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

NO Disproportionation at a Mononuclear Site-Isolated Fe²⁺ Center in Fe²⁺-MOF‑5

The weak-field ligand environments at the metal nodes of metal–organic frameworks (MOFs) mimic the electronic environment of metalloenzyme active sites, but little is known about the reactivity of MOF nodes toward small molecules of biological relevance. Here, we report that the ferrous ions in Fe²⁺-exchanged MOF-5 disproportionate nitric oxide to produce nitrous oxide and a ferric nitrito complex. Although mechanistic studies of N–N bond forming transformations often invoke a hyponitrite species, as in nitric oxide reductase and NO_<i>x</i> reduction catalysis, little is known about this intermediate in its monoanionic state. Together with the first report of N–N coupling between NO molecules in a MOF, we present evidence for a species that is consistent with a ferric hyponitrite radical, whose isolation is enabled by the spatial constraints of the MOF matrix

Solid State Collapse of a High-Spin Square-Planar Fe(II) Complex, Solution Phase Dynamics, and Electronic Structure Characterization of an Fe(II)₂ Dimer

Square-planar high-spin Fe­(II) molecular compounds are rare, and until recently, the only four examples of non-macrocyclic or sterically driven molecular compounds of this kind shared a common FeO₄ core. The trianionic pincer-type ligand [CF₃-ONO]­H₃ (<b>1</b>) supports the high-spin square-planar Fe­(II) complex {[CF₃-ONO]­FeCl}­{Li­(Sv)₂}₂ (<b>2</b>). In the solid state, <b>2</b> forms the dimer complex {[CF₃-ONO]­Fe}₂­{(μ-Cl)₂­(μ-LiTHF)₄} (<b>3</b>) in 96% yield by simply applying a vacuum or stirring it with pentane for 2 h. A detailed high-frequency electron paramagnetic resonance and field-dependent ⁵⁷Fe Mössbauer investigation of <b>3</b> revealed a weak antiferromagnetic exchange interaction between the local iron spins which exhibit a zero-field splitting tensor characterized by negative <i>D</i> parameter. In solution, <b>2</b> is in equilibrium with the solvento complex {[CF₃-ONO]­FeCl­(THF)}­{Li₂(Sv)₄} (<b>2·Sv</b>) and the dimer <b>3</b>. A combination of frozen solution ⁵⁷Fe Mössbauer spectroscopy and single crystal X-ray crystallography helped elucidate the solvent dependent equilibrium between these three species. The oxidation chemistry of <b>2·Sv</b> was investigated. Complex <b>2</b> reacts readily with the one-electron oxidizing agent CuCl₂ to give the Fe­(III) complex {[CF₃-ONO]­FeCl₂}­{Li­(THF)₂}₂ (<b>4</b>). Also, <b>2·Sv</b> reacts with 2 equiv of TlPF₆ to form the Fe­(III) complex [CF₃-ONO]­Fe­(THF)₃ (<b>5</b>)

Spectroscopic and Theoretical Investigation of a Complex with an [OFe^IV–O–Fe^IVO] Core Related to Methane Monooxygenase Intermediate <b>Q</b>

Previous efforts to model the diiron­(IV) intermediate <b>Q</b> of soluble methane monooxygenase have led to the synthesis of a diiron­(IV) TPA complex, <b>2</b>, with an O=Fe^IV–O–Fe^IV–OH core that has two ferromagnetically coupled S_loc = 1 sites. Addition of base to <b>2</b> at −85 °C elicits its conjugate base <b>6</b> with a novel OFe^IV–O–Fe^IVO core. In frozen solution, <b>6</b> exists in two forms, <b>6a</b> and <b>6b</b>, that we have characterized extensively using Mössbauer and parallel mode EPR spectroscopy. The conversion between <b>2</b> and <b>6</b> is quantitative, but the relative proportions of <b>6a</b> and <b>6b</b> are solvent dependent. <b>6a</b> has two equivalent high-spin (<i>S</i>_loc = 2) sites, which are antiferromagnetically coupled; its quadrupole splitting (0.52 mm/s) and isomer shift (0.14 mm/s) match those of intermediate <b>Q</b>. DFT calculations suggest that <b>6a</b> assumes an anti conformation with a dihedral OFe–FeO angle of 180°. Mössbauer and EPR analyses show that <b>6b</b> is a diiron­(IV) complex with ferromagnetically coupled <i>S</i>_loc = 1 and <i>S</i>_loc = 2 sites to give total spin <i>S</i>_t = 3. Analysis of the zero-field splittings and magnetic hyperfine tensors suggests that the dihedral OFe–FeO angle of <b>6b</b> is ∼90°. DFT calculations indicate that this angle is enforced by hydrogen bonding to both terminal oxo groups from a shared water molecule. The water molecule preorganizes <b>6b</b>, facilitating protonation of one oxo group to regenerate <b>2</b>, a protonation step difficult to achieve for mononuclear Fe^IVO complexes. Complex <b>6</b> represents an intriguing addition to the handful of diiron­(IV) complexes that have been characterized

Solid State Collapse of a High-Spin Square-Planar Fe(II) Complex, Solution Phase Dynamics, and Electronic Structure Characterization of an Fe(II)₂ Dimer

