Maywood interim storage site. Annual site environmental report, calendar year 1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-05-01

During 1985, the environmental monitoring program was continued at the Maywood Interim Storage Site (MISS), a US Department of Energy (DOE) facility located in the Borough of Maywood and the Township of Rochelle Park, New Jersey. The MISS is presently used for the storage of low-level radioactively contaminated soils. Monitoring results show that the MISS is in compliance with DOE concentration guides and radiation protection standards. Derived Concentration Guides (DCGs) represent the concentrations of radionuclides in air or water that would limit the radiation dose to 100 mrem/yr. The applicable guides have been revised since the 1984 environmental monitoring reportmore » was published. The guides applied in 1984 were based on a radiation protection standard of 500 mrem/yr; the guides applied for 1985 are based on a standard of 100 mrem/yr.« less

Reassessment of psychological distress and post-traumatic stress disorder in United States Air Force Distributed Common Ground System operators.

PubMed

Prince, Lillian; Chappelle, Wayne L; McDonald, Kent D; Goodman, Tanya; Cowper, Sara; Thompson, William

2015-03-01

The goal of this study was to assess for the main sources of occupational stress, as well as self-reported symptoms of distress and post-traumatic stress disorder among U.S. Air Force (USAF) Distributed Common Ground System (DCGS) intelligence exploitation and support personnel. DCGS intelligence operators (n=1091) and nonintelligence personnel (n = 447) assigned to a USAF Intelligence, Surveillance, and Reconnaissance Wing responded to the web-based survey. The overall survey response rate was 31%. Study results revealed the most problematic stressors among DCGS intelligence personnel included high workload, low manning, as well as organizational leadership and shift work issues. Results also revealed 14.35% of DCGS intelligence operators' self-reported high levels of psychological distress (twice the rate of DCGS nonintelligence support personnel). Furthermore, 2.0% to 2.5% self-reported high levels of post-traumatic stress disorder symptoms, with no significant difference between groups. The implications of these findings are discussed along with recommendations for USAF medical and mental health providers, as well as operational leadership. Reprint & Copyright © 2015 Association of Military Surgeons of the U.S.

Distance caregiving a family member with cancer: A review of the literature on distance caregiving and recommendations for future research.

PubMed

Douglas, Sara L; Mazanec, Polly; Lipson, Amy; Leuchtag, Mary

2016-04-10

Distance caregivers (DCGs) are a growing phenomenon in the United States Family members are struggling to provide care to loved ones with chronic illnesses such as cancer, from a distance. Unlike local caregiving research, distance caregiving research is limited and inconsistent definitions of distance make it difficult to compare studies. To date, DCGs have not been afforded the opportunities for educational and emotional support that local caregivers have received from the health care teams. Because they are not usually present at medical appointments, DCGs do not receive first-hand information from the health care team about the patient's condition, disease progression, and/or treatment options. These caregivers report feeling left out of important family discussions. They experience anxiety related to the uncertainty of the family members' well-being and guilt related to not being available to help local caregivers more. The challenges of distance caregiving are especially evident when the distance caregiver has a parent with advanced cancer. Family-centered care, attending to the needs of the whole family regardless of their geographic location is critical for quality cancer care. In this manuscript, the sparse literature on distance caregiving is reviewed. Recommendations for future research and for the development of creative technologically advanced interventions for this underserved caregiving population are suggested.

Requirements for the identification of dense-core granules.

PubMed

Meldolesi, Jacopo; Chieregatti, Evelina; Luisa Malosio, Maria

2004-01-01

Dense-core granules (DCGs), cytoplasmic organelles competent for regulated exocytosis, show considerable heterogeneity depending upon the specificity of their expressing cells--primarily neurons and neurosecretory cells. DCGs have been mainly identified by detecting their cargo molecules, often members of the granin family, and using conventional electron microscopy and immunocytochemistry. However, by a critical analysis of the various stages of DCG "life" within neurosecretory cells, we have highlighted several specific molecular and functional properties that are common to all these organelles. We propose that these properties be considered as strict requirements for the identification of DCGs.

Diagnostic, pharmacy-based, and self-reported health measures in risk equalization models.

PubMed

Stam, Pieter J A; van Vliet, René C J A; van de Ven, Wynand P M M

2010-05-01

Current research on the added value of self-reported health measures for risk equalization modeling does not include all types of self-reported health measures; and/or is compared with a limited set of medically diagnosed or pharmacy-based diseases; and/or is limited to specific populations of high-risk individuals. The objective of our study is to determine the predictive power of all types of self-reported health measures for prospective modeling of health care expenditures in a general population of adult Dutch sickness fund enrollees, given that pharmacy and diagnostic data from administrative records are already included in the risk equalization formula. We used 4 models of 2002 total, inpatient and outpatient expenditures to evaluate the separate and combined predictive ability of 2 kinds of data: (1) Pharmacy-based (PCGs) and Diagnosis-based (DCGs) Cost Groups and (2) summarized self-reported health information. Model performance is measured at the total population level using R2 and mean absolute prediction error; also, by examining mean discrepancies between model-predicted and actual expenditures (ie, expected over- or undercompensation) for members of potentially "mispriced" subgroups. These subgroups are identified by self-reports from prior-year health surveys and utilization and expenditure data from 5 preceding years. Subjects were 18,617 respondents to a health survey, held among a stratified sample of adult members of the largest Dutch sickness fund in 2002, with an overrepresentation of people in poor health. The data were extracted from a claims database and a health survey. The claims-based data are the outcomes of total, inpatient, and outpatient annualized expenditures in 2002; age, gender, PCGs, DCGs in 2001; and health care expenditures and hospitalizations during the years 1997 to 2001. The SF-36, Organization for Economic Cooperation and Development items, and long-term diseases and conditions were collected by a special purpose health survey conducted in the last quarter of 2001. Out-of-sample R2 equals 17.2%, 2.6%, and 32.4% for the models of total, inpatient and outpatient expenditures including PCGs, DCGs, and self-reported health measures. Self-reported health measures contribute less to predictive power than PCGs and DCGs. PCGs and DCGs also predict better than self-reported health measures for people with top 25% total expenditures or hospitalizations in each year during a 5-year period. On the other hand, self-reported health measures are better predictors than PCGs and DCGs for people without any top 25% expenditures during the 5-year period, for switchers, and for most subgroups of relatively unhealthy people defined by self-reported health measures. Among the set of self-reported health measures, the SF-36 adds most to predictive power in terms of R2, mean absolute prediction error, and for almost all studied subgroups. It is concluded that the self-reported health measures make an independent contribution to forecasting health care expenditures, even if the prediction model already includes diagnostic and pharmacy-based information currently used in Dutch risk equalization models.

Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticity.

PubMed

Lochner, J E; Spangler, E; Chavarha, M; Jacobs, C; McAllister, K; Schuttner, L C; Scalettar, B A

2008-09-01

Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are copackaged and cotransported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively copackaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo cotransport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF colocalize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy.

Formerly Utilized Sites Remedial Action Program (FUSRAP) Hazelwood Interim Storage Site annual site environmental report. Calendar year 1985. [FUSRAP

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-04-01

The Hazelwood Interim Storage Site (HISS) is presently used for the storage of low-level radioactively contaminated soils. Monitoring results show that the HISS is in compliance with DOE concentration guides and radiation protection standards. Derived Concentration Guides (DCGs) represent the concentrations of radionuclides in air or water that would limit the radiation dose to 100 mrem/y. The applicable limits have been revised since the 1984 environmental monitoring report was published. The limits applied in 1984 were based on a radiation protection standard of 500 mrem/y; the limits applied for 1985 are based on a standard of 100 mrem/y. The HISSmore » is part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a DOE program to decontaminate or otherwise control sites where low-level radioactive contamination remains from the early years of the nation's atomic energy program. To determine whether the site is in compliance with DOE standards, environmental measurements are expressed as percentages of the applicable DCG, while the calculated doses to the public are expressed as percentages of the applicable radiation protection standard. The monitoring program at the HISS measures uranium, radium, and thorium concentrations in surface water, groundwater, and sediment; radon gas concentrations in air; and external gamma radiation exposure rates. Potential radiation doses to the public are also calculated. The HISS was designated for remedial action under FUSRAP because radioactivity above applicable limits was found to exist at the site and its vicinity. Elevated levels of radiation still exist in areas where remedial action has not yet been completed.« less

Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells.

PubMed

Redhai, Siamak; Hellberg, Josephine E E U; Wainwright, Mark; Perera, Sumeth W; Castellanos, Felix; Kroeger, Benjamin; Gandy, Carina; Leiblich, Aaron; Corrigan, Laura; Hilton, Thomas; Patel, Benjamin; Fan, Shih-Jung; Hamdy, Freddie; Goberdhan, Deborah C I; Wilson, Clive

2016-10-01

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion.

Dynamic Uncertain Causality Graph for Knowledge Representation and Probabilistic Reasoning: Directed Cyclic Graph and Joint Probability Distribution.

PubMed

Zhang, Qin

2015-07-01

Probabilistic graphical models (PGMs) such as Bayesian network (BN) have been widely applied in uncertain causality representation and probabilistic reasoning. Dynamic uncertain causality graph (DUCG) is a newly presented model of PGMs, which can be applied to fault diagnosis of large and complex industrial systems, disease diagnosis, and so on. The basic methodology of DUCG has been previously presented, in which only the directed acyclic graph (DAG) was addressed. However, the mathematical meaning of DUCG was not discussed. In this paper, the DUCG with directed cyclic graphs (DCGs) is addressed. In contrast, BN does not allow DCGs, as otherwise the conditional independence will not be satisfied. The inference algorithm for the DUCG with DCGs is presented, which not only extends the capabilities of DUCG from DAGs to DCGs but also enables users to decompose a large and complex DUCG into a set of small, simple sub-DUCGs, so that a large and complex knowledge base can be easily constructed, understood, and maintained. The basic mathematical definition of a complete DUCG with or without DCGs is proved to be a joint probability distribution (JPD) over a set of random variables. The incomplete DUCG as a part of a complete DUCG may represent a part of JPD. Examples are provided to illustrate the methodology.

Regulation of Dense-Core Granule Replenishment by Autocrine BMP Signalling in Drosophila Secondary Cells

PubMed Central

Redhai, Siamak; Hellberg, Josephine E. E. U.; Wainwright, Mark; Perera, Sumeth W.; Castellanos, Felix; Kroeger, Benjamin; Gandy, Carina; Leiblich, Aaron; Corrigan, Laura; Hilton, Thomas; Patel, Benjamin; Fan, Shih-Jung; Hamdy, Freddie; Goberdhan, Deborah C. I.

2016-01-01

Regulated secretion by glands and neurons involves release of signalling molecules and enzymes selectively concentrated in dense-core granules (DCGs). Although we understand how many secretagogues stimulate DCG release, how DCG biogenesis is then accelerated to replenish the DCG pool remains poorly characterised. Here we demonstrate that each prostate-like secondary cell (SC) in the paired adult Drosophila melanogaster male accessory glands contains approximately ten large DCGs, which are loaded with the Bone Morphogenetic Protein (BMP) ligand Decapentaplegic (Dpp). These DCGs can be marked in living tissue by a glycophosphatidylinositol (GPI) lipid-anchored form of GFP. In virgin males, BMP signalling is sporadically activated by constitutive DCG secretion. Upon mating, approximately four DCGs are typically released immediately, increasing BMP signalling, primarily via an autocrine mechanism. Using inducible knockdown specifically in adult SCs, we show that secretion requires the Soluble NSF Attachment Protein, SNAP24. Furthermore, mating-dependent BMP signalling not only promotes cell growth, but is also necessary to accelerate biogenesis of new DCGs, restoring DCG number within 24 h. Our analysis therefore reveals an autocrine BMP-mediated feedback mechanism for matching DCG release to replenishment as secretion rates fluctuate, and might explain why in other disease-relevant systems, like pancreatic β-cells, BMP signalling is also implicated in the control of secretion. PMID:27727275

Efficient co-packaging and co-transport yields post-synaptic co-localization of neuromodulators associated with synaptic plasticity

PubMed Central

Lochner, J. E.; Spangler, E.; Chavarha, M.; Jacobs, C.; McAllister, K.; Schuttner, L. C.; Scalettar, B. A.

