Fine scale measurement and mapping of uranium in soil solution in soil and plant-soil microcosms, with special reference to depleted uranium

Background and aims: Residues from use of depleted uranium (DU) munitions pose a lasting environmental impact through persistent contamination of soils. Consequently, an understanding of the factors determining the fate of DU in soil is necessary. An understudied factor is the interaction of root exudates with DU. This study describes the use of ‘Single-Cell-Sampling-and-Analysis' (SiCSA) for the first time in soil and investigates the effects of root exudates on DU dissolution. Methods: Soil solutions from soil and plant-soil microcosms containing DU fragments were sampled and analysed using SiCSA and capillary electrophoresis/ICP-MS for organic acids and uranium. Results: Nanolitre volumes of soil solution were sampled and analysed. Soils with DU fragments but no citrate addition showed low uranium concentrations in contrast to those with added citrate. Lupin root exudation gave concentrations up to 8mM citrate and 4.4mM malate in soil solution which solubilised DU fragments yielding transient solution concentrations of up to 30mM. Conclusions: Root exudates solubilise DU giving high localised soil solution concentrations. This should be considered when assessing the environmental risk of DU munitions. The SiCSA method was used successfully in soil for the first time and enables investigations with high spatial and temporal resolution in the rhizosphere. Figur

A novel method to determine trimethylantimony concentrations in plant tissue

Environmental contextAntimony enters the soil mostly through mining and shooting activities and can thereafter be taken up by plants. In the soil, antimony may undergo several transformations such as biomethylation, leading to the formation of trimethylantimony. Here, we measured for the first time the uptake and translocation of trimethylantimony in a plant using a new extraction and analysis method. AbstractAntimony (Sb) is a relevant pollutant that can be found in elevated concentrations in soils near Sb mines and at shooting ranges. In soils, Sb occurs as trivalent Sb, SbIII, pentavalent Sb, SbV, or trimethylantimony, TMSb ((CH3)3SbO), the latter being the result of microbial biomethylation. It is important to understand the transfer of Sb species from soil to plants to assess the role of Sb in the food chain. However, this research has historically been hampered by the lack of suitable extraction and analytical methods. In this study, we validated an efficient and reliable extraction technique using oxalic acid and ascorbic acid (72.6±1.3% of Sb extracted) as well as a high-pressure liquid chromatography–inductively coupled plasma mass spectrometry (HPLC-ICP-MS) speciation analysis method to assess the uptake of TMSb in ryegrass (Lolium perenne L.), a common pasture plant, in a hydroponics experiment. Our results show that TMSb and SbIII are not converted to other species during extraction and that TMSb is taken up by ryegrass roots and translocated to the shoots. Our study also points at specific methylation–demethylation mechanisms occurring in the plant. Moreover, an unknown Sb species was found in the shoots of TMSb-treated plants, highlighting the need for further research. These new extraction and speciation methods will enable researchers to study the soil–plant transfer of organo-Sb compounds in a reliable and consistent manner. </jats:p

Effects of waterlogging on the solubility and redox state of Sb in a shooting range soil and its uptake by grasses: a tank experiment

Aims: The effects of waterlogging on redox state and solubility of antimony (Sb) in a calcareous shooting range soil and its uptake by forage grass Lolium perenne L. and pasture weed Holcus lanatus L. were investigated. Methods: Grasses were grown on semi-waterlogged or waterlogged shooting range soil in a laboratory tank. The soil solution was sampled at various depths over time and analyzed for the concentrations of Sb(III), Sb(V) and total Sb, as well as other trace elements. Results: Although the reduction of Sb(V) to Sb(III) under increased waterlogging time decreased Sb solubility, it increased Sb uptake by L. perenne from 1.1 to 1.7mg kg−1 (and to a lesser extent H. lanatus), implying preferential uptake of Sb(III) by this grass. The tank showed considerable variation in redox conditions with depth and plant treatment. The soil root zone (30cm for L. perenne and 15cm for H. lanatus) instead of the water saturated bottom, showed the highest manganese (Mn) and iron (Fe) concentrations in solution, accompanied by a higher proportion of Sb(III) in solution than the bottom zone of the tank. Conclusions: Waterlogging can increase the risk of Sb entering the food chain from shooting range soi

Transdifferentiation of pancreatic ductal cells to endocrine β-cells,”

Abstract The regenerative process in the pancreas is of particular interest, since diabetes, whether Type 1 or Type 2, results from an inadequate amount of insulin-producing β-cells. Islet neogenesis, or the formation of new islets, seen as budding of hormone-positive cells from the ductal epithelium, has long been considered to be one of the mechanisms of normal islet growth after birth and in regeneration, and suggested the presence of pancreatic stem cells. Results from the rat regeneration model of partial pancreatectomy led us to hypothesize that differentiated pancreatic ductal cells were the pancreatic progenitors after birth, and that with replication they regressed to a less differentiated phenotype and then could differentiate to form new acini and islets. There are numerous supportive results for this hypothesis of neogenesis, including the ability of purified primary human ducts to form insulin-positive cells budding from ducts. However, to rigorously test this hypothesis, we took a direct approach of genetically marking ductal cells using CAII (carbonic anhydrase II) as a duct-cell-specific promoter to drive Cre recombinase in lineage-tracing experiments using the Cre-Lox system. We show that CAII-expressing pancreatic cells act as progenitors that give rise to both new islets and acini after birth and after injury (ductal ligation). This identification of a differentiated pancreatic cell type as an in vivo progenitor for all differentiated pancreatic cell types has implications for a potential expandable source for new islets for replenishment therapy for diabetes either in vivo or ex vivo

The risk of progression to type 1 diabetes is highly variable in individuals with multiple autoantibodies following screening

Aims/hypothesis: Young children who develop multiple autoantibodies (mAbs) are at very high risk for type 1 diabetes. We assessed whether a population with mAbs detected by screening is also at very high risk, and how risk varies according to age, type of autoantibodies and metabolic status. Methods: Type 1 Diabetes TrialNet Pathway to Prevention participants with mAbs (n = 1815; age, 12.35 ± 9.39 years; range, 1-49 years) were analysed. Type 1 diabetes risk was assessed according to age, autoantibody type/number (insulin autoantibodies [IAA], glutamic acid decarboxylase autoantibodies [GADA], insulinoma-associated antigen-2 autoantibodies [IA-2A] or zinc transporter 8 autoantibodies [ZnT8A]) and Index60 (composite measure of fasting C-peptide, 60 min glucose and 60 min C-peptide). Cox regression and cumulative incidence curves were utilised in this cohort study. Results: Age was inversely related to type 1 diabetes risk in those with mAbs (HR 0.97 [95% CI 0.96, 0.99]). Among participants with 2 autoantibodies, those with GADA had less risk (HR 0.35 [95% CI 0.22, 0.57]) and those with IA-2A had higher risk (HR 2.82 [95% CI 1.76, 4.51]) of type 1 diabetes. Those with IAA and GADA had only a 17% 5 year risk of type 1 diabetes. The risk was significantly lower for those with Index60 <1.0 (HR 0.23 [95% CI 0.19, 0.30]) vs those with Index60 values ≥1.0. Among the 12% (225/1815) ≥12.0 years of age with GADA positivity, IA-2A negativity and Index60 <1.0, the 5 year risk of type 1 diabetes was 8%. Conclusions/interpretation: Type 1 diabetes risk varies substantially according to age, autoantibody type and metabolic status in individuals screened for mAbs. An appreciable proportion of older children and adults with mAbs appear to have a low risk of progressing to type 1 diabetes at 5 years. With this knowledge, clinical trials of type 1 diabetes prevention can better target those most likely to progress

Modelling of long-term Zn, Cu, Cd and Pb dynamics from soils fertilised with organic amendments

Soil contamination by trace elements (TEs) is a major concern for sustainable land management. A potential source of excessive inputs of TEs into agricultural soils are organic amendments. Here, we used dynamic simulations carried out with the Intermediate Dynamic Model for Metals (IDMM) to describe the observed trends of topsoil Zn (zinc), Cu (copper), Pb (lead) and Cd (cadmium) concentrations in a long-term (>60-year) crop trial in Switzerland, where soil plots have been treated with different organic amendments (farmyard manure, sewage sludge and compost). The observed ethylenediaminetetraacetic acid disodium salt (EDTA)-extractable concentrations ranged between 2.6 and 27.1 mg kg−1 for Zn, 4.9 and 29.0 mg kg−1 for Cu, 6.1–26.2 mg kg−1 for Pb, and 0.08 and 0.66 mg kg−1 for Cd. Metal input rates were initially estimated based on literature data. An additional, calibrated metal flux, tentatively attributed to mineral weathering, was necessary to fit the observed data. Dissolved organic carbon fluxes were estimated using a soil organic carbon model. The model adequately reproduced the EDTA-extractable (labile) concentrations when input rates were optimised and soil lateral mixing was invoked to account for the edge effect of mechanically ploughing the trial plots. The global average root mean square error (RMSE) was 2.7, and the average bias (overestimation) was −1.66, −2.18, −4.34 and −0.05 mg kg−1 for Zn, Cu, Pb and Cd, respectively. The calibrated model was used to project the long-term metal trends in field conditions (without soil lateral mixing), under stable climate and management practices, with soil organic carbon estimated by modelling and assumed trends in soil pH. Labile metal concentrations to 2100 were largely projected to remain near constant or to decline, except for some metals in plots receiving compost. Ecotoxicological thresholds (critical limits) were predicted to be exceeded presently under sewage sludge inputs and to remain so until 2100. Ecological risks were largely not indicated in the other plots, although some minor exceedances of critical limits were projected to occur for Zn before 2100. This study advances our understanding of TEs' long-term dynamics in agricultural fields, paving the way to quantitative applications of modelling at field scales

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

BACKGROUND: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. METHODS: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). FINDINGS: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29-146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0- 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25-1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39-1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65-1·60]; p=0·92). INTERPRETATION: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. FUNDING: British Heart Foundation