Effect of spatial configuration of an extended nonlinear Kierstead-Slobodkin reaction-transport model with adaptive numerical scheme

In this paper, we consider the numerical simulations of an extended nonlinear form of Kierstead-Slobodkin reaction-transport system in one and two dimensions. We employ the popular fourth-order exponential time differencing Runge-Kutta (ETDRK4) schemes proposed by Cox and Matthew (J Comput Phys 176:430-455, 2002), that was modified by Kassam and Trefethen (SIAM J Sci Comput 26:1214-1233, 2005), for the time integration of spatially discretized partial differential equations. We demonstrate the supremacy of ETDRK4 over the existing exponential time differencing integrators that are of standard approaches and provide timings and error comparison. Numerical results obtained in this paper have granted further insight to the question "What is the minimal size of the spatial domain so that the population persists?" posed by Kierstead and Slobodkin (J Mar Res 12:141-147, 1953 ), with a conclusive remark that the popula- tion size increases with the size of the domain. In attempt to examine the biological wave phenomena of the solutions, we present the numerical results in both one- and two-dimensional space, which have interesting ecological implications. Initial data and parameter values were chosen to mimic some existing patternsScopus 201

Cross-sectional study of antioxidant status in normotensive and hypertensive pregnancy

Objectives: The study measured the concentrations of antioxidants in women during pregnancy and the Post Partum Period (PPP) with a view to investigating their role in the aetiology of pregnancy induced hypertension(PIH).Study Design: Informed consent was obtained from 105 women who were divided into three groups: 15 age and parity matched normotensive non-pregnant (control group), 45 normotensive and 45 hypertensive pregnant women. The two groups of pregnant women were divided into three groups of 15 each and studied in the second and third trimesters and PPP respectively. Venous blood was obtained from all the participants for measurements of some antioxidants (uric acid, albumin, catalase and vitamin C). Data were analyzed using descriptive and inferential statistical methods.Results: The results show that the mean concentrations of catalase, albumin, vitamin C and uric acid for the control were 3.1 ± 0.18 ì/l, 46.6 ± 6.6 g/l, 0.38 ± 0.01 mg/dl and 0.16 ± 0.03 mmol/l respectively. The meanconcentration of all antioxidants except uric acid were significantly lower during pregnancy when compared with controls (t= 2.06; p<0.01). In the normotensive group of pregnant women, vitamin C was the only antioxidant that showed significant higher concentration when the second trimester concentration and third trimester concentration were compared (t=2.06; p<0.05). Uric acid levels were significantly higher (t=2.06; p<0.05) and catalase and vitamin C levels were significantly lower in the hypertensive group during the 2nd and 3rd trimesters (t=2.06; p<0.05). There was a tendency for all antioxidant concentrations to return to normal values during the PPP in the normotensive group; however in the hypertensive group, uric acid levels remained significantly higher(t=2.06; p<0.05).Conclusion: In conclusion this study showed that pregnancy generally reduced the concentration of antioxidants but vitamin C levels were higher in late pregnancy of normotensive women. Therefore higher levels of vitamin C may protect against PIH.Keywords: Antioxidants, Normal Pregnancy, Pregnancy Induced Hypertension (PIH)

Dynamic and influential interaction of cancer cells with normal epithelial cells in 3D culture

BACKGROUND: The cancer microenvironment has a strong impact on the growth and dynamics of cancer cells. Conventional 2D culture systems, however, do not reflect in vivo conditions, impeding detailed studies of cancer cell dynamics. This work aims to establish a method to reveal the interaction of cancer and normal epithelial cells using 3D time-lapse. METHODS: GFP-labelled breast cancer cells, MDA-MB-231, were co-cultured with mCherry-labelled non-cancerous epithelial cells, MDCK, in a gel matrix. In the 3D culture, the epithelial cells establish a spherical morphology (epithelial sphere) thus providing cancer cells with accessibility to the basal surface of epithelia, similar to the in vivo condition. Cell movement was monitored using time-lapse analyses. Ultrastructural, immunocytochemical and protein expression analyses were also performed following the time-lapse study. RESULTS: In contrast to the 2D culture system, whereby most MDA-MB-231 cells exhibit spindle-shaped morphology as single cells, in the 3D culture the MDA-MB-231 cells were found to be single cells or else formed aggregates, both of which were motile. The single MDA-MB-231 cells exhibited both round and spindle shapes, with dynamic changes from one shape to the other, visible within a matter of hours. When co-cultured with epithelial cells, the MDA-MB-231 cells displayed a strong attraction to the epithelial spheres, and proceeded to surround and engulf the epithelial cell mass. The surrounded epithelial cells were eventually destroyed, becoming debris, and were taken into the MDA-MB-231 cells. However, when there was a relatively large population of normal epithelial cells, the MDA-MB-231 cells did not engulf the epithelial spheres effectively, despite repeated contacts. MDA-MB-231 cells co-cultured with a large number of normal epithelial cells showed reduced expression of monocarboxylate transporter-1, suggesting a change in the cell metabolism. A decreased level of gelatin-digesting ability as well as reduced production of matrix metaroproteinase-2 was also observed. CONCLUSIONS: This culture method is a powerful technique to investigate cancer cell dynamics and cellular changes in response to the microenvironment. The method can be useful for various aspects such as; different combinations of cancer and non-cancer cell types, addressing the organ-specific affinity of cancer cells to host cells, and monitoring the cellular response to anti-cancer drugs. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12935-014-0108-6) contains supplementary material, which is available to authorized users

