Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression

Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H–R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O2), and the presence of and frequency of H–R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups

The seen and the unseen: Impact of a conditional cash transfer program on prenatal sex selection

How is prenatal sex selective behaviour influenced by the presence of cheap fetal gender identification technology and financial incentives? We analyze a conditional cash transfer program in India called Janani Suraksha Yojna. By providing access to prenatal sex detection technology like the ultrasound scans, and simultaneously providing cash incentives to both households and community health workers for every live birth, this program altered existing trends in prenatal sex selection. Using difference-indifferences and triple difference estimators we find that the policy led to an increase in female births. This improvement comes at a cost, as we observe an increase in under5 mortality for girls born at higher birth orders, indicating a shift in discrimination against girls from pre-natal to post-natal. Our calculations show that the net effect of the policy was that nearly 300,000 more girls survived in treatment households between 2006 and 2015. Finally, we find that the role played by community health workers in facilitating the program is a key driver of the decline in prenatal sex selection

Distributed architecture for self-organising smart distribution systems

Automation of emerging smart distribution grids is required to operate the grid efficiently and swiftly. This study draws a vision on grid automation with agent-based cyber-physical system integration to provide a truly distributed architecture. Furthermore, this study introduces a notion of self-organising smart distribution grid that promotes the grid capability to heal and organise itself in the best-suited topology without the intervention of a central operator. The proposed architecture comprises the system of bus agents (BAs) that emulate the given grid. This emulation is used by BAs to comprehend the grid conditions, switch location and compute their representative bus voltage and partial loss and to estimate the best organisation of the BAs as well as the grid. This study details the behavioural designing of BA that incorporates the functioning above. The proposed architecture also uses an event trigger approach to initiate grid organisation, which is showcased by case studies on IEEE 33 bus system. The results showcase the efficiency of the concept regarding solution accuracy with distributed computations; computational efficiency during contingencies; architecture performance under communication latency; and fault-tolerant characteristics of the proposed architecture

Acute vs. Chronic vs. Cyclic Hypoxia: Their Differential Dynamics, Molecular Mechanisms, and Effects on Tumor Progression

Hypoxia has been shown to increase the aggressiveness and severity of tumor progression. Along with chronic and acute hypoxic regions, solid tumors contain regions of cycling hypoxia (also called intermittent hypoxia or IH). Cyclic hypoxia is mimicked in vitro and in vivo by periodic exposure to cycles of hypoxia and reoxygenation (H-R cycles). Compared to chronic hypoxia, cyclic hypoxia has been shown to augment various hallmarks of cancer to a greater extent: angiogenesis, immune evasion, metastasis, survival etc. Cycling hypoxia has also been shown to be the major contributing factor in increasing the risk of cancer in obstructive sleep apnea (OSA) patients. Here, we first compare and contrast the effects of acute, chronic and intermittent hypoxia in terms of molecular pathways activated and the cellular processes affected. We highlight the underlying complexity of these differential effects and emphasize the need to investigate various combinations of factors impacting cellular adaptation to hypoxia: total duration of hypoxia, concentration of oxygen (O-2), and the presence of and frequency of H-R cycles. Finally, we summarize the effects of cycling hypoxia on various hallmarks of cancer highlighting their dependence on the abovementioned factors. We conclude with a call for an integrative and rigorous analysis of the effects of varying extents and durations of hypoxia on cells, including tools such as mechanism-based mathematical modelling and microfluidic setups

Cone beam computed tomography guided surgical stent: A preimplant planning procedure, a pilot study

Aim: The aim of the present study was to evaluate the efficacy of cone-beam computed tomography (CBCT)-based radiologic stent in guidance for preimplant placement procedures. Setting and Design: This study was a pilot study conducted among 5 patients who presented for dental implants and attending the department of Oral Medicine and Radiology, ITS Dental College, Muradnagar for CBCT volumetric scans. Materials and Methods: The dimensions of bone available for implants were measured from the scans. A radiologic stent was prepared on the study model using three radiopaque pins per implant site, which simulated the implant in the CBCT scan. The pin which was in the direction of the residual bone was identified and retained, and the remaining pins were removed. The retained pin was utilized and the final surgical stent was prepared. It was checked if the final implant placement could be accomplished surgically using the modified stent. Results: A total of 7 implants were inserted. The final implant placement was based on the CBCT data and was evaluated by postoperative radiographs. All the implant sites showed proper placement of the implants. Conclusion: The stent used in our study was cost effective and easy to fabricate. Apart from the anteroposterior direction, it was also possible to give buccolingual direction to the implant, reducing the chances of perforation

Social Media and the Broadening of Social Movements: Evidence from Black Lives Matter

How do modern social movements broaden their base? Prompted by the viral video footage of George Floyd's murder, the Black Lives Matter (BLM) movement gained unprecedented scope in the spring of 2020. In this paper, we show that pandemic exposure (COVID-19 related deaths) significantly increased the take-up of social media and subsequently mobilized protesters in whiter, more affluent and suburban counties with low ex-ante probability of protesting. We exploit Super Spreader Events in the early stages of the pandemic as a source of plausibly exogenous variation at the county level and develop a novel index of social media penetration, using information from more than 45 million tweets, google searches and mobility data. We show that a one standard deviation increase in pandemic exposure increased the number of new Twitter accounts by 27% and increased protest propensity by 9 percentage points. Our results suggest that social media can be persuasive and inspire action outside of traditional coalitions