Square-planar high-spin Fe­(II) molecular compounds are rare, and until recently, the only four examples of non-macrocyclic or sterically driven molecular compounds of this kind shared a common FeO₄ core. The trianionic pincer-type ligand [CF₃-ONO]­H₃ (<b>1</b>) supports the high-spin square-planar Fe­(II) complex {[CF₃-ONO]­FeCl}­{Li­(Sv)₂}₂ (<b>2</b>). In the solid state, <b>2</b> forms the dimer complex {[CF₃-ONO]­Fe}₂­{(μ-Cl)₂­(μ-LiTHF)₄} (<b>3</b>) in 96% yield by simply applying a vacuum or stirring it with pentane for 2 h. A detailed high-frequency electron paramagnetic resonance and field-dependent ⁵⁷Fe Mössbauer investigation of <b>3</b> revealed a weak antiferromagnetic exchange interaction between the local iron spins which exhibit a zero-field splitting tensor characterized by negative <i>D</i> parameter. In solution, <b>2</b> is in equilibrium with the solvento complex {[CF₃-ONO]­FeCl­(THF)}­{Li₂(Sv)₄} (<b>2·Sv</b>) and the dimer <b>3</b>. A combination of frozen solution ⁵⁷Fe Mössbauer spectroscopy and single crystal X-ray crystallography helped elucidate the solvent dependent equilibrium between these three species. The oxidation chemistry of <b>2·Sv</b> was investigated. Complex <b>2</b> reacts readily with the one-electron oxidizing agent CuCl₂ to give the Fe­(III) complex {[CF₃-ONO]­FeCl₂}­{Li­(THF)₂}₂ (<b>4</b>). Also, <b>2·Sv</b> reacts with 2 equiv of TlPF₆ to form the Fe­(III) complex [CF₃-ONO]­Fe­(THF)₃ (<b>5</b>)

Evolution of Bonding and Magnetism via Changes in Valence Electron Count in CuFe2–xCoxGe2

A series of solid solutions, CuFe2–xCoxGe2 (x = 0, 0.2, 0.4, 0.8, and 1.0), have been synthesized by arc-melting and characterized by powder X-ray and neutron diffraction, magnetic measurements, Mössbauer spectroscopy, and electronic band structure calculations. All compounds crystallize in the CuFe2Ge2 structure type, which can be considered as a three-dimensional framework built of fused MGe6 octahedra and MGe5 trigonal bipyramids (M = Fe and Co), with channels filled by rows of Cu atoms. As the Co content (x) increases, the unit cell volume decreases in an anisotropic fashion: the b and c lattice parameters decrease while the a parameter increases. The changes in all the parameters are nearly linear, thus following Vegard’s law. CuFe2Ge2 exhibits two successive antiferromagnetic (AFM) orderings, corresponding to the formation of a commensurate AFM structure, followed by an incommensurate AFM structure observed at lower temperatures. Additionally, as the Co content increases, the AFM ordering temperature (TN) gradually decreases, and only one AFM transition is observed for x ≥ 0.2. The magnetic behavior of unsubstituted CuFe2Ge2 was found to be sensitive to the preparation method. The temperature-dependent zero-field 57Fe Mössbauer spectra reveal two hyperfine split components that evolve in agreement with the two consecutive AFM orderings observed in magnetic measurements. In contrast, the field-dependent spectra obtained for fields ≥ 2 T reveal a parallel arrangement of the moments associated with the two crystallographically unique metal sites. Electronic band structure calculations and chemical bonding analysis reveal a mix of strong M–M antibonding and non-bonding states at the Fermi level, in support of the overall AFM ordering observed in zero field. The substitution of Co for Fe reduces the population of the M–M antibonding states and the overall density of states at the Fermi level, thus suppressing the TN value.This is a manuscript of an article published as Tener, Zachary P., Vincent Yannello, V. Ovidiu Garlea, Saul H. Lapidus, Philip Yox, Kirill Kovnir, Sebastian A. Stoian, and Michael Shatruk. "Evolution of Bonding and Magnetism via Changes in Valence Electron Count in CuFe2–x Co x Ge2." Inorganic Chemistry 61, no. 10 (2022): 4257-4269. DOI: 10.1021/acs.inorgchem.1c02997. Copyright 2022 American Chemical Society Posted with permission. DOE Contract Number(s): AC05-00OR22725; DMR-1905499; DMR-1644779; AC02–07CH11358; AC02-06CH11357

Synthesis and Characterization of a Stable High-Valent Cobalt Carbene Complex

The formally Co^IV carbene Co­(OR)₂(CPh₂) is formed upon the reaction of diphenyl­diazo­methane with the cobalt bis­(alkoxide) precursor Co­(OR)₂(THF)₂. Structural, spectroscopic, and theoretical studies demonstrate that Co­(OR)₂(CPh₂) has significant high-valent Co^IVCPh₂ character with non-negligible spin density on the carbene moiety

Synthesis and Characterization of a Stable High-Valent Cobalt Carbene Complex

The formally Co^IV carbene Co­(OR)₂(CPh₂) is formed upon the reaction of diphenyl­diazo­methane with the cobalt bis­(alkoxide) precursor Co­(OR)₂(THF)₂. Structural, spectroscopic, and theoretical studies demonstrate that Co­(OR)₂(CPh₂) has significant high-valent Co^IVCPh₂ character with non-negligible spin density on the carbene moiety