Global mortality from dementia : Application of a new method and results from the Global Burden of Disease Study 2019

Introduction Dementia is currently one of the leading causes of mortality globally, and mortality due to dementia will likely increase in the future along with corresponding increases in population growth and population aging. However, large inconsistencies in coding practices in vital registration systems over time and between countries complicate the estimation of global dementia mortality. Methods We meta-analyzed the excess risk of death in those with dementia and multiplied these estimates by the proportion of dementia deaths occurring in those with severe, end-stage disease to calculate the total number of deaths that could be attributed to dementia. Results We estimated that there were 1.62 million (95% uncertainty interval [UI]: 0.41-4.21) deaths globally due to dementia in 2019. More dementia deaths occurred in women (1.06 million [0.27-2.71]) than men (0.56 million [0.14-1.51]), largely but not entirely due to the higher life expectancy in women (age-standardized female-to-male ratio 1.19 [1.10-1.26]). Due to population aging, there was a large increase in all-age mortality rates from dementia between 1990 and 2019 (100.1% [89.1-117.5]). In 2019, deaths due to dementia ranked seventh globally in all ages and fourth among individuals 70 and older compared to deaths from other diseases estimated in the Global Burden of Disease (GBD) study. Discussion Mortality due to dementia represents a substantial global burden, and is expected to continue to grow into the future as an older, aging population expands globally.Peer reviewe

Mapping age- and sex-specific HIV prevalence in adults in sub-Saharan Africa, 2000–2018

