Identification of two mutant JASON-RELATED genes associated with unreduced pollen production in potato.

KEY MESSAGE: Multiple QTLs control unreduced pollen production in potato. Two major-effect QTLs co-locate with mutant alleles of genes with homology to AtJAS, a known regulator of meiotic spindle orientation. In diploid potato the production of unreduced gametes with a diploid (2n) rather than a haploid (n) number of chromosomes has been widely reported. Besides their evolutionary important role in sexual polyploidisation, unreduced gametes also have a practical value for potato breeding as a bridge between diploid and tetraploid germplasm. Although early articles argued for a monogenic recessive inheritance, the genetic basis of unreduced pollen production in potato has remained elusive. Here, three diploid full-sib populations were genotyped with an amplicon sequencing approach and phenotyped for unreduced pollen production across two growing seasons. We identified two minor-effect and three major-effect QTLs regulating this trait. The two QTLs with the largest effect displayed a recessive inheritance and an additive interaction. Both QTLs co-localised with genes encoding for putative AtJAS homologs, a key regulator of meiosis II spindle orientation in Arabidopsis thaliana. The function of these candidate genes is consistent with the cytological phenotype of mis-oriented metaphase II plates observed in the parental clones. The alleles associated with elevated levels of unreduced pollen showed deleterious mutation events: an exonic transposon insert causing a premature stop, and an amino acid change within a highly conserved domain. Taken together, our findings shed light on the natural variation underlying unreduced pollen production in potato and will facilitate interploidy breeding by enabling marker-assisted selection for this trait.

Effect of Fungicide and Timing of Application on Management of Phoma Black Stem of Cultivated Sunflowers in the United States.

Phoma black stem (PBS), caused by Phoma macdonaldii Boerema (teleomorph Leptosphaeria lindquistii Frezzi), is the most common stem disease of sunflower (Helianthus annuus L.) in the northern Great Plains region of the United States. However, the impact of PBS on sunflower yield in the United States is unclear, and a near complete absence of information on the impact of fungicides on disease management exists. The objectives of this study were to determine the impact of PBS on sunflower yield, the efficacy of available fungicides, the optimal fungicide application timing, and the economic viability of fungicides as a management tool. Fungicide timing efficacy was evaluated by applying single and/or sequential applications of pyraclostrobin fungicide at three sunflower growth stages in 10 field trials between 2017 and 2019. Efficacy of 10 fungicides from the Fungicide Resistance Action Committee (FRAC) groups 3, 7, and 11 were evaluated in four field trials between 2018 and 2019. The impact of treatments on PBS were evaluated by determination of incidence, severity, maximum lesion height, disease severity index (DSI), and harvested yield. Nine of the 10 fungicides evaluated and all fungicide timings that included an early bud application resulted in disease reductions when compared with the nontreated controls. The DSI was negatively correlated to sunflower yield in high-yield environments (P = 0.0004; R2 = 0.3425) but not in low- or moderate-yield environments. Although FRAC 7 fungicides were generally most efficacious, the sufficient efficacy and lower cost of FRAC 11 fungicides make them more economically viable in high-yielding environments at current market conditions.

Evaluation of a super powerful bone-anchored hearing system and its users: A retrospective study.

INTRODUCTION: Although the Baha 5SP has been commercially available for six years, very few studies have been performed on the device's efficacy. The current study aims to evaluate the characteristics and audiological results in patients with severe-to-profound mixed hearing loss fitted with this superpower sound processor. METHODS: This retrospective evaluation was conducted at a tertiary referral centre where a series of 82 adult patients with severe-to-profound mixed hearing loss were implanted with a percutaneous bone-anchored hearing system and fitted with a superpower sound processor between 2016 and 2019. Patients with incomplete or unreliable audiological data (n = 24) were excluded, resulting in 58 data sets for analysis. The main outcome measures were unaided and aided pure-tone thresholds and aided free-field speech perception in quiet. RESULTS: The median unaided air conduction (AC) threshold averaged across 0.5, 1 and 2 kHz (PTA0.5-2kHz) of all patients was 75 dB hearing loss (HL); the median unaided AC averaged across 1, 2 and 4 kHz (PTA1-4kHz) was 84 dB HL. For bone conduction and direct bone conduction, the median PTA0.5-2kHz was 52 and 47 dB HL, respectively. With the superpower device, the median free-field speech reception threshold was 54 dB sound pressure level (SPL), and the median speech perception score at 65 dB SPL was 80%. CONCLUSIONS: At least 75% of the patients reached a maximum phoneme score of 70%. For patients with lower scores, the superpower device still provides a substantial hearing benefit. This makes the superpower device particularly suitable for patients with severe-to-profound mixed hearing loss with a contraindication for conventional hearing aids and/or cochlear implants.

