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A 19-year-old woman with a skeletal Class III pattern, anterior and posterior crossbites, and a low mandibular plane angle was treated with nonextraction camouflage treatment. The total active treatment time was 17 months. After treatment, her occlusion, smile esthetics, and soft tissue profile were significantly improved.

OBJECTIVE xCures operates a direct-to-patient, real-world evidence platform according to the nationwide observational research protocol XCELSIOR (NCT03793088), which aggregates medical data in an FDA-compliant electronic database. There is a relative scarcity of published results on real-world Quality-of-Life (QoL) outcomes and resulting health state utilities for patients with Central Nervous System (CNS) cancers. We sought to use the xCures platform to help address this issue. METHODS XCELSIOR participants were invited weekly to complete the EuroQol 5-Dimension (EQ-5D-5L) QoL survey. A EuroQol-endorsed model was used to estimate health state utilities from patient surveys. Survey results, utility estimates, and clinical information were analyzed to understand the influence of common mutations in glioma on patient reported outcomes. RESULTS 30 patients (21 glioblastoma, 4 oligodendroglioma, 2 diffuse midline glioma, 2 diffuse astrocytoma, 1 Schwannoma) completed at least one EQ-5D-5L survey over the course of 9 weeks. Health state utilities were positively correlated (p< .03) with Karnofsky Performance Score (KPS). The average utility for EGFR-mutated patients (N=6) was .578 (SD=.334) while for EGFR-wildtype patients (N=7) it was .747 (SD=.227). The average utility for MGMT-methylated patients (N=13) was .816 (SD=.139) while for non-methylated patients (N=10) it was .583 (SD=.379). The average utility for IDH-mutated patients (N=9) was .789 (SD=.153) while for non-mutated patients (N=17) it was .685 (SD=.324). The average utility for patients with a 1p/19q co-deletion (N=4) was .837 (SD=.126) while for those without a co-deletion (N=8) it was .744 (SD=.244). CONCLUSION The xCures platform has enabled the study of real-world QoL outcomes for patients with CNS cancers. This is the first report studying the influence of genetic mutations on QoL collected through patient reported outcomes. Future research aims to perform similar studies with larger number of patients.

X-ray Bragg coherent diffraction imaging (BCDI) has been demonstrated as a powerful 3D microscopy approach for the investigation of sub-micrometre-scale crystalline particles. The approach is based on the measurement of a series of coherent Bragg diffraction intensity patterns that are numerically inverted to retrieve an image of the spatial distribution of the relative phase and amplitude of the Bragg structure factor of the diffracting sample. This 3D information, which is collected through an angular rotation of the sample, is necessarily obtained in a non-orthogonal frame in Fourier space that must be eventually reconciled. To deal with this, the approach currently favored by practitioners (detailed in Part I) is to perform the entire inversion in conjugate non-orthogonal real- and Fourier-space frames, and to transform the 3D sample image into an orthogonal frame as a post-processing step for result analysis. In this article, which is a direct follow-up of Part I, two different transformation strategies are demonstrated, which enable the entire inversion procedure of the measured data set to be performed in an orthogonal frame. The new approaches described here build mathematical and numerical frameworks that apply to the cases of evenly and non-evenly sampled data along the direction of sample rotation (i.e. the rocking curve). The value of these methods is that they rely on the experimental geometry, and they incorporate significantly more information about that geometry into the design of the phase-retrieval Fourier transformation than the strategy presented in Part I. Two important outcomes are (1) that the resulting sample image is correctly interpreted in a shear-free frame and (2) physically realistic constraints of BCDI phase retrieval that are difficult to implement with current methods are easily incorporated. Computing scripts are also given to aid readers in the implementation of the proposed formalisms.