2009-01-01

Recent data suggest that tissue plasminogen activator (tPA) influences long-term plasticity at hippocampal synapses by converting plasminogen into plasmin, which then generates mature brain-derived neurotrophic factor (mBDNF) from its precursor, proBDNF. Motivated by this hypothesis, we used fluorescent chimeras, expressed in hippocampal neurons, to elucidate (1) mechanisms underlying plasminogen secretion from hippocampal neurons, (2) if tPA, plasminogen, and proBDNF are co-packaged and co-transported in hippocampal neurons, especially within dendritic spines, and (3) mechanisms mediating the transport of these neuromodulators to sites of release. We find that plasminogen chimeras traffic through the regulated secretory pathway of hippocampal neurons in dense-core granules (DCGs) and that tPA, plasminogen, and proBDNF chimeras are extensively co-packaged in DCGs throughout hippocampal neurons. We also find that 80% of spines that contain DCGs contain chimeras of these neuromodulators in the same DCG. Finally, we demonstrate, for the first time, that neuromodulators undergo co-transport along dendrites in rapidly mobile DCGs, indicating that neuromodulators can be efficiently recruited into active spines. These results support the hypothesis that tPA mediates synaptic activation of BDNF by demonstrating that tPA, plasminogen, and proBDNF co-localize in DCGs in spines, where these neuromodulators can undergo activity-dependent release and then interact and/or mediate changes that influence synaptic efficacy. The results also raise the possibility that frequency-dependent changes in extents of neuromodulator release from DCGs influence the direction of plasticity at hippocampal synapses by altering the relative proportions of two proteins, mBDNF and proBDNF, that exert opposing effects on synaptic efficacy. PMID:18563704

Distance caregiving a family member with cancer: A review of the literature on distance caregiving and recommendations for future research

PubMed Central

Douglas, Sara L; Mazanec, Polly; Lipson, Amy; Leuchtag, Mary

2016-01-01

Distance caregivers (DCGs) are a growing phenomenon in the United States Family members are struggling to provide care to loved ones with chronic illnesses such as cancer, from a distance. Unlike local caregiving research, distance caregiving research is limited and inconsistent definitions of distance make it difficult to compare studies. To date, DCGs have not been afforded the opportunities for educational and emotional support that local caregivers have received from the health care teams. Because they are not usually present at medical appointments, DCGs do not receive first-hand information from the health care team about the patient’s condition, disease progression, and/or treatment options. These caregivers report feeling left out of important family discussions. They experience anxiety related to the uncertainty of the family members’ well-being and guilt related to not being available to help local caregivers more. The challenges of distance caregiving are especially evident when the distance caregiver has a parent with advanced cancer. Family-centered care, attending to the needs of the whole family regardless of their geographic location is critical for quality cancer care. In this manuscript, the sparse literature on distance caregiving is reviewed. Recommendations for future research and for the development of creative technologically advanced interventions for this underserved caregiving population are suggested. PMID:27081643

The Distributed Common Ground System-Army User Interface

DTIC Science & Technology

2015-06-12

its perceived lack of effectiveness. Popular opinion of the DCGS-A user interface within the military is it is unfriendly to use and not intuitive...from members of the United States Congress due to its perceived lack of effectiveness. Popular opinion of the DCGS-A user interface within the

Colonie Interim Storage Site annual environmental report for calendar year 1991, Colonie, New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-01

This document describes the environmental monitoring program at the Colonie Interim Storage Site (CISS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring at CISS began in 1984 when Congress added the site to the US Department of Energy's Formerly Utilized Sites Remedial Action Program. CISS property and surrounding areas were radioactively contaminated by operations conducted by National Lead Industries, which manufactured various components from uranium and thorium from 1958 to 1984. The environmental monitoring program at CISS includes sampling networks for external gamma radiation exposure and for radium-226, thorium-232, and total uranium concentrations inmore » surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in groundwater. In 1992 the program will also include sampling networks for radioactive and chemical contaminants in stormwater to meet permit application requirements under the Clean Water Act. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE.orders. Environmental standards are established to protect public health and the environment. Results of environmental monitoring during 1991 indicate that average concentrations of radioactive contaminants of concern were well below applicable standards and DCGS. Concentrations of some chemical contaminants in groundwater were above-the New York State Department of Environmental Conservation (Class GA) and EPA guidelines for drinking water. The potential annual radiation exposure (excluding background) calculated for a hypothetical maximally exposed individual is 0.23 mrem (milliroentgen equivalent man), which is less than an individual would receive while traveling in an airplane at 12,000 meters (39,000 feet) for one hour.« less

Colonie Interim Storage Site annual environmental report for calendar year 1991, Colonie, New York. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-01

This document describes the environmental monitoring program at the Colonie Interim Storage Site (CISS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring at CISS began in 1984 when Congress added the site to the US Department of Energy`s Formerly Utilized Sites Remedial Action Program. CISS property and surrounding areas were radioactively contaminated by operations conducted by National Lead Industries, which manufactured various components from uranium and thorium from 1958 to 1984. The environmental monitoring program at CISS includes sampling networks for external gamma radiation exposure and for radium-226, thorium-232, and total uranium concentrations inmore » surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in groundwater. In 1992 the program will also include sampling networks for radioactive and chemical contaminants in stormwater to meet permit application requirements under the Clean Water Act. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE.orders. Environmental standards are established to protect public health and the environment. Results of environmental monitoring during 1991 indicate that average concentrations of radioactive contaminants of concern were well below applicable standards and DCGS. Concentrations of some chemical contaminants in groundwater were above-the New York State Department of Environmental Conservation (Class GA) and EPA guidelines for drinking water. The potential annual radiation exposure (excluding background) calculated for a hypothetical maximally exposed individual is 0.23 mrem (milliroentgen equivalent man), which is less than an individual would receive while traveling in an airplane at 12,000 meters (39,000 feet) for one hour.« less

Chromogranin A deficiency in transgenic mice leads to aberrant chromaffin granule biogenesis.

PubMed

Kim, Taeyoon; Zhang, Chun-fa; Sun, Ziqing; Wu, Heling; Loh, Y Peng

2005-07-27

The biogenesis of dense-core secretory granules (DCGs), organelles responsible for the storage and secretion of neurotransmitters and neuropeptides in chromaffin cells, is poorly understood. Chromogranin A (CgA), which binds catecholamines for storage in the lumen of chromaffin granules, has been shown to be involved in DCG biogenesis in neuroendocrine PC12 cells. Here, we report that downregulation of CgA expression in vivo by expressing antisense RNA against CgA in transgenic mice led to a significant reduction in DCG formation in adrenal chromaffin cells. The number of DCGs formed in CgA antisense transgenic mice was directly correlated with the amount of CgA present in adrenal medulla. In addition, DCGs showed an increase in size, with enlargement in the volume around the dense core, a phenomenon that occurs to maintain constant "free" catecholamine concentration in the lumen of these granules. The extent of DCG swelling was inversely correlated with the number of DCGs formed, as well as the amount of CgA present in the adrenal glands of CgA antisense transgenic mice. These data indicate an essential role of CgA in regulating chromaffin DCG biogenesis and catecholamine storage in vivo.

Health-based risk adjustment: improving the pharmacy-based cost group model by adding diagnostic cost groups.

PubMed

Prinsze, Femmeke J; van Vliet, René C J A

Since 1991, risk-adjusted premium subsidies have existed in the Dutch social health insurance sector, which covered about two-thirds of the population until 2006. In 2002, pharmacy-based cost groups (PCGs) were included in the demographic risk adjustment model, which improved the goodness-of-fit, as measured by the R2, to 11.5%. The model's R2 reached 22.8% in 2004, when inpatient diagnostic information was added in the form of diagnostic cost groups (DCGs). PCGs and DCGs appear to be complementary in their ability to predict future costs. PCGs particularly improve the R2 for outpatient expenses, whereas DCGs improve the R2 for inpatient expenses. In 2006, this system of risk-adjusted premium subsidies was extended to cover the entire population.

ILDgenDB: integrated genetic knowledge resource for interstitial lung diseases (ILDs).

PubMed

Mishra, Smriti; Shah, Mohammad I; Sarkar, Malay; Asati, Nimisha; Rout, Chittaranjan

2018-01-01

Interstitial lung diseases (ILDs) are a diverse group of ∼200 acute and chronic pulmonary disorders that are characterized by variable amounts of inflammation, fibrosis and architectural distortion with substantial morbidity and mortality. Inaccurate and delayed diagnoses increase the risk, especially in developing countries. Studies have indicated the significant roles of genetic elements in ILDs pathogenesis. Therefore, the first genetic knowledge resource, ILDgenDB, has been developed with an objective to provide ILDs genetic data and their integrated analyses for the better understanding of disease pathogenesis and identification of diagnostics-based biomarkers. This resource contains literature-curated disease candidate genes (DCGs) enriched with various regulatory elements that have been generated using an integrated bioinformatics workflow of databases searches, literature-mining and DCGs-microRNA (miRNAs)-single nucleotide polymorphisms (SNPs) association analyses. To provide statistical significance to disease-gene association, ILD-specificity index and hypergeomatric test scores were also incorporated. Association analyses of miRNAs, SNPs and pathways responsible for the pathogenesis of different sub-classes of ILDs were also incorporated. Manually verified 299 DCGs and their significant associations with 1932 SNPs, 2966 miRNAs and 9170 miR-polymorphisms were also provided. Furthermore, 216 literature-mined and proposed biomarkers were identified. The ILDgenDB resource provides user-friendly browsing and extensive query-based information retrieval systems. Additionally, this resource also facilitates graphical view of predicted DCGs-SNPs/miRNAs and literature associated DCGs-ILDs interactions for each ILD to facilitate efficient data interpretation. Outcomes of analyses suggested the significant involvement of immune system and defense mechanisms in ILDs pathogenesis. This resource may potentially facilitate genetic-based disease monitoring and diagnosis.Database URL: http://14.139.240.55/ildgendb/index.php.

Differential co-expression analysis of rheumatoid arthritis with microarray data.

PubMed

Wang, Kunpeng; Zhao, Liqiang; Liu, Xuefeng; Hao, Zhenyong; Zhou, Yong; Yang, Chuandong; Li, Hongqiang

2014-11-01

The aim of the present study was to investigate the underlying molecular mechanisms of rheumatoid arthritis (RA) using microarray expression profiles from osteoarthritis and RA patients, to improve diagnosis and treatment strategies for the condition. The gene expression profile of GSE27390 was downloaded from Gene Expression Omnibus, including 19 samples from patients with RA (n=9) or osteoarthritis (n=10). Firstly, the differentially expressed genes (DEGs) were obtained with the thresholds of |logFC|>1.0 and P<0.05, using the t‑test method in LIMMA package. Then, differentially co-expressed genes (DCGs) and differentially co-expressed links (DCLs) were screened with q<0.25 by the differential coexpression analysis and differential regulation analysis of gene expression microarray data package. Secondly, pathway enrichment analysis for DCGs was performed by the Database for Annotation, Visualization and Integrated Discovery and the DCLs associated with RA were selected by comparing the obtained DCLs with known transcription factor (TF)-targets in the TRANSFAC database. Finally, the obtained TFs were mapped to the known TF-targets to construct the network using cytoscape software. A total of 1755 DEGs, 457 DCGs and 101988 DCLs were achieved and there were 20 TFs in the obtained six TF-target relations (STAT3-TNF, PBX1‑PLAU, SOCS3-STAT3, GATA1-ETS2, ETS1-ICAM4 and CEBPE‑GATA1) and 457 DCGs. A number of TF-target relations in the constructed network were not within DCLs when the TF and target gene were DCGs. The identified TFs may have an important role in the pathogenesis of RA and have the potential to be used as biomarkers for the development of novel diagnostic and therapeutic strategies for RA.

Deoxycholate-Based Glycosides (DCGs) for Membrane Protein Stabilisation.

PubMed

Bae, Hyoung Eun; Gotfryd, Kamil; Thomas, Jennifer; Hussain, Hazrat; Ehsan, Muhammad; Go, Juyeon; Loland, Claus J; Byrne, Bernadette; Chae, Pil Seok

2015-07-06

Detergents are an absolute requirement for studying the structure of membrane proteins. However, many conventional detergents fail to stabilise denaturation-sensitive membrane proteins, such as eukaryotic proteins and membrane protein complexes. New amphipathic agents with enhanced efficacy in stabilising membrane proteins will be helpful in overcoming the barriers to studying membrane protein structures. We have prepared a number of deoxycholate-based amphiphiles with carbohydrate head groups, designated deoxycholate-based glycosides (DCGs). These DCGs are the hydrophilic variants of previously reported deoxycholate-based N-oxides (DCAOs). Membrane proteins in these agents, particularly the branched diglucoside-bearing amphiphiles DCG-1 and DCG-2, displayed favourable behaviour compared to previously reported parent compounds (DCAOs) and conventional detergents (LDAO and DDM). Given their excellent properties, these agents should have significant potential for membrane protein studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Distributed Common Ground System-Navy Increment 2 (DCGS-N Inc 2)

DTIC Science & Technology

2016-03-01

15 minutes Enter and be Managed in the Network: Reference SvcV-7, Consolidated Afloat Networks and Enterprise Services ( CANES ) CDD, DCGS-N Inc 2...Red, White , Gray Data and Tracks to Command and Control System. Continuous Stream from SCI Common Intelligence Picture to General Service (GENSER...AIS - Automatic Information System AOC - Air Operations Command CANES - Consolidated Afloat Networks and Enterprise Services CID - Center for

Post-Transplant Blood Transfusions and Pediatric Renal Allograft Outcomes

PubMed Central

Verghese, Priya; Gillingham, Kristen; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche

2016-01-01

The association of blood transfusions with graft survival after pediatric kidney transplant (KTx) is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% > 12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival; antibody-mediated and acute cellular rejection, and donor-specific antibody (DSA) free survival. Transfusions <1 month post-KTx did not impact death-censored graft survival (DCGS) (p=NS). Patients transfused >12 months post-KTx had significantly lower 12 month estimated glomerular filtration rate (eGFR) (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. PMID:27712016

Differential co-expression analysis of a microarray gene expression profiles of pulmonary adenocarcinoma.

PubMed

Fu, Shijie; Pan, Xufeng; Fang, Wentao

2014-08-01

Lung cancer severely reduces the quality of life worldwide and causes high socioeconomic burdens. However, key genes leading to the generation of pulmonary adenocarcinoma remain elusive despite intensive research efforts. The present study aimed to identify the potential associations between transcription factors (TFs) and differentially co‑expressed genes (DCGs) in the regulation of transcription in pulmonary adenocarcinoma. Gene expression profiles of pulmonary adenocarcinoma were downloaded from the Gene Expression Omnibus, and gene expression was analyzed using a computational method. A total of 37,094 differentially co‑expressed links (DCLs) and 251 DCGs were identified, which were significantly enriched in 10 pathways. The construction of the regulatory network and the analysis of the regulatory impact factors revealed eight crucial TFs in the regulatory network. These TFs regulated the expression of DCGs by promoting or inhibiting their expression. In addition, certain TFs and target genes associated with DCGs did not appear in the DCLs, which indicated that those TFs could be synergistic with other factors. This is likely to provide novel insights for research into pulmonary adenocarcinoma. In conclusion, the present study may enhance the understanding of disease mechanisms and lead to an improved diagnosis of lung cancer. However, further studies are required to confirm these observations.

Post-transplant blood transfusions and pediatric renal allograft outcomes.

