Hysteresis-based Voltage and Current Control Techniques for Grid Connected Solar Photovoltaic Systems: Comparative Study

Solar PV system development and integration with existing grid is very fast in recent years all over the world, as they require limited maintenance, pollution free and simple structure. When observing the factors affecting the performance of the grid connected solar photovoltaic system, the inverter output voltage with harmonics add with the harmonics generated due to the non-linear loads, retain a bigger challenge to maintain power quality in the grid. To maintain grid power quality, better inverter control technique should be developed. This paper presents the two control techniques for grid-tied inverters. This study developed the hysteresis controller for the inverter. Hysteresis controller used in this work two way (i) Voltage control mode (ii) Current control mode. Matlab/Simulink model is developed for the proposed system. Further the study presents the comparative evaluation of the performance of both control techniques based on the percentage of total harmonic distortion (THD) with the limits specified by the standards such as IEEE 1547 and IEC 61727 and IEEE Std 519-201

Aufklärung der Wirkmechanismen bioaktiver kleiner Moleküle auf der Basis von High-Content-Analysen

Natural products are a prime source of “lead” compounds who owe their biological diversity to a broad spectrum of mechanisms which are often difficult to elucidate. This study applied high content analysis methods as the basis to get hints towards the mode of action (MoA) of a set of compounds of interest. These methods included two cell-based approaches, one based on automated microscopy which provides information in the form of immunofluorescence images and the other based on the xCELLigence system providing impedance curves as a result of a real-time monitoring of cell perturbations. Profiles from individual approaches were compared with those of reference compounds whose mechanisms were known and well established. The cytotoxic activity of few selected bioactive compounds, namely jerantinine E, paleo-soraphen A & B, and Dsz A1 and Z varied from micro- to subnanomolar ranges in cancer cells. Jerantinine E, an indole alkaloid, was shown to interfere with tubulin polymerisation. Paleo-soraphen A & B, genetic derivatives of soraphen A, were less active than their parent compound and seemed to have different mechanisms. Paleo-soraphen A showed a mechanism similar to that of soraphen A whereas paleo-soraphen B showed effects similar to the topoisomerase I inhibitor camptothecin. Most potent among all were disorazol (Dsz) A1 and Z which have been known as tubulin polymerisation inhibitors. Detailed investigations presented here revealed additional targets which were addressed at lower concentrations. Drug affinity responsive target stability (DARTS) approaches showed that Dsz A1 binds to the phosphatase enzyme PTEN which antagonizes the PI3K/Akt pathway whereas Dsz Z targets dephosphorylation of the regulatory unit of PI3 kinase, p85. Western blot analysis showed that Dsz A1 and Z, though structurally similar, have different biological implication. Dsz A1 affects the PI3K/Akt pathway whereas Dsz Z stalls the PI3K/SGK pathway, independent of Akt. Knockdown studies of the respective target proteins confirmed their involvement in the different pathways. Measuring oligonucleosome enrichment confirmed the decisive role of PTEN in apoptosis induction by Dsz A1. Caspase activity measurements in knockdown cells provided evidence of the role played by p85 in apoptosis induction by Dsz Z.Naturstoffe sind eine vorzügliche Quelle für Leitstrukturen, die ihre biologische Vielfalt einem breiten Spektrum an Wirkmechanismen verdanken, die aber oft schwierig aufzuklären sind. Diese Studie benutzte „High-Content“-Analysemethoden als Grundlage, um Hinweise auf den Wirkmechanismus ausgewählter Verbindungen zu bekommen. Diese Methoden umfassten zwei zell-basierte Ansätze; einer basierend auf automatischer Mikroskopie liefert Informationen in Form von Immunfluoreszenz-Bildern und der andere basierend dem xCELLigence-System Impedanzkurven als Ergebnis eines Echtzeit-Monitoring von Zellstörungen. Die Profile der individuellen Ansätze wurden mit denen von Referenz-Verbindungen verglichen, deren Wirkmechanismus bekannt und gut untersucht ist. Die zytotoxische Aktivität einiger ausgewählter bioaktiver Verbindungen, Jerantinine E, Paläo-Soraphen A und B und Disorazol A1 und Z, bei Krebszellen lag im mikro- bis subnanomolaren Bereich. Für das Indolalkaloid Jerantinine E konnte gezeigt werden, dass es die Tubulinpolymerisation stört. Paläo-Soraphen A und B, „genetische“ Derivate von Soraphen A, waren weniger aktiv als die Mutterverbindung und schienen verschiedene Wirkmechanismen zu haben. Während der Wirkmechanismus von Paläo-Soraphen A dem von Soraphen A glich, zeigte Paläo-Soraphen B Effekte, ähnlich denen des Topoisomerase-I-Hemmers Camptothecin. Am wirksamsten waren Disorazol (Dsz) A1 und Z, bekannt als Hemmer der Tubulin-Polymerisation. Die hier vorgestellten Untersuchungen deckten zusätzliche Zielproteine auf, die bei niedrigeren Konzentrationen adressiert werden. DARTS-Ansätze (drug affinity responsive target stability) zeigten, dass Dsz A1 an das Phosphatase-Enzym PTEN bindet, was zu einer Hemmung des PI3K/Akt-Signalwegs führt, während Dsz Z auf p85 abzielt, die regulatorische Einheit der PI3-Kinase. Western-Blot-Analysen zeigten, dass Dsz A1 und Z, obwohl strukturell ähnlich, verschiedene biologische Wirkungen haben. Dsz A1 beeinflusste den PI3K/Akt-Signalweg, während Dsz Z unabhängig von Akt den PI3K/SGK-Signalweg blockierte. Dsz Z induzierte eine Dephosphorylierung von p85. Knockdown-Studien mit den entsprechenden Zielproteinen bestätigten ihre Einbindung in die verschiedenen Signalwege. Eine Messung der Anreicherung von Oligonuclesomen bestätigte die maßgebende Rolle von PTEN in der Apoptose-Induktion durch Dsz A1. Caspase-Aktivitätsmesssungen in Knockdown-Zellen belegten die Rolle von p85 in der durch Dsz Z induzierten Apoptose

Seroprevalence of COVID-19 infection in a rural district of Tamil Nadu: A population-based seroepidemiological study

Background: Coronavirus disease 2019 (COVID-19) was a recent global pandemic of the era which posed a great challenge for the health care in terms of preventive, diagnostic and treatment dimensions. The seroprevalence rate of COVID IgG antibodies is very crucial in estimating the susceptibility of a particular area to the viral disease. In our study, we estimated the seroprevalence of COVID-19 in a rural area. Aims and Objectives: We aimed to estimate the seroprevalence of COVID-19 in a rural district of Tamil Nadu, 6 months after the index case. Materials and Methods: We conducted a cross-sectional study of 509 adults aged more than 18 years. From all the seven Taluks, two gram panchayats (administrative cluster of 8–10 villages) were randomly selected followed by one village through convenience. The participants were invited for the study to the community-based study kiosk set up in all the eight villages through village health committees. We collected sociodemographic characteristics and symptoms using a mobile application-based questionnaire, and we tested samples for the presence of IgG antibodies for severe acute respiratory syndrome coronavirus 2 using an electro chemiluminescent immunoassay. We calculated age-gender adjusted and test performance adjusted seroprevalence. Results: The age-and gender-adjusted seroprevalence was 8.5% (95% confidence interval [CI] 6.9–10.8%). The unadjusted seroprevalence among participants with hypertension and diabetes was 16.3% (95% CI: 9.2–25.8) and 10.7% (95% CI: 5.5–18.3), respectively. When we adjusted for the test performance, the seroprevalence was 6.1% (95% CI 4.02–8.17). The study estimated 7 (95% CI 1:4.5–1:9) undetected infected individuals for every reverse transcription polymerase chain reaction confirmed case. Infection fatality rate (IFR) was calculated as 12.38/10,000 infections as on October 22, 2020. History of self-reported symptoms and education were significantly associated with positive status (P<0.05). Conclusion: A significant proportion of the rural population in a district of Tamil Nadu remains susceptible to COVID-19. A higher proportion of susceptible, relatively higher IFR, and a poor tertiary health-care network stress the importance of sustaining the public health measures and promoting early access to the vaccine are crucial to preserving the health of this population. Low population density, good housing, adequate ventilation, limited urbanization combined with public, private, and local health leadership are critical components of curbing future respiratory pandemics

Total Synthesis and Biological Evaluation of Jerantinine E

The first total synthesis of the alkaloid natural product jerantinine E is based on a selective cyclization of an aminocyclopropane. Preliminary investigations show that it inhibits the polymerization of tubulin, displaying significant cytotoxicity and antimigratory activity against both breast and lung cancer cell lines

Dysregulated miRNAome and Proteome of PPRV Infected Goat PBMCs Reveal a Coordinated Immune Response

In this study, the miRNAome and proteome of virulent Peste des petits ruminants virus (PPRV) infected goat peripheral blood mononuclear cells (PBMCs) were analyzed. The identified differentially expressed miRNAs (DEmiRNAs) were found to govern genes that modulate immune response based on the proteome data. The top 10 significantly enriched immune response processes were found to be governed by 98 genes. The top 10 DEmiRNAs governing these 98 genes were identified based on the number of genes governed by them. Out of these 10 DEmiRNAs, 7 were upregulated, and 3 were downregulated. These include miR-664, miR-2311, miR-2897, miR-484, miR-2440, miR-3533, miR-574, miR-210, miR-21-5p, and miR-30. miR-664 and miR-484 with proviral and antiviral activities, respectively, were upregulated in PPRV infected PBMCs. miR-210 that inhibits apoptosis was downregulated. miR-21-5p that decreases the sensitivity of cells to the antiviral activity of IFNs and miR-30b that inhibits antigen processing and presentation by primary macrophages were downregulated, indicative of a strong host response to PPRV infection. miR-21-5p was found to be inhibited on IPA upstream regulatory analysis of RNA-sequencing data. This miRNA that was also highly downregulated and was found to govern 16 immune response genes in the proteome data was selected for functional validation vis-a-vis TGFBR2 (TGF-beta receptor type-2). TGFBR2 that regulates cell differentiation and is involved in several immune response pathways was found to be governed by most of the identified immune modulating DEmiRNAs. The decreased luciferase activity in Dual Luciferase Reporter Assay indicated specific binding of miR-21-5p and miR-484 to their target thus establishing specific binding of the miRNAs to their targets.This is the first report on the miRNAome and proteome of virulent PPRV infected goat PBMCs

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019 : A systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

Global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: In an era of shifting global agendas and expanded emphasis on non-communicable diseases and injuries along with communicable diseases, sound evidence on trends by cause at the national level is essential. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides a systematic scientific assessment of published, publicly available, and contributed data on incidence, prevalence, and mortality for a mutually exclusive and collectively exhaustive list of diseases and injuries. Methods: GBD estimates incidence, prevalence, mortality, years of life lost (YLLs), years lived with disability (YLDs), and disability-adjusted life-years (DALYs) due to 369 diseases and injuries, for two sexes, and for 204 countries and territories. Input data were extracted from censuses, household surveys, civil registration and vital statistics, disease registries, health service use, air pollution monitors, satellite imaging, disease notifications, and other sources. Cause-specific death rates and cause fractions were calculated using the Cause of Death Ensemble model and spatiotemporal Gaussian process regression. Cause-specific deaths were adjusted to match the total all-cause deaths calculated as part of the GBD population, fertility, and mortality estimates. Deaths were multiplied by standard life expectancy at each age to calculate YLLs. A Bayesian meta-regression modelling tool, DisMod-MR 2.1, was used to ensure consistency between incidence, prevalence, remission, excess mortality, and cause-specific mortality for most causes. Prevalence estimates were multiplied by disability weights for mutually exclusive sequelae of diseases and injuries to calculate YLDs. We considered results in the context of the Socio-demographic Index (SDI), a composite indicator of income per capita, years of schooling, and fertility rate in females younger than 25 years. Uncertainty intervals (UIs) were generated for every metric using the 25th and 975th ordered 1000 draw values of the posterior distribution. Findings: Global health has steadily improved over the past 30 years as measured by age-standardised DALY rates. After taking into account population growth and ageing, the absolute number of DALYs has remained stable. Since 2010, the pace of decline in global age-standardised DALY rates has accelerated in age groups younger than 50 years compared with the 1990–2010 time period, with the greatest annualised rate of decline occurring in the 0–9-year age group. Six infectious diseases were among the top ten causes of DALYs in children younger than 10 years in 2019: lower respiratory infections (ranked second), diarrhoeal diseases (third), malaria (fifth), meningitis (sixth), whooping cough (ninth), and sexually transmitted infections (which, in this age group, is fully accounted for by congenital syphilis; ranked tenth). In adolescents aged 10–24 years, three injury causes were among the top causes of DALYs: road injuries (ranked first), self-harm (third), and interpersonal violence (fifth). Five of the causes that were in the top ten for ages 10–24 years were also in the top ten in the 25–49-year age group: road injuries (ranked first), HIV/AIDS (second), low back pain (fourth), headache disorders (fifth), and depressive disorders (sixth). In 2019, ischaemic heart disease and stroke were the top-ranked causes of DALYs in both the 50–74-year and 75-years-and-older age groups. Since 1990, there has been a marked shift towards a greater proportion of burden due to YLDs from non-communicable diseases and injuries. In 2019, there were 11 countries where non-communicable disease and injury YLDs constituted more than half of all disease burden. Decreases in age-standardised DALY rates have accelerated over the past decade in countries at the lower end of the SDI range, while improvements have started to stagnate or even reverse in countries with higher SDI. Interpretation: As disability becomes an increasingly large component of disease burden and a larger component of health expenditure, greater research and developm nt investment is needed to identify new, more effective intervention strategies. With a rapidly ageing global population, the demands on health services to deal with disabling outcomes, which increase with age, will require policy makers to anticipate these changes. The mix of universal and more geographically specific influences on health reinforces the need for regular reporting on population health in detail and by underlying cause to help decision makers to identify success stories of disease control to emulate, as well as opportunities to improve. Funding: Bill & Melinda Gates Foundation. © 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 licens

Measuring universal health coverage based on an index of effective coverage of health services in 204 countries and territories, 1990–2019: a systematic analysis for the Global Burden of Disease Study 2019

Background Achieving universal health coverage (UHC) involves all people receiving the health services they need, of high quality, without experiencing financial hardship. Making progress towards UHC is a policy priority for both countries and global institutions, as highlighted by the agenda of the UN Sustainable Development Goals (SDGs) and WHO's Thirteenth General Programme of Work (GPW13). Measuring effective coverage at the health-system level is important for understanding whether health services are aligned with countries' health profiles and are of sufficient quality to produce health gains for populations of all ages. Methods Based on the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, we assessed UHC effective coverage for 204 countries and territories from 1990 to 2019. Drawing from a measurement framework developed through WHO's GPW13 consultation, we mapped 23 effective coverage indicators to a matrix representing health service types (eg, promotion, prevention, and treatment) and five population-age groups spanning from reproductive and newborn to older adults (≥65 years). Effective coverage indicators were based on intervention coverage or outcome-based measures such as mortality-to-incidence ratios to approximate access to quality care; outcome-based measures were transformed to values on a scale of 0–100 based on the 2·5th and 97·5th percentile of location-year values. We constructed the UHC effective coverage index by weighting each effective coverage indicator relative to its associated potential health gains, as measured by disability-adjusted life-years for each location-year and population-age group. For three tests of validity (content, known-groups, and convergent), UHC effective coverage index performance was generally better than that of other UHC service coverage indices from WHO (ie, the current metric for SDG indicator 3.8.1 on UHC service coverage), the World Bank, and GBD 2017. We quantified frontiers of UHC effective coverage performance on the basis of pooled health spending per capita, representing UHC effective coverage index levels achieved in 2019 relative to country-level government health spending, prepaid private expenditures, and development assistance for health. To assess current trajectories towards the GPW13 UHC billion target—1 billion more people benefiting from UHC by 2023—we estimated additional population equivalents with UHC effective coverage from 2018 to 2023. Findings Globally, performance on the UHC effective coverage index improved from 45·8 (95% uncertainty interval 44·2–47·5) in 1990 to 60·3 (58·7–61·9) in 2019, yet country-level UHC effective coverage in 2019 still spanned from 95 or higher in Japan and Iceland to lower than 25 in Somalia and the Central African Republic. Since 2010, sub-Saharan Africa showed accelerated gains on the UHC effective coverage index (at an average increase of 2·6% [1·9–3·3] per year up to 2019); by contrast, most other GBD super-regions had slowed rates of progress in 2010–2019 relative to 1990–2010. Many countries showed lagging performance on effective coverage indicators for non-communicable diseases relative to those for communicable diseases and maternal and child health, despite non-communicable diseases accounting for a greater proportion of potential health gains in 2019, suggesting that many health systems are not keeping pace with the rising non-communicable disease burden and associated population health needs. In 2019, the UHC effective coverage index was associated with pooled health spending per capita (r=0·79), although countries across the development spectrum had much lower UHC effective coverage than is potentially achievable relative to their health spending. Under maximum efficiency of translating health spending into UHC effective coverage performance, countries would need to reach $1398 pooled health spending per capita (US$ adjusted for purchasing power parity) in order to achieve 80 on the UHC effective coverage index. From 2018 to 2023, an estimated 388·9 million (358·6–421·3) more population equivalents would have UHC effective coverage, falling well short of the GPW13 target of 1 billion more people benefiting from UHC during this time. Current projections point to an estimated 3·1 billion (3·0–3·2) population equivalents still lacking UHC effective coverage in 2023, with nearly a third (968·1 million [903·5–1040·3]) residing in south Asia. Interpretation The present study demonstrates the utility of measuring effective coverage and its role in supporting improved health outcomes for all people—the ultimate goal of UHC and its achievement. Global ambitions to accelerate progress on UHC service coverage are increasingly unlikely unless concerted action on non-communicable diseases occurs and countries can better translate health spending into improved performance. Focusing on effective coverage and accounting for the world's evolving health needs lays the groundwork for better understanding how close—or how far—all populations are in benefiting from UHC

Global, regional, and national progress towards Sustainable Development Goal 3.2 for neonatal and child health: all-cause and cause-specific mortality findings from the Global Burden of Disease Study 2019

Background Sustainable Development Goal 3.2 has targeted elimination of preventable child mortality, reduction of neonatal death to less than 12 per 1000 livebirths, and reduction of death of children younger than 5 years to less than 25 per 1000 livebirths, for each country by 2030. To understand current rates, recent trends, and potential trajectories of child mortality for the next decade, we present the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 findings for all-cause mortality and cause-specific mortality in children younger than 5 years of age, with multiple scenarios for child mortality in 2030 that include the consideration of potential effects of COVID-19, and a novel framework for quantifying optimal child survival. Methods We completed all-cause mortality and cause-specific mortality analyses from 204 countries and territories for detailed age groups separately, with aggregated mortality probabilities per 1000 livebirths computed for neonatal mortality rate (NMR) and under-5 mortality rate (USMR). Scenarios for 2030 represent different potential trajectories, notably including potential effects of the COVID-19 pandemic and the potential impact of improvements preferentially targeting neonatal survival. Optimal child survival metrics were developed by age, sex, and cause of death across all GBD location-years. The first metric is a global optimum and is based on the lowest observed mortality, and the second is a survival potential frontier that is based on stochastic frontier analysis of observed mortality and Healthcare Access and Quality Index. Findings Global U5MR decreased from 71.2 deaths per 1000 livebirths (95% uncertainty interval WI] 68.3-74-0) in 2000 to 37.1 (33.2-41.7) in 2019 while global NMR correspondingly declined more slowly from 28.0 deaths per 1000 live births (26.8-29-5) in 2000 to 17.9 (16.3-19-8) in 2019. In 2019,136 (67%) of 204 countries had a USMR at or below the SDG 3.2 threshold and 133 (65%) had an NMR at or below the SDG 3.2 threshold, and the reference scenario suggests that by 2030,154 (75%) of all countries could meet the U5MR targets, and 139 (68%) could meet the NMR targets. Deaths of children younger than 5 years totalled 9.65 million (95% UI 9.05-10.30) in 2000 and 5.05 million (4.27-6.02) in 2019, with the neonatal fraction of these deaths increasing from 39% (3.76 million 95% UI 3.53-4.021) in 2000 to 48% (2.42 million; 2.06-2.86) in 2019. NMR and U5MR were generally higher in males than in females, although there was no statistically significant difference at the global level. Neonatal disorders remained the leading cause of death in children younger than 5 years in 2019, followed by lower respiratory infections, diarrhoeal diseases, congenital birth defects, and malaria. The global optimum analysis suggests NMR could be reduced to as low as 0.80 (95% UI 0.71-0.86) deaths per 1000 livebirths and U5MR to 1.44 (95% UI 1-27-1.58) deaths per 1000 livebirths, and in 2019, there were as many as 1.87 million (95% UI 1-35-2.58; 37% 95% UI 32-43]) of 5.05 million more deaths of children younger than 5 years than the survival potential frontier. Interpretation Global child mortality declined by almost half between 2000 and 2019, but progress remains slower in neonates and 65 (32%) of 204 countries, mostly in sub-Saharan Africa and south Asia, are not on track to meet either SDG 3.2 target by 2030. Focused improvements in perinatal and newborn care, continued and expanded delivery of essential interventions such as vaccination and infection prevention, an enhanced focus on equity, continued focus on poverty reduction and education, and investment in strengthening health systems across the development spectrum have the potential to substantially improve USMR. Given the widespread effects of COVID-19, considerable effort will be required to maintain and accelerate progress. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd