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At least 37 records · Page 2

Texture analysis of placental MRI: can it aid in the prenatal diagnosis of placenta accreta spectrum?

Purpose: To determine if texture analysis can differentiate placenta accreta spectrum (PAS) from normal placenta on MRI. Methods: We performed retrospective image analysis of 80 patients, comprised of 46 patients with PAS and 34 patients without PAS. Histopathology was used as the reference standard. Sagittal single shot fast spin echo T2-weighted MRI sequences acquired from a single institution were analyzed. Placental heterogeneity was quantified using in-house software on a Matlab platform, including the standard deviation of pixel intensity, coefficient of variation, gray-level co-occurrence matrices (GLCM), histogram-oriented gradients (HOG), and fractal analysis with box sizes from 2 to 512. Two-tailed unpaired Student’s t test was used with statistical significance of p < 0.05. Results: PAS was associated with higher values for standard deviation of pixel intensity and fractal analysis at every box size. Fractal analysis at box sizes 256 (p = 0.011) and 32 (p = 0.021), and standard deviation of pixel intensity (p = 0.023) were the most statistically significant. Fractal values at box size 256 for PAS was 0.13 versus 0.090 for patients without PAS, while standard deviation of pixel intensity was 3.7 for PAS versus 2.5 for patients without PAS. No statistically significant association between PAS and GLCM, coefficient of variation, and HOG was found. Conclusion: Statistically significant differences were found between normal and abnormal groups using standard deviation of pixel intensity and fractal analysis.

62 RADIOLOGY AND NUCLEAR MEDICINE↗

The Use of Positrons to Survey Alteration Layers on Synthetic Nuclear Waste Glasses

In order to safeguard society and the environment, understanding radioactive waste glass alteration mechanisms in interactions with solutions and near-field materials, such as Fe, is essential to nuclear waste repository performance assessments. Alteration products are formed at the surface of glasses after reaction with solution. In this study, glass altered in the presence of Fe0 in aqueous solution formed two alteration layers: one embedded with Fe closer to the surface and one without Fe found deeper in the sample. Both layers were found to be thinner than the alteration layer found in glass altered in aqueous solution only. For the first time, Doppler Broadening Positron Annihilation Spectroscopy (DB-PAS) is used to non-destructively characterize the pore structures of glass altered in the presence of Fe0. Advantages and disadvantages of DB-PAS compared to other techniques used to analyze pore structures for altered glass samples are discussed. Ultimately, DB-PAS has shown to be an excellent choice for pore structure characterization for glasses with multiple alteration layers. Monte Carlo modeling predicted positron trajectories through the layers, and helped explain DB-PAS data, which showed that the deeper alteration layer without Fe had a similar composition and pore structure to layers on glass altered in water only.

Doppler Broadening Positron Annihilation Spectrosc↗

A Framework to Delineate Precipitation-Runoff Regimes: Precipitation vs. Snowpack in the Western U.S.

We propose a framework to classify precipitation events accompanied by snow process (precipitation-and-snow, or PAS events) into five regimes, based on the relative contributions of snowpack change and precipitation amount to the runoff response. This framework is applied to a regional climate simulation over the western U.S. to reveal the regions where snow process plays important roles. Over the western U.S., PAS events account for 50-90% of all the precipitation events. About 60-80% of PAS events feature snow accumulation, but snow melting frequently happens in high-elevation areas. Compared with snow accumulation events, snow melting events have a more limited spatial distribution. Different regimes peak in different months between early winter and late spring. Lastly, the impact of atmospheric rivers is investigated. Although accounting for only 2% of the grid-scale precipitation events, atmospheric rivers trigger significant snowmelt and contribute to 20% and 11% of light and heavy snow melting events, respectively.