Safety assessment and adverse drug reaction reporting of tea tree oil (Melaleuca aetheroleum).

Tea tree (Melaleuca alternifolia) essential oil is widely used as an antiseptic. It mainly consists of monoterpenes with terpinen-4-ol as the major constituent. The aim of this study was to review literature on safety data about tea tree oil and to assess its safety by investigating 159 cases of adverse reactions possibly caused by the oil, reported to the World Health Organization (WHO) from December 1987 until September 2021. To extract these data, VigiBase, the WHO global database of individual case safety reports maintained by the Uppsala Monitoring Centre (UMC), was used. All cases were categorized and analysed and 16 serious cases further assessed. It was concluded that tea tree oil should never be administered orally, as it can lead to central nervous system depression and pneumonitis. Applied topically, skin disorders may occur, especially when the oil had been exposed to light or air. This yields monoterpene oxidation products, being potent skin irritants. Tea tree oil stored under appropriate conditions and not exceeding the expiration date should be considered safe to use by non-vulnerable people for non-serious inflammatory skin conditions, although the occurrence of adverse reactions such as contact allergies is difficult to predict.

GWAS in tetraploid potato: identification and validation of SNP markers associated with glycoalkaloid content.

Genome-wide association studies (GWAS) are a useful tool to unravel the genetic architecture of complex traits, but the results can be difficult to interpret. Population structure, genetic heterogeneity, and rare alleles easily result in false positive or false negative associations. This paper describes the analysis of a GWAS panel combined with three bi-parental mapping populations to validate GWAS results, using phenotypic data for steroidal glycoalkaloid (SGA) accumulation and the ratio (SGR) between the two major glycoalkaloids α-solanine and α-chaconine in potato tubers. SGAs are secondary metabolites in the Solanaceae family, functional as a defence against various pests and pathogens and in high quantities toxic for humans. With GWAS, we identified five quantitative trait loci (QTL) of which Sga1.1, Sgr8.1, and Sga11.1 were validated, but not Sga3.1 and Sgr7.1. In the bi-parental populations, Sga5.1 and Sga7.1 were mapped, but these were not identified with GWAS. The QTLs Sga1.1, Sga7.1, Sgr7.1, and Sgr8.1 co-localize with genes GAME9, GAME 6/GAME 11, SGT1, and SGT2, respectively. For other genes involved in SGA synthesis, no QTLs were identified. The results of this study illustrate a number of pitfalls in GWAS of which population structure seems the most important. We also show that introgression breeding for disease resistance has introduced new haplotypes to the gene pool involved in higher SGA levels in certain pedigrees. Finally, we show that high SGA levels remain unpredictable in potato but that α-solanine/α-chaconine ratio has a predictable outcome with specific SGT1 and SGT2 haplotypes. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-022-01344-2.

Wearable-Measured Sleep and Resting Heart Rate Variability as an Outcome of and Predictor for Subjective Stress Measures: A Multiple N-of-1 Observational Study.

The effects of stress may be alleviated when its impact or a decreased stress-resilience are detected early. This study explores whether wearable-measured sleep and resting HRV in police officers can be predicted by stress-related Ecological Momentary Assessment (EMA) measures in preceding days and predict stress-related EMA outcomes in subsequent days. Eight police officers used an Oura ring to collect daily Total Sleep Time (TST) and resting Heart Rate Variability (HRV) and an EMA app for measuring demands, stress, mental exhaustion, and vigor during 15-55 weeks. Vector Autoregression (VAR) models were created and complemented by Granger causation tests and Impulse Response Function visualizations. Demands negatively predicted TST and HRV in one participant. TST negatively predicted demands, stress, and mental exhaustion in two, three, and five participants, respectively, and positively predicted vigor in five participants. HRV negatively predicted demands in two participants, and stress and mental exhaustion in one participant. Changes in HRV lasted longer than those in TST. Bidirectional associations of TST and resting HRV with stress-related outcomes were observed at a weak-to-moderate strength, but not consistently across participants. TST and resting HRV are more consistent predictors of stress-resilience in upcoming days than indicators of stress-related measures in prior days.

