Global age-sex-specific fertility, mortality, healthy life expectancy (HALE), and population estimates in 204 countries and territories, 1950–2019: a comprehensive demographic analysis for the Global Burden of Disease Study 2019

Background: Accurate and up-to-date assessment of demographic metrics is crucial for understanding a wide range of social, economic, and public health issues that affect populations worldwide. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 produced updated and comprehensive demographic assessments of the key indicators of fertility, mortality, migration, and population for 204 countries and territories and selected subnational locations from 1950 to 2019. Methods: 8078 country-years of vital registration and sample registration data, 938 surveys, 349 censuses, and 238 other sources were identified and used to estimate age-specific fertility. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate age-specific fertility rates for 5-year age groups between ages 15 and 49 years. With extensions to age groups 10–14 and 50–54 years, the total fertility rate (TFR) was then aggregated using the estimated age-specific fertility between ages 10 and 54 years. 7417 sources were used for under-5 mortality estimation and 7355 for adult mortality. ST-GPR was used to synthesise data sources after correction for known biases. Adult mortality was measured as the probability of death between ages 15 and 60 years based on vital registration, sample registration, and sibling histories, and was also estimated using ST-GPR. HIV-free life tables were then estimated using estimates of under-5 and adult mortality rates using a relational model life table system created for GBD, which closely tracks observed age-specific mortality rates from complete vital registration when available. Independent estimates of HIV-specific mortality generated by an epidemiological analysis of HIV prevalence surveys and antenatal clinic serosurveillance and other sources were incorporated into the estimates in countries with large epidemics. Annual and single-year age estimates of net migration and population for each country and territory were generated using a Bayesian hierarchical cohort component model that analysed estimated age-specific fertility and mortality rates along with 1250 censuses and 747 population registry years. We classified location-years into seven categories on the basis of the natural rate of increase in population (calculated by subtracting the crude death rate from the crude birth rate) and the net migration rate. We computed healthy life expectancy (HALE) using years lived with disability (YLDs) per capita, life tables, and standard demographic methods. Uncertainty was propagated throughout the demographic estimation process, including fertility, mortality, and population, with 1000 draw-level estimates produced for each metric. Findings: The global TFR decreased from 2•72 (95% uncertainty interval [UI] 2•66–2•79) in 2000 to 2•31 (2•17–2•46) in 2019. Global annual livebirths increased from 134•5 million (131•5–137•8) in 2000 to a peak of 139•6 million (133•0–146•9) in 2016. Global livebirths then declined to 135•3 million (127•2–144•1) in 2019. Of the 204 countries and territories included in this study, in 2019, 102 had a TFR lower than 2•1, which is considered a good approximation of replacement-level fertility. All countries in sub-Saharan Africa had TFRs above replacement level in 2019 and accounted for 27•1% (95% UI 26•4–27•8) of global livebirths. Global life expectancy at birth increased from 67•2 years (95% UI 66•8–67•6) in 2000 to 73•5 years (72•8–74•3) in 2019. The total number of deaths increased from 50•7 million (49•5–51•9) in 2000 to 56•5 million (53•7–59•2) in 2019. Under-5 deaths declined from 9•6 million (9•1–10•3) in 2000 to 5•0 million (4•3–6•0) in 2019. Global population increased by 25•7%, from 6•2 billion (6•0–6•3) in 2000 to 7•7 billion (7•5–8•0) in 2019. In 2019, 34 countries had negative natural rates of increase; in 17 of these, the population declined because immigration was not sufficient to counteract the negative rate of decline. Globally, HALE increased from 58•6 years (56•1–60•8) in 2000 to 63•5 years (60•8–66•1) in 2019. HALE increased in 202 of 204 countries and territories between 2000 and 2019. Interpretation: Over the past 20 years, fertility rates have been dropping steadily and life expectancy has been increasing, with few exceptions. Much of this change follows historical patterns linking social and economic determinants, such as those captured by the GBD Socio-demographic Index, with demographic outcomes. More recently, several countries have experienced a combination of low fertility and stagnating improvement in mortality rates, pushing more populations into the late stages of the demographic transition. Tracking demographic change and the emergence of new patterns will be essential for global health monitoring. 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

