215 research outputs found
Biogeochemical Cycling of 99Tc in Alkaline Sediments
99Tc will be present in significant quantities in radioactive wastes including intermediate-level waste (ILW). The internationally favored concept for disposing of higher activity radioactive wastes including ILW is via deep geological disposal in an underground engineered facility located ∼200–1000 m deep. Typically, in the deep geological disposal environment, the subsurface will be saturated, cement will be used extensively as an engineering material, and iron will be ubiquitous. This means that understanding Tc biogeochemistry in high pH, cementitious environments is important to underpin safety case development. Here, alkaline sediment microcosms (pH 10) were incubated under anoxic conditions under “no added Fe(III)” and “with added Fe(III)” conditions (added as ferrihydrite) at three Tc concentrations (10–11, 10–6, and 10–4 mol L–1). In the 10–6 mol L–1 Tc experiments with no added Fe(III), ∼35% Tc(VII) removal occurred during bioreduction. Solvent extraction of the residual solution phase indicated that ∼75% of Tc was present as Tc(IV), potentially as colloids. In both biologically active and sterile control experiments with added Fe(III), Fe(II) formed during bioreduction and >90% Tc was removed from the solution, most likely due to abiotic reduction mediated by Fe(II). X-ray absorption spectroscopy (XAS) showed that in bioreduced sediments, Tc was present as hydrous TcO2-like phases, with some evidence for an Fe association. When reduced sediments with added Fe(III) were air oxidized, there was a significant loss of Fe(II) over 1 month (∼50%), yet this was coupled to only modest Tc remobilization (∼25%). Here, XAS analysis suggested that with air oxidation, partial incorporation of Tc(IV) into newly forming Fe oxyhydr(oxide) minerals may be occurring. These data suggest that in Fe-rich, alkaline environments, biologically mediated processes may limit Tc mobility.Peer reviewe
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Enabling precision medicine in neonatology, an integrated repository for preterm birth research.
Preterm birth, or the delivery of an infant prior to 37 weeks of gestation, is a significant cause of infant morbidity and mortality. In the last decade, the advent and continued development of molecular profiling technologies has enabled researchers to generate vast amount of 'omics' data, which together with integrative computational approaches, can help refine the current knowledge about disease mechanisms, diagnostics, and therapeutics. Here we describe the March of Dimes' Database for Preterm Birth Research (http://www.immport.org/resources/mod), a unique resource that contains a variety of 'omics' datasets related to preterm birth. The database is open publicly, and as of January 2018, links 13 molecular studies with data across tens of thousands of patients from 6 measurement modalities. The data in the repository are highly diverse and include genomic, transcriptomic, immunological, and microbiome data. Relevant datasets are augmented with additional molecular characterizations of almost 25,000 biological samples from public databases. We believe our data-sharing efforts will lead to enhanced research collaborations and coordination accelerating the overall pace of discovery in preterm birth research
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Measurements of traffic-dominated pollutant emissions in a Chinese megacity
Direct measurements of NOx, CO and aromatic volatile organic compound (VOC) (benzene, toluene, C2-benzenes and C3-benzenes) flux were made for a central area of Beijing using the eddy-covariance technique. Measurements were made during two intensive field campaigns in central Beijing as part of the Air Pollution and Human Health (APHH) project, the first in November–December 2016 and the second during May–June 2017, to contrast wintertime and summertime emission rates. There was little difference in the magnitude of NOx flux between the two seasons (mean NOx flux was 4.41 mg m−2 h−1 in the winter compared to 3.55 mg m−2 h−1in the summer). CO showed greater seasonal variation, with mean CO flux in the winter campaign (34.7 mg m−2 h−1) being over twice that of the summer campaign (15.2 mg m−2 h−1). Larger emissions of aromatic VOCs in summer were attributed to increased evaporation due to higher temperatures. The largest fluxes in NOx and CO generally occurred during the morning and evening rush hour periods, indicating a major traffic source with high midday emissions of CO, indicating an additional influence from cooking fuel. Measured NOx and CO fluxes were then compared to the MEIC 2013 emissions inventory, which was found to significantly overestimate emissions for this region,providing evidence that proxy-based emissions inventories have positive biases in urban centres. This first set of pollutant fluxes measured in Beijing provides an important benchmark of emissions from the city which can help to inform and evaluate current emissions inventories
Full Genome Characterization of the Culicoides-Borne Marsupial Orbiviruses: Wallal Virus, Mudjinbarry Virus and Warrego Viruses
Viruses belonging to the species Wallal virus and Warrego virus of the genus Orbivirus were identified as causative agents of blindness in marsupials in Australia during 1994/5. Recent comparisons of nucleotide (nt) and amino acid (aa) sequences have provided a basis for the grouping and classification of orbivirus isolates. However, full-genome sequence data are not available for representatives of all Orbivirus species. We report full-genome sequence data for three additional orbiviruses: Wallal virus (WALV); Mudjinabarry virus (MUDV) and Warrego virus (WARV). Comparisons of conserved polymerase (Pol), sub-core-shell 'T2' and core-surface 'T13' proteins show that these viruses group with other Culicoides borne orbiviruses, clustering with Eubenangee virus (EUBV), another orbivirus infecting marsupials. WARV shares <70% aa identity in all three conserved proteins (Pol, T2 and T13) with other orbiviruses, consistent with its classification within a distinct Orbivirus species. Although WALV and MUDV share <72.86%/67.93% aa/nt identity with other orbiviruses in Pol, T2 and T13, they share >99%/90% aa/nt identities with each other (consistent with membership of the same virus species - Wallal virus). However, WALV and MUDV share <68% aa identity in their larger outer capsid protein VP2(OC1), consistent with membership of different serotypes within the species - WALV-1 and WALV-2 respectively
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Farmer attitudes and livestock disease: exploring citizenship behaviour and peer monitoring across two BVD control schemes in the UK
The eradication of BVD in the UK is technically possible but appears to be socially untenable. The following study explored farmer attitudes to BVD control schemes in relation to advice networks and information sharing, shared aims and goals, motivation and benefits of membership, notions of BVD as a priority disease and attitudes toward regulation. Two concepts from the organisational management literature framed the study: citizenship behaviour where actions of individuals support the collective good (but are not explicitly recognised as such) and peer to peer monitoring (where individuals evaluate other’s behaviour). Farmers from two BVD control schemes in the UK participated in the study: Orkney Livestock Association BVD Eradication Scheme and Norfolk and Suffolk Cattle Breeders Association BVD Eradication Scheme. In total 162 farmers participated in the research (109 in-scheme and 53 out of scheme). The findings revealed that group helping and information sharing among scheme members was low with a positive BVD status subject to social censure. Peer monitoring in the form of gossip with regard to the animal health status of other farms was high. Interestingly, farmers across both schemes supported greater regulation with regard to animal health, largely due to the mistrust of fellow farmers following voluntary disease control measures. While group cohesiveness varied across the two schemes, without continued financial inducements, longer-term sustainability is questionabl
Maternal sildenafil for severe fetal growth restriction (STRIDER): a multicentre, randomised, placebo-controlled, double-blind trial
Background
Severe early-onset fetal growth restriction can lead to a range of adverse outcomes including fetal or neonatal death, neurodisability, and lifelong risks to the health of the affected child. Sildenafil, a phosphodiesterase type 5 inhibitor, potentiates the actions of nitric oxide, which leads to vasodilatation of the uterine vessels and might improve fetal growth in utero.
Methods
We did this superiority, placebo-controlled randomised trial in 19 fetal medicine units in the UK. We used random computer allocation (1:1) to assign women with singleton pregnancies between 22 weeks and 0 days' gestation and 29 weeks and 6 days' gestation and severe early-onset fetal growth restriction to receive either sildenafil 25 mg three times daily or placebo until 32 weeks and 0 days' gestation or delivery. We stratified women by site and by their gestational age at randomisation (before week 26 and 0 days or at week 26 and 0 days or later). We defined fetal growth restriction as a combination of estimated fetal weight or abdominal circumference below tenth percentile and absent or reversed end-diastolic blood flow in the umbilical artery on Doppler velocimetry. The primary outcome was the time from randomisation to delivery, measured in days. This study is registered with BioMed Central, number ISRCTN 39133303.
Findings
Between Nov 21, 2014, and July 6, 2016, we recruited 135 women and randomly assigned 70 women to sildenafil and 65 women to placebo. We found no difference in the median randomisation to delivery interval between women assigned to sildenafil (17 days [IQR 7–24]) and women assigned to placebo (18 days [8–28]; p=0·23). Livebirths (relative risk [RR] 1·06, 95% CI 0·84 to 1·33; p=0·62), fetal deaths (0·89, 0·54 to 1·45; p=0·64), neonatal deaths (1·33, 0·54 to 3·28; p=0·53), and birthweight (−14 g,–100 to 126; p=0·81) did not differ between groups. No differences were found for any other secondary outcomes. Eight serious adverse events were reported during the course of the study (six in the placebo group and two in the sildenafil group); none of these were attributed to sildenafil.
Interpretation
Sildenafil did not prolong pregnancy or improve pregnancy outcomes in severe early-onset fetal growth restriction and therefore it should not be prescribed for this indication outside of research studies with explicit participants' consent.
Funding
National Institute for Health Research and Medical Research Council
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
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