Background: Human immunodeficiency virus and acquired immune deficiency syndrome (HIV/AIDS) is still among the leading causes of disease burden and mortality in sub-Saharan Africa (SSA), and the world is not on track to meet targets set for ending the epidemic by the Joint United Nations Programme on HIV/AIDS (UNAIDS) and the United Nations Sustainable Development Goals (SDGs). Precise HIV burden information is critical for effective geographic and epidemiological targeting of prevention and treatment interventions. Age- and sex-specific HIV prevalence estimates are widely available at the national level, and region-wide local estimates were recently published for adults overall. We add further dimensionality to previous analyses by estimating HIV prevalence at local scales, stratified into sex-specific 5-year age groups for adults ages 15–59 years across SSA. Methods: We analyzed data from 91 seroprevalence surveys and sentinel surveillance among antenatal care clinic (ANC) attendees using model-based geostatistical methods to produce estimates of HIV prevalence across 43 countries in SSA, from years 2000 to 2018, at a 5 × 5-km resolution and presented among second administrative level (typically districts or counties) units. Results: We found substantial variation in HIV prevalence across localities, ages, and sexes that have been masked in earlier analyses. Within-country variation in prevalence in 2018 was a median 3.5 times greater across ages and sexes, compared to for all adults combined. We note large within-district prevalence differences between age groups: for men, 50% of districts displayed at least a 14-fold difference between age groups with the highest and lowest prevalence, and at least a 9-fold difference for women. Prevalence trends also varied over time; between 2000 and 2018, 70% of all districts saw a reduction in prevalence greater than five percentage points in at least one sex and age group. Meanwhile, over 30% of all districts saw at least a five percentage point prevalence increase in one or more sex and age group. Conclusions: As the HIV epidemic persists and evolves in SSA, geographic and demographic shifts in prevention and treatment efforts are necessary. These estimates offer epidemiologically informative detail to better guide more targeted interventions, vital for combating HIV in SSA. © 2022, The Author(s).Funding text 1: S Afzal acknowledges support of the Pakistan Society of Medical Infectious Diseases and King Edward Medical University to access the relevant data of HIV from various sources. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB; FCT/MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) through the project UIDB/50006/2020. K Deribe acknowledges support by the Wellcome Trust [grant number 201900/Z/16/Z] as part of his International Intermediate Fellowship. C Herteliu and A Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Claudiu Herteliu is partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. Y J Kim acknowledges support by the Research Management Centre, Xiamen University Malaysia [No. XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional support by the Manipal Academy of Higher Education. K Krishan acknowledges non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge NIH/FIC K43 TW010716-04. I Landires is a member of the Sistema Nacional de Investigación (SNI), supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panama. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya was supported by the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z Quazi Syed acknowledges support from JNMC, Datta Meghe Institute of Medical Sciences. A I Ribeiro was supported by National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018. A M Samy acknowledges the support from a fellowship of the Egyptian Fulbright Mission program and Ain Shams University. R Shrestha acknowledges support from NIDA K01 Award: K01DA051346. N Taveira acknowledges support from FCT and Aga Khan Development Network (AKDN) - Portugal Collaborative Research Network in Portuguese speaking countries in Africa (project reference: 332821690), and by the European & Developing Countries Clinical Trials Partnership (EDCTP), UE (project reference: RIA2016MC-1615). B Unnikrishnan acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal. ; Funding text 2: LBD sub-Saharan Africa HIV Prevalence Collaborators S Afzal acknowledges support of the Pakistan Society of Medical Infectious Diseases and King Edward Medical University to access the relevant data of HIV from various sources. T W Bärnighausen was supported by the Alexander von Humboldt Foundation through the Alexander von Humboldt Professor award, funded by the German Federal Ministry of Education and Research. F Carvalho and E Fernandes acknowledge support from Fundação para a Ciência e a Tecnologia (FCT), I.P., in the scope of the project UIDP/04378/2020 and UIDB/04378/2020 of the Research Unit on Applied Molecular Biosciences - UCIBIO and the project LA/P/0140/2020 of the Associate Laboratory Institute for Health and Bioeconomy - i4HB; FCT/MCTES (Ministério da Ciência, Tecnologia e Ensino Superior) through the project UIDB/50006/2020. K Deribe acknowledges support by the Wellcome Trust [grant number 201900/Z/16/Z] as part of his International Intermediate Fellowship. C Herteliu and A Pana are partially supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, project number PN-III-P4-ID-PCCF-2016-0084. Claudiu Herteliu is partially supported by a grant of the Romanian Ministry of Research Innovation and Digitalization, MCID, project number ID-585-CTR-42-PFE-2021. Y J Kim acknowledges support by the Research Management Centre, Xiamen University Malaysia [No. XMUMRF/2020-C6/ITCM/0004]. S L Koulmane Laxminarayana acknowledges institutional support by the Manipal Academy of Higher Education. K Krishan acknowledges non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India. M Kumar would like to acknowledge NIH/FIC K43 TW010716-04. I Landires is a member of the Sistema Nacional de Investigación (SNI), supported by the Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT), Panama. V Nuñez-Samudio is a member of the Sistema Nacional de Investigación (SNI), which is supported by Panama’s Secretaría Nacional de Ciencia, Tecnología e Innovación (SENACYT). O O Odukoya was supported by the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Z Quazi Syed acknowledges support from JNMC, Datta Meghe Institute of Medical Sciences. A I Ribeiro was supported by National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018. A M Samy acknowledges the support from a fellowship of the Egyptian Fulbright Mission program and Ain Shams University. R Shrestha acknowledges support from NIDA K01 Award: K01DA051346. N Taveira acknowledges support from FCT and Aga Khan Development Network (AKDN) - Portugal Collaborative Research Network in Portuguese speaking countries in Africa (project reference: 332821690), and by the European & Developing Countries Clinical Trials Partnership (EDCTP), UE (project reference: RIA2016MC-1615). B Unnikrishnan acknowledges support from Kasturba Medical College, Mangalore, Manipal Academy of Higher Education, Manipal.; Funding text 3: This work was primarily supported by grant OPP1132415 from the Bill & Melinda Gates Foundation. The funder of the study had no role in study design, data collection, data analysis, data interpretation, writing of the report, or decision to publish. The corresponding authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. ; Funding text 4: S Afzal reports leadership or fiduciary role in other board, society, committee or advocacy group, unpaid, with the Pakistan society of Community Medicine & Public Health, the Pakistan Association of Medical Editors, and the Pakistan Society of Medical Infectious Diseases, all outside the submitted work. R Ancuceanu reports 5 payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Avvie, Sandoz, and B Braun, all outside the submitted work. T W Bärnighausen reports research grants from the European Union (Horizon 2020 and EIT Health), German Research Foundation (DFG), US National Institutes of Health, German Ministry of Education and Research, Alexander von Humboldt Foundation, Else-Kröner-Fresenius-Foundation, Wellcome Trust, Bill & Melinda Gates Foundation, KfW, UNAIDS, and WHO; consulting fees from KfW on the OSCAR initiative in Vietnam; participation on a Data Safety Monitoring Board or Advisory Board with the NIH-funded study “Healthy Options” (PIs: Smith Fawzi, Kaaya), Chair, Data Safety and Monitoring Board (DSMB), German National Committee on the “Future of Public Health Research and Education,” Chair of the scientific advisory board to the EDCTP Evaluation, Member of the UNAIDS Evaluation Expert Advisory Committee, National Institutes of Health Study Section Member on Population and Public Health Approaches to HIV/AIDS (PPAH), US National Academies of Sciences, Engineering, and Medicine’s Committee for the “Evaluation of Human Resources for Health in the Republic of Rwanda under the President’s Emergency Plan for AIDS Relief (PEPFAR),” University of Pennsylvania (UPenn) Population Aging Research Center (PARC) External Advisory Board Member; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as co-chair of the Global Health Hub Germany (which was initiated by the German Ministry of Health); all outside the submitted work. J das Neves reports grants or contracts from Ref. 13605 – Programa GÉNESE, Gilead Portugal (PGG/002/2016 – Programa GÉNESE, Gilead Portugal) outside the submitted work. L Dwyer-Lindgren reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415. I Filip reports other financial or non-financial interests from Avicenna Medical and Clinical Research Institute, outside the submitted work. E Haeuser reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415. C Herteliu reports grants from Romanian Ministry of Research Innovation and Digitalization, MCID, for project number ID-585-CTR-42-PFE-2021 (Jan 2022-Jun 2023) “Enhancing institutional performance through development of infrastructure and transdisciplinary research ecosystem within socio-economic domain – PERFECTIS,” from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, for project number PN-III-P4-ID-PCCF-2016-0084 (Oct 2018-Sep 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2.1-SOL-2020-2-0351 (Jun 2020-Oct 2020) “Approaches within public health management in the context of COVID-19 pandemic,” and from the Ministry of Labour and Social Justice, Romania for project number “Agenda for skills Romania 2020-2025”; all outside the submitted work. J J Jozwiak reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Teva, Amgen, Synexus, Boehringer Ingelheim, Zentiva, and Sanofi as personal fees, all outside the submitted work. J Khubchandani reports other financial interests from Teva Pharmaceuticals, all outside the submitted work. K Krishnan reports other non-financial support from UGC Centre of Advanced Study, CAS II, Department of Anthropology, Panjab University, Chandigarh, India, outside the submitted work. H J Larson reports grants or contracts from the MacArthur Foundation and Merck to London School of Hygeine and Tropical Medicine, and from the Vaccine Confidence Fund to the University of Washington; payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from Center for Strategic and International Studies as payment to LSHTM for co-chairing HighLevel Panel and from GSK as personal payment for developing training sessions and lectures; leadership or fiduciary role in other board, society, committee or advocacy group, pair, with the ApiJect Advisory Board; all outside the submitted work. O O Odukoya reports support for the present manuscript from the Fogarty International Center of the National Institutes of Health under the Award Number K43TW010704. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A Pans reports grants from Romanian National Authority for Scientific Research and Innovation, CNDS-UEFISCDI, for project number PN-III-P4-ID-PCCF-2016-0084 (Oct 2018-Sep 2022) “Understanding and modelling time-space patterns of psychology-related inequalities and polarization,” and project number PN-III-P2-2.1-SOL-2020-2-0351 (Jun 2020-Oct 2020) “Approaches within public health management in the context of COVID-19 pandemic,” outside the submitted work. S R Pandi-Perumal reports royalties from Springer for editing services; stock or stock options in Somnogen Canada Inc as the President and Chief Executive Officer; all outside the submitted work. A Radfar reports other financial or non-financial interests from Avicenna Medical and Clinical Research Institute, outside the submitted work. A I Ribeiro reports grants or contracts from National Funds through FCT, under the ‘Stimulus of Scientific Employment – Individual Support’ program within the contract CEECIND/02386/2018, outside the submitted work. J M Ross reports support for the present manuscript from the Bill & Melinda Gates Foundation through grant OPP1132415; grants or contracts from National Institutes of Health and Firland Foundation as payments to their institution; consulting fees from United States Agency for International Development as personal payments, and from KNCV Tuberculosis Foundation as payments to their institution; all outside the submitted work. E Rubagotti reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from the Greenwich China Office and Unviersity Prince Mohammad VI, Morocco, all outside the submitted work. B Sartorius reports grants or contracts from DHSC – GRAM Project; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a member of the GBD Scientific Council and a Member of WHO RGHS; all outside the submitted work. J A Singh reports consulting fees from Crealta/Horizon, Medisys, Fidia, PK Med, Two labs Inc, Adept Field Solutions, Clinical Care options, Clearview healthcare partners, Putnam associates, Focus forward, Navigant consulting, Spherix, MedIQ, Jupiter Life Science LLC, UBM LLC, Trio Health, Medscape, WebMD, and Practice Point communications, and the National Institutes of Health and the American College of Rheumatology; payment or honoraria for participating in the speakers bureau for Simply Speaking; support for attending meetings and/or travel from the steering committee of OMERACT, to attend their meeting every 2 years; participation on a Data Safety Monitoring Board or Advisory Board as an unpaid member of the FDA Arthritis Advisory Committee; leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid, as a member of the steering committee of OMERACT, an international organization that develops measures for clinical trials and receives arm’s length funding from 12 pharmaceutical companies, with the Veterans Affairs Rheumatology Field Advisory Committee as Chair, and with the UAB Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis as a director and editor; stock or stock options in TPT Global Tech, Vaxart pharmaceuticals, Atyu Biopharma, Adaptimmune Therapeutics, GeoVax Labs, Pieris Pharmaceuticals, Enzolytics Inc, Series Therapeutics, Tonix Pharmaceuticals, and Charlotte’s Web Holdings Inc. and previously owned stock options in Amarin, Viking, and Moderna pharmaceuticals; all outside the submitted work. N Taveira reports grants or contracts from FCT and Aga Khan Development Network (AKDN) – Portugal Collaborative Research Network in Portuguese speaking countries in Africa (Project reference: 332821690) and from European & Developing Countries Clinical Trials Partnership (EDCTP), UE (Project reference: RIA2016MC-1615), as payments made to their institution, all outside the submitted work

