Fractionation of arsenic in soil by a continuous-flow sequential extraction method

Batch sequential extraction techniques for fractionating metals or metalloids in soils are time consuming and subject to several potential errors. The development of a continuous-flow sequential extraction method for soil As is described and assessed, having the benefits of simplicity, rapidity, less risk of contamination, and less vulnerability to changes in extraction conditions compared with traditional batch methods. The validated method was used to fractionate soil As using water, NaHCO₃, NaOH, and HCl, followed by digestion of the residue with HNO₃, and HF acids. The extracts and digests were analyzed for As by graphite furnace atomic absorption spectrometry. Good recoveries of total soil As (97–115%) were obtained and fractionation data generally comparable with those obtained using conventional batch techniques. Soils from a tin-mining area in Thailand and soils from As-contaminated cattle (Bos taurus) dip sites in Australia were used to test the applicability of the method, and to demonstrate the usefulness of the extractogram obtained. The ability to produce detailed extractograms for As and other elements (Al, Fe, and Ca) enabled an examination of elemental associations in individual fractions. With the exception of As extracted with HCl, the extractograms generally support previous suggestions of the likely forms or associations of As present in the different soil fractions

Heavy metals in suburban gardens and the implications of land-use change following a major earthquake

Numerous studies have shown that urban soils can contain elevated concentrations of heavy metals (HMs). Christchurch, New Zealand, is a relatively young city (150 years old) with a population of 390,000. Most soils in Christchurch are sub-urban, with food production in residential gardens a popular activity. Earthquakes in 2010 and 2011 have resulted in the re-zoning of 630 ha of Christchurch, with suggestions that some of this land could be used for community gardens. We aimed to determine the HM concentrations in a selection of suburban gardens in Christchurch as well as in soils identified as being at risk of HM contamination due to hazardous former land uses or nearby activities. Heavy metal concentrations in suburban Christchurch garden soils were higher than normal background soil concentrations. Some 46% of the urban garden samples had Pb concentrations higher than the residential land use national standard of 210 mg kg⁻¹, with the most contaminated soil containing 2615 mg kg⁻¹ Pb. Concentrations of As and Zn exceeded the residential land use national standards (20 mg kg⁻¹ As and 400 mg kg⁻¹ Zn) in 20% of the soils. Older neighbourhoods had significantly higher soil HM concentrations than younger neighbourhoods. Neighbourhoods developed pre-1950s had a mean Pb concentration of 282 mg kg⁻¹ in their garden soils. Soil HM concentrations should be key criteria when determining the future land use of former residential areas that have been demolished because of the earthquakes in 2010 and 2011. Redeveloping these areas as parklands or forests would result in less human HM exposure than agriculture or community gardens where food is produced and bare soil is exposed

Chemoprevention of nonmelanoma skin cancer: experience with a polyphenol from green tea.

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed

Effect of Native American ancestry on iron-related phenotypes of Alabama hemochromatosis probands with HFE C282Y homozygosity

BACKGROUND: In age-matched cohorts of screening study participants recruited from primary care clinics, mean serum transferrin saturation values were significantly lower and mean serum ferritin concentrations were significantly higher in Native Americans than in whites. Twenty-eight percent of 80 Alabama white hemochromatosis probands with HFE C282Y homozygosity previously reported having Native American ancestry, but the possible effect of this ancestry on hemochromatosis phenotypes was unknown. METHODS: We compiled observations in these 80 probands and used univariate and multivariate methods to analyze associations of age, sex, Native American ancestry (as a dichotomous variable), report of ethanol consumption (as a dichotomous variable), percentage transferrin saturation and log(e )serum ferritin concentration at diagnosis, quantities of iron removed by phlebotomy to achieve iron depletion, and quantities of excess iron removed by phlebotomy. RESULTS: In a univariate analysis in which probands were grouped by sex, there were no significant differences in reports of ethanol consumption, transferrin saturation, log(e )serum ferritin concentration, quantities of iron removed to achieve iron depletion, and quantities of excess iron removed by phlebotomy in probands who reported Native American ancestry than in those who did not. In multivariate analyses, transferrin saturation (as a dependent variable) was not significantly associated with any of the available variables, including reports of Native American ancestry and ethanol consumption. The independent variable quantities of excess iron removed by phlebotomy was significantly associated with log(e )serum ferritin used as a dependent variable (p < 0.0001), but not with reports of Native American ancestry or reports of ethanol consumption. Log(e )serum ferritin was the only independent variable significantly associated with quantities of excess iron removed by phlebotomy used as a dependent variable (p < 0.0001) (p < 0.0001; ANOVA of regression). CONCLUSION: We conclude that the iron-related phenotypes of hemochromatosis probands with HFE C282Y homozygosity are similar in those with and without Native American ancestry reports

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Human knockouts and phenotypic analysis in a cohort with a high rate of consanguinity

A major goal of biomedicine is to understand the function of every gene in the human genome. Loss-of-function mutations can disrupt both copies of a given gene in humans and phenotypic analysis of such 'human knockouts' can provide insight into gene function. Consanguineous unions are more likely to result in offspring carrying homozygous loss-of-function mutations. In Pakistan, consanguinity rates are notably high. Here we sequence the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. We identified individuals carrying homozygous predicted loss-of-function (pLoF) mutations, and performed phenotypic analysis involving more than 200 biochemical and disease traits. We enumerated 49,138 rare (<1% minor allele frequency) pLoF mutations. These pLoF mutations are estimated to knock out 1,317 genes, each in at least one participant. Homozygosity for pLoF mutations at PLA2G7 was associated with absent enzymatic activity of soluble lipoprotein-associated phospholipase A2; at CYP2F1, with higher plasma interleukin-8 concentrations; at TREH, with lower concentrations of apoB-containing lipoprotein subfractions; at either A3GALT2 or NRG4, with markedly reduced plasma insulin C-peptide concentrations; and at SLC9A3R1, with mediators of calcium and phosphate signalling. Heterozygous deficiency of APOC3 has been shown to protect against coronary heart disease; we identified APOC3 homozygous pLoF carriers in our cohort. We recruited these human knockouts and challenged them with an oral fat load. Compared with family members lacking the mutation, individuals with APOC3 knocked out displayed marked blunting of the usual post-prandial rise in plasma triglycerides. Overall, these observations provide a roadmap for a 'human knockout project', a systematic effort to understand the phenotypic consequences of complete disruption of genes in humans.D.S. is supported by grants from the National Institutes of Health, the Fogarty International, the Wellcome Trust, the British Heart Foundation, and Pfizer. P.N. is supported by the John S. LaDue Memorial Fellowship in Cardiology from Harvard Medical School. H.-H.W. is supported by a grant from the Samsung Medical Center, Korea (SMO116163). S.K. is supported by the Ofer and Shelly Nemirovsky MGH Research Scholar Award and by grants from the National Institutes of Health (R01HL107816), the Donovan Family Foundation, and Fondation Leducq. Exome sequencing was supported by a grant from the NHGRI (5U54HG003067-11) to S.G. and E.S.L. D.G.M. is supported by a grant from the National Institutes of Health (R01GM104371). J.D. holds a British Heart Foundation Chair, European Research Council Senior Investigator Award, and NIHR Senior Investigator Award. The Cardiovascular Epidemiology Unit at the University of Cambridge, which supported the field work and genotyping of PROMIS, is funded by the UK Medical Research Council, British Heart Foundation, and NIHR Cambridge Biomedical Research Centre ... Fieldwork in the PROMIS study has been supported through funds available to investigators at the Center for Non-Communicable Diseases, Pakistan and the University of Cambridge, UK

Metal chemistry and bioavailability in a biosolids-amended forest soil following conversion of the land for agricultural usage

Application of biosolids to forests as a method of disposal is currently being used by authorities around the world, including New Zealand. This practice can lead to a build up of metals (from the biosolids) within the forest litter layer. However, as long as the land remains under forest, the chance of these metals entering the human food chain is low. This may cease to be the case if the forest is cleared for conversion of the land back for agriculture. This study, using incubation and plant growth techniques, examines the fate of metals in a Pinus radiata plantation forest treated with metal-spiked biosolids, following simulated conversion of the land back for agricultural use. Mixing of the biosolids-treated forest litter into the underlying mineral soil resulted in high concentrations of metals (Cu, Ni and Zn) in easily extractable forms, and there was also very little change in these concentrations during a subsequent 2-year incubation of the samples. Soil solution concentrations of the metals were also enhanced substantially by the various original biosolids treatments. Chemical speciation of the soil solutions using WHAM 6 showed that whereas solution Cu was dominated by organic complexes, most Ni and Zn was present at Ni²⁺ and Zn²⁺, with generally less than 5% of these elements present as organic complexes. Addition of lime to the soils substantially decreased both readily extractable and soil solution metal concentrations, however, even in their unlimed state there were no adverse effects due to the metals on plant growth as determined in a wheat germination and seedling growth test. Nevertheless, metal concentrations in the wheat seedlings were increased by the various original biosolids treatments. Plant metal concentrations showed strong correlations with either soil solution metal ion activities, or effective soil solution concentrations as determined by diffusive gradients in thin films (DGT). The results from this study are discussed in relation to the possible consequences of growing agricultural crops on land converted from forest soils that have previously received applications of biosolids.New Zealand Foundation for Research, Science and Technology through the Institute of Environmental Science and Research Ltd. (ESR)

Fractionation and distribution of arsenic in soils contaminated by cattle dip

Soils surrounding cattle dips in Australia are known to be highly contaminated with As and are potentially of major concern to the environment and human health. A study of 11 dip sites in northern New South Wales (NSW) has revealed considerable surface soil (0–10 cm) contamination with As (37–3542 mg As kg⁻¹ soil). In addition it was shown that considerable movement of As down through the soils had occurred with concentrations at 20 to 40 cm ranging from 57 to 2282 mg As kg⁻¹ soil. At one particular site, an As concentration of above 14 000 mg As kg⁻¹ soil was determined at a depth of 40 to 45 cm. A sequential fractionation scheme, based on a soil P fractionation, was developed to assess the chemical nature, and thus the potential bioavailability and mobility of As, at the sites. Soil As is separated into six fractions with (i) anion exchange resin, (ii) NaHCO₃, (iii) NaOH, (iv) NaOH following sonication, (v) HCl, and (vi) HCl/HNO₃. Although substantial differences between sites and soil depths were present, some general trends were apparent. Most sites contained substantial concentrations of As in the two most labile fractions, indicating high potential for phytotoxicity and leaching. The bulk of the contaminant As at the sites seemed to be associated with soil amorphous Fe and Al minerals