Global burden of 87 risk factors in 204 countries and territories, 1990�2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Rigorous analysis of levels and trends in exposure to leading risk factors and quantification of their effect on human health are important to identify where public health is making progress and in which cases current efforts are inadequate. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 provides a standardised and comprehensive assessment of the magnitude of risk factor exposure, relative risk, and attributable burden of disease. Methods: GBD 2019 estimated attributable mortality, years of life lost (YLLs), years of life lived with disability (YLDs), and disability-adjusted life-years (DALYs) for 87 risk factors and combinations of risk factors, at the global level, regionally, and for 204 countries and territories. GBD uses a hierarchical list of risk factors so that specific risk factors (eg, sodium intake), and related aggregates (eg, diet quality), are both evaluated. This method has six analytical steps. (1) We included 560 risk�outcome pairs that met criteria for convincing or probable evidence on the basis of research studies. 12 risk�outcome pairs included in GBD 2017 no longer met inclusion criteria and 47 risk�outcome pairs for risks already included in GBD 2017 were added based on new evidence. (2) Relative risks were estimated as a function of exposure based on published systematic reviews, 81 systematic reviews done for GBD 2019, and meta-regression. (3) Levels of exposure in each age-sex-location-year included in the study were estimated based on all available data sources using spatiotemporal Gaussian process regression, DisMod-MR 2.1, a Bayesian meta-regression method, or alternative methods. (4) We determined, from published trials or cohort studies, the level of exposure associated with minimum risk, called the theoretical minimum risk exposure level. (5) Attributable deaths, YLLs, YLDs, and DALYs were computed by multiplying population attributable fractions (PAFs) by the relevant outcome quantity for each age-sex-location-year. (6) PAFs and attributable burden for combinations of risk factors were estimated taking into account mediation of different risk factors through other risk factors. Across all six analytical steps, 30 652 distinct data sources were used in the analysis. Uncertainty in each step of the analysis was propagated into the final estimates of attributable burden. Exposure levels for dichotomous, polytomous, and continuous risk factors were summarised with use of the summary exposure value to facilitate comparisons over time, across location, and across risks. Because the entire time series from 1990 to 2019 has been re-estimated with use of consistent data and methods, these results supersede previously published GBD estimates of attributable burden. Findings: The largest declines in risk exposure from 2010 to 2019 were among a set of risks that are strongly linked to social and economic development, including household air pollution; unsafe water, sanitation, and handwashing; and child growth failure. Global declines also occurred for tobacco smoking and lead exposure. The largest increases in risk exposure were for ambient particulate matter pollution, drug use, high fasting plasma glucose, and high body-mass index. In 2019, the leading Level 2 risk factor globally for attributable deaths was high systolic blood pressure, which accounted for 10·8 million (95 uncertainty interval UI 9·51�12·1) deaths (19·2% 16·9�21·3 of all deaths in 2019), followed by tobacco (smoked, second-hand, and chewing), which accounted for 8·71 million (8·12�9·31) deaths (15·4% 14·6�16·2 of all deaths in 2019). The leading Level 2 risk factor for attributable DALYs globally in 2019 was child and maternal malnutrition, which largely affects health in the youngest age groups and accounted for 295 million (253�350) DALYs (11·6% 10·3�13·1 of all global DALYs that year). The risk factor burden varied considerably in 2019 between age groups and locations. Among children aged 0�9 years, the three leading detailed risk factors for attributable DALYs were all related to malnutrition. Iron deficiency was the leading risk factor for those aged 10�24 years, alcohol use for those aged 25�49 years, and high systolic blood pressure for those aged 50�74 years and 75 years and older. Interpretation: Overall, the record for reducing exposure to harmful risks over the past three decades is poor. Success with reducing smoking and lead exposure through regulatory policy might point the way for a stronger role for public policy on other risks in addition to continued efforts to provide information on risk factor harm to the general public. 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