Diabetes mortality and trends before 25 years of age: an analysis of the Global Burden of Disease Study 2019

Background Diabetes, particularly type 1 diabetes, at younger ages can be a largely preventable cause of death with the correct health care and services. We aimed to evaluate diabetes mortality and trends at ages younger than 25 years globally using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. Methods We used estimates of GBD 2019 to calculate international diabetes mortality at ages younger than 25 years in 1990 and 2019. Data sources for causes of death were obtained from vital registration systems, verbal autopsies, and other surveillance systems for 1990–2019. We estimated death rates for each location using the GBD Cause of Death Ensemble model. We analysed the association of age-standardised death rates per 100 000 population with the Socio-demographic Index (SDI) and a measure of universal health coverage (UHC) and described the variability within SDI quintiles. We present estimates with their 95% uncertainty intervals. Findings In 2019, 16 300 (95% uncertainty interval 14 200 to 18 900) global deaths due to diabetes (type 1 and 2 combined) occurred in people younger than 25 years and 73·7% (68·3 to 77·4) were classified as due to type 1 diabetes. The age-standardised death rate was 0·50 (0·44 to 0·58) per 100 000 population, and 15 900 (97·5%) of these deaths occurred in low to high-middle SDI countries. The rate was 0·13 (0·12 to 0·14) per 100 000 population in the high SDI quintile, 0·60 (0·51 to 0·70) per 100 000 population in the low-middle SDI quintile, and 0·71 (0·60 to 0·86) per 100 000 population in the low SDI quintile. Within SDI quintiles, we observed large variability in rates across countries, in part explained by the extent of UHC (r2=0·62). From 1990 to 2019, age-standardised death rates decreased globally by 17·0% (−28·4 to −2·9) for all diabetes, and by 21·0% (–33·0 to −5·9) when considering only type 1 diabetes. However, the low SDI quintile had the lowest decline for both all diabetes (−13·6% [–28·4 to 3·4]) and for type 1 diabetes (−13·6% [–29·3 to 8·9]). Interpretation Decreasing diabetes mortality at ages younger than 25 years remains an important challenge, especially in low and low-middle SDI countries. Inadequate diagnosis and treatment of diabetes is likely to be major contributor to these early deaths, highlighting the urgent need to provide better access to insulin and basic diabetes education and care. This mortality metric, derived from readily available and frequently updated GBD data, can help to monitor preventable diabetes-related deaths over time globally, aligned with the UN's Sustainable Development Targets, and serve as an indicator of the adequacy of basic diabetes care for type 1 and type 2 diabetes across nations.publishedVersio