Chen, Xiaodong↗

Coiled-coil coactivators play a structural role mediating interactions in hypoxia-inducible factor heterodimerization

The hypoxia-inducible factor complex (HIF-α·aryl hydrocarbon receptor nuclear translocator (ARNT)) requires association with several transcription coactivators for a successful cellular response to hypoxic stress. In addition to the conventional global transcription coactivator CREB-binding protein/p300 (CBP/p300) that binds to the HIF-α transactivation domain, a new group of transcription coactivators called the coiled-coil coactivators (CCCs) interact directly with the second PER-ARNT-SIM (PAS) domain of ARNT (ARNT PAS-B). These less studied transcription coactivators play essential roles in the HIF-dependent hypoxia response, and CCC misregulation is associated with several forms of cancer. To better understand CCC protein recruitment by the heterodimeric HIF transcription factor, we used x-ray crystallography, NMR spectroscopy, and biochemical methods to investigate the structure of the ARNT PAS-B domain in complex with the C-terminal fragment of a coiled-coil coactivator protein, transforming acidic coiled-coil coactivator 3 (TACC3). We found that the HIF-2α PAS-B domain also directly interacts with TACC3, motivating an NMR data-derived model suggesting a means by which TACC3 could form a ternary complex with HIF-2α PAS-B and ARNT PAS-B via β-sheet/coiled-coil interactions. Furthermore, these findings suggest that TACC3 could be recruited as a bridge to cooperatively mediate between the HIF-2α PAS-B·ARNT PAS-B complex, thereby participating more directly in HIF-dependent gene transcription than previously anticipated.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

Mechanochemistry of Phosphorus and Arsenic Alloys for Visible and Infrared Photonics

Incorporating few‐layer 2D phosphorus–arsenic alloys (PAs) into optoelectronic devices requires a synthesis technique that allows control of the alloy composition while producing volumes of material suitable for application development such as photodetectors, solar cells, and lasers. With that goal in mind, high‐energy ball milling allows production of both orthorhombic (o‐PAs) and trigonal (t‐PAs) alloys by reacting red phosphorus and metallic arsenic powders. The synthesis follows a two‐step process in which arsenic rapidly reacts with red phosphorus to first produce t‐PAs followed by a slower phase transformation into o‐PAs; synthesis time and overall conversion rate are slightly enhanced by the presence of arsenic. Optical measurements on exfoliated alloys at the few‐layer atomic limit of the 2D PAs reveal emission spanning from the visible (≈1.9 eV) into the near‐infrared region, covering a broad application space. Rapid powder synthesis within a closed system for stochiometric control of the solid‐solution PAs alloys combined with solution‐based exfoliation opens up opportunities for a whole new class of optoelectronic devices based on PA nanomaterials.

Pedersen, Samuel V.↗

The role of protected areas in land use/land cover change and the carbon cycle in the conterminous United States

Protected areas (PAs) cover about 22% of the conterminous United States. Understanding their role on historical land use and land cover change (LULCC) and on the carbon cycle is essential to provide guidance for environmental policies. In this study, we compiled historical LULCC and PAs data to explore these interactions within the terrestrial ecosystem model (TEM). We found that intensive LULCC occurred in the conterminous United States from 1700 to 2005. More than 3 million km2 of forest, grassland and shrublands were converted into agricultural lands, which caused 10,607 Tg C release from land ecosystems to atmosphere. PAs had experienced little LULCC as they were generally established in the 20th century after most of the agricultural expansion had occurred. PAs initially acted as a carbon source due to land use legacies, but their accumulated carbon budget switched to a carbon sink in the 1960s, sequestering an estimated 1,642 Tg C over 1700–2005, or 13.4% of carbon losses in non-PAs. We also find that PAs maintain larger carbon stocks and continue sequestering carbon in recent years (2001–2005), but at a lower rate due to increased heterotrophic respiration as well as lower productivity associated to aging ecosystems. It is essential to continue efforts to maintain resilient, biodiverse ecosystems and avoid large-scale disturbances that would release large amounts of carbon in PAs.

Lu, Xiaoliang↗

Formation of a repressive complex in the mammalian circadian clock is mediated by the secondary pocket of CRY1

The basic helix-loop-helix PAS domain (bHLH-PAS) transcription factor CLOCK:BMAL1 (brain and muscle Arnt-like protein 1) sits at the core of the mammalian circadian transcription/translation feedback loop. Precise control of CLOCK:BMAL1 activity by coactivators and repressors establishes the ~24-h periodicity of gene expression. Formation of a repressive complex, defined by the core clock proteins cryptochrome 1 (CRY1):CLOCK:BMAL1, plays an important role controlling the switch from repression to activation each day. Here in this paper, we show that CRY1 binds directly to the PAS domain core of CLOCK: BMAL1, driven primarily by interaction with the CLOCK PAS-B domain. Integrative modeling and solution X-ray scattering studies unambiguously position a key loop of the CLOCK PAS-B domain in the secondary pocket of CRY1, analogous to the antenna chromophore-binding pocket of photolyase. CRY1 docks onto the transcription factor alongside the PAS domains, extending above the DNA-binding bHLH domain. Single point mutations at the interface on either CRY1 or CLOCK disrupt formation of the ternary complex, highlighting the importance of this interface for direct regulation of CLOCK:BMAL1 activity by CRY1.

60 APPLIED LIFE SCIENCES↗

Atheroma Niche-Responsive Nanocarriers for Immunotherapeutic Delivery

Nanomedicine is a promising, noninvasive approach to reduce atherosclerotic plaque burden. However, drug delivery is limited without the ability of nanocarriers to sense and respond to the diseased microenvironment. Here, nanomaterials are developed from peptide amphiphiles (PAs) that respond to the increased levels of matrix metalloproteinases 2 and 9 (MMP2/9) or reactive oxygen species (ROS) found within the atherosclerotic niche. A pro-resolving therapeutic, Ac2-26, derived from annexin-A1 protein, is tethered to PAs using peptide linkages that cleave in response to MMP2/9 or ROS. By adjusting the molar ratios and processing conditions, the Ac2-26 PA can be co-assembled with a PA containing an apolipoprotein A1-mimetic peptide to create a targeted, therapeutic nanofiber (ApoA1-Ac226 PA). The ApoA1-Ac2-26 PAs demonstrate release of Ac2-26 within 24 h after treatment with MMP2 or ROS. The niche-responsive ApoA1-Ac2-26 PAs are cytocompatible and reduce macrophage activation from interferon gamma and lipopolysaccharide treatment, evidenced by decreased nitric oxide production. Interestingly, the linkage chemistry of ApoA1-Ac2-26 PAs significantly affects macrophage uptake and retention. Taken together, these findings demonstrate the potential of PAs to serve as an atheroma niche-responsive nanocarrier system to modulate the inflammatory microenvironment, with implications for atherosclerosis treatment.

60 APPLIED LIFE SCIENCES↗

Equatorial coordination of uranyl: Correlating ligand charge donation with the O yl -U-O yl asymmetric stretch frequency

In uranyl coordination complexes, UO 2 (L) n 2+ , uranium in the formally dipositive [O=U=O] 2+ moiety is coordinated by n neutral organic electron donor ligands, L. The extent of ligand electron donation, which results in partial reduction of uranyl and weakening of the U=O bonds, is revealed by the magnitude of the red-shift of the uranyl asymmetric stretch frequency, ν 3 . This phenomenon appears in gas-phase complexes in which uranyl is coordinated by electron donor ligands: the ν 3 red-shift increases as the number of ligands and their proton affinity (PA) increases. Because PA is a measure of the enthalpy change associated with a proton-ligand interaction, which is much stronger and of a different nature than metal ion-ligand bonding, it is not necessarily expected that ligand PAs should reliably predict uranyl-ligand bonding and the resulting ν 3 red-shift. In this study, ν 3 was measured for uranyl coordinated by ligands with a relatively broad range of PAs, revealing a surprisingly good correlation between PA and ν 3 frequency. From computed ν 3 frequencies for bare UO 2 cations and neutrals, it is inferred that the effective charge of uranyl in UO 2 (L) n 2+ complexes can be reduced to near zero upon ligation by sufficiently strong charge-donor ligands. The basis for the correlation between ν 3 and ligand PAs, as well as limitations and deviations from it, are considered. It is demonstrated that the correlation evidently extends to a ligand that exhibits polydentate metal ion coordination.

Gibson, John K.↗

1‐Formyl‐7‐hydroxy‐6,7‐dihydro‐5 H ‐pyrrolizine (9‐CHO‐DHP) ‐ A Biologically Proximate Pyrrolic Metabolite of Carcinogenic Pyrrolizidine Alkaloids