Comparison of the efficacy of biodegradable and non-biodegradable scintillation liquids on the counting of tritium- and [14C]-labeled compounds

The widespread use of ³H and 14C in research has generated a large volume of waste mixed with scintillation liquid, requiring an effective control and appropriate storage of liquid radioactive waste. In the present study, we compared the efficacy of three commercially available scintillation liquids, Optiphase HiSafe 3, Ultima-Gold(TM) AB (biodegradable) and Insta-Gel-XF (non-biodegradable), in terms of [14C]-glucose and [³H]-thymidine counting efficiency. We also analyzed the effect of the relative amount of water (1.6 to 50%), radioisotope concentration (0.1 to 100 nCi/ml), pH (2 to 10) and color of the solutions (samples containing 0.1 to 1.0 mg/ml of Trypan blue) on the counting efficiency in the presence of these scintillation liquids. There were few significant differences in the efficiency of 14C and ³H counting obtained with biodegradable or non-biodegradable scintillation liquids. However, there was an 83 and 94% reduction in the efficiency of 14C and ³H counting, respectively, in samples colored with 1 mg/ml Trypan blue, but not with 0.1 mg/ml, independent of the scintillation liquid used. Considering the low cost of biodegradable scintillation cocktails and their efficacy, these results show that traditional hazardous scintillation fluids may be replaced with the new safe biodegradable fluids without impairment of ³H and 14C counting efficiency. The use of biodegradable scintillation cocktails minimizes both human and environmental exposure to hazardous solvents. In addition, some biodegradable scintillation liquids can be 40% less expensive than the traditional hazardous cocktails

The Relationship between Circular Economy, Industry 4.0 and Supply Chain Performance: A Combined ISM/Fuzzy MICMAC Approach

This paper aims to assess the relationship between Industry 4.0 (I4.0) and the circular economy that could contribute to supply chain management performance. To achieve this, a combination of the interpretative structural modelling (ISM) and (cross-impact matrix multiplication applied to classification) MICMAC approach was used to establish the interrelationships between these topics. The developed analysis reveals that there are 19 constructs capable of elucidating this relationship and that there is a hierarchy between these constructs, which are presented in a structural model. Further, the different levels of dependency and driving power are compared in a cluster diagram. As the main result, it was found that there is a strong mutual relationship between the basic technologies. The use of Internet of Things and cloud computing technologies influences the collection of large amounts of data, leading to big data, which in turn influence the use of data analytics tools to obtain competitive advantages. These outcomes may contribute to managers' more assertive decision-making regarding the selection, implementation, and evaluation of projects adopting Industry 4.0 technologies and circular economy approaches in supply chains. Moreover, our study could be the basis for future empirical research to investigate how companies incorporate Industry 4.0 technologies into their processes and how this influences the quest for sustainable supply chains. \textcopyright 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)

The Effects of the COVID-19 Crisis on Startups' Performance: The~Role~of Resilience

Purpose: This paper aims to evaluate the impacts of the COVID-19 crisis on startups performance and the moderating effects played by several resilience-related startup characteristics during times of crisis. Design/methodology/approach: To achieve this, 94 Brazil-based startups were surveyed, and multivariate data techniques (PLS-SEM) were applied. Findings: The results show that despite the startups performance having been affected by the pandemic crisis, the response measures, when influenced by the resilience characteristics of these companies, moderated this effect. Furthermore, our findings suggest the future challenges to be faced by these organisations in the post-pandemic period. Research limitations/implications: Proposing a framework, our survey research contributes to the dynamic capabilities theory by showing that startups resilience is linked to the micro-foundations of sensing (e.g. innovation systems, resilience culture, pivoting practices, innovativeness products), seizing (e.g. leadership/focused skills, people development and selection, agility, clear vision of business process) and reconfiguring capabilities. Practical implications: Not only for theory, but this paper also contributes insights and guidelines for business practice in the face of challenges arising from times of crisis. By demonstrating the positive effect of early response measures based on resilience, our findings provide genuine managerial input that can help managers, funders and decision-makers in these companies operations against turbulent crises early on, thereby supporting the traction phase and sustaining their performance. Originality/value: Previous research has examined the effects of the COVID-19 crisis in several sectors and perspectives. However, this study is the first to empirically test and clarify how the resilience and singularities of these new business models based on innovation could react to the changes caused by the pandemic. \textcopyright 2022, Emerald Publishing Limited

