DE-FG02-06ER15364: Final Technical Report Nanoscale Reactivity of Clays, Clay Analogues (Micas), and Clay Minerals

The project objectives were to determine the nanoscale to molecular scale structure of the interface between muscovite mica and aqueous solutions containing various sorbates and to explore systematics that control the incorporation of inorganic and organic chemical components during aging of nanoparticles of iron-oxides and aluminosilicate clays. The basal surface of phyllosilicates is a primary sorbent of environmental contaminants, natural organic matter, and nutrients. Micas are also superb atomically-flat substrates used in materials science and surface physics applications. We applied X-ray scattering techniques using high brilliance synchrotron radiation to investigate molecular-scale details of mica’s interface structure in solutions containing common and toxic cations, anions, and natural organic molecules. Nanoparticles are ubiquitous in the environment and have a high capacity for sorbing contaminants through the combined effects of their high surface areas and pH-dependent surface charge. Aging of nanoparticles from metastable to stable phases can be inhibited by sorption of nonstructural components, but exact mechanisms are unknown. We synthesized Fe-oxides and aluminosilicate clay minerals from aqueous solutions in the presence of selected anions, and organic molecules, and quantified the uptake of these additives during aging and some implications for nanoparticle formation

Phase Chemistry of Tank Sludge Residual Components

About four or five distinct reprocessing technologies were used at various times in Hanford's history. After removing U and Pu (or later 137Cs and 90Sr), the strongly acidic HLW was ''neutralized'' to high pH (>13) and stored in steel-lined tanks. High pH was necessary to prevent tank corrosion. While each technology produced chemically distinct waste, all wastes were similar in that they were high pH, concentrated, aqueous solutions. Dominant dissolved metals were Fe and/or Al, usually followed by Ni, Mn, or Cr. In an effort to reduce waste volume, many of the wastes were placed in evaporators or allowed to ''self-boil'' from the heat produced by their own radioactive decay. Consequently, today's HLW has been aging at temperatures ranging from 20 to 160 C. Previous studies of synthetic HLW sludge analogues have varied in their exact synthesis procedures and recipes, although each involved ''neutralization'' of acidic nitrate salt solutions by concentrated NaOH. Some recipes included small amounts of Si, SO4 2-, CO3 2-, and other minor chemical components in the Hanford sludges. The work being conducted at the University of Colorado differs from previous studies and from parallel current investigations at Sandia National Laboratories in the simplicity of the synthetic sludge we are investigating. We are emphasizing the dominant role of Fe and Al, and secondarily, the effects of Ni and Si on the aging kinetics of the solid phases in the sludge

The Effect of Dissolved Humic Acids on Aluminosilicate Formation and Associated Carbon Sequestration

Allophane and imogolite neogenesis in soils may occur in the presence of organic matter. To understand this process under conditions relevant to soils, the influence of dissolved organic carbon (DOC) as humic acid (HA), on aluminosilicate formation was studied at 25◦C, pH 6, and low-DOC concentrations. For solutions with initial Al/Si ratios of 1–2.1, and 0–6mg/L DOC, precipitates recovered after 20h had Al/Si ratios of 2.2–2.7. The formation of allophane, imogolite-like material, and aluminosilicate gel was confirmed by XRD, FTIR, and NMR. The effect of DOC was to produce a small, but systematic increase in imogolite-like Si in the precipitate, and a decrease in the formation of aluminosilicate gel. Results suggest that the presence of DOC as HA slows the otherwise rapid polymerization of Al and Si at low temperature, and may also promote the formation of imogolite. The high C content of these precipitates indicates that this process may facilitate the sequestration of organic matter, slowing C cycling in soils

Phase Chemistry of Tank Sludge Residual Components

Experiments began with ''neutralization'' of iron (III)-aluminum nitrate solutions by addition of sodium hydroxide at room temperature. The final pH of most experiments was approximately 13.7. The samples were neutralized in PP or HDPE bottles that were then submerged in a water bath and aged at 90 C for up to 120 h. (In the low-Al systems, X-ray diffraction (XRD) results suggest that transformation of the initial amorphous precipitate to crystalline phases was complete after this time.) Experiments were run either as a single 250 mL sample (''single age experiments'') or as 2 L batches, from which 250 mL aliquots were drawn (''batch experiments''). Both solid phase chemistry and solution composition were monitored throughout the aging process. Samples were centrifuged and the experimental supernatant solutions were decanted and passed through a 0.4 mm syringe filter prior to analysis. Solids were dialyzed to removed excess salts. Aqueous Al and Fe were measured by the catechol violet (Dougan and Wilson, 1974) and Ferrozine (Dawson and Lyle, 1990) techniques, respectively. X-ray diffraction data were taken with a Scintag powder diffractometer scanning at 1{sup o} 2Q per minute using Cu K-a radiation and a graphite beam monochromator

In situ clay formation : evaluation of a proposed new technology for stable containment barriers.

