Finite-State Genericity : on the Diagonalization Strength of Finite Automata

Algorithmische Generizit¨atskonzepte spielen eine wichtige Rolle in der Berechenbarkeitsund Komplexit¨atstheorie. Diese Begriffe stehen in engem Zusammenhang mit grundlegenden Diagonalisierungstechniken, und sie wurden zur Erzielung starker Trennungen von Komplexit¨atsklassen verwendet. Da f¨ur jedes Generizit¨atskonzept die zugeh¨origen generischen Mengen eine co-magere Klasse bilden, ist die Analyse generischer Mengen ein wichtiges Hifsmittel f¨ur eine quantitative Analyse struktureller Ph¨anomene. Typischerweise werden Generizit¨atskonzepte mit Hilfe von Erweiterungsfunktionen definiert, wobei die St¨arke eines Konzepts von der Komplexit¨at der zugelassenen Erwiterungsfunktionen abh¨angt. Hierbei erweisen sich die sog. schwachen Generizit¨atskonzepte, bei denen nur totale Erweiterungsfunktionen ber¨ucksichtigt werden, meist als wesentlich schw¨acher als die vergleichbaren allgemeinen Konzepte, bei denen auch partielle Funktionen zugelassen sind. Weiter sind die sog. beschr¨ankten Generizit¨atskonzepte – basierend auf Erweiterungen konstanter L¨ange – besonders interessant, da hier die Klassen der zugeh¨origen generischen Mengen nicht nur co-mager sind sondern zus¨atzlich Maß 1 haben. Generische Mengen diesen Typs sind daher typisch sowohl im topologischen wie im maßtheoretischen Sinn. In dieser Dissertation initiieren wir die Untersuchung von Generizit¨at im Bereich der Theorie der Formalen Sprachen: Wir f¨uhren finite-state-Generizit¨atskonzepte ein und verwenden diese, um die Diagonalisierungsst¨arke endlicher Automaten zu erforschen. Wir konzentrieren uns hierbei auf die beschr¨ankte finite-state-Generizit¨at und Spezialf ¨alle hiervon, die wir durch die Beschr¨ankung auf totale Erweiterungsfunktionen bzw. auf Erweiterungen konstanter L¨ange erhalten. Wir geben eine rein kombinatorische Charakterisierung der beschr¨ankt finite-state-generischen Mengen: Diese sind gerade die Mengen, deren charakteristische Folge saturiert ist, d.h. jedes Bin¨arwort als Teilwort enth¨alt. Mit Hilfe dieser Charakterisierung bestimmen wir die Komplexit¨at der beschr¨ankt finitestate- generischen Mengen und zeigen, dass solch eine generische Menge nicht regul¨ar sein kann es aber kontext-freie Sprachen mit dieser Generizit¨atseigenschaft gibt. Die von uns betrachteten unbeschr¨ankten finite-state-Generizit¨atskonzepte basieren auf Moore-Funktionen und auf Verallgemeinerungen dieser Funktionen. Auch hier vergleichen wir die St¨arke der verschiedenen korrespondierenden Generizit¨atskonzepte und er¨ortern die Frage, inwieweit diese Konzepte m¨achtiger als die beschr¨ankte finite-state-Generizit ¨at sind. Unsere Untersuchungen der finite-state-Generizit¨at beruhen zum Teil auf neuen Ergebnissen ¨uber Bi-Immunit¨at in der Chomsky-Hierarchie, einer neuen Chomsky-Hierarchie f¨ur unendliche Folgen und einer gr¨undlichen Untersuchung der saturierten Folgen. Diese Ergebnisse – die von unabh¨angigem Interesse sind – werden im ersten Teil der Dissertation vorgestellt. Sie k¨onnen unabh¨angig von dem Hauptteil der Arbeit gelesen werden

Lektürehinweis

Das Handbuch ist eine periodische und mehrsprachige Online-Publikation. Die bisher veröffentlichten Bände wurden bereits über 8.500 Mal heruntergeladen. Für Leserinnen und Leser, die das haptische Leseerlebnis bevorzugen, ist die Publikation zudem im Printformat erhältlich. Zu ausgewählten Konzepten der Sprachkritik werden sukzessive enzyklopädische Artikel veröffentlicht, die ein sprachkritisches Schlüsselkonzept betreffen und die für die europäische Perspektive von kultureller Bedeutung sind. Das Ziel ist demnach, eine Konzeptgeschichte der europäischen Sprachkritik zu präsentieren. Zum einen liefert das Handbuch einen spezifischen Blick auf die jeweiligen Sprachkulturen. Zum anderen werden diese vergleichend in den Blick genommen.The handbook is a periodical and multilingual online publication. The volumes published to date have already been downloaded more than 8,500 times. For readers who prefer the tactile pleasures of reading, a print version is available. Encyclopaedic articles are published successively on selected topics that highlight key issues in language criticism and that are of cultural relevance for the European perspective. The handbook is aimed at presenting a conceptual history of European language criticism. The handbook not only provides insight into the specific language cultures, but also compares and contrasts them.Ce manuel est une publication en ligne périodique et polyglotte. Les tomes publiés jusqu’à maintenant ont déjà connu plus de 8500 téléchargements. Pour des lectrices et des lecteurs qui privilégieraient une lecture sur papier, la publication de ces tomes est également disponible dans un format imprimé. Sont publiés successivement sur des thèmes à propos de concepts particuliers de Sprachkritik des articles encyclopédiques qui traitent d’un concept clé de Sprachkritik et qui sont porteurs d’une grande signification culturelle dans la perspective européenne. L’objectif est de présenter une histoire conceptuelle de la Sprachkritik européenne. D’une part, ce manuel fournit un regard spécifique sur les cultures linguistiques concernées. D’autre part, ces concepts font l’objet d’une étude comparative.Il Manuale è una pubblicazione online periodica e plurilingue. I volumi finora pubblicati sono stati scaricati più di 8500 volte. Per i lettori, che preferiscono la lettura su carta, la pubblicazione è disponibi-le anche in formato cartaceo. In seguito verranno pubblicati ulteriori articoli enciclopedici su concetti legati alla Sprachkritik, nei quali si approfondisca un concetto chiave legato alla Sprachkritik stessa e che abbiano un’importanza culturale per la prospettiva europea. L’obiettivo è dunque quello di presentare una storia concettuale della Sprachkritik europea: da una parte il Manuale fornisce una visione specifi-ca alle rispettive culture linguistiche; dall’altra esse vengono considerate in chiave comparativa.Priručnik periodički izlazi u obliku višejezične internetske publikacije, a dosad objavljeni svesci preuzeti su s interneta više od 8500 puta. Za one čitateljice i čitatelje koji preferiraju taktilni doživljaj čitanja, publikacija je dostupna i u tiskanom obliku. Na odabrane jezičnokritičke teme postepeno se objavljuju enciklopedijski članci koji obrađuju ključne jezičnokritičke koncepte te su od kulturološkog značaja iz europske perspektive. Cilj je pritom prezentirati povijest koncepta jezične kritike u Europi, pa tako priručnik s jedne strane omogućava jedinstveni uvid u pojedinačne jezične kulture, dok s druge strane uzima u obzir i komparativnu perspektivu istih