Pyrrolizidine alkaloids (PAs) are phytochemical constituents of more than 6000 plant species worldwide; approximately half of the PAs are hepatotoxic, genotoxic, and carcinogenic. Because of their wide exposure and carcinogenicity, the International Programme on Chemical Safety (IPCS) concluded that PAs are a threat to human health and safety. We recently determined that the metabolic activation pathway of PA‐induced liver tumor initiation is mediated by a set of four (±)‐6,7‐dihydro‐7‐hydroxy‐1‐hydroxymethyl‐5H‐pyrrolizine (DHP)‐derived DNA adducts, and proposed that these DHP‐DNA adducts are potential biomarkers of PA exposure and liver tumor initiation. To validate the generality of this metabolic activation pathway and DHP‐DNA adducts as biomarkers, it is important to identify the spectrum of reactive metabolites associated with this metabolic activation pathway. Segall et al. ( Drug Metab. Disposit. , 12, 68–71, 1984) reported that 1‐formyl‐7‐hydroxy‐6,7‐dihydro‐5 H ‐pyrrolizine (9‐CHO‐DHP) is a metabolite formed from the mouse liver microsomal metabolism of senecionine. In this present study, we examined the metabolism of six hepatocarcinogenic PAs (riddelliine, senecionine, monocrotaline, senkirkine, intermedine, and heliotrine) and one non‐carcinogenic PA (platphylline) by human, rat, and mouse liver microsomes. 9‐CHO‐DHP was found as a common metabolite from the metabolism of the six hepatotoxic PAs, but not from platphylline. Incubation of 9‐CHO‐DHP in HepG2 cells and A549 cells resulted in the formation of the same set of DHP‐DNA adducts, as assessed by both LC/MS SRM mode and selected ion monitoring analyses through comparison to synthetic standards. In the incubation medium of HepG2 cells, both DHP and 7‐cysteine‐DHP were identified. These metabolites have previously shown to be capable of binding to cellular DNA to produce DHP‐DNA adducts. Thus, when incubated with HepG2 cells, 9‐CHO‐DHP was metabolized to the reactive metabolites DHP and 7‐cysteine‐DHP, metabolites associated with the DHP‐DNA adduct formation. These results indicate that 9‐CHO‐DHP is a DNA proximate metabolite of hepatotoxic PAs and further support the generality of this metabolic activation pathway mediated by the formation of these DHP‐DNA adducts. [This abstract is not an official U.S. Food and Drug Administration (FDA) guidance or policy statement. No offcial support or endorsement by the U.S. FDA is intended or should be inferred. The authors declare no competing financial interest.] Support or Funding Information This research was supported in part by appointment (X.H.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .

Xia, Qingsu↗

Communicating Performance Assessments Results - 13609

The F-Area Tank Farms (FTF) and H-Area Tank Farm (HTF) are owned by the U.S. Department of Energy (DOE) and operated by Savannah River Remediation LLC (SRR), Liquid Waste Operations contractor at DOE's Savannah River Site (SRS). The FTF and HTF are active radioactive waste storage and treatment facilities consisting of 51 carbon steel waste tanks and ancillary equipment such as transfer lines, evaporators and pump tanks. Performance Assessments (PAs) for each Tank Farm have been prepared to support the eventual closure of the underground radioactive waste tanks and ancillary equipment. PAs provide the technical bases and results to be used in subsequent documents to demonstrate compliance with the pertinent requirements for final closure of the Tank Farms. The Tank Farms are subject to a number of regulatory requirements. The State regulates Tank Farm operations through an industrial waste water permit and through a Federal Facility Agreement approved by the State, DOE and the Environmental Protection Agency (EPA). Closure documentation will include State-approved Tank Farm Closure Plans and tank-specific closure modules utilizing information from the PAs. For this reason, the State of South Carolina and the EPA must be involved in the performance assessment review process. The residual material remaining after tank cleaning is also subject to reclassification prior to closure via a waste determination pursuant to Section 3116 of the Ronald W. Reagan National Defense Authorization Act of Fiscal Year 2005. PAs are performance-based, risk-informed analyses of the fate and transport of FTF and HTF residual wastes following final closure of the Tank Farms. Since the PAs serve as the primary risk assessment tools in evaluating readiness for closure, it is vital that PA conclusions be communicated effectively. In the course of developing the FTF and HTF PAs, several lessons learned have emerged regarding communicating PA results. When communicating PA results it is important to stress that the primary goal of the PA results is to provide risk understanding, recognizing the magnitude of risk and identifying the conceptual model decisions and critical assumptions that most impact the results. Conceptual models that describe reality using simplified, mathematical approaches, and their roles in arriving at the PA results, must also be communicated. When presenting PA results, evaluations will typically be focused on a single baseline (or Base Case) to provide a foundation for discussion. The PA results are supplemented by other studies (alternate configurations, uncertainty analyses, and sensitivity analyses) which provide a breadth of modeling to supplement the Base Case. The suite of information offered by the various modeling cases and studies provides confidence that the overall risk is understood along with the underlying parameters and conditions that contribute to risk. (author)

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P{sub 2} synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P{sub 2} conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P{sub 2} in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the homeostasis of these lipids in TNBC. Together, our results uncover an unexpected role for Sac3 phosphatase in TNBC cell proliferation. Database analyses, discussed herein, reinforce the involvement of Sac3 in breast cancer pathogenesis.

60 APPLIED LIFE SCIENCES↗

Photoacoustic infrared spectroscopy for conducting gas tracer tests and measuring water saturations in landfills

Highlights: Black-Right-Pointing-Pointer Photoacoustic infrared spectroscopy tested for measuring tracer gas in landfills. Black-Right-Pointing-Pointer Measurement errors for tracer gases were 1-3% in landfill gas. Black-Right-Pointing-Pointer Background signals from landfill gas result in elevated limits of detection. Black-Right-Pointing-Pointer Technique is much less expensive and easier to use than GC. - Abstract: Gas tracer tests can be used to determine gas flow patterns within landfills, quantify volatile contaminant residence time, and measure water within refuse. While gas chromatography (GC) has been traditionally used to analyze gas tracers in refuse, photoacoustic spectroscopy (PAS) might allow real-time measurements with reduced personnel costs and greater mobility and ease of use. Laboratory and field experiments were conducted to evaluate the efficacy of PAS for conducting gas tracer tests in landfills. Two tracer gases, difluoromethane (DFM) and sulfur hexafluoride (SF{sub 6}), were measured with a commercial PAS instrument. Relative measurement errors were invariant with tracer concentration but influenced by background gas: errors were 1-3% in landfill gas but 4-5% in air. Two partitioning gas tracer tests were conducted in an aerobic landfill, and limits of detection (LODs) were 3-4 times larger for DFM with PAS versus GC due to temporal changes in background signals. While higher LODs can be compensated by injecting larger tracer mass, changes in background signals increased the uncertainty in measured water saturations by up to 25% over comparable GC methods. PAS has distinct advantages over GC with respect to personnel costs and ease of use, although for field applications GC analyses of select samples are recommended to quantify instrument interferences.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗

Sandia National Laboratories performance assessment methodology for long-term environmental programs : the history of nuclear waste management.

Sandia National Laboratories (SNL) is the world leader in the development of the detailed science underpinning the application of a probabilistic risk assessment methodology, referred to in this report as performance assessment (PA), for (1) understanding and forecasting the long-term behavior of a radioactive waste disposal system, (2) estimating the ability of the disposal system and its various components to isolate the waste, (3) developing regulations, (4) implementing programs to estimate the safety that the system can afford to individuals and to the environment, and (5) demonstrating compliance with the attendant regulatory requirements. This report documents the evolution of the SNL PA methodology from inception in the mid-1970s, summarizing major SNL PA applications including: the Subseabed Disposal Project PAs for high-level radioactive waste; the Waste Isolation Pilot Plant PAs for disposal of defense transuranic waste; the Yucca Mountain Project total system PAs for deep geologic disposal of spent nuclear fuel and high-level radioactive waste; PAs for the Greater Confinement Borehole Disposal boreholes at the Nevada National Security Site; and PA evaluations for disposal of high-level wastes and Department of Energy spent nuclear fuels stored at Idaho National Laboratory. In addition, the report summarizes smaller PA programs for long-term cover systems implemented for the Monticello, Utah, mill-tailings repository; a PA for the SNL Mixed Waste Landfill in support of environmental restoration; PA support for radioactive waste management efforts in Egypt, Iraq, and Taiwan; and, most recently, PAs for analysis of alternative high-level radioactive waste disposal strategies including repositories deep borehole disposal and geologic repositories in shale and granite. Finally, this report summarizes the extension of the PA methodology for radioactive waste disposal toward development of an enhanced PA system for carbon sequestration and storage systems. These efforts have produced a generic PA methodology for the evaluation of waste management systems that has gained wide acceptance within the international community. This report documents how this methodology has been used as an effective management tool to evaluate different disposal designs and sites; inform development of regulatory requirements; identify, prioritize, and guide research aimed at reducing uncertainties for objective estimations of risk; and support safety assessments.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

2011 Performance Assessment Community of Practice Technical Exchange – Summary

The Performance Assessment Community of Practice (PA CoP) was developed in 2008 to improve consistency and quality in the preparation of performance assessments (PAs) and risk assessments across the Department of Energy (DOE) Complex. The term, PA, is used to represent all of these modeling applications in this report. The PA CoP goals are to foster the exchange of information among PA practitioners and to share lessons learned from PAs conducted for DOE, commercial disposal facilities, and international entities. Technical exchanges and workshops are a cornerstone of PA CoP activities. Previous technical exchanges have addressed Engineered Barriers (2009 - http://www.cresp.org/education/workshops/pacop/), the Advanced Simulation Capability for Environmental Management and the Cementitious Barriers Partnership (2010 - http://srnl.doe.gov/copexchange/links.htm). Each technical exchange also includes summary presentations regarding activities at DOE, the Nuclear Regulatory Commission (NRC) and other organizations (e.g., International Atomic Energy Agency (IAEA)) as well as a number of presentations from selected sites to provide insight and perspective from on-going modeling activities. Through the deployment of PA Assistance Teams, the PA CoP has also been engaged in the development of new PAs across the DOE Complex. As a way of improving consistency in the preparation of new PAs, the teams provide technical advice and share experiences, noteworthy practices, and lessons learned from previous Low-Level Waste Disposal Facility Federal Review Group (LFRG) reviews. Teams have provided support for PAs at Hanford, Idaho, Paducah and Portsmouth. The third annual PA CoP Technical Exchange was held on May 25-26, 2011 in Atlanta, GA. The PA CoP Steering Committee Meeting held its first meeting on May 24 prior to the Technical Exchange. Decision making using models and software quality assurance were the topical emphasis for the exchange. A new feature at the 2011 technical exchange was the use of panel discussions to solicit feedback from regulators and practitioners. This report summarizes discussions and recommendations from the steering committee meeting and presentations and feedback obtained at the technical exchange. Appendix I includes the steering committee meeting agenda and Appendix II includes the agenda for the technical exchange and a screenshot of the presentations and video files that are available online.

99 GENERAL AND MISCELLANEOUS↗

Evolution Of USDOE Performance Assessments Over 20 Years

Performance assessments (PAs) have been used for many years for the analysis of post-closure hazards associated with a radioactive waste disposal facility and to provide a reasonable expectation of the ability of the site and facility design to meet objectives for the protection of members of the public and the environment. The use of PA to support decision-making for LLW disposal facilities has been mandated in United States Department of Energy (USDOE) directives governing radioactive waste management since 1988 (currently DOE Order 435.1, Radioactive Waste Management). Prior to that time, PAs were also used in a less formal role. Over the past 20+ years, the USDOE approach to conduct, review and apply PAs has evolved into an efficient, rigorous and mature process that includes specific requirements for continuous improvement and independent reviews. The PA process has evolved through refinement of a graded and iterative approach designed to help focus efforts on those aspects of the problem expected to have the greatest influence on the decision being made. Many of the evolutionary changes to the PA process are linked to the refinement of the PA maintenance concept that has proven to be an important element of USDOE PA requirements in the context of supporting decision-making for safe disposal of LLW. The PA maintenance concept represents the evolution of the graded and iterative philosophy and has helped to drive the evolution of PAs from a deterministic compliance calculation into a systematic approach that helps to focus on critical aspects of the disposal system in a manner designed to provide a more informed basis for decision-making throughout the life of a disposal facility (e.g., monitoring, research and testing, waste acceptance criteria, design improvements, data collection, model refinements). A significant evolution in PA modeling has been associated with improved use of uncertainty and sensitivity analysis techniques to support efficient implementation of the graded and iterative approach. Rather than attempt to exactly predict the migration of radionuclides in a disposal unit, the best PAs have evolved into tools that provide a range of results to guide decision-makers in planning the most efficient, cost effective, and safe disposal of radionuclides.

12 MANAGEMENT OF RADIOACTIVE AND NON-RADIOACTIVE W↗