FOREWARNS: development and multifaceted verification of enhanced regional-scale surface water flood forecasts

Surface water flooding (SWF) is a severe hazard associated with extreme convective rainfall, whose spatial and temporal sparsity belie the significant impacts it has on populations and infrastructure. Forecasting the intense convective rainfall that causes most SWF on the temporal and spatial scales required for effective flood forecasting remains extremely challenging. National-scale flood forecasts are currently issued for the UK and are well regarded amongst flood responders, but there is a need for complementary enhanced regional information. Here we present a novel SWF-forecasting method, FOREWARNS (Flood fOREcasts for Surface WAter at a RegioNal Scale), that aims to fill this gap in forecast provision. FOREWARNS compares reasonable worst-case rainfall from a neighbourhood-processed, convection-permitting ensemble forecast system against pre-simulated flood scenarios, issuing a categorical forecast of SWF severity. We report findings from a workshop structured around three historical flood events in Northern England, in which forecast users indicated they found the forecasts helpful and would use FOREWARNS to complement national guidance for action planning in advance of anticipated events. We also present results from objective verification of forecasts for 82 recorded flood events in Northern England from 2013–2022, as well as 725 daily forecasts spanning 2019–2022, using a combination of flood records and precipitation proxies. We demonstrate that FOREWARNS offers good skill in forecasting SWF risk, with high spatial hit rates and low temporal false alarm rates, confirming that user confidence is justified and that FOREWARNS would be suitable for meeting the user requirements of an enhanced operational forecast

Identification of clonal hematopoiesis mutations in solid tumor patients undergoing unpaired next-generation sequencing assays

Purpose: In this era of precision-based medicine, for optimal patient care, results reported from commercial next-generation sequencing (NGS) assays should adequately reflect the burden of somatic mutations in the tumor being sequenced. Here, we sought to determine the prevalence of clonal hematopoiesis leading to possible misattribution of tumor mutation calls on unpaired Foundation Medicine NGS assays. Experimental Design: This was a retrospective cohort study of individuals undergoing NGS of solid tumors from two large cancer centers. We identified and quantified mutations in genes known to be frequently altered in clonal hematopoiesis (DNMT3A, TET2, ASXL1, TP53, ATM, CHEK2, SF3B1, CBL, JAK2) that were returned to physicians on clinical Foundation Medicine reports. For a subset of patients, we explored the frequency of true clonal hematopoiesis by comparing mutations on Foundation Medicine reports with matched blood sequencing. Results: Mutations in genes that are frequently altered in clonal hematopoiesis were identified in 65% (1,139/1,757) of patients undergoing NGS. When excluding TP53, which is often mutated in solid tumors, these events were still seen in 35% (619/1,757) of patients. Utilizing paired blood specimens, we were able to confirm that 8% (18/226) of mutations reported in these genes were true clonal hematopoiesis events. The majority of DNMT3A mutations (64%, 7/11) and minority of TP53 mutations (4%, 2/50) were clonal hematopoiesis. Conclusions: Clonal hematopoiesis mutations are commonly reported on unpaired NGS testing. It is important to recognize clonal hematopoiesis as a possible cause of misattribution of mutation origin when applying NGS findings to a patient's care

Reducing nitrous oxide emissions by changing N fertiliser use from calcium ammonium nitrate (CAN) to urea based formulations

This research was financially supported under the National Development Plan, through the Research Stimulus Fund, administered by the Department of Agriculture, Food and the Marine (Grant numbers RSF10-/RD/SC/716 and RSF11S138) and from the Department of Agriculture and Rural Development (Ref: DARD Evidence and Innovation project 13/04/06) for Northern Ireland. The first author gratefully acknowledges funding received from the Teagasc Walsh Fellowship Scheme (Ref: 2012005).peer-reviewedThe accelerating use of synthetic nitrogen (N) fertilisers, to meet the world's growing food demand, is the primary driver for increased atmospheric concentrations of nitrous oxide (N2O). The IPCC default emission factor (EF) for N2O from soils is 1% of the N applied, irrespective of its form. However, N2O emissions tend to be higher from nitrate-containing fertilisers e.g. calcium ammonium nitrate (CAN) compared to urea, particularly in regions, which have mild, wet climates and high organic matter soils. Urea can be an inefficient N source due to NH3 volatilisation, but nitrogen stabilisers (urease and nitrification inhibitors) can improve its efficacy. This study evaluated the impact of switching fertiliser formulation from calcium ammonium nitrate (CAN) to urea-based products, as a potential mitigation strategy to reduce N2O emissions at six temperate grassland sites on the island of Ireland. The surface applied formulations included CAN, urea and urea with the urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and/or the nitrification inhibitor dicyandiamide (DCD). Results showed that N2O emissions were significantly affected by fertiliser formulation, soil type and climatic conditions. The direct N2O emission factor (EF) from CAN averaged 1.49% overall sites, but was highly variable, ranging from 0.58% to 3.81. Amending urea with NBPT, to reduce ammonia volatilisation, resulted in an average EF of 0.40% (ranging from 0.21 to 0.69%)-compared to an average EF of 0.25% for urea (ranging from 0.1 to 0.49%), with both fertilisers significantly lower and less variable than CAN. Cumulative N2O emissions from urea amended with both NBPT and DCD were not significantly different from background levels. Switching from CAN to stabilised urea formulations was found to be an effective strategy to reduce N2O emissions, particularly in wet, temperate grassland.Department of Agriculture and Rural Development for Northern IrelandTeagasc Walsh Fellowship ProgrammeDepartment of Agriculture, Food and the Marin

SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance.

Item does not contain fulltextCancer cells adapt their metabolic processes to support rapid proliferation, but less is known about how cancer cells alter metabolism to promote cell survival in a poorly vascularized tumour microenvironment. Here we identify a key role for serine and glycine metabolism in the survival of brain cancer cells within the ischaemic zones of gliomas. In human glioblastoma multiforme, mitochondrial serine hydroxymethyltransferase (SHMT2) and glycine decarboxylase (GLDC) are highly expressed in the pseudopalisading cells that surround necrotic foci. We find that SHMT2 activity limits that of pyruvate kinase (PKM2) and reduces oxygen consumption, eliciting a metabolic state that confers a profound survival advantage to cells in poorly vascularized tumour regions. GLDC inhibition impairs cells with high SHMT2 levels as the excess glycine not metabolized by GLDC can be converted to the toxic molecules aminoacetone and methylglyoxal. Thus, SHMT2 is required for cancer cells to adapt to the tumour environment, but also renders these cells sensitive to glycine cleavage system inhibition