Einleitung

Der vorliegende Band „Sprachinstitutionen und Sprachkritik“ weist eine unmittelbare Verbindung zu den ersten drei Bänden unserer Handbuchreihe und der Frage auf, wie sich das viel diskutierte und diskursiv konstituierte Konzept der sprachlichen Normierung und Standardisierung einer Nationalsprache im Vergleich der Sprachkulturen entwickelt hat und wie es sich aktuell wandelt. Diese Gesichtspunkte lassen aufschlussreiche Verbindungen zum ersten Handbuchband „Sprachnormierung und Sprachkritik“ erkennen, aber auch zum zweiten („Standardisierung und Sprachkritik“) und zum dritten Handbuchband („Sprachpurismus und Sprachkritik“).This present volume, "Language institutions and language criticism", is directly linked to the first three volumes of our Handbook series and to the question, within a comparison of linguistic cultures, as to the ways in which the much-discussed and discursively constituted concept of linguistic standardisation of a national language has developed, along with the ways in which it is currently changing. This perspective reveals enlightening links to the first volume of the Handbook, "Critique of language norms", along with both the second and third volumes ("Standardisation and language criticism" and "Linguistic purism und language criticism").Le volume suivant, intitulé « Institutions linguistiques et Sprachkritik » présente un lien immédiat avec les trois premiers volumes de notre manuel ainsi qu’avec la question de savoir comment le concept, constitué par le discours et beaucoup discuté, d’uniformisation linguistique et de standardisation d’une langue nationale s’est développé dans une comparaison des cultures linguistiques et comment ce concept change, à l’heure actuelle. Ces points de vue laissent apparaître des liens révélateurs avec le premier volume du manuel intitulé « Normalisation linguistique et Sprachkritik », mais aussi avec le deuxième volume (« Standardisation et Sprachkritik » ) et le troisième (« Purisme linguistique et Sprachkritik »).Il presente volume “Istituzioni linguistiche e Sprachkritik” si collega direttamente ai primi tre volumi della collana del nostro Manuale e alla domanda su come si sia sviluppato il concetto discusso e costruito discorsivamente delle norme linguistiche e della standardizzazione di una lingua nazionale nel confronto tra le diverse culture linguistiche e come questo sia cambiato nella situazione attuale. Questi punti di vista permettono di riconoscere collegamenti tra il primo volume del Manuale “Critica delle norme linguistiche e Sprachkritik”, il secondo “Standardizzazione e Sprachkritik” e il terzo “Purismo e Sprachkritik”.Ovaj svezak „Jezične institucije i jezična kritika“ usko je povezan s prethodnim trima svescima našeg priručnika te se nastavlja baviti pitanjem jezičnog normiranja i standardizacije nacionalnog jezika kao i njegovim razvojem i suvremenim stanjem u različitim jezičnim kulturama. Spomenuta pitanja jasno ukazuju na poveznice ovog dijela priručnika s prvim sveskom „Jezično normiranje i jezična kritika“, kao i s drugim („Standardizacija i jezična kritika“) i trećim („Jezični purizam i jezična kritika“) sveskom

A new lineage of Cryptococcus gattii (VGV) discovered in the central Zambezian Miombo woodlands

This is the final version. Available from the American Society for Microbiology via the DOI in this record.ABSTRACT We discovered a new lineage of the globally important fungal pathogen Cryptococcus gattii on the basis of analysis of six isolates collected from three locations spanning the Central Miombo Woodlands of Zambia, Africa. All isolates were from environments (middens and tree holes) that are associated with a small mammal, the African hyrax. Phylogenetic and population genetic analyses confirmed that these isolates form a distinct, deeply divergent lineage, which we name VGV. VGV comprises two subclades (A and B) that are capable of causing mild lung infection with negligible neurotropism in mice. Comparing the VGV genome to previously identified lineages of C. gattii revealed a unique suite of genes together with gene loss and inversion events. However, standard URA5 restriction fragment length polymorphism (RFLP) analysis could not distinguish between VGV and VGIV isolates. We therefore developed a new URA5 RFLP method that can reliably identify the newly described lineage. Our work highlights how sampling understudied ecological regions alongside genomic and functional characterization can broaden our understanding of the evolution and ecology of major global pathogens. IMPORTANCE Cryptococcus gattii is an environmental pathogen that causes severe systemic infection in immunocompetent individuals more often than in immunocompromised humans. Over the past 2 decades, researchers have shown that C. gattii falls within four genetically distinct major lineages. By combining field work from an understudied ecological region (the Central Miombo Woodlands of Zambia, Africa), genome sequencing and assemblies, phylogenetic and population genetic analyses, and phenotypic characterization (morphology, histopathological, drug-sensitivity, survival experiments), we discovered a hitherto unknown lineage, which we name VGV (variety gattii five). The discovery of a new lineage from an understudied ecological region has far-reaching implications for the study and understanding of fungal pathogens and diseases they cause

Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma Cells

Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM). Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ∼30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response

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

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

Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017

Background: Population estimates underpin demographic and epidemiological research and are used to track progress on numerous international indicators of health and development. To date, internationally available estimates of population and fertility, although useful, have not been produced with transparent and replicable methods and do not use standardised estimates of mortality. We present single-calendar year and single-year of age estimates of fertility and population by sex with standardised and replicable methods. Methods: We estimated population in 195 locations by single year of age and single calendar year from 1950 to 2017 with standardised and replicable methods. We based the estimates on the demographic balancing equation, with inputs of fertility, mortality, population, and migration data. Fertility data came from 7817 location-years of vital registration data, 429 surveys reporting complete birth histories, and 977 surveys and censuses reporting summary birth histories. We estimated age-specific fertility rates (ASFRs; the annual number of livebirths to women of a specified age group per 1000 women in that age group) by use of spatiotemporal Gaussian process regression and used the ASFRs to estimate total fertility rates (TFRs; the average number of children a woman would bear if she survived through the end of the reproductive age span [age 10–54 years] and experienced at each age a particular set of ASFRs observed in the year of interest). Because of sparse data, fertility at ages 10–14 years and 50–54 years was estimated from data on fertility in women aged 15–19 years and 45–49 years, through use of linear regression. Age-specific mortality data came from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 estimates. Data on population came from 1257 censuses and 761 population registry location-years and were adjusted for underenumeration and age misreporting with standard demographic methods. Migration was estimated with the GBD Bayesian demographic balancing model, after incorporating information about refugee migration into the model prior. Final population estimates used the cohort-component method of population projection, with inputs of fertility, mortality, and migration data. Population uncertainty was estimated by use of out-of-sample predictive validity testing. With these data, we estimated the trends in population by age and sex and in fertility by age between 1950 and 2017 in 195 countries and territories. Findings: From 1950 to 2017, TFRs decreased by 49\ub74% (95% uncertainty interval [UI] 46\ub74–52\ub70). The TFR decreased from 4\ub77 livebirths (4\ub75–4\ub79) to 2\ub74 livebirths (2\ub72–2\ub75), and the ASFR of mothers aged 10–19 years decreased from 37 livebirths (34–40) to 22 livebirths (19–24) per 1000 women. Despite reductions in the TFR, the global population has been increasing by an average of 83\ub78 million people per year since 1985. The global population increased by 197\ub72% (193\ub73–200\ub78) since 1950, from 2\ub76 billion (2\ub75–2\ub76) to 7\ub76 billion (7\ub74–7\ub79) people in 2017; much of this increase was in the proportion of the global population in south Asia and sub-Saharan Africa. The global annual rate of population growth increased between 1950 and 1964, when it peaked at 2\ub70%; this rate then remained nearly constant until 1970 and then decreased to 1\ub71% in 2017. Population growth rates in the southeast Asia, east Asia, and Oceania GBD super-region decreased from 2\ub75% in 1963 to 0\ub77% in 2017, whereas in sub-Saharan Africa, population growth rates were almost at the highest reported levels ever in 2017, when they were at 2\ub77%. The global average age increased from 26\ub76 years in 1950 to 32\ub71 years in 2017, and the proportion of the population that is of working age (age 15–64 years) increased from 59\ub79% to 65\ub73%. At the national level, the TFR decreased in all countries and territories between 1950 and 2017; in 2017, TFRs ranged from a low of 1\ub70 livebirths (95% UI 0\ub79–1\ub72) in Cyprus to a high of 7\ub71 livebirths (6\ub78–7\ub74) in Niger. The TFR under age 25 years (TFU25; number of livebirths expected by age 25 years for a hypothetical woman who survived the age group and was exposed to current ASFRs) in 2017 ranged from 0\ub708 livebirths (0\ub707–0\ub709) in South Korea to 2\ub74 livebirths (2\ub72–2\ub76) in Niger, and the TFR over age 30 years (TFO30; number of livebirths expected for a hypothetical woman ageing from 30 to 54 years who survived the age group and was exposed to current ASFRs) ranged from a low of 0\ub73 livebirths (0\ub73–0\ub74) in Puerto Rico to a high of 3\ub71 livebirths (3\ub70–3\ub72) in Niger. TFO30 was higher than TFU25 in 145 countries and territories in 2017. 33 countries had a negative population growth rate from 2010 to 2017, most of which were located in central, eastern, and western Europe, whereas population growth rates of more than 2\ub70% were seen in 33 of 46 countries in sub-Saharan Africa. In 2017, less than 65% of the national population was of working age in 12 of 34 high-income countries, and less than 50% of the national population was of working age in Mali, Chad, and Niger. Interpretation: Population trends create demographic dividends and headwinds (ie, economic benefits and detriments) that affect national economies and determine national planning needs. Although TFRs are decreasing, the global population continues to grow as mortality declines, with diverse patterns at the national level and across age groups. To our knowledge, this is the first study to provide transparent and replicable estimates of population and fertility, which can be used to inform decision making and to monitor progress. Funding: Bill & Melinda Gates Foundation

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic