Strontium sorption and precipitation behaviour during bioreduction in nitrate impacted sediments

AbstractThe behaviour of strontium (Sr2+) during microbial reduction in nitrate impacted sediments was investigated in sediment microcosm experiments relevant to nuclear sites. Although Sr2+ is not expected to be influenced directly by redox state, bioreduction of nitrate caused reduced Sr2+ solubility due to an increase in pH during bioreduction and denitrification. Sr2+ removal was greatest in systems with the highest initial nitrate loading and consequently more alkaline conditions at the end of denitrification. After denitrification, a limited re-release of Sr2+ back into solution occurred coincident with the onset of metal (Mn(IV) and Fe(III)) reduction which caused minor pH changes in all microcosms with the exception of the bicarbonate buffered system with initial nitrate of 100mM and final pH>9. In this system ~95% of Sr2+ remained associated with the sediment throughout the progression of bioreduction. Analysis of this pH 9 system using X-ray absorption spectroscopy (XAS) and electron microscopy coupled to thermodynamic modelling showed that Sr2+ became partially incorporated within carbonate phases which were formed at higher pH. This is in contrast to all other systems where final pH was <9, here XAS analysis showed that outer sphere Sr2+ sorption predominated. These results provide novel insight into the likely environmental fate of the significant radioactive contaminant, 90Sr, during changes in sediment biogeochemistry induced by bioreduction in nitrate impacted nuclear contaminated environments

Neptunium and manganese biocycling in nuclear legacy sediment systems

Understanding the behaviour of the highly radiotoxic, long half-life radionuclide neptunium in the environment is important for the management of radioactively contaminated land and the safe disposal of radioactive wastes. Recent studies have identified that microbial reduction can reduce the mobility of neptunium via reduction of soluble Np(V) to poorly soluble Np(IV), with coupling to both Mn- and Fe(III)- reduction implicated in neptunyl reduction. To further explore these processes Mn(IV) as δMnO2 was added to sediment microcosms to create a sediment microcosm experiment "poised" under Mn-reducing conditions. Enhanced removal of Np(V) from solution occurred during Mn-reduction, and parallel X-ray absorption spectroscopy (XAS) studies confirmed Np(V) reduction to Np(IV) commensurate with microbially-mediated Mn-reduction. Molecular ecology analysis of the XAS systems, which contained up to 0.2 mM Np showed no significant impact of elevated Np concentrations on the microbial population. These results demonstrate the importance of Mn cycling on Np biogeochemistry, and clearly highlight new pathways to reductive immobilisation for this highly radiotoxic actinide

Prediction of 7-year psychopathology from mother-infant joint attention behaviours: a nested case–control study

&lt;br&gt;Background: To investigate whether later diagnosis of psychiatric disorder can be predicted from analysis of mother-infant joint attention (JA) behaviours in social-communicative interaction at 12 months.&lt;/br&gt; &lt;br&gt;Method: Using data from a large contemporary birth cohort, we examined 159 videos of a mother-infant interaction for joint attention behaviour when children were aged one year, sampled from within the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Fifty-three of the videos involved infants who were later considered to have a psychiatric disorder at seven years and 106 were same aged controls. Psychopathologies included in the case group were disruptive behaviour disorders, oppositional-conduct disorder, attention-deficit/hyperactivity disorder, pervasive development disorder, anxiety and depressive disorders. Psychiatric diagnoses were obtained using the Development and Wellbeing Assessment when the children were seven years old.&lt;/br&gt; &lt;br&gt;Results: None of the three JA behaviours (shared look rate, shared attention rate and shared attention intensity) showed a significant association with the primary outcome of case–control status. Only shared look rate predicted any of the exploratory sub-diagnosis outcomes and was found to be positively associated with later oppositional-conduct disorders (OR [95% CI]: 1.5 [1.0, 2.3]; p = 0.041).&lt;/br&gt;&lt;br&gt;Conclusions: JA behaviours did not, in general, predict later psychopathology. However, shared look was positively associated with later oppositional-conduct disorders. This suggests that some features of JA may be early markers of later psychopathology. Further investigation will be required to determine whether any JA behaviours can be used to screen for families in need of intervention.&lt;/br&gt

The Sorcerer II Global Ocean Sampling Expedition: Northwest Atlantic through Eastern Tropical Pacific

The world's oceans contain a complex mixture of micro-organisms that are for the most part, uncharacterized both genetically and biochemically. We report here a metagenomic study of the marine planktonic microbiota in which surface (mostly marine) water samples were analyzed as part of the Sorcerer II Global Ocean Sampling expedition. These samples, collected across a several-thousand km transect from the North Atlantic through the Panama Canal and ending in the South Pacific yielded an extensive dataset consisting of 7.7 million sequencing reads (6.3 billion bp). Though a few major microbial clades dominate the planktonic marine niche, the dataset contains great diversity with 85% of the assembled sequence and 57% of the unassembled data being unique at a 98% sequence identity cutoff. Using the metadata associated with each sample and sequencing library, we developed new comparative genomic and assembly methods. One comparative genomic method, termed “fragment recruitment,” addressed questions of genome structure, evolution, and taxonomic or phylogenetic diversity, as well as the biochemical diversity of genes and gene families. A second method, termed “extreme assembly,” made possible the assembly and reconstruction of large segments of abundant but clearly nonclonal organisms. Within all abundant populations analyzed, we found extensive intra-ribotype diversity in several forms: (1) extensive sequence variation within orthologous regions throughout a given genome; despite coverage of individual ribotypes approaching 500-fold, most individual sequencing reads are unique; (2) numerous changes in gene content some with direct adaptive implications; and (3) hypervariable genomic islands that are too variable to assemble. The intra-ribotype diversity is organized into genetically isolated populations that have overlapping but independent distributions, implying distinct environmental preference. We present novel methods for measuring the genomic similarity between metagenomic samples and show how they may be grouped into several community types. Specific functional adaptations can be identified both within individual ribotypes and across the entire community, including proteorhodopsin spectral tuning and the presence or absence of the phosphate-binding gene PstS

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

Genetic mechanisms of critical illness in COVID-19.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079, P = 1.65 × 10-8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1, OAS2 and OAS3); on chromosome 19p13.2 (rs74956615, P = 2.3 × 10-8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069, P = 3.98 ×  10-12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757, P = 4.99 × 10-8) in the interferon receptor gene IFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression of IFNAR2, or high expression of TYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte-macrophage chemotactic receptor CCR2 is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice

Adjunctive rifampicin for Staphylococcus aureus bacteraemia (ARREST): a multicentre, randomised, double-blind, placebo-controlled trial.

BACKGROUND: Staphylococcus aureus bacteraemia is a common cause of severe community-acquired and hospital-acquired infection worldwide. We tested the hypothesis that adjunctive rifampicin would reduce bacteriologically confirmed treatment failure or disease recurrence, or death, by enhancing early S aureus killing, sterilising infected foci and blood faster, and reducing risks of dissemination and metastatic infection. METHODS: In this multicentre, randomised, double-blind, placebo-controlled trial, adults (≥18 years) with S aureus bacteraemia who had received ≤96 h of active antibiotic therapy were recruited from 29 UK hospitals. Patients were randomly assigned (1:1) via a computer-generated sequential randomisation list to receive 2 weeks of adjunctive rifampicin (600 mg or 900 mg per day according to weight, oral or intravenous) versus identical placebo, together with standard antibiotic therapy. Randomisation was stratified by centre. Patients, investigators, and those caring for the patients were masked to group allocation. The primary outcome was time to bacteriologically confirmed treatment failure or disease recurrence, or death (all-cause), from randomisation to 12 weeks, adjudicated by an independent review committee masked to the treatment. Analysis was intention to treat. This trial was registered, number ISRCTN37666216, and is closed to new participants. FINDINGS: Between Dec 10, 2012, and Oct 25, 2016, 758 eligible participants were randomly assigned: 370 to rifampicin and 388 to placebo. 485 (64%) participants had community-acquired S aureus infections, and 132 (17%) had nosocomial S aureus infections. 47 (6%) had meticillin-resistant infections. 301 (40%) participants had an initial deep infection focus. Standard antibiotics were given for 29 (IQR 18-45) days; 619 (82%) participants received flucloxacillin. By week 12, 62 (17%) of participants who received rifampicin versus 71 (18%) who received placebo experienced treatment failure or disease recurrence, or died (absolute risk difference -1·4%, 95% CI -7·0 to 4·3; hazard ratio 0·96, 0·68-1·35, p=0·81). From randomisation to 12 weeks, no evidence of differences in serious (p=0·17) or grade 3-4 (p=0·36) adverse events were observed; however, 63 (17%) participants in the rifampicin group versus 39 (10%) in the placebo group had antibiotic or trial drug-modifying adverse events (p=0·004), and 24 (6%) versus six (2%) had drug interactions (p=0·0005). INTERPRETATION: Adjunctive rifampicin provided no overall benefit over standard antibiotic therapy in adults with S aureus bacteraemia. FUNDING: UK National Institute for Health Research Health Technology Assessment

Evidence-based Kernels: Fundamental Units of Behavioral Influence

This paper describes evidence-based kernels, fundamental units of behavioral influence that appear to underlie effective prevention and treatment for children, adults, and families. A kernel is a behavior–influence procedure shown through experimental analysis to affect a specific behavior and that is indivisible in the sense that removing any of its components would render it inert. Existing evidence shows that a variety of kernels can influence behavior in context, and some evidence suggests that frequent use or sufficient use of some kernels may produce longer lasting behavioral shifts. The analysis of kernels could contribute to an empirically based theory of behavioral influence, augment existing prevention or treatment efforts, facilitate the dissemination of effective prevention and treatment practices, clarify the active ingredients in existing interventions, and contribute to efficiently developing interventions that are more effective. Kernels involve one or more of the following mechanisms of behavior influence: reinforcement, altering antecedents, changing verbal relational responding, or changing physiological states directly. The paper describes 52 of these kernels, and details practical, theoretical, and research implications, including calling for a national database of kernels that influence human behavior

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care