Lattice Boltzmann method investigation of a reactive electro-kinetic flow in porous media: towards a phenomenological model.

A model based on the Lattice Boltzmann method is developed to study the flow of reactive electro-kinetic fluids in porous media. The momentum, concentration and electric/potential fields are simulated via the Navier-Stokes, advection-diffusion/Nernst-Planck and Poisson equations, respectively. With this model, the total density and velocity fields, the concentration of reactants and reaction products, including neutral and ionized species, the electric potential and the interaction forces between the fields can be studied, and thus we provide an insight into the interplay between chemistry, flow and the geometry of the porous medium. The results show that the conversion efficiency of the reaction can be strongly influenced by the fluid velocity, reactant concentration and by porosity of the porous medium. The fluid velocity determines how long the reactants stay in the reaction areas, the reactant concentration controls the amount of the reaction material and with different dielectric constant, the porous medium can distort the electric field differently. All these factors make the reaction conversion efficiency display a non-trivial and non-monotonic behaviour as a function of the flow and reaction parameters. To better illustrate the dependence of the reaction conversion efficiency on the control parameters, based on the input from a number of numerical investigations, we developed a phenomenological model of the reactor. This model is capable of capturing the main features of the causal relationship between the performance of the reactor and the main test parameters. Using this model, one could optimize the choice of reaction and flow parameters in order to improve the performance of the reactor and achieve higher production rates. This article is part of the theme issue 'Progress in mesoscale methods for fluid dynamics simulation'.

Homo erectus at Trinil on Java used shells for tool production and engraving.

The manufacture of geometric engravings is generally interpreted as indicative of modern cognition and behaviour. Key questions in the debate on the origin of such behaviour are whether this innovation is restricted to Homo sapiens, and whether it has a uniquely African origin. Here we report on a fossil freshwater shell assemblage from the Hauptknochenschicht ('main bone layer') of Trinil (Java, Indonesia), the type locality of Homo erectus discovered by Eugène Dubois in 1891 (refs 2 and 3). In the Dubois collection (in the Naturalis museum, Leiden, The Netherlands) we found evidence for freshwater shellfish consumption by hominins, one unambiguous shell tool, and a shell with a geometric engraving. We dated sediment contained in the shells with (40)Ar/(39)Ar and luminescence dating methods, obtaining a maximum age of 0.54 ± 0.10 million years and a minimum age of 0.43 ± 0.05 million years. This implies that the Trinil Hauptknochenschicht is younger than previously estimated. Together, our data indicate that the engraving was made by Homo erectus, and that it is considerably older than the oldest geometric engravings described so far. Although it is at present not possible to assess the function or meaning of the engraved shell, this discovery suggests that engraving abstract patterns was in the realm of Asian Homo erectus cognition and neuromotor control.

Beyond the Tip of the Blade: An Investigation of Upper Extremity Machete Injuries in Honduras.

BACKGROUND: Machete injuries constitute a major cause of morbidity in Honduras. In this study, we aimed to determine the incidence, initial management, surgical treatment, and follow-up patterns for machete injuries at the national public hospital in Honduras. Microsurgery in Honduras is currently in transition with limitations at multiple levels. This study aims to provide critical information to better prepare visiting surgeons and establishes a blueprint to improve microsurgical reconstruction. METHODS: A retrospective chart review was performed to identify patients with machete injuries to the upper extremity (UE) who presented to the Hospital Escuela Universitario (HEU) for treatment from 2015 to 2017. Additional microsurgical data was obtained by personal communication with members of the plastic surgery department at the HEU. RESULTS: Complete data was retrieved for 100 patients who presented to the HEU with a UE machete wound. The cohort was male dominated (93%), employed as farmers (47%), and had a mean age of 32.1 years. Violence was the most common mechanism of injury (p < 0.001). The majority of UE machete injuries involved tendon (70%), nerve (28%), and an open fracture (55%). Of the 76% of patients who were scheduled for a follow-up visit, only 25% attended. Within the last calendar year, one replantation, 10 revascularizations at the wrist and forearm level, three microvascular free tissue transfers, and 175 nerve repairs were performed. CONCLUSION: Management of UE machete injuries in Honduras is challenging and requires early recognition of possible injuries to multiple anatomical systems. The majority of injuries required operative intervention. Only a small percentage of patients presented for follow up. A program to streamline care starting at injury recognition up to final follow-up is currently unavailable and needs to be developed to optimize microsurgical care.

Competition between Ekman Plumes and Vortex Condensates in Rapidly Rotating Thermal Convection.

We perform direct numerical simulations of rotating Rayleigh-Bénard convection (RRBC) of fluids with low (Pr=0.1) and high (Pr≈5) Prandtl numbers in a horizontally periodic layer with no-slip bottom and top boundaries. No-slip boundaries are known to actively promote the formation of plumelike vertical disturbances, through so-called Ekman pumping, that control the ambient flow at sufficiently high rotation rates. At both Prandtl numbers, we demonstrate the presence of competing large-scale vortices (LSVs) in the bulk. Strong buoyant forcing and rotation foster the quasi-two-dimensional turbulent state of the flow that leads to the upscale transfer of kinetic energy that forms the domain-filling LSV condensate. The Ekman plumes from the boundary layers are sheared apart by the large-scale flow, yet we find that their energy feeds the upscale transfer. Our results of RRBC simulations substantiate the emergence of large-scale flows in nature regardless of the specific details of the boundary conditions.

Distribution of P1(D1) wart disease resistance in potato germplasm and GWAS identification of haplotype-specific SNP markers.

KEY MESSAGE: A Genome-Wide Association Study using 330 commercial potato varieties identified haplotype specific SNP markers associated with pathotype 1(D1) wart disease resistance. Synchytrium endobioticum is a soilborne obligate biotrophic fungus responsible for wart disease. Growing resistant varieties is the most effective way to manage the disease. This paper addresses the challenge to apply molecular markers in potato breeding. Although markers linked to Sen1 were published before, the identification of haplotype-specific single-nucleotide polymorphisms may result in marker assays with high diagnostic value. To identify hs-SNP markers, we performed a genome-wide association study (GWAS) in a panel of 330 potato varieties representative of the commercial potato gene pool. SNP markers significantly associated with pathotype 1 resistance were identified on chromosome 11, at the position of the previously identified Sen1 locus. Haplotype specificity of the SNP markers was examined through the analysis of false positives and false negatives and validated in two independent full-sib populations. This paper illustrates why it is not always feasible to design markers without false positives and false negatives for marker-assisted selection. In the case of Sen1, founders could not be traced because of a lack of identity by descent and because of the decay of linkage disequilibrium between Sen1 and flanking SNP markers. Sen1 appeared to be the main source of pathotype 1 resistance in potato varieties, but it does not explain all the resistance observed. Recombination and introgression breeding may have introduced new, albeit rare haplotypes involved in pathotype 1 resistance. The GWAS approach, in such case, is instrumental to identify SNPs with the best possible diagnostic value for marker-assisted breeding.

The origin and widespread occurrence of Sli-based self-compatibility in potato.

Self-compatible (SC) diploid potatoes allow innovative potato breeding. Therefore, the Sli gene, originally described in S. chacoense, has received much attention. In elite S. tuberosum diploids, spontaneous berry set is occasionally observed. We aimed to map SC from S. tuberosum origin. Two full-sib mapping populations from non-inbred diploids were used. Bulks were composed based on both pollen tube growth and berry set upon selfing. After DNA sequencing of the parents and bulks, we generated k-mer tables. Set algebra and depth filtering were used to identify bulk-specific k-mers. Coupling and repulsion phase k-mers, transmitted from the SC parent, mapped in both populations to the distal end of chromosome 12. Intersection between the k-mers from both populations, in coupling phase with SC, exposed a shared haplotype of approximately 1.5 Mb. Subsequently, we screened read archives of potatoes and wild relatives for k-mers specific to this haplotype. The well-known SC clones US-W4 and RH89-039-16, but surprisingly, also S. chacoense clone M6 were positives. Hence, the S. tuberosum source of SC seems identical to Sli. Furthermore, the candidate region drastically reduced to 333 kb. Haplotype-specific KASP markers were designed and validated on a panel of diploid clones including another renown SC dihaploid G254. Interestingly, k-mers specific to the SC haplotype were common in tetraploid varieties. Pedigree information suggests that the SC haplotype was introduced into tetraploid varieties via the founder "Rough Purple Chili". We show that Sli is surprisingly widespread and indigenous to the cultivated gene pool of potato.

A Hitchhiker's guide to the potato wart disease resistance galaxy.

KEY MESSAGE: Two novel major effect loci (Sen4 and Sen5) and several minor effect QTLs for potato wart disease resistance have been mapped. The importance of minor effect loci to bring full resistance to wart disease was investigated. Using the newly identified and known wart disease resistances, a panel of potato breeding germplasm and Solanum wild species was screened. This provided a state-of-the-art "hitch-hikers-guide" of complementary wart disease resistance sources. Potato wart disease, caused by the obligate biotrophic soil-born fungus Synchytrium endobioticum, is the most important quarantine disease of potato. Because of its huge impact on yield, the lack of chemical control and the formation of resting spores with long viability, breeding for resistant varieties combined with strict quarantine measures are the only way to efficiently and durably manage the disease. In this study, we set out to make an inventory of the different resistance sources. Using a Genome-Wide Association Study (GWAS) in the potato breeding genepool, we identified Sen4, associated with pathotypes 2, 6 and 18 resistance. Associated SNPs mapped to the south arm of chromosome 12 and were validated to be linked to resistance in one full-sib population. Also, a bulked segregant analysis combined with a Comparative Subsequence Sets Analysis (CoSSA) resulted in the identification of Sen5, associated with pathotypes 2, 6 and 18 resistance, on the south arm of chromosome 5. In addition to these two major effect loci, the GWAS and CoSSA allowed the identification of several quantitative trait loci necessary to bring full resistance to certain pathotypes. Panels of varieties and Solanum accessions were screened for the presence of Sen1, Sen2, Sen3, Sen4 and Sen5. Combined with pedigree analysis, we could trace back some of these genes to the ancestral resistance donors. This analysis revealed complementary resistance sources and allows elimination of redundancy in wart resistance breeding programs.

Systematic review and quality ranking of studies of two phthalate metabolites and anogenital distance, bone health, inflammation, and oxidative stress.

Phthalates are ubiquitous chemical compounds, and two-di-ethyl phthalate (DEP) and di-isobutyl phthalate (DiBP)-are not currently regulated by the U.S. Congress or the European Union. While many reviews of phthalates have been published, none have examined bone health, inflammation, or oxidative stress; anogenital distance was most recently reviewed in 2014. The objective of this paper is to determine if an association exists between mono-ethyl phthalate (MEP) or mono-isobutyl phthalate (MiBP), metabolites of DEP and DiBP, respectively, and the four outcomes indicated above. We conducted a literature search of PubMed through December 2017 and included 29 observational epidemiologic studies published in English that assessed MEP and/or MiBP in relation to one of the above four health outcomes in humans. Two authors rated each paper using a modified Downs and Black (DB) assessment tool; a third author settled score disagreements. A single author extracted information related to the study population, exposure and outcome assessment, covariates, and significant results from each article. Ten studies were identified on anogenital distance, four on bone health, five on inflammation, and thirteen on oxidative stress. Score percentages (total points given out of total possible points) were calculated for each study. The current research suggests a positive association between MiBP and two measures of oxidative stress, 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane. MEP is potentially associated with 8-OHdG as well, although the evidence is limited by fewer high-quality studies. There does not appear to be an association between anogenital distance and MEP or MiBP, and it is unclear if relationships exist between these phthalate metabolites and bone health and inflammation. Given the role that oxidative stress plays in a number of diseases and the ubiquity of MEP and MiBP, it is important that individuals be aware of potential sources of exposure to these chemicals.

Statistical properties of thermally expandable particles in soft-turbulence Rayleigh-Bénard convection.

The dynamics of inertial particles in Rayleigh-Bénard convection, where both particles and fluid exhibit thermal expansion, is studied using direct numerical simulations (DNS) in the soft-turbulence regime. We consider the effect of particles with a thermal expansion coefficient larger than that of the fluid, causing particles to become lighter than the fluid near the hot bottom plate and heavier than the fluid near the cold top plate. Because of the opposite directions of the net Archimedes' force on particles and fluid, particles deposited at the plate now experience a relative force towards the bulk. The characteristic time for this motion towards the bulk to happen, quantified as the time particles spend inside the thermal boundary layers (BLs) at the plates, is shown to depend on the thermal response time, [Formula: see text], and the thermal expansion coefficient of particles relative to that of the fluid, [Formula: see text]. In particular, the residence time is constant for small thermal response times, [Formula: see text], and increasing with [Formula: see text] for larger thermal response times, [Formula: see text]. Also, the thermal BL residence time is increasing with decreasing K. A one-dimensional (1D) model is developed, where particles experience thermal inertia and their motion is purely dependent on the buoyancy force. Although the values do not match one-to-one, this highly simplified 1D model does predict a regime of a constant thermal BL residence time for smaller thermal response times and a regime of increasing residence time with [Formula: see text] for larger response times, thus explaining the trends in the DNS data well.

Naturally occurring allele diversity allows potato cultivation in northern latitudes.

Potato (Solanum tuberosum L.) originates from the Andes and evolved short-day-dependent tuber formation as a vegetative propagation strategy. Here we describe the identification of a central regulator underlying a major-effect quantitative trait locus for plant maturity and initiation of tuber development. We show that this gene belongs to the family of DOF (DNA-binding with one finger) transcription factors and regulates tuberization and plant life cycle length, by acting as a mediator between the circadian clock and the StSP6A mobile tuberization signal. We also show that natural allelic variants evade post-translational light regulation, allowing cultivation outside the geographical centre of origin of potato. Potato is a member of the Solanaceae family and is one of the world's most important food crops. This annual plant originates from the Andean regions of South America. Potato develops tubers from underground stems called stolons. Its equatorial origin makes potato essentially short-day dependent for tuberization and potato will not make tubers in the long-day conditions of spring and summer in the northern latitudes. When introduced in temperate zones, wild material will form tubers in the course of the autumnal shortening of day-length. Thus, one of the first selected traits in potato leading to a European potato type is likely to have been long-day acclimation for tuberization. Potato breeders can exploit the naturally occurring variation in tuberization onset and life cycle length, allowing varietal breeding for different latitudes, harvest times and markets.

Global burden of cancer and coronary heart disease resulting from dietary exposure to arsenic, 2015.

Arsenic is a ubiquitous, naturally occurring metalloid that poses a significant risk for human cancer and non-cancer diseases. It is now evident that arsenic contamination in food, especially rice and grains, presents a significant exposure to hundreds of millions of individuals worldwide. However, the disease risk from chronic exposure to the low amounts of arsenic found in food remains to be established. Thus, this research estimates the global burdens of disease expressed as Disability-Adjusted Life Years (DALYs) for lung, skin and bladder cancers, as well as coronary heart disease (CHD) attributable to inorganic arsenic in food. To determine foodborne inorganic arsenic exposures worldwide, we used the World Health Organization (WHO) estimates of food consumption in 17 country clusters, in conjunction with the reported measurements of total and inorganic arsenic in different foods. We estimated cancer potency factors for arsenic related bladder and lung cancers, and from US Environmental Protection Agency risk estimates for skin cancer to calculate the cancer incidence in males and females within each of the WHO member states. Summary relative risk estimates and population attributable fractions were developed to estimate the YLD, YLL, and DALYs for arsenic-induced CHD. The findings indicate that, globally, each year the combined DALYs for all cancers attributable to inorganic arsenic in food are approximately 1.4 million with variation in global distribution based on population and food consumption patterns. The global burden of CHD attributable to foodborne inorganic arsenic also varied with WHO region and may contribute as much as 49 million DALYs. However, in contrast to cancer burden, there is a threshold effect for arsenic-associated CHD with no increased risk of heart disease at the expected lower bound of arsenic consumption in food. These estimates indicate that foodborne arsenic exposure causes a significant yet avoidable global burden of human disease.

Global burden of intellectual disability resulting from dietary exposure to lead, 2015.

Lead is a ubiquitous dietary contaminant that occurs in food because of natural and anthropogenic sources and pathways of exposure. Lead adversely affects a number of tissues and organ systems and the severity of effect on each is dependent on the level and duration of exposure. The most sensitive and notable effects are those that occur on the nervous system. This is particularly the case in the exposure to the fetus, infant and child. Infants and children generally have higher lead exposures on a body weight basis. While lead exposure can come from many sources, a major source of exposure for at least some individuals comes from food. Estimates for the impact of dietary lead on IQ were developed from published total diet studies. While most of these were designed to characterize intake of chemical contaminants on a national basis, some sampled market baskets from a single city. To develop global estimates, default ranges were created for countries with no data which encompassed the values encountered elsewhere. Blood lead levels and IQ decrements were estimated using functions previously developed by the WHO Joint Expert Committee for Food Additives. Since both the exposure and dose response components were variable and uncertain, a two dimensional Monte-Carlo simulation was used to develop the estimates for the impact of dietary lead on IQ. In addition to estimating blood lead and IQ decrements attributable to dietary lead from those countries with published market basket data, simulations were also run for WHO regions that sampled in the variability dimension based on the population size of the individual countries in each region. Dietary exposure to lead occurs throughout the world. The global average IQ decrement attributable to dietary lead was 1.1. The total number of Disability-Adjusted Life Years (DALYs) arising from those IQ decrements were estimated to be 5.2 million DALYs, with an uncertainty range of 0-31 million DALYs. Significant uncertainties regarding exposure and dose-response relationships, however, warrant continued investigation.

Global burden of intellectual disability resulting from prenatal exposure to methylmercury, 2015.

We describe analyses to estimate the global burden of disease associated with methylmercury (MeHg). An intelligence quotient < 70, indicating intellectual disability (ID), was selected as the critical disease, maternal hair Hg concentration during pregnancy selected as the critical exposure biomarker, and a dose-effect relationship of an 0.18 point IQ reduction per µg/g increase in maternal hair Hg was assumed, based on a meta-analysis. A systematic review was conducted to obtain country-specific data on the distribution of maternal hair Hg concentrations. The country-specific incidence of MeHg-associated ID was calculated, and a random effects model was used to impute the incidence for countries for which no exposure data could be found. The global burden of MeHg-associated ID was quantified in terms of Disability-Adjusted Life Years (DALYs) using the World Health Organization (WHO) Global Health Estimates methodology, and presented by 14 subregions. In 2015, the global total for MeHg-associated cases of ID was 226,655; 210,074 of these cases (93%) were mild cases of ID. The highest rate of ID (6 cases per 100,000 population) was found in the Americas D subregion. The global DALY estimate was 1,963,869. The Western Pacific B subregion contributed the most to this total (696,417), although the Americas D subregion had the greatest rate (54 DALYs per 100,000 population). The burden of disease associated with MeHg is therefore highly subregion-dependent even in areas that are geographically related. The priority given to reducing this burden can therefore be expected to vary considerably by subregion depending on other health needs.

Global burden of late-stage chronic kidney disease resulting from dietary exposure to cadmium, 2015.

Chronic exposures to cadmium (Cd) are associated with reduced glomerular filtration rate (GFR), increasing the risk of chronic kidney disease (CKD). In support of the World Health Organization (WHO)'s initiative to estimate the global burden of foodborne diseases, a risk assessment was performed to estimate the Disability-Adjusted Life Years (DALYs) due to late-stage CKD associated with dietary exposures to cadmium. Using the distribution of population GFRs, the prevalence of CKD was calculated as the proportion of humans whose GFR fall in the ranges corresponding to Stage 4 or Stage 5 CKD. The increase in the CKD prevalence due to cadmium exposure was simulated based on a previously reported pharmacokinetic model describing the relationship between dietary cadmium intake and urinary cadmium (UCd), as well as a previously published dose-response relationship between UCd and GFR. Cadmium-related incidence rate, calculated as the change in the prevalence during a one-year period, were used to compute the mortality and DALY in all WHO regions. It is estimated that dietary cadmium would result in a median of 12,224 stage 4 and stage 5 new CKD cases per year worldwide, resulting in 2064 global deaths and 70,513 DALYs. These data translate into a median global burden of 1.0 DALY per 100,000 population, which account for 0.2% of the global DALYs of CKD. While these results suggest that the overall impact of dietary cadmium exposure on global CKD is low, they do indicate that reasonable efforts to reduce dietary exposure will result a positive public health impact. This would be particularly the case in areas with elevated levels of dietary cadmium.