Analysis of the F2LR3 (PAR4) single nucleotide polymorphism (rs773902) in an Indigenous Australian population

The F2RL3 gene encoding protease activated receptor 4 (PAR4) contains a single nucleotide variant, rs773902, that is functional. The resulting PAR4 variants, Thr120, and Ala120, are known to differently affect platelet reactivity to thrombin. Significant population differences in the frequency of the allele indicate it may be an important determinant in the ethnic differences that exist in thrombosis and hemostasis, and for patient outcomes to PAR antagonist anti-platelet therapies. Here we determined the frequency of rs773902 in an Indigenous Australian group comprising 467 individuals from the Tiwi Islands. These people experience high rates of renal disease that may be related to platelet and PAR4 function and are potential recipients of PAR-antagonist treatments. The rs773902 minor allele frequency (Thr120) in the Tiwi Islanders was 0.32, which is similar to European and Asian groups and substantially lower than Melanesians and some African groups. Logistic regression and allele distortion testing revealed no significant associations between the variant and several markers of renal function, as well as blood glucose and blood pressure. These findings suggest that rs773902 is not an important determinant for renal disease in this Indigenous Australian group. However, the relationships between rs773902 genotype and platelet and drug responsiveness in the Tiwi, and the allele frequency in other Indigenous Australian groups should be evaluated

Burned area and carbon emissions across northwestern boreal North America from 2001-2019

Fire is the dominant disturbance agent in Alaskan and Canadian boreal ecosystems and releases large amounts of carbon into the atmosphere. Burned area and carbon emissions have been increasing with climate change, which have the potential to alter the carbon balance and shift the region from a historic sink to a source. It is therefore critically important to track the spatiotemporal changes in burned area and fire carbon emissions over time. Here we developed a new burned-area detection algorithm between 2001-2019 across Alaska and Canada at 500 m (meters) resolution that utilizes finer-scale 30 m Landsat imagery to account for land cover unsuitable for burning. This method strictly balances omission and commission errors at 500 m to derive accurate landscape- and regional-scale burned-area estimates. Using this new burned-area product, we developed statistical models to predict burn depth and carbon combustion for the same period within the NASA Arctic-Boreal Vulnerability Experiment (ABoVE) core and extended domain. Statistical models were constrained using a database of field observations across the domain and were related to a variety of response variables including remotely sensed indicators of fire severity, fire weather indices, local climate, soils, and topographic indicators. The burn depth and aboveground combustion models performed best, with poorer performance for belowground combustion. We estimate 2.37×106 ha (2.37 Mha) burned annually between 2001-2019 over the ABoVE domain (2.87 Mha across all of Alaska and Canada), emitting 79.3 ± 27.96 Tg (±1 standard deviation) of carbon (C) per year, with a mean combustion rate of 3.13 ± 1.17 kg C m-2. Mean combustion and burn depth displayed a general gradient of higher severity in the northwestern portion of the domain to lower severity in the south and east. We also found larger-fire years and later-season burning were generally associated with greater mean combustion. Our estimates are generally consistent with previous efforts to quantify burned area, fire carbon emissions, and their drivers in regions within boreal North America; however, we generally estimate higher burned area and carbon emissions due to our use of Landsat imagery, greater availability of field observations, and improvements in modeling. The burned area and combustion datasets described here (the ABoVE Fire Emissions Database, or ABoVE-FED) can be used for local- to continental-scale applications of boreal fire science

Model comparisons for estimating carbon emissions from North American wildland fire

Research activities focused on estimating the direct emissions of carbon from wildland fires across North America are reviewed as part of the North American Carbon Program disturbance synthesis. A comparison of methods to estimate the loss of carbon from the terrestrial biosphere to the atmosphere from wildland fires is presented. Published studies on emissions from recent and historic time periods and five specific cases are summarized, and new emissions estimates are made using contemporary methods for a set of specific fire events. Results from as many as six terrestrial models are compared. We find that methods generally produce similar results within each case, but estimates vary based on site location, vegetation (fuel) type, and fire weather. Area normalized emissions range from 0.23 kg C m−2 for shrubland sites in southern California/NW Mexico to as high as 6.0 kg C m−2 in northern conifer forests. Total emissions range from 0.23 to 1.6 Tg C for a set of 2003 fires in chaparral-dominated landscapes of California to 3.9 to 6.2 Tg C in the dense conifer forests of western Oregon. While the results from models do not always agree, variations can be attributed to differences in model assumptions and methods, including the treatment of canopy consumption and methods to account for changes in fuel moisture, one of the main drivers of variability in fire emissions. From our review and synthesis, we identify key uncertainties and areas of improvement for understanding the magnitude and spatial-temporal patterns of pyrogenic carbon emissions across North America

Comparison of creatinine and cystatin C based eGFR in the estimation of glomerular filtration rate in Indigenous Australians: the eGFR Study

Background: The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation that combines creatinine and cystatin C is superior to equations that include either measure alone in estimating glomerular filtration rate (GFR). However, whether cystatin C can provide any additional benefits in estimating GFR for Indigenous Australians, a population at high risk of end-stage kidney disease (ESKD) is unknown

Life, time, and the organism:Temporal registers in the construction of life forms

In this paper, we articulate how time and temporalities are involved in the making of living things. For these purposes, we draw on an instructive episode concerning Norfolk Horn sheep. We attend to historical debates over the nature of the breed, whether it is extinct or not, and whether presently living exemplars are faithful copies of those that came before. We argue that there are features to these debates that are important to understanding contemporary configurations of life, time and the organism, especially as these are articulated within the field of synthetic biology. In particular, we highlight how organisms are configured within different material and semiotic assemblages that are always structured temporally. While we identify three distinct structures, namely the historical, phyletic and molecular registers, we do not regard the list as exhaustive. We also highlight how these structures are related to the care and value invested in the organisms at issue. Finally, because we are interested ultimately in ways of producing time, our subject matter requires us to think about historiographical practice reflexively. This draws us into dialogue with other scholars interested in time, not just historians, but also philosophers and sociologists, and into conversations with them about time as always multiple and never an inert background

The prevalence of insufficient iodine intake in pregnancy in Africa: Protocol for a systematic review and meta-analysis

Background: Insufficient iodine intake in pregnancy is associated with many adverse pregnancy outcomes. About 90% of African countries are at risk of iodine deficiency due to poor soils and dietary goitrogens. Pregnancy predisposes to insufficient iodine nutrition secondary to increased physiological demand and increased renal loss. Iodine deficiency is re-emerging in countries thought to be replete with pregnant women being the most affected. This review seeks to identify the degree of iodine nutrition in pregnancy on the entire African continent before and after the implementation of national iodization programmes. Methods: A systematic search of published literature will be conducted for observational studies that directly determined the prevalence of insufficient iodine intake among pregnant women in Africa. Electronic databases and grey literature will be searched for baseline data before the implementation of population-based iodine supplementation and for follow-up data up to December 2018. Screening of identified articles and data extraction will be conducted independently by two investigators. Risk of bias and methodological quality of the included studies will be assessed using a risk of bias tool. Appropriate meta-analytic techniques will be used to pool prevalence estimates from studies with similar features, overall and by major characteristics including the region of the study, time period (before and after implementation of iodization programmes), sample size and age. Heterogeneity of the estimates across studies will be quantified and publication bias investigated. This protocol is reported according to Preferred Reporting Items for Systematic reviews and Meta-Analysis protocols (PRISMA-P) 2015 guidelines. Discussion This review will help ascertain the impact of national iodization programmes on the iodine nutrition status in pregnancy in Africa and advise policy on the necessity for monitoring and mitigating iodine deficiency in pregnancy in Africa. This review is part of a thesis that will be submitted to the Faculty of Health Sciences, University of Cape Town, for the award of a PhD in Medicine whose protocol has been granted ethics approval (UCT HREC 135/2018). In addition, the results will be published in a peer-reviewed journal

Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013

BACKGROUND: The Millennium Declaration in 2000 brought special global attention to HIV, tuberculosis, and malaria through the formulation of Millennium Development Goal (MDG) 6. The Global Burden of Disease 2013 study provides a consistent and comprehensive approach to disease estimation for between 1990 and 2013, and an opportunity to assess whether accelerated progress has occured since the Millennium Declaration. METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets. FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990. INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action. FUNDING: Bill & Melinda Gates Foundation

Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

BACKGROUND: Measurement of changes in health across locations is useful to compare and contrast changing epidemiological patterns against health system performance and identify specific needs for resource allocation in research, policy development, and programme decision making. Using the Global Burden of Diseases, Injuries, and Risk Factors Study 2016, we drew from two widely used summary measures to monitor such changes in population health: disability-adjusted life-years (DALYs) and healthy life expectancy (HALE). We used these measures to track trends and benchmark progress compared with expected trends on the basis of the Socio-demographic Index (SDI). METHODS: We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2016 for all-cause mortality, cause-specific mortality, and non-fatal disease burden to derive HALE and DALYs by sex for 195 countries and territories from 1990 to 2016. We calculated DALYs by summing years of life lost and years of life lived with disability for each location, age group, sex, and year. We estimated HALE using age-specific death rates and years of life lived with disability per capita. We explored how DALYs and HALE differed from expected trends when compared with the SDI: the geometric mean of income per person, educational attainment in the population older than age 15 years, and total fertility rate. FINDINGS: The highest globally observed HALE at birth for both women and men was in Singapore, at 75·2 years (95% uncertainty interval 71·9-78·6) for females and 72·0 years (68·8-75·1) for males. The lowest for females was in the Central African Republic (45·6 years [42·0-49·5]) and for males was in Lesotho (41·5 years [39·0-44·0]). From 1990 to 2016, global HALE increased by an average of 6·24 years (5·97-6·48) for both sexes combined. Global HALE increased by 6·04 years (5·74-6·27) for males and 6·49 years (6·08-6·77) for females, whereas HALE at age 65 years increased by 1·78 years (1·61-1·93) for males and 1·96 years (1·69-2·13) for females. Total global DALYs remained largely unchanged from 1990 to 2016 (-2·3% [-5·9 to 0·9]), with decreases in communicable, maternal, neonatal, and nutritional (CMNN) disease DALYs offset by increased DALYs due to non-communicable diseases (NCDs). The exemplars, calculated as the five lowest ratios of observed to expected age-standardised DALY rates in 2016, were Nicaragua, Costa Rica, the Maldives, Peru, and Israel. The leading three causes of DALYs globally were ischaemic heart disease, cerebrovascular disease, and lower respiratory infections, comprising 16·1% of all DALYs. Total DALYs and age-standardised DALY rates due to most CMNN causes decreased from 1990 to 2016. Conversely, the total DALY burden rose for most NCDs; however, age-standardised DALY rates due to NCDs declined globally. INTERPRETATION: At a global level, DALYs and HALE continue to show improvements. At the same time, we observe that many populations are facing growing functional health loss. Rising SDI was associated with increases in cumulative years of life lived with disability and decreases in CMNN DALYs offset by increased NCD DALYs. Relative compression of morbidity highlights the importance of continued health interventions, which has changed in most locations in pace with the gross domestic product per person, education, and family planning. The analysis of DALYs and HALE and their relationship to SDI represents a robust framework with which to benchmark location-specific health performance. Country-specific drivers of disease burden, particularly for causes with higher-than-expected DALYs, should inform health policies, health system improvement initiatives, targeted prevention efforts, and development assistance for health, including financial and research investments for all countries, regardless of their level of sociodemographic development. The presence of countries that substantially outperform others suggests the need for increased scrutiny for proven examples of best practices, which can help to extend gains, whereas the presence of underperforming countries suggests the need for devotion of extra attention to health systems that need more robust support. FUNDING: Bill & Melinda Gates Foundation

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