PubMed

Verghese, Priya; Gillingham, Kristen; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche

2016-11-01

The association of blood transfusions with GS after pediatric KTx is unclear. We retrospectively analyzed blood transfusions post-KTx and subsequent outcomes. Between 1984 and 2013, 482 children (<18 years of age) underwent KTx at our center. Recipient demographics, outcomes and transfusion data were collected. Cox regression with post-KTx blood transfusion as a time-dependent covariate was performed to model the impact of blood transfusion on outcomes. Of the 208 (44%) that were transfused, 39% had transfusion <1 month post-KTx; 48% >12 months. Transfused and non-transfused recipients were not significantly different. In univariate and multivariate analyses, there was no difference between transfused and non-transfused recipient patient survival, antibody-mediated and ACR, and DSA free survival. Transfusions <1 month post-KTx did not impact DCGS (P=NS). Patients transfused >12 months post-KTx had significantly lower 12 month eGFR (compared to non-transfused) and worse subsequent DCGS. Post-KTx blood transfusions have increased in pediatric KTx over time but have no negative association with rejection or DSA production. DCGS is unaffected by transfusion within first month. Transfusions after the first year occur in patients with more advanced chronic kidney disease and are associated with significantly worse DCGS. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

St. Louis airport site annual environmental report for calendar year 1990, St. Louis, Missouri

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-08-01

Environmental monitoring of the US Department of Energy's (DOE) St. Louis Airport Site (SLAPS) and surrounding area began in 1984. SLAPS is part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a DOE program to decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation's atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards; federal, state, and local applicable or relevant and appropriate requirements (ARARs); and/or DOE derived concentration guidelines (DCGs). Environmental standards, ARARs,more » and DCGs are established to protect public health and the environment. Results from the 1990 environmental monitoring program demonstrated that the concentrations of contaminants of concern were all below applicable standards, ARARs, and guidelines. Site activities in 1990 were limited to maintenance. SLAPS was in compliance with all applicable regulations during 1990 and has remained in compliance since 1984, when the environmental monitoring program and remedial action began.« less

A decision-theoretic approach to identifying future high-cost patients.

PubMed

Pietz, Kenneth; Byrne, Margaret M; Petersen, Laura A

2006-09-01

The objective of this study was to develop and evaluate a method of allocating funding for very-high-cost (VHC) patients among hospitals. Diagnostic cost groups (DCGs) were used for risk adjustment. The patient population consisted of 253,013 veterans who used Department of Veterans Affairs (VA) medical care services in fiscal year (FY) 2003 (October 1, 2002-September 30, 2003) in a network of 8 VA hospitals. We defined VHC as greater than 75,000 dollars (0.81%). The upper fifth percentile was also used for comparison. A Bayesian decision rule for classifying patients as VHC/not VHC using DCGs was developed and evaluated. The method uses FY 2003 DCGs to allocate VHC funds for FY 2004. We also used FY 2002 DCGs to allocate VHC funds for FY 2003 for comparison. The resulting allocation was compared with using the allocation of VHC patients among the hospitals in the previous year. The decision rule identified DCG 17 as the optimal cutoff for identifying VHC patients for the next year. The previous year's allocation came closest to the actual distribution of VHC patients. The decision-theoretic approach may provide insight into the economic consequences of classifying a patient as VHC or not VHC. More research is needed into methods of identifying future VHC patients so that capitation plans can fairly reimburse healthcare systems for appropriately treating these patients.

Diagnoses-based cost groups in the Dutch risk-equalization model: the effects of including outpatient diagnoses.

PubMed

van Kleef, R C; van Vliet, R C J A; van Rooijen, E M

2014-03-01

The Dutch basic health-insurance scheme for curative care includes a risk equalization model (RE-model) to compensate competing health insurers for the predictable high costs of people in poor health. Since 2004, this RE-model includes the so-called Diagnoses-based Cost Groups (DCGs) as a risk adjuster. Until 2013, these DCGs have been mainly based on diagnoses from inpatient hospital treatment. This paper examines (1) to what extent the Dutch RE-model can be improved by extending the inpatient DCGs with diagnoses from outpatient hospital treatment and (2) how to treat outpatient diagnoses relative to their corresponding inpatient diagnoses. Based on individual-level administrative costs we estimate the Dutch RE-model with three different DCG modalities. Using individual-level survey information from a prior year we examine the outcomes of these modalities for different groups of people in poor health. We find that extending DCGs with outpatient diagnoses has hardly any effect on the R-squared of the RE-model, but reduces the undercompensation for people with a chronic condition by about 8%. With respect to incentives, it may be preferable to make no distinction between corresponding inpatient and outpatient diagnoses in the DCG-classification, although this will be at the expense of the predictive accuracy of the RE-model. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs

PubMed Central

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-01-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.—Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. PMID:27451412

Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor X (RFX) transcription factors through X-box promoter motifs.

PubMed

Tammimies, Kristiina; Bieder, Andrea; Lauter, Gilbert; Sugiaman-Trapman, Debora; Torchet, Rachel; Hokkanen, Marie-Estelle; Burghoorn, Jan; Castrén, Eero; Kere, Juha; Tapia-Páez, Isabel; Swoboda, Peter

2016-10-01

DYX1C1, DCDC2, and KIAA0319 are three of the most replicated dyslexia candidate genes (DCGs). Recently, these DCGs were implicated in functions at the cilium. Here, we investigate the regulation of these DCGs by Regulatory Factor X transcription factors (RFX TFs), a gene family known for transcriptionally regulating ciliary genes. We identify conserved X-box motifs in the promoter regions of DYX1C1, DCDC2, and KIAA0319 and demonstrate their functionality, as well as the ability to recruit RFX TFs using reporter gene and electrophoretic mobility shift assays. Furthermore, we uncover a complex regulation pattern between RFX1, RFX2, and RFX3 and their significant effect on modifying the endogenous expression of DYX1C1 and DCDC2 in a human retinal pigmented epithelial cell line immortalized with hTERT (hTERT-RPE1). In addition, induction of ciliogenesis increases the expression of RFX TFs and DCGs. At the protein level, we show that endogenous DYX1C1 localizes to the base of the cilium, whereas DCDC2 localizes along the entire axoneme of the cilium, thereby validating earlier localization studies using overexpression models. Our results corroborate the emerging role of DCGs in ciliary function and characterize functional noncoding elements, X-box promoter motifs, in DCG promoter regions, which thus can be targeted for mutation screening in dyslexia and ciliopathies associated with these genes.-Tammimies, K., Bieder, A., Lauter, G., Sugiaman-Trapman, D., Torchet, R., Hokkanen, M.-E., Burghoorn, J., Castrén, E., Kere, J., Tapia-Páez, I., Swoboda, P. Ciliary dyslexia candidate genes DYX1C1 and DCDC2 are regulated by Regulatory Factor (RF) X transcription factors through X-box promoter motifs. © The Author(s).

Uncovering glacier dynamics beneath a debris mantle

NASA Astrophysics Data System (ADS)

Lefeuvre, P.-M.; Ng, F. S. L.

2012-04-01

Debris-covered glaciers (DCGs) have an extensive sediment mantle whose low albedo influences their surface energy balance to cause a buffering effect that could enhance or reduce ablation rates depending on the sediment thickness. The last effect suggests that some DCGs may be less sensitive to climate change and survive for longer than debris-free (or 'clean') glaciers under sustained climatic warming. However, the origin of DCGs is debated and the precise impact of the debris mantle on their flow dynamics and surface geometry has not been quantified. Here we investigate these issues with a numerical model that encapsulates ice-flow physics and surface debris evolution and transport along a glacier flow-line, as well as couples these with glacier mass balance. We model the impact of surface debris on ablation rates by a mathematical function based on published empirical data (including Ostrem's curve). A key interest is potential positive feedback of ablation on debris thickening and lowering of surface albedo. Model simulations show that when DCGs evolve to attain steady-state profiles, they reach lower elevations than clean glaciers do for the same initial and climatic conditions. Their mass-balance profile at steady state displays an inversion near the snout (where the debris cover is thickest) that is not observed in the clean-glacier simulations. In these cases, where the mantle causes complete buffering to inhibit ablation, the DCG does not reach a steady-state profile, and the sediment thickness evolves to a steady value that depends sensitively on the glacier surface velocities. Variation in the assumed englacial debris concentration in our simulations also determines glacier behaviour. With low englacial debris concentration, the DCG retreats initially while its mass-balance gradient steepens, but the glacier re-advances if it subsequently builds up a thick enough debris cover to cause complete buffering. We identify possible ways and challenges of testing this model with field observations of DCGs, given the inherent difficulty that such glaciers may not be in steady state.

Distributed Common Ground System - Army (DCGS-A) Increment 1 Release 2 Follow-on Operational Test and Evaluation (FOT and E) Report

DTIC Science & Technology

2016-01-01

Moving Target Indicator, Unmanned Aircraft System (UAS), Rivet Joint, U-2, and ground signals intelligence (PROPHET). At the BCT, Ranger Regiment and... metadata catalog managed by the DIB management office (outside of the DCGS-A system ). A metadata is a searchable description of data, and users across...challenge for users . The system required reboots about every 20 hours for users who had heavy workloads such as the fire support analysts and data

Niagara Falls Storage Site annual environmental report for calendar year 1991, Lewiston, New York. [Niagara Falls Storage Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-01

This document describes the environmental monitoring program at the Niagara Falls Storage Site (NFSS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring at NFSS began in 1981. The site is owned by the US Department of Energy (DOE) and is assigned to the DOE Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a program to decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation's atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental monitoring program atmore » NFSS includes sampling networks for radon concentrations in air; external gamma radiation exposure; and total uranium and radium-226 concentrations in surface water, sediments, and groundwater. Additionally, several nonradiological parameters including seven metals are routinely measured in groundwater. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE orders. Environmental standards are established to protect public health and the environment.« less

Niagara Falls Storage Site annual environmental report for calendar year 1991, Lewiston, New York

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-01

This document describes the environmental monitoring program at the Niagara Falls Storage Site (NFSS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring at NFSS began in 1981. The site is owned by the US Department of Energy (DOE) and is assigned to the DOE Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a program to decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation`s atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental monitoring program atmore » NFSS includes sampling networks for radon concentrations in air; external gamma radiation exposure; and total uranium and radium-226 concentrations in surface water, sediments, and groundwater. Additionally, several nonradiological parameters including seven metals are routinely measured in groundwater. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE orders. Environmental standards are established to protect public health and the environment.« less

Activity and Accumulation of Cell Division-Promoting Phenolics in Tobacco Tissue Cultures 1

PubMed Central

Teutonico, Rita A.; Dudley, Matthew W.; Orr, John D.; Lynn, David G.; Binns, Andrew N.

1991-01-01

Dehydrodiconiferyl alcohol glucosides (DCGs) are derivatives of the phenylpropanoid pathway that have been isolated from Catharansus roseus L. (Vinca rosea) crown gall tumors. Fractions containing purified DCGs have been shown previously to promote the growth of cytokinin-requiring tissues of tobacco in the absence of exogenous cytokinins. In this study, we utilized synthetic DCG isomers to confirm the cell division-promoting activity of DCG isomers A and B and show that they neither promote shoot meristem initiation on Nicotiana tabacum L., cv Havana 425, leaf explants nor induce betacyanin synthesis in amaranth seedlings. Analysis of cultured tobacco pith tissue demonstrated that DCG accumulation was stimulated by cytokinin treatment and correlated with cytokinin-induced cell division. Thus, the accumulation of metabolites that could replace cytokinin in cell division bioassays is stimulated by cytokinins. These data support the model that DCGs are a component of a cytokinin-mediated regulatory circuit controlling cell division. ImagesFigure 2 PMID:16668384

Impact of donor obesity and donation after cardiac death on outcomes after kidney transplantation.

PubMed

Ortiz, Jorge; Gregg, Austin; Wen, Xuerong; Karipineni, Farah; Kayler, Liise K

2012-01-01

The effect of donor body mass index (BMI) and donor type on kidney transplant outcomes has not been well studied. Scientific Registry of Transplant Recipients data on recipients of deceased-donor kidneys between 1997 and 2010 were reviewed. Donors were categorized by DCD status (DCD, 6932; non-DCD, 90,158) and BMI groups at 5 kg/m(2) increments: 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, 40-44.9, and ≥ 45 kg/m(2) . The primary outcome, death-censored graft survival (DCGS), was adjusted for donor, recipient, and transplant characteristics. Among recipients of non-DCD kidneys, donor BMI was not associated with DCGS. Among DCD recipients, donor BMI was not associated with DCGS for donor BMI categories < 45 kg/m(2) ; however, donor BMI ≥ 45 kg/m(2) was independently associated with DCGS compared to BMI of 20-24.9 kg/m(2) (adjusted hazard ratio, 1.84; 95% CI, 1.23, 2.74). The adjusted odds of delayed graft function (DGF) was greater for each level of BMI above reference for both DCD and non-DCD groups. There was no association of donor BMI with one-yr acute rejection for either type of donor. Although BMI is associated with DGF, long-term graft survival is not affected except in the combination of DCD with extreme donor BMI ≥ 45. © 2012 John Wiley & Sons A/S.

Materials for VPHGs: practical considerations in the case of astronomical instrumentation

NASA Astrophysics Data System (ADS)

Bianco, Andrea; Pariani, Giorgio; Zanutta, Alessio; Bertarelli, Chiara

2012-09-01

Volume Phase Holographic Gratings are interesting dispersing elements for astronomical instrumentation. An important point, in the realization of the grating, is the choice of the holographic material. Dichromated Gelatines (DCGs) are the best candidate, but they show some drawback especially regarding their water sensitivity and the complex developing process required to enhance their performances. New holographic materials are becoming interesting, such as photopolymers and photochromic materials. An exhaustive review of these classes of materials will be reported and their performances compared to those of DCGs, focusing mainly to the astronomical instrumentation field.

