41 research outputs found
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Solid low-level waste forecasting guide
Guidance for forecasting solid low-level waste (LLW) on a site-wide basis is described in this document. Forecasting is defined as an approach for collecting information about future waste receipts. The forecasting approach discussed in this document is based solely on hanford`s experience within the last six years. Hanford`s forecasting technique is not a statistical forecast based upon past receipts. Due to waste generator mission changes, startup of new facilities, and waste generator uncertainties, statistical methods have proven to be inadequate for the site. It is recommended that an approach similar to Hanford`s annual forecasting strategy be implemented at each US Department of Energy (DOE) installation to ensure that forecast data are collected in a consistent manner across the DOE complex. Hanford`s forecasting strategy consists of a forecast cycle that can take 12 to 30 months to complete. The duration of the cycle depends on the number of LLW generators and staff experience; however, the duration has been reduced with each new cycle. Several uncertainties are associated with collecting data about future waste receipts. Volume, shipping schedule, and characterization data are often reported as estimates with some level of uncertainty. At Hanford, several methods have been implemented to capture the level of uncertainty. Collection of a maximum and minimum volume range has been implemented as well as questionnaires to assess the relative certainty in the requested data
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Solid waste integrated forecast technical (SWIFT) report: FY1997 to FY 2070, Revision 1
This web site provides an up-to-date report on the radioactive solid waste expected to be managed by Hanford's Waste Management (WM) Project from onsite and offsite generators. It includes: an overview of Hanford-wide solid waste to be managed by the WM Project; program-level and waste class-specific estimates; background information on waste sources; and comparisons with previous forecasts and with other national data sources. This web site does not include: liquid waste (current or future generation); waste to be managed by the Environmental Restoration (EM-40) contractor (i.e., waste that will be disposed of at the Environmental Restoration Disposal Facility (ERDF)); or waste that has been received by the WM Project to date (i.e., inventory waste). The focus of this web site is on low-level mixed waste (LLMW), and transuranic waste (both non-mixed and mixed) (TRU(M)). Some details on low-level waste and hazardous waste are also provided. Currently, this web site is reporting data th at was requested on 10/14/96 and submitted on 10/25/96. The data represent a life cycle forecast covering all reported activities from FY97 through the end of each program's life cycle. Therefore, these data represent revisions from the previous FY97.0 Data Version, due primarily to revised estimates from PNNL. There is some useful information about the structure of this report in the SWIFT Report Web Site Overview
Experimental pulse technique for the study of microbial kinetics in continuous culture
A novel technique was developed for studying the growth kinetics of microorganisms in continuous culture. The method is based on following small perturbations of a chemostat culture by on-line measurement of the dynamic response in oxygen consumption rates. A mathematical model, incorporating microbial kinetics and mass transfer between gas and liquid phases, was applied to interpret the data. Facilitating the use of very small disturbances, the technique is non-disruptive as well as fast and accurate. The technique was used to study the growth kinetics of two cultures, Methylosinus trichosporium OB3b growing on methane, both in the presence and in the absence of copper, and Burkholderia (Pseudomonas) cepacia G4 growing on phenol. Using headspace flushes, gas blocks and liquid substrate pulse experiments, estimates for limiting substrate concentrations, maximum conversion rates Vmax and half saturation constants Ks could rapidly be obtained. For M. trichosporium OB3b it was found that it had a far higher affinity for methane when particulate methane monooxygenase (pMMO) was expressed than when the soluble form (sMMO) was expressed under copper limitation. While for B. cepacia G4 the oxygen consumption pattern during a phenol pulse in the chemostat indicated that phenol was transiently converted to an intermediate (4-hydroxy-2-oxovalerate), so that initially less oxygen was used per mole of phenol.
Seminal plasma and prostaglandin E2 up-regulate fibroblast growth factor 2 expression in endometrial adenocarcinoma cells via E-series prostanoid-2 receptor-mediated transactivation of the epidermal growth factor receptor and extracellular signal-regulated kinase pathway
BACKGROUND: Prostaglandin E(2) (PGE(2)) has been shown to modulate angiogenesis and tumour progression via the E-series prostanoid-2 (EP2) receptor. Endometrial adenocarcinomas may be exposed to endogenous PGE(2) and exogenous PGE(2), present at high concentration in seminal plasma. METHODS: This study investigated fibroblast growth factor 2 (FGF2) mRNA expression and cell signalling in response to seminal plasma or PGE(2), using an endometrial adenocarcinoma (Ishikawa) cell line stably expressing the EP2 receptor (EP2 sense cells) and endometrial adenocarcinoma explants. RESULTS: Seminal plasma and PGE(2) induced a significant up-regulation of FGF2 expression in EP2 sense but not parental untransfected Ishikawa (wild-type) cells (P < 0.05). These effects were inhibited by co-treatment with EP2 receptor antagonist or inhibitors of protein kinase A, c-Src, epidermal growth factor receptor (EGFR) kinase or extracellular signal-regulated kinase (ERK) signalling. The treatment of EP2 sense cells with seminal plasma induced cAMP accumulation and phosphorylation of c-Src, EGFR kinase and ERK via the EP2 receptor. Finally, seminal plasma and PGE(2) significantly increased FGF2 mRNA expression in endometrial adenocarcinoma tissue explants via the EP2 receptor (P < 0.05). CONCLUSIONS: Seminal plasma and PGE(2) can similarly activate FGF2 expression and EP2 receptor signalling in endometrial adenocarcinoma cells. These data highlight the potential for seminal plasma exposure to facilitate tumorigenesis–angiogenesis in endometrial adenocarcinomas in vivo
Evaluating the Effects of SARS-CoV-2 Spike Mutation D614G on Transmissibility and Pathogenicity
Global dispersal and increasing frequency of the SARS-CoV-2 spike protein variant D614G are suggestive of a selective advantage but may also be due to a random founder effect. We investigate the hypothesis for positive selection of spike D614G in the United Kingdom using more than 25,000 whole genome SARS-CoV-2 sequences. Despite the availability of a large dataset, well represented by both spike 614 variants, not all approaches showed a conclusive signal of positive selection. Population genetic analysis indicates that 614G increases in frequency relative to 614D in a manner consistent with a selective advantage. We do not find any indication that patients infected with the spike 614G variant have higher COVID-19 mortality or clinical severity, but 614G is associated with higher viral load and younger age of patients. Significant differences in growth and size of 614G phylogenetic clusters indicate a need for continued study of this variant
Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study
Background
The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility.
Methods
We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates.
Findings
From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant.
Interpretation
The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant.
Funding
Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society
Whole-genome sequencing reveals host factors underlying critical COVID-19
Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease
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Hanford`s remote-handled transuranic and transuranic mixed waste volume assessment
This study documents the results of an assessment of each Hanford program`s potential RH-TRU(M) waste forecast volumes. Of this 3,470 m{sup 3} of remote-handled transuranic and transuranic mixed (RH-TRU[M]) forecast waste, the Environmental Restoration program is the only program generating waste (360 m{sup 3}) after the closure of the WIPP in FY 2033. Previous forecast assessments have estimated Hanford`s RH-TRU(M) waste volumes to range from 4,000 m{sup 3} to 45,000 m{sup 3}. In FY 1995, the RH-TRU(M) waste forecast was approximately 22,200 m{sup 3} (BIR), which exceeds the WIPP remote-handled capacity. The FY-1996 Solid Waste Integrated Life-Cycle Forecast Volume Summary (WHC-EP-0900) published in February 1996 stated that the baseline RH-TRU(M) waste volume was 13,350 m{sup 3}. The primary reason for the three different estimates results from two programmatic baseline revisions: Tank Waste Remediation Systems (TWRS) and Environmental Restoration (EM-40). The difference in the TWRS programmatic baseline is due to a revised programmatic baseline for the disposition of the long-length equipment currently present in the tanks. The difference in the Environmental Restoration programmatic baseline is due to an assessment based on recent experience that many of the facilities at Hanford will not contain RH-TRU(M) waste during decontamination and decommissioning and that for many other facilities, the RH-TRU(M) waste volumes will not be as great as previously estimated
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1995 solid waste 30-year container volume summary
This report describes a 30-year forecast of the solid waste volumes by container category. The volumes described are low-level mixed waste (LLMW) and transuranic/transuranic mixed (TRU-TRUM) waste. These volumes and their associated container categories will be generated or received at the US Department of Energy Hanford Site for storage, treatment, and disposal at Westinghouse Hanford Company`s Solid Waste Operations Complex (SWOC) during a 30-year period from FY 1995 through FY 2024. The data presented in this report establish a baseline for solid waste management both in the present and future. With knowledge of the volumes by container type, decisions on the facility handling and storage requirements can be adequately made. It is recognized that the forecast estimates will vary as facility planning and missions continue to change and become better defined; however, the data presented in this report still provide useful insight into Hanford`s future solid waste management requirements