Containment of chemical wastes in near-surface and repository environments is accomplished by designing engineered barriers to fluid flow. Containment barrier technologies such as clay liners, soil/bentonite slurry walls, soil/plastic walls, artificially grouted sediments and soils, and colloidal gelling materials are intended to stop fluid transport and prevent plume migration. However, despite their effectiveness in the short-term, all of these barriers exhibit geochemical or geomechanical instability over the long-term resulting in degradation of the barrier and its ability to contain waste. No technologically practical or economically affordable technologies or methods exist at present for accomplishing total remediation, contaminant removal, or destruction-degradation in situ. A new type of containment barrier with a potentially broad range of environmental stability and longevity could result in significant cost-savings. This report documents a research program designed to establish the viability of a proposed new type of containment barrier derived from in situ precipitation of clays in the pore space of contaminated soils or sediments. The concept builds upon technologies that exist for colloidal or gel stabilization. Clays have the advantages of being geologically compatible with the near-surface environment and naturally sorptive for a range of contaminants, and further, the precipitation of clays could result in reduced permeability and hydraulic conductivity, and increased mechanical stability through cementation of soil particles. While limited success was achieved under certain controlled laboratory conditions, the results did not warrant continuation to the field stage for multiple reasons, and the research program was thus concluded with Phase 2

Haplotype-based association analysis of general cognitive ability in Generation Scotland, the English Longitudinal Study of Ageing, and UK Biobank

Background: Cognitive ability is a heritable trait with a polygenic architecture, for which several associated variants have been identified using genotype-based and candidate gene approaches. Haplotype-based analyses are a complementary technique that take phased genotype data into account, and potentially provide greater statistical power to detect lower frequency variants. Methods: In the present analysis, three cohort studies (ntotal = 48,002) were utilised: Generation Scotland: Scottish Family Health Study (GS:SFHS), the English Longitudinal Study of Ageing (ELSA), and the UK Biobank. A genome-wide haplotype-based meta-analysis of cognitive ability was performed, as well as a targeted meta-analysis of several gene coding regions. Results: None of the assessed haplotypes provided evidence of a statistically significant association with cognitive ability in either the individual cohorts or the meta-analysis. Within the meta-analysis, the haplotype with the lowest observed P-value overlapped with the D-amino acid oxidase activator (DAOA) gene coding region. This coding region has previously been associated with bipolar disorder, schizophrenia and Alzheimer’s disease, which have all been shown to impact upon cognitive ability. Another potentially interesting region highlighted within the current genome-wide association analysis (GS:SFHS: P = 4.09 x 10-7), was the butyrylcholinesterase (BCHE) gene coding region. The protein encoded by BCHE has been shown to influence the progression of Alzheimer’s disease and its role in cognitive ability merits further investigation. Conclusions: Although no evidence was found for any haplotypes with a statistically significant association with cognitive ability, our results did provide further evidence that the genetic variants contributing to the variance of cognitive ability are likely to be of small effect

Effect of Neutralizing Monoclonal Antibody Treatment on Early Trajectories of Virologic and Immunologic Biomarkers in Patients Hospitalized With COVID-19

BACKGROUND: Neutralizing monoclonal antibodies (nmAbs) failed to show clear benefit for hospitalized patients with coronavirus disease 2019 (COVID-19). Dynamics of virologic and immunologic biomarkers remain poorly understood. METHODS: Participants enrolled in the Therapeutics for Inpatients with COVID-19 trials were randomized to nmAb versus placebo. Longitudinal differences between treatment and placebo groups in levels of plasma nucleocapsid antigen (N-Ag), anti-nucleocapsid antibody, C-reactive protein, interleukin-6, and D-dimer at enrollment, day 1, 3, and 5 were estimated using linear mixed models. A 7-point pulmonary ordinal scale assessed at day 5 was compared using proportional odds models. RESULTS: Analysis included 2149 participants enrolled between August 2020 and September 2021. Treatment resulted in 20% lower levels of plasma N-Ag compared with placebo (95% confidence interval, 12%-27%; P \u3c .001), and a steeper rate of decline through the first 5 days (P \u3c .001). The treatment difference did not vary between subgroups, and no difference was observed in trajectories of other biomarkers or the day 5 pulmonary ordinal scale. CONCLUSIONS: Our study suggests that nmAb has an antiviral effect assessed by plasma N-Ag among hospitalized patients with COVID-19, with no blunting of the endogenous anti-nucleocapsid antibody response. No effect on systemic inflammation or day 5 clinical status was observed. CLINICAL TRIALS REGISTRATION: NCT04501978

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

SOX9 Governs Differentiation Stage-Specific Gene Expression in Growth Plate Chondrocytes via Direct Concomitant Transactivation and Repression

Cartilage and endochondral bone development require SOX9 activity to regulate chondrogenesis, chondrocyte proliferation, and transition to a non-mitotic hypertrophic state. The restricted and reciprocal expression of the collagen X gene, Col10a1, in hypertrophic chondrocytes and Sox9 in immature chondrocytes epitomise the precise spatiotemporal control of gene expression as chondrocytes progress through phases of differentiation, but how this is achieved is not clear. Here, we have identified a regulatory element upstream of Col10a1 that enhances its expression in hypertrophic chondrocytes in vivo. In immature chondrocytes, where Col10a1 is not expressed, SOX9 interacts with a conserved sequence within this element that is analogous to that within the intronic enhancer of the collagen II gene Col2a1, the known transactivation target of SOX9. By analysing a series of Col10a1 reporter genes in transgenic mice, we show that the SOX9 binding consensus in this element is required to repress expression of the transgene in non-hypertrophic chondrocytes. Forced ectopic Sox9 expression in hypertrophic chondrocytes in vitro and in mice resulted in down-regulation of Col10a1. Mutation of a binding consensus motif for GLI transcription factors, which are the effectors of Indian hedgehog signaling, close to the SOX9 site in the Col10a1 regulatory element, also derepressed transgene expression in non-hypertrophic chondrocytes. GLI2 and GLI3 bound to the Col10a1 regulatory element but not to the enhancer of Col2a1. In addition to Col10a1, paired SOX9–GLI binding motifs are present in the conserved non-coding regions of several genes that are preferentially expressed in hypertrophic chondrocytes and the occurrence of pairing is unlikely to be by chance. We propose a regulatory paradigm whereby direct concomitant positive and negative transcriptional control by SOX9 ensures differentiation phase-specific gene expression in chondrocytes. Discrimination between these opposing modes of transcriptional control by SOX9 may be mediated by cooperation with different partners such as GLI factors