Wayne Interim Storage Site environmental report for calendar year 1992, 868 Black Oak Ridge Road, Wayne, New Jersey. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-05-01

This report describes the environmental surveillance program at the Wayne Interim Storage Site (WISS) and provides the results for 1992. The fenced, site, 32 km (20 mi) northwest of Newark, New Jersey, was used between 1948 and 1971 for commercial processing of monazite sand to separate natural radioisotopes - predominantly thorium. Environmental surveillance of WISS began in 1984 in accordance with Department of Energy (DOE) Order 5400.1 when Congress added the site to DOE`s Formerly Utilized Sites Remedial Action Program (FUSRAP). The environmental surveillance program at WISS includes sampling networks for radon and thoron in air; external gamma radiation exposure;more » radium-226, radium-228, thorium-230, thorium-232, total uranium, and several chemicals in surface water and sediment; and total uranium, radium-226, radium-228, thorium-230, thorium-232, and organic and inorganic chemicals in groundwater. Monitoring results are compared with applicable Environmental Protection Agency (EPA) and state standards, DOE derived concentration guides (DCGs), dose limits, and other DOE requirements. This monitoring program assists in fulfilling the DOE policy of measuring and monitoring effluents from DOE activities and calculating hypothetical doses. Results for environmental surveillance in 1992 show that the concentrations of all radioactive and most chemical contaminants were below applicable standards.« less

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles.

PubMed

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection.

Biological mechanism analysis of acute renal allograft rejection: integrated of mRNA and microRNA expression profiles

PubMed Central

Huang, Shi-Ming; Zhao, Xia; Zhao, Xue-Mei; Wang, Xiao-Ying; Li, Shan-Shan; Zhu, Yu-Hui

2014-01-01

Objectives: Renal transplantation is the preferred method for most patients with end-stage renal disease, however, acute renal allograft rejection is still a major risk factor for recipients leading to renal injury. To improve the early diagnosis and treatment of acute rejection, study on the molecular mechanism of it is urgent. Methods: MicroRNA (miRNA) expression profile and mRNA expression profile of acute renal allograft rejection and well-functioning allograft downloaded from ArrayExpress database were applied to identify differentially expressed (DE) miRNAs and DE mRNAs. DE miRNAs targets were predicted by combining five algorithm. By overlapping the DE mRNAs and DE miRNAs targets, common genes were obtained. Differentially co-expressed genes (DCGs) were identified by differential co-expression profile (DCp) and differential co-expression enrichment (DCe) methods in Differentially Co-expressed Genes and Links (DCGL) package. Then, co-expression network of DCGs and the cluster analysis were performed. Functional enrichment analysis for DCGs was undergone. Results: A total of 1270 miRNA targets were predicted and 698 DE mRNAs were obtained. While overlapping miRNA targets and DE mRNAs, 59 common genes were gained. We obtained 103 DCGs and 5 transcription factors (TFs) based on regulatory impact factors (RIF), then built the regulation network of miRNA targets and DE mRNAs. By clustering the co-expression network, 5 modules were obtained. Thereinto, module 1 had the highest degree and module 2 showed the most number of DCGs and common genes. TF CEBPB and several common genes, such as RXRA, BASP1 and AKAP10, were mapped on the co-expression network. C1R showed the highest degree in the network. These genes might be associated with human acute renal allograft rejection. Conclusions: We conducted biological analysis on integration of DE mRNA and DE miRNA in acute renal allograft rejection, displayed gene expression patterns and screened out genes and TFs that may be related to acute renal allograft rejection. PMID:25664019

Modelling Internal Heterogeneities in Debris-Covered Glaciers: the Potential to Link Morphology and Climate

NASA Astrophysics Data System (ADS)

Stuurman, C. M.; Holt, J.; Levy, J.

2016-12-01

On Earth and Mars, debris-covered glaciers (DCGs) often exhibit arcuate ridges transverse to the flow direction. Additionally, there exists some evidence linking internal structure (which is controlled in part by climate) in DCGs with surface microtopography. A better understanding of the relationship between englacial debris bands, compressional stresses, and debris-covered glacier microtopography will augment understanding of formational environments and mechanisms for terrestrial and martian DCGs. In order to better understand relationships between DCG surface morphology and internal debris bands, we combine field observations with finite-element modeling techniques to relate internal structure of DCGs to their surface morphologies. A geophysical survey including time-domain electromagnetic and ground-penetrating radar techniques of the Galena Creek Rock Glacier, WY was conducted over two field seasons in 2015/2016. Geomorphic analysis by surface observation and photogrammetry, including examination of a cirque-based thermokarst, was used to guide and complement geophysical sounding methods. Very clean ice below a 1 m thick layer of debris was directly observed on the walls of a 40 m diameter thermokarst pond near the accumulation zone. An englacial debris band 0.7 m thick dipping 30o intersected the wall of the pond. Transverse ridges occur at varying ridge-to-ridge wavelengths at different locations on the glacier. The GPR data supports the idea that surface ridges correlate with the intersection of debris layers and the surface. Modelling evidence is consistent with the observation of ridges at debris-layer/surface intersections, with compressional stresses buckling ice up-stream of the debris band.

Using risk-adjustment models to identify high-cost risks.

PubMed

Meenan, Richard T; Goodman, Michael J; Fishman, Paul A; Hornbrook, Mark C; O'Keeffe-Rosetti, Maureen C; Bachman, Donald J

2003-11-01

We examine the ability of various publicly available risk models to identify high-cost individuals and enrollee groups using multi-HMO administrative data. Five risk-adjustment models (the Global Risk-Adjustment Model [GRAM], Diagnostic Cost Groups [DCGs], Adjusted Clinical Groups [ACGs], RxRisk, and Prior-expense) were estimated on a multi-HMO administrative data set of 1.5 million individual-level observations for 1995-1996. Models produced distributions of individual-level annual expense forecasts for comparison to actual values. Prespecified "high-cost" thresholds were set within each distribution. The area under the receiver operating characteristic curve (AUC) for "high-cost" prevalences of 1% and 0.5% was calculated, as was the proportion of "high-cost" dollars correctly identified. Results are based on a separate 106,000-observation validation dataset. For "high-cost" prevalence targets of 1% and 0.5%, ACGs, DCGs, GRAM, and Prior-expense are very comparable in overall discrimination (AUCs, 0.83-0.86). Given a 0.5% prevalence target and a 0.5% prediction threshold, DCGs, GRAM, and Prior-expense captured $963,000 (approximately 3%) more "high-cost" sample dollars than other models. DCGs captured the most "high-cost" dollars among enrollees with asthma, diabetes, and depression; predictive performance among demographic groups (Medicaid members, members over 64, and children under 13) varied across models. Risk models can efficiently identify enrollees who are likely to generate future high costs and who could benefit from case management. The dollar value of improved prediction performance of the most accurate risk models should be meaningful to decision-makers and encourage their broader use for identifying high costs.

Rapid Discontinuation of Prednisone in Kidney Transplant Recipients: 15-Year Outcomes From the University of Minnesota.

PubMed

Serrano, Oscar Kenneth; Kandaswamy, Raja; Gillingham, Kristen; Chinnakotla, Srinath; Dunn, Ty B; Finger, Erik; Payne, William; Ibrahim, Hassan; Kukla, Aleksandra; Spong, Richard; Issa, Naim; Pruett, Timothy L; Matas, Arthur

2017-10-01

Short- and intermediate-term results have been reported after rapid discontinuation of prednisone (RDP) in kidney transplant recipients. Yet there has been residual concern about late graft failure in the absence of maintenance prednisone. From October 1, 1999, through June 1, 2015, we performed a total of 1553 adult first and second kidney transplants-1021 with a living donor, 532 with a deceased donor-under our RDP protocol. We analyzed the 15-year actuarial overall patient survival (PS), graft survival (GS), death-censored GS (DCGS), and acute rejection-free survival (ARFS) rates for RDP compared with historical controls on maintenance prednisone. For living donor recipients, the actuarial 15-year PS rates were similar between groups. But RDP was associated with increased GS (P = 0.02) and DCGS (P = 0.01). For deceased donor recipients, RDP was associated with significantly better PS (P < 0.01), GS (P < 0.01) and DCGS (P < 0.01). There was no difference between groups in the rate of acute or chronic rejection, or in the mean estimated glomerular filtration rate at 15 years. However, RDP-treated recipients had significantly lower rates of avascular necrosis, cytomegalovirus, cataracts, new-onset diabetes after transplant, and cardiac complications. Importantly, for recipients with GS longer than 5 years, there was no difference between groups in subsequent actuarial PS, GS, and DCGS. In summary, at 15 years postkidney transplant, RDP did not lead to decreased in PS or GS, or an increase in graft dysfunction but as associated with reduced complication rates.

Host CD40 Is Essential for DCG Treatment Against Metastatic Lung Cancer.

PubMed

Yamashita, Kimihiro; Hasegawa, Hiroshi; Fujita, Mitsugu; Nishi, Masayasu; Tanaka, Tomoko; Arimoto, Akira; Suzuki, Satoshi; Kamigaki, Takashi; Kakeji, Yoshihiro

2016-07-01

For the application of invariant natural killer T (iNKT) cells in cancer therapy, the CD40-CD40L interaction is indispensable in administering alpha-galactosylceramide (αGalCer). We hypothesized that CD40 plays an important role in dendritic cells (DC) pulsed with αGalCer (DCGs) in the treatment of lung metastases. Wild-type (WT) and CD40(-/-) mice were treated with DCGs isolated from WT or CD40(-/-) mice in a B16F10 lung metastases model and NK and NKT cell activity in lungs and the spleen were examined. DCG treatment improved WT mice survival but CD40(-/-) hosts received no survival benefit. Conversely, attenuation of a therapeutic effect in mice treated with CD40(-/-) DCGs was not observed. The functional activities of NK and NKT cells in DCG-treated CD40(-/-) mice were partially suppressed. Host CD40 is essential for DCG treatment to have a therapeutic effect on B16F10 lung metastases. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Maywood Interim Storage Site environmental report for calendar year 1992, 100 West Hunter Avenue, Maywood, New Jersey. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-05-01

This report describes the environmental surveillance program at the Maywood Interim Storage Site (MISS) and provides the results for 1992. Environmental monitoring of MISS began in 1984, when the site was assigned to DOE by Congress through the Energy and Water Development Appropriations Act and was placed under DOE`s Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP was established to identify and decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation`s atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. MISS is part of amore » National Priorities List (NPL) site. The environmental surveillance program at MISS includes sampling networks for radon and thoron in air; external gamma radiation exposure; and radium-226, radium-228, thorium-232, and total uranium in surface water, sediment, and groundwater. Additionally, chemical analysis includes metals and organic compounds in surface water and groundwater and metals in sediments. This program assists in fulfilling the DOE objective of measuring and monitoring effluents from DOE activities and calculating hypothetical doses to members of the general public. Monitoring results are compared with applicable Environmental Protection Agency (EPA) and state standards, DOE derived concentration guides (DCGs), dose limits, and other DOE requirements. Environmental standards are established to protect public health and the environment. The radiological data for all media sampled support the conclusion that doses to the public are not distinguishable from natural background radiation.« less

Independent Transport and Sorting of Functionally Distinct Protein Families in Tetrahymena thermophila Dense Core Secretory Granules▿ †

PubMed Central

Rahaman, Abdur; Miao, Wei; Turkewitz, Aaron P.

2009-01-01

Dense core granules (DCGs) in Tetrahymena thermophila contain two protein classes. Proteins in the first class, called granule lattice (Grl), coassemble to form a crystalline lattice within the granule lumen. Lattice expansion acts as a propulsive mechanism during DCG release, and Grl proteins are essential for efficient exocytosis. The second protein class, defined by a C-terminal β/γ-crystallin domain, is poorly understood. Here, we have analyzed the function and sorting of Grt1p (granule tip), which was previously identified as an abundant protein in this family. Cells lacking all copies of GRT1, together with the closely related GRT2, accumulate wild-type levels of docked DCGs. Unlike cells disrupted in any of the major GRL genes, ΔGRT1 ΔGRT2 cells show no defect in secretion, indicating that neither exocytic fusion nor core expansion depends on GRT1. These results suggest that Grl protein sorting to DCGs is independent of Grt proteins. Consistent with this, the granule core lattice in ΔGRT1 ΔGRT2 cells appears identical to that in wild-type cells by electron microscopy, and the only biochemical component visibly absent is Grt1p itself. Moreover, gel filtration showed that Grl and Grt proteins in cell homogenates exist in nonoverlapping complexes, and affinity-isolated Grt1p complexes do not contain Grl proteins. These data demonstrate that two major classes of proteins in Tetrahymena DCGs are likely to be independently transported during DCG biosynthesis and play distinct roles in granule function. The role of Grt1p may primarily be postexocytic; consistent with this idea, DCG contents from ΔGRT1 ΔGRT2 cells appear less adhesive than those from the wild type. PMID:19684282

Independent transport and sorting of functionally distinct protein families in Tetrahymena thermophila dense core secretory granules.

PubMed

Rahaman, Abdur; Miao, Wei; Turkewitz, Aaron P

2009-10-01

Dense core granules (DCGs) in Tetrahymena thermophila contain two protein classes. Proteins in the first class, called granule lattice (Grl), coassemble to form a crystalline lattice within the granule lumen. Lattice expansion acts as a propulsive mechanism during DCG release, and Grl proteins are essential for efficient exocytosis. The second protein class, defined by a C-terminal beta/gamma-crystallin domain, is poorly understood. Here, we have analyzed the function and sorting of Grt1p (granule tip), which was previously identified as an abundant protein in this family. Cells lacking all copies of GRT1, together with the closely related GRT2, accumulate wild-type levels of docked DCGs. Unlike cells disrupted in any of the major GRL genes, DeltaGRT1 DeltaGRT2 cells show no defect in secretion, indicating that neither exocytic fusion nor core expansion depends on GRT1. These results suggest that Grl protein sorting to DCGs is independent of Grt proteins. Consistent with this, the granule core lattice in DeltaGRT1 DeltaGRT2 cells appears identical to that in wild-type cells by electron microscopy, and the only biochemical component visibly absent is Grt1p itself. Moreover, gel filtration showed that Grl and Grt proteins in cell homogenates exist in nonoverlapping complexes, and affinity-isolated Grt1p complexes do not contain Grl proteins. These data demonstrate that two major classes of proteins in Tetrahymena DCGs are likely to be independently transported during DCG biosynthesis and play distinct roles in granule function. The role of Grt1p may primarily be postexocytic; consistent with this idea, DCG contents from DeltaGRT1 DeltaGRT2 cells appear less adhesive than those from the wild type.