Nitrate and radioiodine (129I) contamination is widespread in groundwater underneath the Central Plateau of the Hanford Site. 129I, a byproduct of nuclear fission, is of concern due to a 15.7 million year half-life, and toxicity. The Hanford 200 West Area contains plumes covering 4.3 km2 with average 129I concentrations of 3.5 pCi/L. Iodate accounts for 70.6% of the iodine present and organo-iodine and iodide make up 25.8% and 3.6%, respectively. Nitrate plumes encompassing the 129I plumes have a surface area of 16 km2 averaging 130 mg/L. A nitrate and iodate reducing bacterium closely related to Agrobacterium, strain DVZ35, was isolated from sediment incubated in a 129I plume. Iodate removal efficiency was 36.3% in transition cultures, and 47.8% in anaerobic cultures. Nitrate (10 mM) was also reduced in the microcosm. When nitrate was spiked into the microcosms, iodate removal efficiency was 84.0% and 69.2% in transition and anaerobic cultures, respectively. Iodate reduction was lacking when nitrate was absent from the growth medium. These data indicate there is simultaneous reduction of nitrate and iodate by DVZ35, and iodate is reduced to iodide. Results provide the scientific basis for combined nitrogen and iodine cycling throughout the Hanford Site.

Microbial iodate (IO3−) reduction is a major component of iodine biogeochemical cycling and is the basis of alternative strategies for remediation of iodine-contaminated environments. The m...

Pump-and-treat (P&T) is a widely applied remedy for groundwater remediation at many types of sites for multiple types of contaminants. Decisions regarding major changes in the remediation approach are an important element of environmental remediation management for a site using P&T. While existing guidance documents provide information on design, operation, and optimization for P&T systems, these documents do not provide specific technical guidance to support remedy decisions regarding when to transition to a new remedy or to initiate closure of the P&T remedy. A structured approach for P&T performance assessment was developed and is described herein, using analysis of three example P&T systems. These examples highlight key aspects of the performance assessment decision logic and represent assessment outcomes associated with optimizing the P&T system, transitioning from P&T to natural attenuation, and supplementing P&T with another technology to hasten transition to natural attenuation.

Silicon carbide has recently been developed as a platform for optically addressable spin defects. In particular, the neutral divacancy in the 4H polytype displays an optically addressable spin-1 ground state and near-infrared optical emission. Here, we present the Purcell enhancement of a single neutral divacancy coupled to a photonic crystal cavity. We utilize a combination of nanolithographic techniques and a dopant-selective photoelectrochemical etch to produce suspended cavities with quality factors exceeding 5,000. Subsequent coupling to a single divacancy leads to a Purcell factor of ~50, which manifests as increased photoluminescence into the zero-phonon line and a shortened excited-state lifetime. Additionally, we measure coherent control of the divacancy ground state spin inside the cavity nanostructure and demonstrate extended coherence through dynamical decoupling. This spin-cavity system represents an advance towards scalable long-distance entanglement protocols using silicon carbide that require the interference of indistinguishable photons from spatially separated single qubits., 13 pages, 4 figures

Complex sites in the subsurface are defined as those with difficult access, deep, and/or thick zones of contamination, large areal extent, heterogeneities that limit the effectiveness of remediation, or where long-term remedies are needed to address contamination (e.g., because of long-term sources or large extent). The Test Area North at the Idaho National Laboratory, developed for nuclear fuel operations and heavy metal manufacturing, is a complex site that demonstrates the endpoints strategy for adaptive remediation. Liquid wastes and sludge from experimental facilities were disposed in an injection well, which contaminated the subsurface aquifer located deep within fractured basalt. The mixed wastes included organic, inorganic, and low-level radioactive constituents, with the focus of this study on the remediation of trichloroethylene within a systems-based, regulatory framework. The framework facilitates site, regulator, and stakeholder interactions during the remedial planning and implementation process by using a conceptual model description as a technical foundation for decisions identifying endpoints. Endpoints are defined as interim remediation targets or decision points on the path to an ultimate end, and maintaining protectiveness during the remediation process. Results demonstrate that the three-component remedy used at Test Area North as an example of the structured framework is largely functioning as intended and is projected to meet remedial action objectives by 2095. The remedy approach is being adjusted as new data become available. The framework provides a structured process for evaluating and adjusting the remediation approach, allowing site owners, regulators, and stakeholders to manage contamination at complex sites where adaptive remedies are needed. ©2016 Wiley Periodicals, Inc.

The metal-reducing gammaproteobacterium Shewanella oneidensis reduces iodate (IO(3)(−)) as an anaerobic terminal electron acceptor. Microbial IO(3)(−) electron transport pathways are postulated to terminate with nitrate (NO(3)(−)) reductase, which reduces IO(3)(−) as an alternative electron acceptor. Recent studies with S. oneidensis, however, have demonstrated that NO(3)(−) reductase is not involved in IO(3)(−) reduction. The main objective of the present study was to determine the metal reduction and protein secretion genes required for IO(3)(−) reduction by Shewanella oneidensis with lactate, formate, or H(2) as the electron donor. With all electron donors, the type I and type V protein secretion mutants retained wild-type IO(3)(−) reduction activity, while the type II protein secretion mutant lacking the outer membrane secretin GspD was impaired in IO(3)(−) reduction. Deletion mutants lacking the cyclic AMP receptor protein (CRP), cytochrome maturation permease CcmB, and inner membrane-tethered c-type cytochrome CymA were impaired in IO(3)(−) reduction with all electron donors, while deletion mutants lacking c-type cytochrome MtrA and outer membrane β-barrel protein MtrB of the outer membrane MtrAB module were impaired in IO(3)(−) reduction with only lactate as an electron donor. With all electron donors, mutants lacking the c-type cytochromes OmcA and MtrC of the metal-reducing extracellular electron conduit MtrCAB retained wild-type IO(3)(−) reduction activity. These findings indicate that IO(3)(−) reduction by S. oneidensis involves electron donor-dependent metal reduction and protein secretion pathway components, including the outer membrane MtrAB module and type II protein secretion of an unidentified IO(3)(−) reductase to the S. oneidensis outer membrane. IMPORTANCE Microbial iodate (IO(3)(−)) reduction is a major component in the biogeochemical cycling of iodine and the bioremediation of iodine-contaminated environments; however, the molecular mechanism of microbial IO(3)(−) reduction is poorly understood. Results of the present study indicate that outer membrane (type II) protein secretion and metal reduction genes encoding the outer membrane MtrAB module of the extracellular electron conduit MtrCAB are required for IO(3)(−) reduction by S. oneidensis. On the other hand, the metal-reducing c-type cytochrome MtrC of the extracellular electron conduit is not required for IO(3)(−) reduction by S. oneidensis. These findings indicate that the IO(3)(−) electron transport pathway terminates with an as yet unidentified IO(3)(−) reductase that associates with the outer membrane MtrAB module to deliver electrons extracellularly to IO(3)(−).

For more than 10 years, electron donor has been injected into the Snake River aquifer beneath the Test Area North site of the Idaho National Laboratory for the purpose of stimulating microbial reductive dechlorination of trichloroethene (TCE) in groundwater. This has resulted in significant TCE removal from the source area of the contaminant plume and elevated dissolved CH(4) in the groundwater extending 250 m from the injection well. The delta(13)C of the CH(4) increases from -56 per thousand in the source area to -13 per thousand with distance from the injection well, whereas the delta(13)C of dissolved inorganic carbon decreases from 8 per thousand to -13 per thousand, indicating a shift from methanogenesis to methane oxidation. This change in microbial activity along the plume axis is confirmed by PhyloChip microarray analyses of 16S rRNA genes obtained from groundwater microbial communities, which indicate decreasing abundances of reductive dechlorinating microorganisms (e.g., Dehalococcoides ethenogenes) and increasing CH(4)-oxidizing microorganisms capable of aerobic co-metabolism of TCE (e.g., Methylosinus trichosporium). Incubation experiments with (13)C-labeled TCE introduced into microcosms containing basalt and groundwater from the aquifer confirm that TCE co-metabolism is possible. The results of these studies indicate that electron donor amendment designed to stimulate reductive dechlorination of TCE may also stimulate co-metabolism of TCE.

Idaho National Laboratory's Test Area North is the site of a trichloroethene (TCE) plume resulting from waste injections. Previous investigations revealed that TCE was being attenuated relative to two codisposed internal tracers, tritium and tetrachloroethene, with a half-life of 9 to 21 years. Biological attenuation mechanisms were investigated using a novel suite of assays, including enzyme activity probes designed for the soluble methane monooxygenase (sMMO) enzyme. Samples were analyzed for chlorinated solvents, tritium, redox parameters, primary substrates, degradation products, bacterial community methanotrophic potential, and bacterial DNA. The enzyme probe assays, methanotrophic enrichments and isolations, and DNA analysis documented the presence and activity of indigenous methanotrophs expressing the sMMO enzyme. Three-dimensional groundwater data showed plume-wide aerobic conditions, with low levels of methane and detections of carbon monoxide, a by-product of TCE cometabolism. The TCE ...

The Test Area North (TAN) site at the Idaho National Laboratory near Idaho Falls, ID, USA, sits over a trichloroethylene (TCE) contaminant plume in the Snake River Plain fractured basalt aquifer. Past observations have provided evidence that TCE at TAN is being transformed by biological natural attenuation that may be primarily due to co-metabolism in aerobic portions of the plume by methanotrophs. TCE co-metabolism by methanotrophs is the result of the broad substrate specificity of microbial methane monooxygenase which permits non-specific oxidation of TCE in addition to the primary substrate, methane. Arrays of experimental approaches have been utilized to understand the biogeochemical processes driving intrinsic TCE co-metabolism at TAN. In this study, aerobic methanotrophs were enumerated by qPCR using primers targeting conserved regions of the genes pmoA and mmoX encoding subunits of the particulate MMO (pMMO) and soluble MMO (sMMO) enzymes, respectively, as well as the gene mxa encoding the downstream enzyme methanol dehydrogenase. Identification of proteins in planktonic and biofilm samples from TAN was determined using reverse phase ultra-performance liquid chromatography (UPLC) coupled with a quadrupole-time-of-flight (QToF) mass spectrometer to separate and sequence peptides from trypsin digests of the protein extracts. Detection of MMO in unenriched water samples from TAN provides direct evidence of intrinsic methane oxidation and TCE co-metabolic potential of the indigenous microbial population. Mass spectrometry is also well suited for distinguishing which form of MMO is expressed in situ either soluble or particulate. Using this method, pMMO proteins were found to be abundant in samples collected from wells within and adjacent to the TCE plume at TAN.

Trichloroethene (TCE) (also known as trichloroethylene) is a common contaminant in groundwater. TCE is regulated in drinking water at a concentration of 5 µg/L, and a small mass of TCE has the potential to contaminant large volumes of water. The physical and chemical characteristics of TCE allow it to migrate quickly in most subsurface environments, and thus large plumes of contaminated groundwater can form from a single release. The migration and persistence of TCE in groundwater can be limited by biodegradation. TCE can be biodegraded via different processes under either anaerobic or aerobic conditions. Anaerobic biodegradation is widely recognized, but aerobic degradation is less well recognized. Under aerobic conditions, TCE can be oxidized to non hazardous conditions via cometabolic pathways. This study applied enzyme activity probes to demonstrate that cometabolic degradation of TCE occurs in aerobic groundwater at several locations, used laboratory microcosm studies to determine aerobic degradation rates, and extrapolated lab-measured rates to in situ rates based on concentrations of microorganisms with active enzymes involved in cometabolic TCE degradation. Microcosms were constructed using basalt chips that were inoculated with microorganisms to groundwater at the Idaho National Laboratory Test Area North TCE plume by filling a set of Flow-Through In more » Situ Reactors (FTISRs) with chips and placing the FTISRs into the open interval of a well for several months. A parametric study was performed to evaluate predicted degradation rates and concentration trends using a competitive inhibition kinetic model, which accounts for competition for enzyme active sites by both a growth substrate and a cometabolic substrate. The competitive inhibition kinetic expression was programmed for use in the RT3D reactive transport package. Simulations of TCE plume evolution using both competitive inhibition kinetics and first order decay were performed. « less

The overarching objective of the Paducah Gaseous Diffusion Plant (PGDP) enzyme activity probe (EAP) effort is to determine if aerobic cometabolism is contributing to the attenuation of trichloroethene (TCE) and other chlorinated solvents in the contaminated groundwater beneath PGDP. The site-specific objective for the EAP assessment is to identify if key metabolic pathways are present and expressed in the microbial community--namely the pathways that are responsible for degradation of methane and aromatic (e.g. toluene, benzene, phenol) substrates. The enzymes produced to degrade methane and aromatic compounds also break down TCE through a process known as cometabolism. EAPs directly measure if methane and/or aromatic enzyme production pathways are operating and, for the aromatic pathways, provide an estimate of the number of active organisms in the sampled groundwater. This study in the groundwater plumes at PGDP is a major part of a larger scientific effort being conducted by Interstate Technology and Regulatory Council (ITRC), U.S. Department of Energy (DOE) Office of Environmental Management (EM), Savannah River National Laboratory (SRNL), and North Wind Inc. in which EAPs are being applied to contaminated groundwater from diverse hydrogeologic and plume settings throughout the U.S. to help standardize their application as well as their interpretation. While EAP data provide key information to support the site specific objective for PGDP, several additional lines of evidence are being evaluated to increase confidence in the determination of the occurrence of biodegradation and the rate and sustainability of aerobic cometabolism. These complementary efforts include: (1) Examination of plume flowpaths and comparison of TCE behavior to 'conservative' tracers in the plume (e.g., {sup 99}Tc); (2) Evaluation of geochemical conditions throughout the plume; and (3) Evaluation of stable isotopes in the contaminants and their daughter products throughout the plume. If the multiple lines of evidence support the occurrence of cometabolism and the potential for the process to contribute to temporal and spatial attenuation of TCE in PGDP groundwater, then a follow-up enzyme probe microcosm study to better estimate biological degradation rate(s) is warranted.

A variety of naturally occurring bacteria produce enzymes that cometabolically degrade trichloroethene (TCE), including organisms with aerobic oxygenases. Groundwater contaminated with TCE was collected from the aerobic region of the Test Area North site of the Idaho National Laboratory. Samples were evaluated with enzyme activity probes, and resulted in measurable detection of toluene oxygenase activity (6-79% of the total microbial cells). Wells from both inside and outside contaminated plume showed activity. Toluene oxygenase-specific PCR primers determined that toluene-degrading genes were present in all groundwater samples evaluated. In addition, bacterial isolates were obtained and possessed toluene oxygenase enzymes, demonstrated activity, and were dominated by the phylotype Pseudomonas. This study demonstrated, through the use of enzymatic probes and oxygenase gene identification, that indigenous microorganisms at a contaminated site were cometabolically active. Documentation such as this can be used to substantiate observations of natural attenuation of TCE-contaminated groundwater plumes.

Chlorinated solvent wastes (e.g., trichloroethene or TCE) often occur as diffuse subsurface plumes in complex geological environments where coupled processes must be understood in order to implement remediation strategies. Monitored natural attenuation (MNA) warrants study as a remediation technology because it minimizes worker and environment exposure to the wastes and because it costs less than other technologies. However, to be accepted MNA requires different ?lines of evidence? indicating that the wastes are effectively destroyed. We are studying the coupled biogeochemical processes that dictate the rate of TCE co-metabolism first in the medial zone (TCE concentration: 1,000 to 20,000 ?g/L) of a plume at the Idaho National Laboratory?s Test Area North (TAN) site and then at Paducah or the Savannah River Site. We will use flow-through in situ reactors (FTISR) to investigate the rate of methanotrophic co-metabolism of TCE and the coupling of the responsible biological processes with the dissolved methane flux and groundwater flow velocity. TCE co-metabolic rates at TAN are being assessed and interpreted in the context of enzyme activity, gene expression, and cellular inactivation related to intermediates of TCE co-metabolism. By determining the rate of TCE co-metabolism at different groundwater flow velocities, we will derive key modeling parametersmore » for the computational simulations that describe the attenuation, and thereby refine such models while assessing the contribution of microbial co-metabolism relative to other natural attenuation processes. This research will strengthen our ability to forecast the viability of MNA at DOE and other sites contaminated with chlorinated hydrocarbons.« less