2] per 100 000). The GBD 2023 Chagas disease estimates are notably higher than previous GBD estimates, reflecting additional data and methodological improvements, and those published by the Pan American Health Organization. Nevertheless, these updated estimates show decreasing prevalence and incidence in endemic countries, highlighting the importance of socioeconomic development, housing conditions, and vector-control policies. Conversely, the increase in prevalence in non-endemic countries, mainly due to migration, requires new strategies for screening, early recognition, and access to care. Although the marked decrease in mortality and YLLs might be due to better access to care at different levels, the shift in age distribution highlights the importance of preparing and funding health systems for caring for older populations with advanced sequelae. Finally, the continuous refinement of data-source quality, including adequate coding and classification, is crucial for the accuracy of global estimates, which can ultimately drive health and social policies. The Gates Foundation, the World Heart Federation, and Novartis Pharma.
Quality of life (QoL) in patients with Sjögren's disease (SjD) is a critical area of research that demands attention due to the impact of SjD on patients' lives. This study utilised bibliometric methods, aiming to comprehensively explore the research content and hotspots in the field of QoL in patients with SjD. The literature data source for this study was the Web of Science Core Collection. CiteSpace and VOSviewer were used to analyse publications in relation to authors, countries, institutions, journals, references, and keywords. The study focused on literature that addressed QoL in SjD patients, involving a total of 922 authors and 336 articles published across 151 journals. The study revealed that the number of publications in this field has remained relatively low, exhibiting a stable yet gradual upward trend, with no evidence of explosive growth. Key journals in this field include the Journal of Annals of the Rheumatic Diseases, Rheumatology (Oxford), Clinical and Experimental Rheumatology, and the Journal of Arthritis & Rheumatology. Asghar Bowman Simon J is the most prolific author in the field (21 publications), and England and the University Hospitals Birmingham NHS Foundation Trust and University of Groningen have the most publications. The most high-frequency keywords are "Sjögren's syndrome", "quality of life," "fatigue", "xerostomia", "depression", "sexual dysfunction" and "xerophthalmia". This study represents a bibliometric analysis focusing on QoL in patients with SjD. It underscores the need for more extensive and systematic research in this area, emphasising the importance of a multidisciplinary approach. Despite advancements in medical research for SjD, there is a crucial need to focus on QoL to enhance patient satisfaction and overall well-being. The findings advocate for more personalised treatment plans and a better understanding of the psychosocial needs of patients with SjD to improve their quality of life.
A manuscript now in Bamberg preserves the only surviving fragment of a thirteenth-century treatise on comets or 'new stars', which was written as a letter addressed by an unknown Dominican author to the Master General of his order, John of Vercelli. The present article offers the first discussion of this forgotten work, which was composed in the year after the Great Comet of 1264. Although most of the text has been lost, the inclusion of a geometrical diagram in the manuscript makes it possible to reconstruct a crucial part of its overall argument. The Dominican author was openly critical of the Aristotelian doctrine of comets as atmospheric phenomena and considered the possibility that reliable distance estimates might instead place such objects in the celestial realm. His geometrical investigation of this question is historically significant for containing the earliest known analysis of the effect of cometary distance on its observable parallax, thus anticipating aspects of Johannes Regiomontanus's seminal 16 Problems on comets.
This article explores the interdisciplinary career and overlooked legacy of Henri Devaux (1862-1956), a French botanist-turned-physicist whose pioneering work on thin films and surface science predated the field's maturity. Trained as a botanist, Devaux crossed disciplinary boundaries to make foundational contributions to the study of thin films anticipating key developments in molecular biology and colloid chemistry. Despite this, his work remains marginalized in narratives dominated by figures like Irving Langmuir and Agnes Pockels. Devaux's career reflects the tensions of disciplinary transgression in early 20th-century France, bridging botany, physics, and chemistry while serving as an "ambassador" of plant physiology within physics. His devout Protestant faith further shaped his scientific identity: he framed research as a divine mission and conceived of "Complete Science"-a synthesis of empirical inquiry and religious revelation-that distinguished him from both secular and Catholic contemporaries. Drawing on his personal archives, this study argues that Devaux's legacy was shaped by experimental ingenuity, religious conviction, and deliberate navigation between institutional constraints. His story challenges standard narratives of scientific progress, illuminating how personal belief and disciplinary boundary-crossing can simultaneously drive innovation and limit historical recognition.
