Detection of Azoxystrobin Fungicide and Metabolite Azoxystrobin-Acid in Pregnant Women and Children, Estimation of Daily Intake, and Evaluation of Placental and Lactational Transfer in Mice

BACKGROUND: Azoxystrobin (AZ) is a broad-spectrum strobilurin fungicide that is used in agriculture and was recently added to mold- and mildew-resistant wallboards. AZ was found to have toxic effects in animals at embryonic stages and was listed as a frontline target for biomonitoring in children. OBJECTIVES: This study investigated exposure to AZ in pregnant women and young children, whether AZ could be transferred from an exposed mother to offspring, and whether AZ or one of its primary metabolites, AZ-acid, was neurotoxic in vitro. METHODS: We quantified AZ-acid, a sensitive indicator of AZ exposure, in urine samples collected from 8 pregnant women (12 urine samples) and 67 children (40-84 months old; 96 urine samples) with high-resolution mass spectrometry. Gestational and lactational transfer was assessed in C57Bl/6 mice. Neurotoxicity of AZ and AZ-acid was investigated in vitro with mouse cortical neuron cultures. RESULTS: AZ-acid was present above the limit of quantification (formula presented ) in 100% of the urine samples from pregnant women and in 70% of the urine samples from children, with median concentration of 0.10 and formula presented , and maximal concentration of 2.70 and formula presented , respectively. Studies in mice revealed that AZ transferred from the mother to offspring during gestation by crossing the placenta and entered the developing brain. AZ was also transferred to offspring via lactation. High levels of cytotoxicity were observed in embryonic mouse cortical neurons at concentrations that modeled environmentally relevant exposures. DISCUSSION: Our study suggested that pregnant women and children were exposed to AZ, and at least 10% of the children (2 out of 20 that were evaluated at two ages) showed evidence of chronic exposure. Future studies are warranted to evaluate whether chronic AZ exposure affects human health and development

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

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Mercury concentrations in a contaminated river system in Kazakhstan and biomonitoring of the local population

The River Nura in central Kazakhstan has been heavily contaminated by mercury (Hg). […] Humans are exposed to Hg primarily via the consumption of contaminated fish from the river. A survey was undertaken in June/July 2005 to investigate Hg concentrations in river water, drinking water, sediments and fish. To estimate the risk posed to the local population, approximately 300 hair samples were collected from people living in villages near the most contaminated section of the river, at a distance of between 5 and 30 km downstream of the acetaldehyde plant, and their dietary habits were recorded. Mercury concentrations in river water ranged from 2-3 ng/L upstream of the source of the pollution to 348 ng/L downstream of the factory outfall pipe. Some drinking water wells close to the river were contaminated, but deeper wells had Hg concentrations below the detection limit. An earlier investigation conducted by us in 2002 found that average Hg concentrations in fish are between 0.4 and 0.5 mg/kg within 30 km from the outfall. Fish collected in 2005 also contained up to 0.5 mg/kg of Hg in their tissue. Mercury concentrations in human hair samples were found to be strongly linked with fish consumption. Overall, Hg concentrations in human hair ranged from 0.01 to 5.18 mg/kg, with a mean of 0.58 mg/kg (compared to 0.03-0.9 mg/kg for samples taken from a control group in an uncontaminated area). Mean Hg concentrations in hair were found to be twice as high for males (0.84 mg/kg, n=115) compared to females (0.41 mg/kg, n=175). Most significantly, people living in a village ~30 km downstream had a higher Hg bodyburden (as estimated from hair samples) than people living in villages in the most contaminated section of the river. This could be due to higher rates of MeHg production in less contaminated areas and has important implications for planned remediation work

Genetic diversity and microgeographic differentiation of Yushan cane (Yushania niitakayamensis ; Poaceae) in Taiwan

Yushan cane (Yushania niitakayamensis) is distributed in southeast Asia. In Taiwan, the species occurs in mountains 1000-3600 m above sea level. The species appears to spread mainly by rhizomes and flowers only rarely. Nine locations across its distribution range in Taiwan were sampled. Locations at higher altitudes generally consist of grassland and forest undergrowth habitats while those of lower altitudes generally consist of forest undergrowth only. Thus two sampling sites (montane grassland and forest undergrowth) were selected from each location at higher altitudes while only one sampling site was selected from each location at lower altitudes, resulting in a total of 13 sampling sites. Within each sampling site, 20 individual plants were sampled. The results of the cluster analysis and the principal coordinate analysis based on random amplified polymorphic DNA (RAPD) indicated that the populations are generally differentiated according to geographical separation and altitudinal differences that interrupt gene flow. The populations at higher altitudes, where the species is distributed somewhat contiguously, were found to be more similar genetically. Analysis of molecular variance (AMOVA) revealed that the among-location, between sampling sites within location, and among individuals within sampling site components accounted for 15.27%, 4.80% and 79.93% of the total variance, respectively. For locations with two sampling sites, two-level AMOVA revealed that the diversities between sampling sites (sun and shade habitats) within locations ranged from 2.91% to 7.99% of the total diversity. Random permutation tests revealed that these diversities were significant, implying that there is microgeographic differentiation due to habitat differences

The Effect of Contaminant on Xylene Separation by Zeolite Adsorption

Possible contaminants arising from the oxidation of xylene isomers are detrimental to industrial adsorptive xylene separation processes since they lower the selectivity and recovery of p-xylene. A model compound, acetophenone, has been used to simulate the contaminant and it has been shown via pulse tests to adsorb strongly on to a K-BaY zeolite, thereby lowering the selectivity of p-xylene. Although the liquid desorbent PDEB (p-diethylbenzene) was not effective in removing the adsorbed acetophenone, nitrogen at 400°C and 1 atm was effective both in removing the adsorbed acetophenone and regenerating the adsorbent. Measurements of the adsorption capacity of acetophenone have shown that Molecular Sieve 13 X and K-BaY zeolites are both good adsorbents for acetophenone

Quantification of the risk associated with high levels of mercury pollution at Temirtau, Kazakhstan

This research aims to establish the risks of human exposure to high environmental mercury levels, based on a quantitative risk modelling approach. The study site was located on the River Nura in central Kazakhstan. From the 1950s until its closure in the mid 1990s, an acetaldehyde production plant located in the industrial city of Temirtau released Hg-containing wastewater into the river. River sediments are highly contaminated with Hg up to a distance of 25 km and beyond. In addition, a local power station released an estimated 6 million tonnes of fly-ash into the water and the Hg has become quite tightly associated with the ash deposits. River water, fish and agricultural land in the floodplain are also contaminated with mercury, yet the risks posed to the local population have not been evaluated to date. In June and July 2005, we took samples of soil, interior and exterior dust, drinking water, and food from individual households, communal areas and markets. Additionally, water and sediment samples and fish were taken from the river. Interviews were conducted with householders to establish their age and body weight, general living conditions and sources of irrigation and drinking water. A food frequency questionnaire (FFQ) was designed to investigate the frequencies of consumption of several common regional food items, including fish from the river and/or local market. Human hair samples were also collected to estimate the Hg bioburden and to enable the validity of the modelling approach to be established. The paper expands on the main pathways of contamination and looks at linkages between exposure pathways and Hg concentrations found in peoples’ hair. Uncertainties inherent in risk analysis as well as their influence on the relative importance of different exposure routes are also discussed. The analysis showed that the risk was less than originally expected, the most likely cause being the ability of the fly-ash to reduce the bioavailability of the mercury