Global, regional, and national burden of stroke and its risk factors, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Regularly updated data on stroke and its pathological types, including data on their incidence, prevalence, mortality, disability, risk factors, and epidemiological trends, are important for evidence-based stroke care planning and resource allocation. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) aims to provide a standardised and comprehensive measurement of these metrics at global, regional, and national levels. Methods: We applied GBD 2019 analytical tools to calculate stroke incidence, prevalence, mortality, disability-adjusted life-years (DALYs), and the population attributable fraction (PAF) of DALYs (with corresponding 95% uncertainty intervals [UIs]) associated with 19 risk factors, for 204 countries and territories from 1990 to 2019. These estimates were provided for ischaemic stroke, intracerebral haemorrhage, subarachnoid haemorrhage, and all strokes combined, and stratified by sex, age group, and World Bank country income level. Findings: In 2019, there were 12·2 million (95% UI 11·0–13·6) incident cases of stroke, 101 million (93·2–111) prevalent cases of stroke, 143 million (133–153) DALYs due to stroke, and 6·55 million (6·00–7·02) deaths from stroke. Globally, stroke remained the second-leading cause of death (11·6% [10·8–12·2] of total deaths) and the third-leading cause of death and disability combined (5·7% [5·1–6·2] of total DALYs) in 2019. From 1990 to 2019, the absolute number of incident strokes increased by 70·0% (67·0–73·0), prevalent strokes increased by 85·0% (83·0–88·0), deaths from stroke increased by 43·0% (31·0–55·0), and DALYs due to stroke increased by 32·0% (22·0–42·0). During the same period, age-standardised rates of stroke incidence decreased by 17·0% (15·0–18·0), mortality decreased by 36·0% (31·0–42·0), prevalence decreased by 6·0% (5·0–7·0), and DALYs decreased by 36·0% (31·0–42·0). However, among people younger than 70 years, prevalence rates increased by 22·0% (21·0–24·0) and incidence rates increased by 15·0% (12·0–18·0). In 2019, the age-standardised stroke-related mortality rate was 3·6 (3·5–3·8) times higher in the World Bank low-income group than in the World Bank high-income group, and the age-standardised stroke-related DALY rate was 3·7 (3·5–3·9) times higher in the low-income group than the high-income group. Ischaemic stroke constituted 62·4% of all incident strokes in 2019 (7·63 million [6·57–8·96]), while intracerebral haemorrhage constituted 27·9% (3·41 million [2·97–3·91]) and subarachnoid haemorrhage constituted 9·7% (1·18 million [1·01–1·39]). In 2019, the five leading risk factors for stroke were high systolic blood pressure (contributing to 79·6 million [67·7–90·8] DALYs or 55·5% [48·2–62·0] of total stroke DALYs), high body-mass index (34·9 million [22·3–48·6] DALYs or 24·3% [15·7–33·2]), high fasting plasma glucose (28·9 million [19·8–41·5] DALYs or 20·2% [13·8–29·1]), ambient particulate matter pollution (28·7 million [23·4–33·4] DALYs or 20·1% [16·6–23·0]), and smoking (25·3 million [22·6–28·2] DALYs or 17·6% [16·4–19·0]). Interpretation: The annual number of strokes and deaths due to stroke increased substantially from 1990 to 2019, despite substantial reductions in age-standardised rates, particularly among people older than 70 years. The highest age-standardised stroke-related mortality and DALY rates were in the World Bank low-income group. The fastest-growing risk factor for stroke between 1990 and 2019 was high body-mass index. Without urgent implementation of effective primary prevention strategies, the stroke burden will probably continue to grow across the world, particularly in low-income countries. Funding: Bill & Melinda Gates Foundation

Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. // Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. // Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. // Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines