Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions. Funding: Bill & Melinda Gates Foundation

Hydrography, nutrients and chlorophyll during El Niño and La Niña 1997-99 winters in the Gulf of the Farallones, California

Nutrient and chlorophyll concentrations were measured in January 1997, 1998 and 1999 in the Gulf of the Farallones, CA at locations stretching north/south from Point Reyes to Half Moon Bay, and seaward from the Golden Gate to the Farallon Islands. The cruises were all carried out during periods of high river flow, but under different climatological conditions with 1997 conditions described as relatively typical or ‘neutral/normal’, compared to the El Niño warmer water temperatures in 1998, and the cooler La Niña conditions in 1999. Near-shore sea-surface temperatures ranged from cold (9.5–10.5°C) during La Niña 1999, to average (11–13°C) during 1997 to warm (13.5–15°C) during El Niño 1998. Nutrients are supplied to the Gulf of the Farallones both from San Francisco Bay (SFB) and from oceanic sources, e.g. coastal upwelling near Point Reyes. Nutrient supplies are strongly influenced by the seasonal cycle of fall calms, with storms (commencing in January), and the spring transition to high pressure and northerly upwelling favorable winds. The major effect of El Niño and La Niña climatic conditions was to modulate the relative contribution of SFB to nutrient concentrations in the coastal waters of the Gulf of the Farallones; this was intensified during the El Niño winter and reduced during La Niña. During January 1998 (El Niño) the oceanic water was warm and had low or undetectable nitrate, that did not reach the coast. Instead, SFB dominated the supply of nutrients to the coastal waters Additionally, these data indicate that silicate may be a good tracker of SFB water. In January, delta outflow into SFB produces low salinity, high silicate, high nitrate water that exits the bay at the Golden Gate and is advected northward along the coast. This occurred in both 1997 and 1998. However during January 1999, a La Niña, this SFB feature was reduced and the near-shore water was more characteristic of high salinity oceanic water penetrated all the way to the coast and was cold (10°C) and nutrient rich (16 μM NO3, 30 μM Si(OH)4). January chlorophyll concentrations ranged from 1–1.5 μg l 1 in all years with the highest values measured in 1999 (2.5–3 μg l 1) as a result of elevated nutrients in the area. The impact of climatic conditions on chlorophyll concentrations was not as pronounced as might be expected from the high temperatures and low nutrient concentrations measured offshore during El Niño due to the sustained supply of nutrients from the Bay supporting continued primary production

Modeling Phytoplankton New Production in the Peru Upwelling from Nitrate Reductase Activity and Light

V Simposio Internacional de Ciencias del Mar, 20-22 July 2016, Alicante.-- 2 pages, 3 figuresOceanic New Production is limited by nitrate (NO3-), ammonium (NH4+), and light. Measuring it by 15NO3- incubations is the current gold-standard, but the data acquisition rate is slow. Calculating it from plankton nitrate reductase activity (NR) is an inexpensive alternative with a higher data acquisition rate. Here, we calculate phytoplankton new production for the Peru upwelling ecosystem from measurements of NR activity using an enzyme kinetic model based on lighth -limitation. Calculations for the C-Line section at 155°S find new production ranging from 0.1 to 0.4 micro M N h-1 at the shelf edge and compares well to gross primary productivity when Redfield equivalents are used for N-C conversiion. JASON-CUEA expedition data for r September 1976 were usedThis study was supported by CUEA-12 (OCE75-23718) to ttp and BIOMBA (CTM2012-2729-MAR) to mgPeer Reviewe

New production modeled from nitrate reductase activity in the Peru current upwelling

VI Simposio Internacional de Ciencias del Mar - VI International Symposium of Marine Sciences (ISMS 2018), 20- 22 June 2018, Vigo.-- 2 pagesWe have developed alight-dependent, nitrate and ammonium independent model of New Production based on phytoplankton nitrate reductase (NR) activity that predicts strong New Production off Peru. The model is based on measurements from the Coastal Upwelling Ecosystem Analysis(CUEA) JASON expedition from September 1976. The samples were taken along a transect line (C-Line) across the Peru current at 15°S, which extended from the coast, at position C-1, across the Peru trench to position C-14, 200 km offshore. Sampling depths were established according tolightpenetration; euphotic zone samples were taken at depths where the light was 100, 50, 30, 15, 5, 1 and 0.1% of the surface incident radiation. The model responded to the equation: =·[ℎ]/67+[ℎ] which depends on the NR activity [NR] expressed in μM h-1, the amount of light [hv] expressed in % of incident radiation (I0) and the Michaelis-Menten constant(KLT),the amount of light [ℎ] at which half of themaximum NR activity is reached, which took a value of2.4% of I0. The developed model showed that the New Production at the 50% light level in the euphotic zone ranged from 3.49 μM C h−1, 12 km downstream from the upwelling center to 0.15 μM C h−1, 46 km further downstream over the 4000 m deep Peru Trench where the upwelling was relatively weak. It compared well with 14C carbon productivity measurements whose range was 0-4.2 μM C h−1and 0-1.5 μM C h−1for the 6 h (gross) and 24 h (net) productivity, respectively. In nitrogen units, the overall New Production ranged from 4 to 510 nM of N h−1. The oceanographic conditions found during September 1976 made this site in the Peruvian upwelling an ideal one to model new production. Temperature in the center of the upwelling in Septemberof 1976 reached 14.07°C, while NO3−and NO2−ranged from 6.65 to 7.5 and 0.51 to 1.6 μM respectively. Chlorophyll, averaging 3.85 μg L−1for the section stations in September 1976, was similar to what it was for all the stations 6 months later in March 1977 (3.23 μg L−1). NR, averaging 0.20 μM N h−1for the section stations in September 1976, was twice what it was for all stations, 6 month later in March 1977 (0.09 μM N h-1)NSF (USA) grant OCE 75-23718A01 (TTP) funded JASON-76. S.G.-G. was self-funded. T.T.P. was largely supported by TIAA-CREF and Social Security (USA), but also partially by the Canary Islands CEI: Tricontinental Atlantic CampusPeer Reviewe

Calculating new production from nitrate reductase activity and light in the Peru current upwelling

8 pages, 3 figures, 3 tablesWe have calculated new production from phytoplankton nitrate reductase (NR) activity and light in the euphotic zone of the Peruvian upwelling system at 15° S. The calculation is based on unique measurements from the Coastal Upwelling Ecosystem Analysis (CUEA) JASON expedition from September 1976. The new production at the 50% light level in the euphotic zone ranged from 3.49 µM C h−1, 12 km downstream from the upwelling center to 0.15 µM C h−1, 46 km further downstream over the 4000 m deep Peru Trench where the upwelling was relatively weak. It compared well with 14C carbon productivity measurements whose range was 0–4.2 µM C h−1 and 0–1.5 µM C h−1 for the 6 h (gross) and 24 h (net) productivity, respectively. In nitrogen units, the overall new production ranged from 4 to 510 nM of N h−1. The oceanographic conditions found during September 1976 made this upwelling site an ideal one to calculate new production. Temperature in the center of the upwelling in September of 1976 reached 14.07 °C, while NO3− ranged from 6.65 to 7.5 µM, and NH4+ stayed below 0.1 µM. Chlorophyll, averaging 3.85 µg L−1 for the section stations in September 1976, was similar to what it was for all the stations 6 months later in March 1977 (3.23 µg L−1). NR, averaging 0.20 µM N h−1 for the section stations in September 1976, was twice what it was for all stations, 6 month later in March 1977 (0.09 µM N h−1).SGG. was self-funded. NSF (USA) grant, OCE 75-23718A01, to TTP, funded JASON-76. TTP was supported by TIAA-CREF, Social Security (USA), and al by the Canary Islands CEI: Tricontinental Atlantic CampusPeer Reviewe

The genome of the diatom Thalassiosira pseudonana: Ecology, evolution, and metabolism

Diatoms are unicellular algae with plastids acquired by secondary endosymbiosis. They are responsible for {approx}20% of global carbon fixation. We report the 34 Mbp draft nuclear genome of the marine diatom, Thalassiosira pseudonana and its 129 Kbp plastid and 44 Kbp mitochondrial genomes. Sequence and optical restriction mapping revealed 24 diploid nuclear chromosomes. We identified novel genes for silicic acid transport and formation of silica-based cell walls, high-affinity iron uptake, biosynthetic enzymes for several types of polyunsaturated fatty acids, utilization of a range of nitrogenous compounds and a complete urea cycle, all attributes that allow diatoms to prosper in the marine environment. Diatoms are unicellular, photosynthetic, eukaryotic algae found throughout the world's oceans and freshwater systems. They form the base of short, energetically-efficient food webs that support large-scale coastal fisheries. Photosynthesis by marine diatoms generates as much as 40% of the 45-50 billion tonnes of organic carbon produced each year in the sea (1), and their role in global carbon cycling is predicted to be comparable to that of all terrestrial rainforests combined (2, 3). Over geological time, diatoms may have influenced global climate by changing the flux of atmospheric carbon dioxide into the oceans (4). A defining feature of diatoms is their ornately patterned silicified cell wall or frustule, which displays species-specific nano-structures of such fine detail that diatoms have long been used to test the resolution of optical microscopes. Recent attention has focused on biosynthesis of these nano-structures as a paradigm for future silica nanotechnology (5). The long history (over 180 million years) and dominance of diatoms in the oceans is reflected by their contributions to vast deposits of diatomite, most cherts and a significant fraction of current petroleum reserves (6). As photosynthetic heterokonts, diatoms reflect a fundamentally different evolutionary history from the higher plants that dominate photosynthesis on land. Higher plants and green, red and glaucophyte algae are derived from a primary endosymbiotic event in which a non-photosynthetic eukaryote acquired a chloroplast by engulfing (or being invaded by) a prokaryotic cyanobacterium. In contrast, dominant bloom-forming eukaryotic phytoplankton in the ocean, such as diatoms and haptophytes, were derived by secondary endosymbiosis whereby a non-photosynthetic eukaryote acquired a chloroplast by engulfing a photosynthetic eukaryote, probably a red algal endosymbiont (Fig. 1). Each endosymbiotic event led to new combinations of genes derived from the hosts and endosymbionts (7). Prior to this project, relatively few diatom genes had been sequenced, few chromosome numbers were known, and genetic maps did not exist (8). The ecological and evolutionary importance of diatoms motivated our sequencing and analysis of the nuclear, plastid, and mitochondrial genomes of the marine centric diatom Thalassiosira pseudonana