Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Design an Iterative Learning Observer to Reconstruct the Interaction Force in AM-AFM

Trabajo presentado en la conferencia Fuerzas y Túnel (FyT2014), celebrada en San Sebastián del 27 al 29 de agosto de 2014.Extracting the time varying tip-sample interaction force in dynamic atomic force microscopy has been an important goal to improve the imaging capabilities of AFM with simultaneous measurements of material properties. Here, we design an Iterative Learning Observer to reconstruct the interaction force from the wave profile of the cantilever. In this method, the interaction force is considered as an unknown time varying parameter and estimated by the designed observer. Simulations and experiments prove the accuracy of this method in liquid and air for different materials. From the reconstructed force signals, we are able to obtain the average peak force, and consequently, using Hu and Raman equation, the Young modulus of the materials.N

Molecular and Nanoscale Compositional Contrast of Soft Matter in Liquid: Interplay Between Elastic and Dissipative Interactions

We demonstrate that the phase contrast observed with an amplitude modulation atomic force microscope depends on two factors, the generation of higher harmonics components and the energy dissipated on the sample surface. Those factors are ultimately related to the chemical composition and structure of the surface. Our findings are general, but they specifically describe the results obtained while imaging soft materials in liquid. Molecular resolution experiments performed on a protein membrane surface in liquid confirm the theory.This work was supported by the Spanish Ministry of Science (MICINN) through Grants CSD2010-00024 and MAT2009-08650. J.R.R. has a JAE-Predoc fellowship from the European Social fund.Peer reviewe

General Force Reconstruction Method for Amplitude Modulation Force Microscopy Experiment

Trabajo presentado en la conferencia Fuerzas y Túnel (FyT2014), celebrada en San Sebastián del 27 al 29 de agosto de 2014.Amplitude Modulation Atomic Force Microscopy (AM-AFM) is the most widely used technique for nanoscale characterization of materials and surfaces in the air and liquid environments. High detection or sensitivities and smaller lateral forces with respect to contact AFM are the advantages of the dynamic modes of AFM. However, in AM-AFM experiments the interaction force is not direct observable.N

Optimization of Basic Magnetic Field Homogeneity in MR Tomography

This thesis is concerned with problems of measuring and mapping of magnetic field in MR tomograph, for purpose of magnetic flux density homogeneity optimization. Attention is paid to mapping techniques on rotary symmetric volume and to ways of magnetic fields optimization with utilization of passive and active correction systems. Theoretical analysis of magnetic field decomposition with utilization of spherical harmonics and numerical decomposition is made. Mapping and approximation techniques of basic magnetic field are verified by experiments in the laboratory at the Institute of Scientific Instruments AS CR in Brno

Biopolymer-based composites for tissue engineering applications:a basis for future opportunities

Abstract Biomimetic scaffolds supporting tissue regeneration are complex materials with multifunctional characteristics. The unique biocompatibility and biodegradability of biopolymers make them excellent candidates for tissue engineering and regenerative medicine. Biopolymers, which have a wide range of properties, can be obtained from different natural sources. Depending on the target tissue, biopolymers can be engineered to meet a series of specific functions. We review different types of biopolymers and their composites, besides their interactions with specific cells and tissues. Specific cellular mechanisms in tissue regeneration are also considered to elucidate the effects of biopolymers on controlling cellular mechanisms given their advantages and challenging aspects. Furthermore, the modifications required to mimic the properties of neural, cardiac, bone, and skin tissues are discussed. Utilization of biopolymer-based composites in tissue engineering requires additional improvements, where several challenges should be overcome. This work is mainly focused on biopolymers used in tissue engineering, providing support for engineering of future biocomposites for the same purpose. Some examples of biocomposites are also provided, a general guide for selection of biopolymers and the secondary component (biopolymers as complements, additives, or nano-scale biomaterials) to develop biocomposites

Safety and outcomes of intravenous thrombolytic therapy in ischemic stroke patients with COVID-19: CASCADE initiative

BACKGROUND: There is little information regarding the safety of intravenous tissue plasminogen activator (IV-tPA) in patients with stroke and COVID-19. METHODS: This multicenter study included consecutive stroke patients with and without COVID-19 treated with IV-tPA between February 18, 2019, to December 31, 2020, at 9 centers participating in the CASCADE initiative. Clinical outcomes included modified Rankin Scale (mRS) at hospital discharge, in-hospital mortality, the rate of hemorrhagic transformation. Using Bayesian multiple regression and after adjusting for variables with significant value in univariable analysis, we reported the posterior adjusted odds ratio (OR, with 95% Credible Intervals [CrI]) of the main outcomes. RESULTS: A total of 545 stroke patients, including 101 patients with COVID-19 were evaluated. Patients with COVID-19 had a more severe stroke at admission. In the study cohort, 85 (15.9%) patients had a hemorrhagic transformation, and 72 (13.1%) died in the hospital. After adjustment for confounding variables, discharge mRS score ≥2 (OR: 0.73, 95% CrI: 0.16, 3.05), in-hospital mortality (OR: 2.06, 95% CrI: 0.76, 5.53), and hemorrhagic transformation (OR: 1.514, 95% CrI: 0.66, 3.31) were similar in COVID-19 and non COVID-19 patients. High-sensitivity C reactive protein level was a predictor of hemorrhagic transformation in all cases (OR:1.01, 95%CI: 1.0026, 1.018), including those with COVID-19 (OR:1.024, 95%CI:1.002, 1.054). CONCLUSION: IV-tPA treatment in patients with acute ischemic stroke and COVID-19 was not associated with an increased risk of disability, mortality, and hemorrhagic transformation compared to those without COVID-19. IV-tPA should continue to be considered as the standard of care in patients with hyper acute stroke and COVID-19