Implante de tubo de silicone com e sem colágeno na regeneração de nervos em eqüinos Implant of silicone tube with or without collagen in nerve regeneration of horses

A reconstituição cirúrgica de nervos em humanos, em cães e em diversos animais de laboratório é bastante utilizada e tem indicações clínicas e experimentais importantes. No entanto, em eqüinos há poucas informações sobre esta prática. Há relatos sobre a excessiva proliferação de tecido conjuntivo e a formação de neuromas à neurorrafia experimental, mesmo quando se utilizam tubos de silicone para condução do crescimento axonal. O presente estudo teve o objetivo de acrescentar informações sobre o processo de reparação de nervos periféricos em eqüinos por meio de implante de tubo de silicone preenchido ou não com colágeno. Para tanto, foram utilizados oito eqüinos, alocados em dois grupos: GI-13 semanas e GII-26 semanas de observação. Foi realizada secção dos nervos ulnares (NUs) e dos ramos cutâneos laterais dos 17&deg; nervos torácicos (NTs), bilateralmente, seguindo tubulização, realizada em cada animal, alternando-se tubos de silicone vazios (TS), em um dos antímeros, ou preenchidos com solução de colágeno (TSC), no contralateral, deixando-se um espaço de 5mm entre os cotos. Nenhuma alteração foi encontrada ao exame do aparelho locomotor e as primeiras reações positivas ao teste de sensibilidade cutânea nos NUs e NTs com TS e TSC foram observadas a partir da 9&ordf; semana, em ambos os grupos. Ao final do período de observação, verificou-se, macroscopicamente, que os nervos encontravam-se envolvidos por tecido conjuntivo e o interior da câmara estava preenchido por tecido de coloração esbranquiçada, de forma cilíndrica, interligando os cotos proximal e distal. Microscopicamente, constatou-se a presença de axônios mielinizados interligando os cotos, as células de Schwann e o processo de remielinização do coto distal, principalmente no TSC. Em ambos os grupos, não houve formação de neuromas e o processo inflamatório limitou-se às áreas perineurais. Concluiu-se que o implante de tubo de silicone conduz à regeneração de NUs e NTs de eqüinos sem formação de neuromas e que a adição de colágeno promove aumento do número de fibras mielinizadas.<br>Surgical nerve repair in humans, dogs and laboratory animals is widely utilized for important clinical and experimental purposes. However, in horses there is scarce information. Neuroma and excessive conjunctive proliferation are reported. The aim of the present study was to add information about the repair process utilizing implant of silicone tubes with or without collagen in nerve regeneration of horses. Eight horses were allocated in two groups: GI-13 weeks and GII-26 weeks of observation. A complete section of the ulnar nerves (UNs) and of the lateral cutaneous branch of the 17th thoracic nerves (TNs), bilaterally, was followed by repair with silicone tubes alternately filled with (STC) or without collagen (ST), with a 5mm gap between stumps. Clinical evaluation was performed weekly, by cutaneous sensitivity testing of the region innervated by the respective operated nerves and physical examination of the thoracic limbs. No alterations were found in the locomotor apparatus. The first positive reactions to the cutaneous test occurred at the 9th week post-surgery. At the end of the observation period it was verified, grossly, that the nerves were involved by conjunctive tissue and the lumen of the tube was filled by a whitish tissue, in a cylindrical shape. The ends nerves were interconnected. Microscopically, myelinated axons and Schwann cells were present in the gap between the stumps. In the GII the number of myelinated fibers was greater. The distal nerve showed remyelination process. There was no presence of neuroma and the inflammatory process was limited to the perineural areas. It was concluded that the implant of silicone tubes results in regeneration of UNs and TNs of horses without formation of neuromas and that de addition of collagen promotes an increase in the number of myelinated fibers