This essay investigates the reception of William Gilbert's foundational work on magnetism, De Magnete, through a comprehensive analysis of extant copies of its early modern printed editions (1600, 1628, 1629, 1633). By employing a hybrid methodology combining quantitative and qualitative approaches to readers' annotations, this study charts patterns of engagement with Gilbert's text across diverse contexts and intellectual traditions. While celebrated for its experimental innovations and practical applications in navigation, it also elicited cosmological and humanist interests. Statistical analyses of readers' marks demonstrate a skewed distribution of engagement, with the majority of annotations concentrated in a small fraction of extant copies. This study moreover contributes to the historiography of early modern science by illustrating the methodological potential of combining large-scale digital datasets with close textual analysis, advocating for more systematic, collaborative approaches to the history of reading and book culture. In addition, a near-complete census of copies of De magnete is provided.
In his Universal Natural History and Theory of the Heavens (1755), Kant claims that the Universe has existed for 'a series of millions of years and centuries'. In light of the authority of biblical chronology, according to which God created the world some 6000 years ago, this claim is remarkable. In this paper, I argue that the novelty of Kant's account of the age of the world does not only lie in the sheer size of the number he gives, but also in the fact that it was motivated by cosmological considerations (as opposed to the proto-geological considerations that motivated other contemporary theories that challenged the biblical dogma). Since Kant does not explain how he comes to claim such a high number for the age of the world, I give two possible reasons that can be reconstructed from his 1755 works, both of which rely on his conception of the vast spatial dimension of the visible Universe. The first reason combines this conception with Kant's cosmogony, the second states that the vast spatial extension of the Universe implies an extremely long duration of its existence due to the finitude of the speed of light.
Age-related macular degeneration (AMD) is a growing public health concern worldwide, as one of the leading causes of vision impairment. We aimed to estimate global, national, and region-specific prevalence and disability-adjusted life-years (DALYs) along with tobacco as a modifiable risk factor to aid public policy addressing AMD. Data on AMD were extracted from the Global Burden of Disease, Injuries, and Risk Factor Study 2021 database in 204 countries and territories, 1990-2021. Vision impairment was defined and categorised by severity as follows: moderate to severe vision loss (visual acuity from <6/18 to 3/60) and blindness (visual acuity <3/60 or a visual field <10 degrees around central fixation). The burden of vision impairment attributable to AMD was subsequently estimated. These estimates were further stratified by geographical region, age, year, sex, Healthcare Access and Quality (HAQ) Index, and Socio-demographic Index (SDI) levels. Additionally, the effect of tobacco use, a modifiable risk factor, on the burden of AMD was analysed, and projections of AMD burden were estimated through to 2050. These projections also included scenario modelling to assess the potential effects of tobacco elimination. Globally, the number of individuals with vision impairment due to AMD more than doubled, rising from 3·64 million (95% uncertainty inverval [UI] 3·04-4·35) in 1990 to 8·06 million (6·71-9·82) in 2021. Similarly, DALYs increased by 91% over the same period, from 0·30 million (95% UI 0·21-0·42) to 0·58 million (0·40-0·80). By contrast, age-standardised prevalence and DALY rates declined, with prevalence rates decreasing by 5·53% (99·50 per 100 000 of the population [95% UI 83·16-118·04] in 1990 to 94·00 [78·32-114·42] in 2021) and DALY rates dropping by 19·09% (8·38 [5·70-11·53] to 6·78 [4·70-9·32]). These rates showed a consistent decrease in higher SDI quintiles, reflecting the negative correlation between HAQ Index and AMD burden. A general downward trend was observed from 1990 to 2021, with the largest age-standardised reduction occurring in the low-middle SDI quintile. The global contribution of tobacco to age-standardised DALYs decreased by 20%, declining from 12·45% (95% UI 7·73-17·37) in 1990 to 9·96% (6·12-14·06) in 2021. By 2050, the number of individuals affected by AMD is projected to increase from 3·40 million males (95% UI 2·81-4·17) in 2021 to 9·02 million (5·72-14·20) and from 4·66 million females (3·88-5·65) to 12·32 million (8·88-17·08). Eliminating tobacco use could reduce these numbers to 8·17 million males (5·59-11·92) and 11·15 million females (8·58-14·48) in 2050. While the total prevalence and DALYs due to AMD have steadily increased from 1990 to 2021, age-standardised prevalence and DALY rates have declined, probably reflecting the effect of population ageing and growth. The consistent decrease in age-standardised rates with higher SDI levels highlights the crucial role of health-care resources and public policies in mitigating AMD-related vision impairment. The downward trend observed from 1990 to 2021 might also be partially attributed to the reduced effect of tobacco as a modifiable risk factor, with declines in tobacco use seen globally and across all SDI quintiles. The burden of vision impairment due to AMD is projected to increase to about 21·34 million in 2050. However, effective tobacco regulation has the potential to substantially reduce AMD-related vision impairment, particularly in lower SDI quintiles where health-care resources are limited. Gates Foundation.
This article reframes the Analyst Controversy, incited by George Berkeley's incendiary tract The Analyst: A Discourse Addressed to an Infidel Mathematician (1734), as not merely a debate about Newtonian fluxions but as a conflict over epistemic authority and competing ideas and ideals of reason in the Age of Reason. While often treated as a technical episode in the history of calculus, the controversy also reveals deeper tensions about the legitimate production of mathematical knowledge and the status of its truths. By situating the controversy in the broader social and political context of Augustan Britain, this article argues that Berkeley's critique challenged not only the foundations of Newtonian mathematics but also the Lockean social epistemology and Whig ideologies of order in which they were embedded.
The Cold War's bipolarity between the Free World and the Communist World was evident across diplomacy, literature, military competition. Science, where research and publications often reflected opposing ideologies, is undoubtedly a crucial area. Julian Huxley's Evolution in Action (1953), a scientific work on genetics, exemplifies the scientific outlook of the Free World. Under the auspices of Aid Refugee Chinese Intellectuals, an American anti-communist organization helping with the resettlement of Chinese refugees, Huxley's Evolution in Action was translated by Xu Guansan and published in Hong Kong in 1953. Through Xu's translation, both the political image of Huxley and the political elements of Evolution were deliberately downplayed. For Xu, genetic knowledge was not merely an expression of political ideology but a means to promote his academic beliefs, particularly integrating historical studies with scientific disciplines. In this sense, Evolution lost the original political significance attributed to it by the Cold War bipolarity when it traveled to Hong Kong via translation. Examing Xu Guansan's translation of genetic knowledge complicates the history of science in Cold War Hong Kong by offering an aspect from the individual who reproduced the scientific work.
As a complement to his version of Euclid's Optics, the Portuguese mathematician Francisco the Melo (1490-1536) wrote a short treatise on the principles of vision that also included a summary description of the components of the eye. Combining arguments of geometric and anatomical nature, that text helps us to understand some of the conflicting ideas of the Renaissance period, before Kepler, but it also invites us to reread the contributions of a number of authors from the Middle Ages, with a particular focus on Alhacen and Witelo. Although Melo's theory of vision cannot be classified as exactly groundbreaking, it presents many interesting and singular peculiarities. In particular the way in which Melo justifies the existence of rays emitted by the eye while incorporating, at the same time, some elements of the intromission theories, and the clear steps he gives to single out the perpendicular ray in the mechanism behind a faithful and distinct vision.
This paper deals with Kant's elaboration of a metaphysical foundation of the principle of inertia in the Metaphysical Foundations of Natural Science. Many of Kant's contemporaries treat inertia not as an issue of mathematical physics but rather as a general feature of material objects that is addressed by metaphysics and, to some extent, by theology as well. In turn, inertia is often seen as the reason why matter is fundamentally passive, thus providing an argument against materialism. In particular, Abraham Gotthelf Kästner and Johann Samuel Traugott Gehler are considered on this score. They agree with Kant in that the principle of inertia follows from the general causal principle. Contrary to Kant, Kästner and Gehler treat inertia as a phenomenon of experience, whereas it seems a unique feature of Kant's approach to conceive of inertia as expressing the lifelessness of matter.