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

Luria–Delbrück, revisited: the classic experiment does not rule out Lamarckian evolution

We re-examined data from the classic Luria–Delbrück fluctuation experiment, which is often credited with establishing a Darwinian basis for evolution. We argue that, for the Lamarckian model of evolution to be ruled out by the experiment, the experiment must favor pure Darwinian evolution over both the Lamarckian model and a model that allows both Darwinian and Lamarckian mechanisms (as would happen for bacteria with CRISPR-Cas immunity). Analysis of the combined model was not performed in the original 1943 paper. The Luria–Delbrück paper also did not consider the possibility of neither model fitting the experiment. Using Bayesian model selection, we find that the Luria–Delbrück experiment, indeed, favors the Darwinian evolution over purely Lamarckian. However, our analysis does not rule out the combined model, and hence cannot rule out Lamarckian contributions to the evolutionary dynamics

FEM Analysis of Sezawa Mode SAW Sensor for VOC Based on CMOS Compatible AlN/SiO2/Si Multilayer Structure

A Finite Element Method (FEM) simulation study is conducted, aiming to scrutinize the sensitivity of Sezawa wave mode in a multilayer AlN/SiO2/Si Surface Acoustic Wave (SAW) sensor to low concentrations of Volatile Organic Compounds (VOCs), that is, trichloromethane, trichloroethylene, carbon tetrachloride and tetrachloroethene. A Complimentary Metal-Oxide Semiconductor (CMOS) compatible AlN/SiO2/Si based multilayer SAW resonator structure is taken into account for this purpose. In this study, first, the influence of AlN and SiO2 layers’ thicknesses over phase velocities and electromechanical coupling coefficients (k2) of two SAW modes (i.e., Rayleigh and Sezawa) is analyzed and the optimal thicknesses of AlN and SiO2 layers are opted for best propagation characteristics. Next, the study is further extended to analyze the mass loading effect on resonance frequencies of SAW modes by coating a thin Polyisobutylene (PIB) polymer film over the AlN surface. Finally, the sensitivity of the two SAW modes is examined for VOCs. This study concluded that the sensitivity of Sezawa wave mode for 1 ppm of selected volatile organic gases is twice that of the Rayleigh wave mode

Films of metal nanocrystals formed at aqueous-organic interfaces

Nanocrystalline films of Au, Ag, and Cu have been prepared at the toluene-water interface by the interaction of metal-triphenylphosphine complexes in the organic layer with partially hydrolyzed tetrakishydroxymethylphosphonium chloride in the aqueous layer. The nanocrystals have been characterized by a host of microscopic and spectroscopic techniques. The free-standing films could be transferred from the interface onto solid supports. Furthermore, films could be dissolved to yield either a hydrosol or an organosol with the help of appropriate surfactants

Differentiation of speech-induced artifacts from physiological high gamma activity in intracranial recordings

There is great interest in identifying the neurophysiological underpinnings of speech production. Deep brain stimulation (DBS) surgery is unique in that it allows intracranial recordings from both cortical and subcortical regions in patients who are awake and speaking. The quality of these recordings, however, may be affected to various degrees by mechanical forces resulting from speech itself. Here we describe the presence of speech-induced artifacts in local-field potential (LFP) recordings obtained from mapping electrodes, DBS leads, and cortical electrodes. In addition to expected physiological increases in high gamma (60–200 Hz) activity during speech production, time-frequency analysis in many channels revealed a narrowband gamma component that exhibited a pattern similar to that observed in the speech audio spectrogram. This component was present to different degrees in multiple types of neural recordings. We show that this component tracks the fundamental frequency of the participant's voice, correlates with the power spectrum of speech and has coherence with the produced speech audio. A vibration sensor attached to the stereotactic frame recorded speech-induced vibrations with the same pattern observed in the LFPs. No corresponding component was identified in any neural channel during the listening epoch of a syllable repetition task. These observations demonstrate how speech-induced vibrations can create artifacts in the primary frequency band of interest. Identifying and accounting for these artifacts is crucial for establishing the validity and reproducibility of speech-related data obtained from intracranial recordings during DBS surgery.Fil: Bush, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Chrabaszcz, Anna. University of Pittsburgh; Estados UnidosFil: Peterson, Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe. Instituto de Matemática Aplicada del Litoral. Universidad Nacional del Litoral. Instituto de Matemática Aplicada del Litoral; Argentina. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados UnidosFil: Saravanan, Varun. Massachusetts General Hospital; Estados Unidos. Massachusetts Institute of Technology; Estados UnidosFil: Dastolfo Hromack, Christina. West Virginia University; Estados Unidos. University of Pittsburgh; Estados UnidosFil: Lipski, Witold J.. Univeristy of Pittsburgh. School of Medicine; Estados UnidosFil: Richardson, R. Mark. Massachusetts General Hospital; Estados Unidos. Harvard Medical School; Estados Unido

Photocatalytic activity and antibacterial efficacy of titanium dioxide nanoparticles mediated by Myristica fragrans seed extract

The synthesis of semiconductor metal/metal oxide nanoparticles (NP) via the green synthesis routes is desirable due to its effectiveness, economical, and eco-friendly nature of the products. The present study aims to synthesize the titanium dioxide (TiO2) NP via the green synthesis route, using Myristica fragrans plant extract as the reducing agent, where the photocatalytic activity was evaluated. The physicochemical and morphological properties of TiO2 NP have been analyzed using spectroscopic and electron microscopic techniques. From the analysis, the powdered X-ray diffraction (XRD) indicated the formation of very well crystalline TiO2 particles in the anatase phase, while the Fourier transform infrared (FTIR) spectroscopy confirmed the presence of Ti[sbnd]O bonds, and UV–Vis spectroscopy proofed the optical properties. The field emission scanning electron microscopy (FESEM) analysis provided the surface morphological characteristics and the formation of spherical shape particles; and the electron diffraction X-ray analysis (EDX) indicated the elemental composition. The photocatalytic activity of the TiO2 NP was evaluated based on the degradation rate of two aqueous dye solutions, i.e. methylene blue (MB) and congo red (Con-R) using the 8 W Xenon lamp as the light source for the visible irradiation. The degradation activity of the Con-R dye is slightly higher (99% degradation in 45 min) than that of the MB dye (97% degradation in 60 min). Both degradations activity followed the first-order kinetic model. The high activity of TiO2 NP on both dyes was supported by the increased absorption of light, associated charge separation efficiency, and specific surface area as provided by the UV–Vis DRS analysis. The plant extract mediated the synthesis of TiO2 which formed stable particles without losing the semiconducting and photocatalytic properties, where the holes (h+) and superoxide radicals ([rad]O2-) contributed to the enhanced degradation of dye. The antibacterial activity of the TiO2 NP (50 and 100 µg/mL; 6 h) synthesized was evaluated by testing against two different bacterial cultures of K. pneumoniae and S. aureus. The results proved that the particles became active only in the presence of UV light exposed and no significant differences in bacterial inhibition efficiency between the two cell types (79% and 72%) as observed. The antibacterial activity of the TiO2 NP was proven by the epifluorescence microscopic analysis, total viable count (TVC), and zone of inhibition (ZOI)