Maywood Interim Storage Site annual environmental report for calendar year 1991, Maywood, New Jersey. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1992-09-01

This document describes the environmental monitoring program at the Maywood Interim Storage Site (MISS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring of MISS began in 1984 when congress added the site to the US Department of Energy`s (DOE) Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a DOE program to identify and decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation`s atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental monitoring program at MISS includesmore » sampling networks for radon and thoron concentrations in air; external gamma radiation-exposure; and total uranium, radium-226, radium-228, thorium-232, and thorium-230 concentrations in surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in surface water, sediment, and groundwater. Monitoring results are compared with applicable Environmental Protection Agency standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE orders. Environmental standards are established to protect public health and the environment.« less

Maywood Interim Storage Site annual environmental report for calendar year 1991, Maywood, New Jersey. [Maywood Interim Storage Site

DOE Office of Scientific and Technical Information (OSTI.GOV)

None

1992-09-01

This document describes the environmental monitoring program at the Maywood Interim Storage Site (MISS) and surrounding area, implementation of the program, and monitoring results for 1991. Environmental monitoring of MISS began in 1984 when congress added the site to the US Department of Energy's (DOE) Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a DOE program to identify and decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation's atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental monitoring program at MISS includesmore » sampling networks for radon and thoron concentrations in air; external gamma radiation-exposure; and total uranium, radium-226, radium-228, thorium-232, and thorium-230 concentrations in surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in surface water, sediment, and groundwater. Monitoring results are compared with applicable Environmental Protection Agency standards, DOE derived concentration guides (DCGs), dose limits, and other requirements in DOE orders. Environmental standards are established to protect public health and the environment.« less

Application of dynamic uncertain causality graph in spacecraft fault diagnosis: Logic cycle

NASA Astrophysics Data System (ADS)

Yao, Quanying; Zhang, Qin; Liu, Peng; Yang, Ping; Zhu, Ma; Wang, Xiaochen

2017-04-01

Intelligent diagnosis system are applied to fault diagnosis in spacecraft. Dynamic Uncertain Causality Graph (DUCG) is a new probability graphic model with many advantages. In the knowledge expression of spacecraft fault diagnosis, feedback among variables is frequently encountered, which may cause directed cyclic graphs (DCGs). Probabilistic graphical models (PGMs) such as bayesian network (BN) have been widely applied in uncertain causality representation and probabilistic reasoning, but BN does not allow DCGs. In this paper, DUGG is applied to fault diagnosis in spacecraft: introducing the inference algorithm for the DUCG to deal with feedback. Now, DUCG has been tested in 16 typical faults with 100% diagnosis accuracy.

Diaminopropionic Acid Reinforced Graphene Sponge and Its Use for Hemostasis.

PubMed

Quan, Kecheng; Li, Guofeng; Tao, Lei; Xie, Qian; Yuan, Qipeng; Wang, Xing

2016-03-01

2,3-Diaminopropionic acid (DapA), a medicinal amino acid, is used for the first time to prepare a DapA cross-linked graphene sponge (DCGS) for hemostasis treatment. In a comparison with the reported ethanediamine (EDA) cross-linked graphene sponge (CGS), this carboxyl-functionalized DCGS can not only quickly absorb plasma, but also stimulate erythrocytes and platelets to change their normal form and structure at the interface, which largely affects a cell's metabolism and biofunction, thus further promoting blood coagulation. Whole blood clotting and rat-tail amputation tests indicated that on the basis of the additional interfacial stimulation, the hemostatic efficiency of the DCGS has been significantly improved in comparison with that of the CGS control (P < 0.05). In-depth insight revealed that the increased oxidation degree and the negative charge density play the crucial rule in the enhanced hemostatic performance. The chiral effect contributes mainly to the selective adhesion of erythrocytes and platelets rather than practical hemostasis. Nevertheless, this presentation demonstrated that, on the premise of keeping the fast absorbability, this is an effective method to improve the hemostatic efficiency by enhancing the cell/graphene interface interaction.

Microarray gene expression profiling analysis combined with bioinformatics in multiple sclerosis.

PubMed

Liu, Mingyuan; Hou, Xiaojun; Zhang, Ping; Hao, Yong; Yang, Yiting; Wu, Xiongfeng; Zhu, Desheng; Guan, Yangtai

2013-05-01

Multiple sclerosis (MS) is the most prevalent demyelinating disease and the principal cause of neurological disability in young adults. Recent microarray gene expression profiling studies have identified several genetic variants contributing to the complex pathogenesis of MS, however, expressional and functional studies are still required to further understand its molecular mechanism. The present study aimed to analyze the molecular mechanism of MS using microarray analysis combined with bioinformatics techniques. We downloaded the gene expression profile of MS from Gene Expression Omnibus (GEO) and analysed the microarray data using the differentially coexpressed genes (DCGs) and links package in R and Database for Annotation, Visualization and Integrated Discovery. The regulatory impact factor (RIF) algorithm was used to measure the impact factor of transcription factor. A total of 1,297 DCGs between MS patients and healthy controls were identified. Functional annotation indicated that these DCGs were associated with immune and neurological functions. Furthermore, the RIF result suggested that IKZF1, BACH1, CEBPB, EGR1, FOS may play central regulatory roles in controlling gene expression in the pathogenesis of MS. Our findings confirm the presence of multiple molecular alterations in MS and indicate the possibility for identifying prognostic factors associated with MS pathogenesis.

Colonie Interim Storage Site environmental report for calendar year 1992, 1130 Central Avenue, Colonie, New York. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-05-01

This report describes the environmental surveillance program at the Colonie Interim Storage Site (CISS) and provides the results for 1992. The site is located in eastern New York State, approximately 6.4 km (4.0 mi) northwest of downtown Albany. From 1958 to 1984, National Lead (NL) Industries used the facility to manufacture various components from depleted and enriched uranium natural thorium. Environmental monitoring of CISS began in 1984 when Congress added, the site to the US Department of Energy`s (DOE) Formerly Utilized Sites Remedial Action Program (FUSRAP). FUSRAP is a program established to identify and decontaminate or otherwise control sites wheremore » residual radioactive materials remain from the early years of the nation`s atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The environmental surveillance program at CISS includes sampling networks for external gamma radiation exposure and for thorium-232 and total uranium concentrations in surface water, sediment, and groundwater. Several chemical parameters are also measured in groundwater, including total metals, volatile organics, and water quality parameters. This surveillance program assists in fulfilling the DOE policy of measuring and monitoring effluents from DOE activities and calculating hypothetical doses. Results are compared with applicable Environmental Protection Agency (EPA) and New York State Department of Environmental Conservation (NYSDEC) standards, DOE derived concentration guides (DCGs), dose limits, and other DOE requirements.« less

Identification of transcription regulatory relationships in rheumatoid arthritis and osteoarthritis.

PubMed

Li, Guofeng; Han, Ning; Li, Zengchun; Lu, Qingyou

2013-05-01

Rheumatoid arthritis (RA) is recognized as the most crippling or disabling type of arthritis, and osteoarthritis (OA) is the most common form of arthritis. These diseases severely reduce the quality of life, and cause high socioeconomic burdens. However, the molecular mechanisms of RA and OA development remain elusive despite intensive research efforts. In this study, we aimed to identify the potential transcription regulatory relationships between transcription factors (TFs) and differentially co-expressed genes (DCGs) in RA and OA, respectively. We downloaded the gene expression profiles of RA and OA from the Gene Expression Omnibus and analyzed the gene expression using computational methods. We identified a set of 4,076 DCGs in pairwise comparisons between RA and OA patients, RA and normal donors (NDs), or OA and ND. After regulatory network construction and regulatory impact factor analysis, we found that EGR1, NFE2L1, and NFYA were crucial TFs in the regulatory network of RA and NFYA, CBFB, CREB1, YY1 and PATZ1 were crucial TFs in the regulatory network of OA. These TFs could regulate the DCGs expression to involve RA and OA by promoting or inhibiting their expression. Altogether, our work may extend our understanding of disease mechanisms and may lead to an improved diagnosis. However, further experiments are still needed to confirm these observations.

The Relationship of the Severity and Category of Acute Rejection With Intimal Arteritis Defined in Banff Classification to Clinical Outcomes.

PubMed

Wu, Kaiyin; Budde, Klemens; Schmidt, Danilo; Neumayer, Hans-Helmut; Rudolph, Birgit

2015-08-01

It is unclear if the category of acute rejection with intimal arteritis (ARV) is relevant to short- and long-term clinical outcomes and if the graft outcomes are affected by the severity of intimal arteritis. One hundred forty-eight ARV episodes were reviewed and categorized according to the 2013 Banff criteria of AMR: T cell-mediated rejection with intimal arteritis (v) lesion (TCMRV; n = 78), total antibody-mediated rejection with v lesion (AMRV), which were further divided into suspicious AMRV (n = 37) and AMRV (n = 33). The Banff scores of intimal arteritis (v1, v2 and v3) represented low, moderate, and high ARV severity. The grafts with TCMRV, suspicious AMRV (sAMRV), and AMRV showed similar responses to antirejection therapy, whereas the grafts with v2- or v3-ARV responded significantly poorer compared to those with v1-ARV. The 8-year death-censored graft survival (DCGS) rate was 56.8% of TCMRV versus 34.1% of total AMRV (Log rank, P = 0.03), but the 1- and 5-year DCGS rates were comparable between the 2 groups; moreover, the 1-, 5-, and 8-year DCGS rates of v1-ARV were evidently higher than v2- and v3-ARV (each pairwise comparison to v1-AVR yields P < 0.01); in contrast, the DCGS rates were similar between sAMRV and AMRV. The existing donor-specific antibodies or moderate microvascular inflammation or C4d-positive staining or intensive tubulointerstitial inflammation played a less significant role on the long-term graft survival. Compared to the category, the ARV severity is more closely associated with the initial response to antirejection therapy and long-term graft failure. The sAMRV and AMRV might represent a spectrum of the same disorder.

Infection rates in tacrolimus versus cyclosporine-treated pediatric kidney transplant recipients on a rapid discontinuation of prednisone protocol: 1-year analysis.

PubMed

Kizilbash, Sarah J; Rheault, Michelle N; Bangdiwala, Ananta; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche M

2017-06-01

AR is lower in pKTx recipients on Tac vs CsA. Data comparing infection outcomes for children treated with these agents are limited. We retrospectively studied infection outcomes in 96 pKTx recipients on a RDP. PS, DCGS, AR, and infection-free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; P = .044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; P = .007) in Tac recipients. The incidence of EBV viremia was similar between the groups (P = .56). PostTx lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract, or Clostridium difficile infections between Tac and CsA recipients. Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1 year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Air pathway effects of nuclear materials production at the Hanford Site, 1983 to 1992

DOE Office of Scientific and Technical Information (OSTI.GOV)

Patton, G.W.; Cooper, A.T.

1993-10-01

This report describes the air pathway effects of Hanford Site operations from 1983 to 1992 on the local environment by summarizing the air concentrations of selected radionuclides at both onsite and offsite locations, comparing trends in environment concentrations to changing facility emissions, and briefly describing trends in the radiological dose to the hypothetical maximally exposed member of the public. The years 1983 to 1992 represent the last Hanford Site plutonium production campaign, and this report deals mainly with the air pathway effects from the 200 Areas, in which the major contributors to radiological emissions were located. An additional purpose formore » report was to review the environmental data for a long period of time to provide insight not available in an annual report format. The sampling and analytical systems used by the Surface Environmental Surveillance Project (SESP) to collect air samples during the period of this report were sufficiently sensitive to observe locally elevated concentrations of selected radionuclides near onsite source of emission as well as observing elevated levels, compared to distant locations, of some radionuclides at the down wind perimeter. The US DOE Derived Concentration Guides (DCGs) for airborne radionuclides were not exceeded for any air sample collected during 1983 to 1992, with annual average concentrations of all radionuclides at the downwind perimeter being considerably below the DCG values. Air emissions at the Hanford Site during the period of this report were dominated by releases from the PUREX Plant, with {sup 85}Kr being the major release on a curie basis and {sup 129}I being the major release on a radiological dose basis. The estimated potential radiological dose from Hanford Site point source emissions to the hypothetical maximally exposed individual (MEI) ranged from 0. 02 to 0.22 mrem/yr (effective dose equivalent), which is well below the DOE radiation limit to the public of 100 mrem/yr.« less

Do different case-mix measures affect assessments of provider efficiency? Lessons from the Department of Veterans Affairs.

PubMed

Rosen, Amy K; Loveland, Susan A; Rakovski, Carter C; Christiansen, Cindy L; Berlowitz, Dan R

2003-01-01

Although case-mix adjustment is critical for provider profiling, little is known regarding whether different case-mix measures affect assessments of provider efficiency. We examine whether two case-mix measures, Adjusted Clinical Groups (ACGs) and Diagnostic Cost Groups (DCGs), result in different assessments of efficiency across service networks within the Department of Veterans Affairs (VA). Three profiling indicators examine variation in resource use. Although results from the ACGs and DCGs generally agree on which networks have greater or lesser efficiency than average, assessments of individual network efficiency vary depending upon the case-mix measure used. This suggests that caution should be used so that providers are not misclassified based on reported efficiency.

Hanford Site near-facility environmental monitoring annual report, calendar year 1997

DOE Office of Scientific and Technical Information (OSTI.GOV)

Perkins, C.J.

1998-07-28

Near-facility environmental monitoring provides a means to measure the impacts of operations, waste management, and remediation activities on the environment adjacent to facilities and ensure compliance with local, state, and federal environmental regulations. Specifically, near-facility environmental monitoring monitors new and existing sites, processes, and facilities for potential impacts and releases; fugitive emissions and diffuse sources associated with contaminated areas, facilities (both active and those undergoing surveillance and maintenance), and environmental restoration activities. External radiation, ambient air particulates, ground and surface water, soil, sediment, and biota (plants and animals) are sampled or monitored. Parameters include, as appropriate, radionuclides; radiation fields; chemicalmore » or physical constituents, such as nitrates; pH; and water temperature. All ambient air results were below the US Department of Energy (DOE) Derived Concentration Guides (DCGs). Groundwater concentrations at the two wells at the 107-N Facility were below both the DOE DCG and US Environmental Protection Agency Interim Drinking Water Standards for gamma emitting radionuclides. Soil and vegetation results were generally within historic ranges and mostly below the Accessible Soil Concentration limits (included in HNF-PRO-454, Inactive Waste Sites) with the exception of one soil sampling location at 1 00 N Area. External radiation fields continued an overall downward trend. Surface water disposal unit samples (water, sediment, and aquatic vegetation) showed radionuclide concentrations below their respective DCG and Accessible Soil Concentration limits. The 100 N Area Columbia river shoreline springs results were below DCGs with the exception of one Sr concentration. More than 4,600 ha (11,300 acres) of radiologically controlled areas were surveyed in 1997, approximately the same as in 1996.« less

Ultrastructural Analysis of In Vivo Hypoglycemiant Effect of Two Polyoxometalates in Rats with Streptozotocin-Induced Diabetes.

PubMed

Bâlici, Ştefana; Wankeu-Nya, Modeste; Rusu, Dan; Nicula, Gheorghe Z; Rusu, Mariana; Florea, Adrian; Matei, Horea

2015-10-01

Two polyoxometalates (POMs), synthesized through a self-assembling method, were used in the treatment of streptozotocin (STZ)-induced diabetic rats. One of these nanocompounds [tris(vanadyl)-substituted tungsto-antimonate(III)-anions—POM1] was previously described in the literature, whereas the second [tris-butyltin-21-tungsto-9-antimonate(III)-anions—POM2], was prepared by us based on our original formula. In rats with STZ-induced diabetes treated with POMs (up to a cumulative dose of 4 mg/kg bodyweight at the end of the treatments), statistically significant reduced levels of blood glucose were measured after 3 weeks, as compared with the diabetic control groups (DCGs). Ultrastructural analysis of pancreatic β-cells (including the mean diameter of secretory vesicles and of their insulin granules) in the treated diabetic rats proved the POMs contribute to limitation of cellular degeneration triggered by STZ, as well as to the presence of increased amounts of insulin-containing vesicles as compared with the DCG. The two POMs also showed hepatoprotective properties when ultrastructural aspects of hepatocytes in the experimental groups of rats were studied. Based on our in vivo studies, we concluded that the two POMs tested achieved hypoglycemiant effects by preventing STZ-triggered apoptosis of pancreatic β-cells and stimulation of insulin synthesis.

Niagara Falls Storage Site environmental report for calendar year 1992, 1397 Pletcher Road, Lewiston, New York. Formerly Utilized Sites Remedial Action Program (FUSRAP)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1993-05-01

This report describes the environmental surveillance program at the Niagara Falls Storage Site (NFSS) and provides the results for 1992. From 1944 to the present, the primary use of NFSS has been storage of radioactive residues produced as a by-product of uranium production. All onsite areas of residual radioactivity above guidelines have been remediated. Materials generated during remediation are stored onsite in the 4-ha (10-acre) waste containment structure (WCS). The WCS is a clay-lined, clay-capped, and grass-covered storage pile. The environmental surveillance program at NFSS includes sampling networks for radon concentrations in air; external gamma radiation exposure; and total uraniummore » and radium-226 concentrations in surface water, sediments, and groundwater. Several chemical parameters, including seven metals, are also routinely measured in groundwater. This surveillance program assists in fulfilling the DOE policy of measuring and monitoring effluents from DOE activities and calculating hypothetical doses. Monitoring results are compared with applicable Environmental Protection Agency (EPA) and New York State Department of Environmental Conservation (NYSDEC) standards, DOE derived concentration guides (DCGs), dose limits, and other DOE requirements. Results of environmental monitoring during 1992 indicate that levels of the parameters measured were in compliance with all but one requirement: Concentrations of iron and manganese in groundwater were above NYSDEC groundwater quality standards. However, these elements occur naturally in the soils and groundwater associated with this region. In 1992 there were no environmental occurrences or reportable quantity releases.« less

Infection Rates in Tacrolimus versus Cyclosporine Treated Pediatric Kidney Transplant Recipients on a Rapid Discontinuation of Prednisone Protocol: 1-year Analysis

PubMed Central

Kizilbash, Sarah J; Rheault, Michelle N; Bangdiwala, Ananta; Matas, Arthur; Chinnakotla, Srinath; Chavers, Blanche M

2017-01-01

Introduction Acute rejection (AR) is lower in pediatric kidney transplant (pKTx) recipients on tacrolimus (Tac) versus cyclosporine (CsA). Data comparing infection outcomes for children treated with these agents are limited. Methods We retrospectively studied infection outcomes in 96 pKTx recipients on a rapid discontinuation of prednisone protocol (RDP). Patient survival (PS), death-censored graft survival (DCGS), AR and infection free survival were assessed using Kaplan-Meier/log-rank tests and proportional hazards models. Results There were no differences in 1-year PS, DCGS, or AR between Tac and CsA recipients. After adjusting for AR, the hazard of CMV viremia was 4.0 times higher (95%CI: 1.04, 15.5; p=0.044) and that of BK viremia was 3.8 times higher (95%CI: 1.5, 10.2; p=0.007) in Tac recipients. The incidence of EBV viremia was similar between the groups (p=0.56). Posttransplant lymphoproliferative disease was only observed in Tac recipients (3%). There was no difference in the incidence of pneumonia, urinary tract or clostridium difficile infections between Tac and CsA recipients. Conclusion Among KTx recipients on RDP, the hazards of CMV and BK viremia within 1-year post-KTx were significantly higher in Tac recipients compared to CsA. Regular assessment for infections and lower Tac trough levels may be warranted in Tac recipients. PMID:28371243

Distinct molecular profile of diffuse cerebellar gliomas.

PubMed

Nomura, Masashi; Mukasa, Akitake; Nagae, Genta; Yamamoto, Shogo; Tatsuno, Kenji; Ueda, Hiroki; Fukuda, Shiro; Umeda, Takayoshi; Suzuki, Tomonari; Otani, Ryohei; Kobayashi, Keiichi; Maruyama, Takashi; Tanaka, Shota; Takayanagi, Shunsaku; Nejo, Takahide; Takahashi, Satoshi; Ichimura, Koichi; Nakamura, Taishi; Muragaki, Yoshihiro; Narita, Yoshitaka; Nagane, Motoo; Ueki, Keisuke; Nishikawa, Ryo; Shibahara, Junji; Aburatani, Hiroyuki; Saito, Nobuhito

2017-12-01

Recent studies have demonstrated that tumor-driving alterations are often different among gliomas that originated from different brain regions and have underscored the importance of analyzing molecular characteristics of gliomas stratified by brain region. Therefore, to elucidate molecular characteristics of diffuse cerebellar gliomas (DCGs), 27 adult, mostly glioblastoma cases were analyzed. Comprehensive analysis using whole-exome sequencing, RNA sequencing, and Infinium methylation array (n = 17) demonstrated their distinct molecular profile compared to gliomas in other brain regions. Frequent mutations in chromatin-modifier genes were identified including, noticeably, a truncating mutation in SETD2 (n = 4), which resulted in loss of H3K36 trimethylation and was mutually exclusive with H3F3A K27M mutation (n = 3), suggesting that epigenetic dysregulation may lead to DCG tumorigenesis. Alterations that cause loss of p53 function including TP53 mutation (n = 9), PPM1D mutation (n = 2), and a novel type of PPM1D fusion (n = 1), were also frequent. On the other hand, mutations and copy number changes commonly observed in cerebral gliomas were infrequent. DNA methylation profile analysis demonstrated that all DCGs except for those with H3F3A mutations were categorized in the "RTK I (PDGFRA)" group, and those DCGs had a gene expression signature that was highly associated with PDGFRA. Furthermore, compared with the data of 315 gliomas derived from different brain regions, promoter methylation of transcription factors genes associated with glial development showed a characteristic pattern presumably reflecting their tumor origin. Notably, SOX10, a key transcription factor associated with oligodendroglial differentiation and PDGFRA regulation, was up-regulated in both DCG and H3 K27M-mutant diffuse midline glioma, suggesting their developmental and biological commonality. In contrast, SOX10 was silenced by promoter methylation in most cerebral gliomas. These findings may suggest potential tailored targeted therapy for gliomas according to their brain region, in addition to providing molecular clues to identify the region-related cellular origin of DCGs.

Identification and staining of distinct populations of secretory organelles in astrocytes.

PubMed

Bezzi, Paola; Volterra, Andrea

2014-05-01

Increasing evidence indicates that astrocytes, the most abundant glial cell type in the brain, respond to an elevation in cytoplasmic calcium concentration ([Ca(2+)]i) by releasing chemical transmitters (also called gliotransmitters) via regulated exocytosis of heterogeneous classes of organelles. By this process, astrocytes exert modulatory influences on neighboring cells and are thought to participate in the control of synaptic circuits and cerebral blood flow. Studying the properties of exocytosis in astrocytes is a challenge, because the cell biological basis of this process is incompletely defined. Astrocytic exocytosis involves multiple populations of secretory vesicles, including synaptic-like microvesicles (SLMVs), dense-core granules (DCGs), and lysosomes. Here we summarize the available information for identifying individual populations of secretory organelles in astrocytes, including DCGs, SLMVs, and lysosomes, and present experimental procedures for specifically staining such populations.

Gene expression patterns combined with bioinformatics analysis identify genes associated with cholangiocarcinoma.

PubMed

Li, Chen; Shen, Weixing; Shen, Sheng; Ai, Zhilong

2013-12-01

To explore the molecular mechanisms of cholangiocarcinoma (CC), microarray technology was used to find biomarkers for early detection and diagnosis. The gene expression profiles from 6 patients with CC and 5 normal controls were downloaded from Gene Expression Omnibus and compared. As a result, 204 differentially co-expressed genes (DCGs) in CC patients compared to normal controls were identified using a computational bioinformatics analysis. These genes were mainly involved in coenzyme metabolic process, peptidase activity and oxidation reduction. A regulatory network was constructed by mapping the DCGs to known regulation data. Four transcription factors, FOXC1, ZIC2, NKX2-2 and GCGR, were hub nodes in the network. In conclusion, this study provides a set of targets useful for future investigations into molecular biomarker studies. Copyright © 2013 Elsevier Ltd. All rights reserved.

The impact of C4d and microvascular inflammation before we knew them.

PubMed

Verghese, Priya; Dunn, Ty; Najafian, Behzad; Kim, Youngki; Matas, Arthur

2013-01-01

It is important to identify prognostically important morphologic criteria in post-transplant management to tailor therapy and improve outcomes. Therefore, using biopsies carried out for cause <1-yr post-transplant, from an era when C4d staining and microvascular inflammation (MVI) were not clinically utilized, we studied the importance of C4d and MVI on graft survival. Snap-frozen first renal allograft biopsy specimens (done for cause) in the first post-transplant year from 1996 to 2001 were stained/examined for C4d, and pathology re-examined by a separate blinded pathologist. Graft outcomes in patients with and without MVI and/or C4d were compared. Of 128 patients, 39 (30.5%) biopsies were C4d+ and 89 (69.5%) were C4d-; 67 (52.3%) had no MVI (MVI-) while 61 (47.7%) had glomerulitis, peritubular capillaritis, or both (MVI+). There were no significant demographic differences between MVI+ and MVI- patients. A greater proportion of C4d+ biopsies was MVI+ (67%) than MVI- (33%; p = 0.004). C4d positivity had no impact on death-censored graft survival (DCGS). In contrast DCGS was worse in MVI+ than MVI- regardless of presence/absence of C4d (p = 0.005). In biopsies for cause carried out <1-yr post-transplant, MVI is associated with decreased DCGS, independent of the presence of C4d. © 2013 John Wiley & Sons A/S.

Sorting of the Neuroendocrine Secretory Protein Secretogranin II into the Regulated Secretory Pathway

PubMed Central

Courel, Maïté; Vasquez, Michael S.; Hook, Vivian Y.; Mahata, Sushil K.; Taupenot, Laurent

2008-01-01

Secretogranin II (SgII) belongs to the granin family of prohormones widely distributed in dense-core secretory granules (DCGs) of endocrine, neuroendocrine, and neuronal cells, including sympathoadrenal chromaffin cells. The mechanisms by which secretory proteins, and granins in particular, are sorted into the regulated secretory pathway are unsettled. We designed a strategy based on novel chimeric forms of human SgII fused to fluorescent (green fluorescent protein) or chemiluminescent (embryonic alkaline phosphatase) reporters to identify trafficking determinants mediating DCG targeting of SgII in sympathoadrenal cells. Three-dimensional deconvolution fluorescence microscopy and secretagogue-stimulated release studies demonstrate that SgII chimeras are correctly targeted to DCGs and released by exocytosis in PC12 and primary chromaffin cells. Results from a Golgi-retained mutant form of SgII suggest that sorting of SgII into DCGs depends on a saturable sorting machinery at the trans-Golgi/trans-Golgi network. Truncation analyses reveal the presence of DCG-targeting signals within both the N- and C-terminal regions of SgII, with the putative α-helix-containing SgII-(25-41) and SgII-(334-348) acting as sufficient, independent sorting domains. This study defines sequence features of SgII mediating vesicular targeting in sympathoadrenal cells and suggests a mechanism by which discrete domains of the molecule function in sorting, perhaps by virtue of a particular arrangement in tertiary structure and/or interaction with a specific component of the DCG membrane. PMID:18299326

Predicting long-term graft survival in adult kidney transplant recipients.

PubMed

Pinsky, Brett W; Lentine, Krista L; Ercole, Patrick R; Salvalaggio, Paolo R; Burroughs, Thomas E; Schnitzler, Mark A

2012-07-01

The ability to accurately predict a population's long-term survival has important implications for quantifying the benefits of transplantation. To identify a model that can accurately predict a kidney transplant population's long-term graft survival, we retrospectively studied the United Network of Organ Sharing data from 13,111 kidney-only transplants completed in 1988- 1989. Nineteen-year death-censored graft survival (DCGS) projections were calculated and compared with the population's actual graft survival. The projection curves were created using a two-part estimation model that (1) fits a Kaplan-Meier survival curve immediately after transplant (Part A) and (2) uses truncated observational data to model a survival function for long-term projection (Part B). Projection curves were examined using varying amounts of time to fit both parts of the model. The accuracy of the projection curve was determined by examining whether predicted survival fell within the 95% confidence interval for the 19-year Kaplan-Meier survival, and the sample size needed to detect the difference in projected versus observed survival in a clinical trial. The 19-year DCGS was 40.7% (39.8-41.6%). Excellent predictability (41.3%) can be achieved when Part A is fit for three years and Part B is projected using two additional years of data. Using less than five total years of data tended to overestimate the population's long-term survival, accurate prediction of long-term DCGS is possible, but requires attention to the quantity data used in the projection method.

Is prolonged cold ischemia a contraindication to using kidneys from acute kidney injury donors?

PubMed

Orlando, Giuseppe; Khan, Muhammad A; El-Hennawy, Hany; Farney, Alan C; Rogers, Jeffrey; Reeves-Daniel, Amber; Gautreaux, Michael D; Doares, William; Kaczmorski, Scott; Stratta, Robert J

2018-03-01

To determine the impact of prolonged cold ischemia time (CIT) on the outcome of acute kidney injury (AKI) renal grafts, we therefore performed a single-center retrospective analysis in adult patients receiving kidney transplantation (KT) from AKI donors. Outcomes were stratified according to duration of CIT. A total of 118 patients receiving AKI grafts were enrolled. Based on CIT, patients were stratified as follows: (i) <20 hours, 27 patients; (ii) 20-30 hours, 52 patients; (iii) 30-40 hours, 30 patients; (iv) ≥40 hours, nine patients. The overall incidence of delayed graft function DGF was 41.5%. According to increasing CIT category, DGF rates were 30%, 42%, 40%, and 78%, respectively (P = .03). With a mean follow-up of 48 months, overall patient and graft survival rates were 91% and 81%. Death-censored graft survival (DCGS) rates were 84% and 88% for patients with and without DGF (P = NS). DCGS rates were 92% in patients with CIT <20 hours compared to 85% with CIT >20 hours (P = NS). In the nine patients with CIT >40 hours, the 4-year DCGS rate was 100%. We conclude that prolonged CIT in AKI grafts may not adversely influence outcomes and so discard of AKI kidneys because of projected long CIT is not warranted when donors are wisely triaged. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Sorting of the neuroendocrine secretory protein Secretogranin II into the regulated secretory pathway: role of N- and C-terminal alpha-helical domains.

PubMed

Courel, Maïté; Vasquez, Michael S; Hook, Vivian Y; Mahata, Sushil K; Taupenot, Laurent

2008-04-25

Secretogranin II (SgII) belongs to the granin family of prohormones widely distributed in dense-core secretory granules (DCGs) of endocrine, neuroendocrine, and neuronal cells, including sympathoadrenal chromaffin cells. The mechanisms by which secretory proteins, and granins in particular, are sorted into the regulated secretory pathway are unsettled. We designed a strategy based on novel chimeric forms of human SgII fused to fluorescent (green fluorescent protein) or chemiluminescent (embryonic alkaline phosphatase) reporters to identify trafficking determinants mediating DCG targeting of SgII in sympathoadrenal cells. Three-dimensional deconvolution fluorescence microscopy and secretagogue-stimulated release studies demonstrate that SgII chimeras are correctly targeted to DCGs and released by exocytosis in PC12 and primary chromaffin cells. Results from a Golgi-retained mutant form of SgII suggest that sorting of SgII into DCGs depends on a saturable sorting machinery at the trans-Golgi/trans-Golgi network. Truncation analyses reveal the presence of DCG-targeting signals within both the N- and C-terminal regions of SgII, with the putative alpha-helix-containing SgII-(25-41) and SgII-(334-348) acting as sufficient, independent sorting domains. This study defines sequence features of SgII mediating vesicular targeting in sympathoadrenal cells and suggests a mechanism by which discrete domains of the molecule function in sorting, perhaps by virtue of a particular arrangement in tertiary structure and/or interaction with a specific component of the DCG membrane.

Parsing with logical variables (logic-based programming systems)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finin, T.W.; Stone Palmer, M.

1983-01-01

Logic based programming systems have enjoyed an increasing popularity in applied AI work in the last few years. One of the contributions to computational linguistics made by the logic programming paradigm has been the definite clause grammar. In comparing DCGS with previous parsing mechanisms such as ATNS, certain clear advantages are seen. The authors feel that the most important of these advantages are due to the use of logical variables with unification as the fundamental operation on them. To illustrate the power of the logical variable, they have implemented an experimental atn system which treats atn registers as logical variablesmore » and provides a unification operation over them. They aim to simultaneously encourage the use of the powerful mechanisms available in DCGS and demonstrate that some of these techniques can be captured without reference to a resolution theorem prover. 14 references.« less

Search for Minimal and Semi-Minimal Rule Sets in Incremental Learning of Context-Free and Definite Clause Grammars

NASA Astrophysics Data System (ADS)

Imada, Keita; Nakamura, Katsuhiko

This paper describes recent improvements to Synapse system for incremental learning of general context-free grammars (CFGs) and definite clause grammars (DCGs) from positive and negative sample strings. An important feature of our approach is incremental learning, which is realized by a rule generation mechanism called “bridging” based on bottom-up parsing for positive samples and the search for rule sets. The sizes of rule sets and the computation time depend on the search strategies. In addition to the global search for synthesizing minimal rule sets and serial search, another method for synthesizing semi-optimum rule sets, we incorporate beam search to the system for synthesizing semi-minimal rule sets. The paper shows several experimental results on learning CFGs and DCGs, and we analyze the sizes of rule sets and the computation time.

ESD protection design for advanced CMOS

NASA Astrophysics Data System (ADS)

Huang, Jin B.; Wang, Gewen

2001-10-01

ESD effects in integrated circuits have become a major concern as today's technologies shrink to sub-micron/deep- sub-micron dimensions. The thinner gate oxide and shallower junction depth used in the advanced technologies make them very vulnerable to ESD damages. The advanced techniques like silicidation and STI (shallow trench insulation) used for improving other device performances make ESD design even more challenging. For non-silicided technologies, a certain DCGS (drain contact to gate edge spacing) is needed to achieve ESD hardness for nMOS output drivers and nMOS protection transistors. The typical DCGS values are 4-5um and 2-3um for 0.5um and 0.25um CMOS, respectively. The silicidation reduces the ballast resistance provided by DCGS with at least a factor of 10. As a result, scaling of the ESD performance with device width is lost and even zero ESD performance is reported for standard silicided devices. The device level ESD design is focused in this paper, which includes GGNMOS (gate grounded NMOS) and GCNMOS (gate coupled NMOS). The device level ESD testing including TLP (transmission line pulse) is given. Several ESD issues caused by advanced technologies have been pointed out. The possible solutions have been developed and summarized including silicide blocking, process optimization, back-end ballasting, and new protection scheme, dummy gate/n-well resistor ballsting, etc. Some of them require process cost increase, and others provide novel, compact, and simple design but involving royalty/IP (intellectual property) issue. Circuit level ESD design and layout design considerations are covered. The top-level ESD protection strategies are also given.

Effect of HCV, HIV and coinfection in kidney transplant recipients: mate kidney analyses.

PubMed

Xia, Y; Friedmann, P; Yaffe, H; Phair, J; Gupta, A; Kayler, L K

2014-09-01

Reports of kidney transplantation (KTX) in recipients with hepatitis C virus (HCV+), human immunodeficiency virus (HIV+) or coinfection often do not provide adequate adjustment for donor risk factors. We evaluated paired deceased-donor kidneys (derived from the same donor transplanted to different recipients) in which one kidney was transplanted into a patient with viral infection (HCV+, n = 1700; HIV+, n = 243) and the other transplanted into a recipient without infection (HCV- n = 1700; HIV- n = 243) using Scientific Registry of Transplant Recipients data between 2000 and 2013. On multivariable analysis (adjusted for recipient risk factors), HCV+ conferred increased risks of death-censored graft survival (DCGS) (adjusted hazard ratio [aHR] 1.24, 95% confidence interval [CI] 1.04-1.47) and patient survival (aHR 1.24, 95% CI 1.06-1.45) compared with HCV-. HIV+ conferred similar DCGS (aHR 0.85, 95% CI 0.48-1.51) and patient survival (aHR 0.80, 95% CI 0.39-1.64) compared with HIV-. HCV coinfection was a significant independent risk factor for DCGS (aHR 2.33; 95% CI 1.06, 5.12) and patient survival (aHR 2.88; 95% CI 1.35, 6.12). On multivariable analysis, 1-year acute rejection was not associated with HCV+, HIV+ or coinfection. Whereas KTX in HIV+ recipients were associated with similar outcomes relative to noninfected recipients, HCV monoinfection and, to a greater extent, coinfection were associated with poor patient and graft survival. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

Outcomes following Kidney transplantation in IgA nephropathy: a UNOS/OPTN analysis.

PubMed

Kadiyala, Aditya; Mathew, Anna T; Sachdeva, Mala; Sison, Cristina P; Shah, Hitesh H; Fishbane, Steven; Jhaveri, Kenar D

2015-10-01

This study updates assessment of post-transplant outcomes in IgAN patients in the modern era of immunosuppression. Using UNOS/OPTN data, patients ≥18 yr of age with first kidney transplant (1/1/1999 to 12/31/2008) were analyzed. Multivariable Cox regression models and propensity score-based matching techniques were used to estimate hazard ratios (HRs) for death-censored allograft survival (DCGS) and patient survival in IgAN compared to non-IgAN. Results of multivariable regression were stratified by donor type (living vs. deceased). A total of 107, 747 recipients were included (4589 with IgAN and 103 158 with non-IgAN). Adjusted HR for DCGS showed no significant difference between IgAN and non-IgAN. IgAN had higher patient survival compared to non-IgAN (HR 0.54, 95% CI 0.47-0.62, p < 0.0001 for deceased donors; HR 0.42, 95% CI 0.33-0.54, p < 0.0001 for living donors). Propensity score-matched analysis was similar, with no significant difference in DCGS between matched groups and higher patient survival in IgAN patients compared to non-IgAN group (HR 0.54, 95% CI 0.47, 0.63; p-value <0.0001). IgAN patients with first kidney transplant have superior patient survival and similar graft survival compared to non-IgAN recipients. Results can be used in prognostication and informed decision-making about kidney transplantation in patients with IgAN. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers.

PubMed

Bing, Feng; Zhao, Yu

2016-01-01

To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan-Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20) and poor (such as ARID4A) prognoses following chemotherapy. Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A) in breast cancer patients.

Bacteria at glacier surfaces: microbial community structures in debris covered glaciers and cryoconites in the Italian Alps

NASA Astrophysics Data System (ADS)

Azzoni, Roberto; Franzetti, Andrea; Ambrosini, Roberto; D'Agata, Carlo; Senese, Antonella; Minora, Umberto; Tagliaferri, Ilario; Diolaiuti, Guglielmina

2014-05-01

Supraglacial debris has an important role in the glacier energy budget and has strong influence on the glacial ecosystem. Sediment derives generally from rock inputs from nesting rockwalls and are abundant and continuous at the surface of debris-covered glaciers (i.e. DCGs; glaciers where the ablation area is mainly covered by rock debris) and sparse and fine on debris-free glaciers (DFGs). Recently, evidence for significant tongue darkening on retreating debris-free glaciers has been drawing increasing attention. Fine particles, the cryoconite, are locally abundant and may form cryoconite holes that are water-filled depressions on the surface of DFGs that form when a thin layer of cryoconite is heated by the sun and melts the underlying ice. There is increasing evidence that cryoconite holes also host highly diverse microbial communities and can significantly contribute to global carbon cycle. However, there is almost no study on microbial communities of the debris cover of DCGs and there is a lack of data from the temporal evolution of the microbial communities in the cryoconites. To fill these gaps in our knowledge we characterized the supraglacial debris of two Italian DCGs and we investigated the temporal evolution of microbial communities on cryoconite holes in DFG. We used the Illumina technology to analyse the V5 and V6 hypervariable regions of the bacterial 16S rRNA gene amplified from samples collected distances from the terminus of two DCGs (Miage and Belvedere Glaciers - Western Italian Alps). Heterotrophic taxa dominated bacterial communities, whose structure changed during downwards debris transport. Organic carbon of these recently exposed substrates therefore is probably provided more by allochthonous deposition of organic matter than by primary production by autotrophic organisms. We used ARISA fingerprinting and quantitative PCR to describe the structure and the evolution of the microbial communities and to estimate the number of the total bacteria and the copy of Rubisco genes found on cryoconite holes collected on a wide Italian DFG (Forni Glacier - Central Alps). The structure of the microbial communities in cryoconite holes seem to be determined mainly by a turnover process. This work was carried out under the umbrella of the SHARE Stelvio Project which has been funded by the Lombardy Region government and managed by FLA (Lombardy Foundation for the Enviroment) and EvK2-CNR Committee.

THE TOXICITY OF INDIUM

DOE Office of Scientific and Technical Information (OSTI.GOV)

Downs, W.L.; Scott, J.K.; Steadman, L.T.

1959-09-16

Data are presented on the toxic effects of indium, administered as a chloride (InCl/sub 3/) or as an oxide (In/sub 2/O/sub 3/), in rats, rabbits, and dcgs. Data are included on the tissue distribution and excretion of indium-114. (C.H.)

Comparing self-reported health status and diagnosis-based risk adjustment to predict 1- and 2 to 5-year mortality.

PubMed

Pietz, Kenneth; Petersen, Laura A

2007-04-01

To compare the ability of two diagnosis-based risk adjustment systems and health self-report to predict short- and long-term mortality. Data were obtained from the Department of Veterans Affairs (VA) administrative databases. The study population was 78,164 VA beneficiaries at eight medical centers during fiscal year (FY) 1998, 35,337 of whom completed an 36-Item Short Form Health Survey for veterans (SF-36V) survey. We tested the ability of Diagnostic Cost Groups (DCGs), Adjusted Clinical Groups (ACGs), SF-36V Physical Component score (PCS) and Mental Component Score (MCS), and eight SF-36V scales to predict 1- and 2-5 year all-cause mortality. The additional predictive value of adding PCS and MCS to ACGs and DCGs was also evaluated. Logistic regression models were compared using Akaike's information criterion, the c-statistic, and the Hosmer-Lemeshow test. The c-statistics for the eight scales combined with age and gender were 0.766 for 1-year mortality and 0.771 for 2-5-year mortality. For DCGs with age and gender the c-statistics for 1- and 2-5-year mortality were 0.778 and 0.771, respectively. Adding PCS and MCS to the DCG model increased the c-statistics to 0.798 for 1-year and 0.784 for 2-5-year mortality. The DCG model showed slightly better performance than the eight-scale model in predicting 1-year mortality, but the two models showed similar performance for 2-5-year mortality. Health self-report may add health risk information in addition to age, gender, and diagnosis for predicting longer-term mortality.

Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof of principle study with colorectal cancer

PubMed Central

Tang, Jie; Li, Yaping; Lyon, Kenneth; Camps, Jordi; Dalton, Stephen; Ried, Thomas; Zhao, Shaying

2014-01-01

Herein we report a proof of principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver–passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human- and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, while PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A, and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals. PMID:23416983

Intranasal anatomy of the nasolacrimal sac in endoscopic dacryocystorhinostomy.

PubMed

Wormald, P J; Kew, J; Van Hasselt, A

2000-09-01

Intranasal surface anatomy is fundamental to the technique of endoscopic dacryocystorhinostomy. In the current literature the lacrimal sac is described as being situated anterior to the anterior end of the middle turbinate with between 0% and 20% of the sac above the insertion of the middle turbinate on the lateral nasal wall (the axilla of the middle turbinate). The aim of this study was to use CT dacryocystograms (DCGs) and CT scans to establish the relationship of the lacrimal sac to the lateral nasal wall. Forty-seven individual lacrimal sacs were measured in relation to the common canaliculus, and 76 were measured in relation to the insertion of the middle turbinate. Measurements taken from the long axis of the sac showed the mean height of the sac above the middle turbinate insertion was 8.8 mm (SD = 0.2, 95% CI = 1.3) and below it was 4.1 mm (SD = 2.3, 95% CI = 1.1). The average measurement of the sac above the com-mon canaliculus on CT DCGs was 5.3 mm (SD = 1.7, 95% CI = 0.56), whereas the average measurement below the common canaliculus was 7.7 mm (SD = 2, 95% CI = 1.3) (n = 47 CT DCGs). The findings in this study show that a major portion of the sac is locat-ed above the insertion of the anterior end of the middle turbinate and, in addition, that a significant part of the sac lies above the entry point of the common canaliculus. Knowledge of these findings can ensure that the sac is adequately exposed during dacryocystorhinostomy by removal of sufficient bone and mucosa above the anterior insertion of the middle turbinate.

Comparing Self-Reported Health Status and Diagnosis-Based Risk Adjustment to Predict 1- and 2 to 5-Year Mortality

PubMed Central

Pietz, Kenneth; Petersen, Laura A

2007-01-01

Objectives To compare the ability of two diagnosis-based risk adjustment systems and health self-report to predict short- and long-term mortality. Data Sources/Study Setting Data were obtained from the Department of Veterans Affairs (VA) administrative databases. The study population was 78,164 VA beneficiaries at eight medical centers during fiscal year (FY) 1998, 35,337 of whom completed an 36-Item Short Form Health Survey for veterans (SF-36V) survey. Study Design We tested the ability of Diagnostic Cost Groups (DCGs), Adjusted Clinical Groups (ACGs), SF-36V Physical Component score (PCS) and Mental Component Score (MCS), and eight SF-36V scales to predict 1- and 2–5 year all-cause mortality. The additional predictive value of adding PCS and MCS to ACGs and DCGs was also evaluated. Logistic regression models were compared using Akaike's information criterion, the c-statistic, and the Hosmer–Lemeshow test. Principal Findings The c-statistics for the eight scales combined with age and gender were 0.766 for 1-year mortality and 0.771 for 2–5-year mortality. For DCGs with age and gender the c-statistics for 1- and 2–5-year mortality were 0.778 and 0.771, respectively. Adding PCS and MCS to the DCG model increased the c-statistics to 0.798 for 1-year and 0.784 for 2–5-year mortality. Conclusions The DCG model showed slightly better performance than the eight-scale model in predicting 1-year mortality, but the two models showed similar performance for 2–5-year mortality. Health self-report may add health risk information in addition to age, gender, and diagnosis for predicting longer-term mortality. PMID:17362210

Influence of delayed graft function and acute rejection on outcomes after kidney transplantation from donors after cardiac death.

PubMed

Nagaraja, Pramod; Roberts, Gareth W; Stephens, Michael; Horvath, Szabolcs; Fialova, Jana; Chavez, Rafael; Asderakis, Argiris; Kaposztas, Zsolt

2012-12-27

Delayed graft function (DGF) and acute rejection (AR) exert an adverse impact on graft outcomes after kidney transplantation using organs from donation after brain-stem death (DBD) donors. Here, we examine the impact of DGF and AR on graft survival in kidney transplants using organs from donation after cardiac death (DCD) donors. We conducted a single-center retrospective study of DCD and DBD donor kidney transplants. We compared 1- and 4-year graft and patient survival rates, as well as death-censored graft survival (DCGS) rates, between the two groups using univariate analysis, and the impact of DGF and AR on graft function was compared using multivariate analysis. Eighty DCD and 206 DBD donor transplants were analyzed. Median follow-up was 4.5 years. The incidence of DGF was higher among DCD recipients (73% vs. 27%, P<0.001), and AR was higher among DBD recipients (23% vs. 9%, P<0.001). One-year and 4-year graft survival rates were similar (DCD 94% and 79% vs. DBD 90% and 82%). Among recipients with DGF, the 4-year DCGS rate was better for DCD recipients compared with DBD recipients (100% vs. 92%, P=0.04). Neither DGF nor AR affected the 1-year graft survival rate in DCD recipients, whereas in DBD recipients, the 1-year graft survival rate was worse in the presence of DGF (88% vs. 96%, P=0.04) and the 4-year DCGS rate was worse in the presence of AR (88% vs. 96%, P=0.04). Despite the high incidence of DGF, medium-term outcomes of DCD kidney transplants are comparable to those from DBD transplants. Short-term graft survival from DCD transplants is not adversely influenced by DGF and AR, unlike in DBD transplants.

Early Outcomes of the New UK Deceased Donor Kidney Fast-Track Offering Scheme.

PubMed

Callaghan, Chris J; Mumford, Lisa; Pankhurst, Laura; Baker, Richard J; Bradley, J Andrew; Watson, Christopher J E

2017-12-01

The UK Kidney Fast-Track Scheme (KFTS) was introduced in 2012 to identify kidneys at high risk of discard and to rapidly facilitate transplantation. A retrospective analysis of kidneys transplanted through the KFTS was undertaken. UK Transplant Registry data were collected on deceased donor kidneys implanted between November 1, 2012, and April 30, 2015, (donation after brain death [DBD] donors) and March 1, 2013, and April 30, 2015 (donation after circulatory death [DCD] donors). Posttransplant outcomes included 1-year estimated glomerular filtration rate and death-censored graft survival (DCGS). Over the study period, 523 deceased donor kidneys were transplanted through the KFTS and 4174 via the standard National Kidney Allocation Scheme (NKAS). Kidneys in the KFTS were more likely to be from older diabetic donors, had a higher frequency of poor ex vivo perfusion, had longer cold ischemic times, and were transplanted into older recipients. One-year DCGS of KFTS and NKAS DBD donor kidneys was similar (94% vs 95%; P = 0.70), but for DCD donor kidneys, DCGS was lower in those allocated via the KFTS (91% versus 95%; P = 0.04). Median 1-year estimated glomerular filtration rate for DBD donor kidneys was lower in those allocated via the KFTS (49 vs 52 mL/min per 1.73 m; P = 0.01), but for DCD kidneys, there was no difference (45 vs 48 mL/min per 1.73 m; P = 0.10). Although KFTS kidneys have less favorable donor, graft, and recipient risk factors than NKAS kidneys, short-term graft and patient outcomes are acceptable. National schemes that identify and rapidly offer kidneys at high risk of discard may contribute to minimizing the unnecessary discard of organs.

Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers

PubMed Central

Bing, Feng; Zhao, Yu

2016-01-01

Objective To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Methods Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan–Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. Results A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20) and poor (such as ARID4A) prognoses following chemotherapy. Conclusion Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A) in breast cancer patients. PMID:27217777

Analysis of differentially co-expressed genes based on microarray data of hepatocellular carcinoma.

PubMed

Wang, Y; Jiang, T; Li, Z; Lu, L; Zhang, R; Zhang, D; Wang, X; Tan, J

2017-01-01

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide. Although great progress in diagnosis and management of HCC have been made, the exact molecular mechanisms remain poorly understood. The study aims to identify potential biomarkers for HCC progression, mainly at transcription level. In this study, chip data GSE 29721 was utilized, which contains 10 HCC samples and 10 normal adjacent tissue samples. Differentially expressed genes (DEGs) between two sample types were selected by t-test method. Following, the differentially co-expressed genes (DCGs) and differentially co-expressed Links (DCLs) were identified by DCGL package in R with the threshold of q < 0.25. Afterwards, pathway enrichment analysis of the DCGs was carried out by DAVID. Then, DCLs were mapped to TRANSFAC database to reveal associations between relevant transcriptional factors (TFs) and their target genes. Quantitative real-time RT-PCR was performed for TFs or genes of interest. As a result, a total of 388 DCGs and 35,771 DCLs were obtained. The predominant pathways enriched by these genes were Cytokine-cytokine receptor interaction, ECM-receptor interaction and TGF-β signaling pathway. Three TF-target interactions, LEF1-NCAM1, EGR1-FN1 and FOS-MT2A were predicted. Compared with control, expressions of the TF genes EGR1, FOS and ETS2 were all up-regulated in the HCC cell line, HepG2; while LEF1 was down-regulated. Except NCAM1, all the target genes were up-regulated in HepG2. Our findings suggest these TFs and genes might play important roles in the pathogenesis of HCC and may be used as therapeutic targets for HCC management.

The severity of acute cellular rejection defined by Banff classification is associated with kidney allograft outcomes.

PubMed

Wu, Kaiyin; Budde, Klemens; Lu, Huber; Schmidt, Danilo; Liefeldt, Lutz; Glander, Petra; Neumayer, Hans Helmut; Rudolph, Birgit

2014-06-15

It is unclear if the severity or the timing of acute cellular rejection (ACR) defined by Banff classification 2009 is associated with graft survival. Borderline changes, TCMR I (interstitial rejection), and TCMR II/III (vascular rejection) were defined as low, moderate, and high ACR severity, respectively. Approximately 270 patients who had at least one episode of ACR were enrolled, 270 biopsies were chosen which showed the highest ACR severity of each patient and were negative for donor-specific antibodies (DSA), C4d, and microcirculation changes (MC). Six months were used as the cutoff to define early and late ACR; 370 patients without biopsy posttransplantation were recruited in the control group. Up to 8-year posttransplantation, death-censored graft survival (DCGS) rates of control, borderline, TCMR I, and TCMR II/III groups were 97.6%, 93.3%, 79.6%, and 73.6% (log rank test, P<0.001); the control group had significantly higher DCGS rate than the three ACR groups (each pairwise comparison yields P<0.05). The DCGS rate of late ACR was significantly lower compared with early ACR (63.6% vs. 87.4%, P<0.001). Intimal arteritis (Banff v-lesion) was an independent histologic risk factor correlated with long-term graft loss regardless of the timing of ACR. The v-lesions with minimal or high-grade tubulitis displayed similar graft survival (72.7% vs. 72.9%, P=0.96). All types of ACR affect long-term graft survival. Vascular or late ACR predict poorer graft survival; the extent of tubulointerstitial inflammation (TI) is of no prognostic significance for vascular rejection.

Exploring Transcription Factors-microRNAs Co-regulation Networks in Schizophrenia.

PubMed

Xu, Yong; Yue, Weihua; Yao Shugart, Yin; Li, Sheng; Cai, Lei; Li, Qiang; Cheng, Zaohuo; Wang, Guoqiang; Zhou, Zhenhe; Jin, Chunhui; Yuan, Jianmin; Tian, Lin; Wang, Jun; Zhang, Kai; Zhang, Kerang; Liu, Sha; Song, Yuqing; Zhang, Fuquan

2016-07-01

Transcriptional factors (TFs) and microRNAs (miRNAs) have been recognized as 2 classes of principal gene regulators that may be responsible for genome coexpression changes observed in schizophrenia (SZ). This study aims to (1) identify differentially coexpressed genes (DCGs) in 3 mRNA expression microarray datasets; (2) explore potential interactions among the DCGs, and differentially expressed miRNAs identified in our dataset composed of early-onset SZ patients and healthy controls; (3) validate expression levels of some key transcripts; and (4) explore the druggability of DCGs using the curated database. We detected a differential coexpression network associated with SZ and found that 9 out of the 12 regulators were replicated in either of the 2 other datasets. Leveraging the differentially expressed miRNAs identified in our previous dataset, we constructed a miRNA-TF-gene network relevant to SZ, including an EGR1-miR-124-3p-SKIL feed-forward loop. Our real-time quantitative PCR analysis indicated the overexpression of miR-124-3p, the under expression of SKIL and EGR1 in the blood of SZ patients compared with controls, and the direction of change of miR-124-3p and SKIL mRNA levels in SZ cases were reversed after a 12-week treatment cycle. Our druggability analysis revealed that many of these genes have the potential to be drug targets. Together, our results suggest that coexpression network abnormalities driven by combinatorial and interactive action from TFs and miRNAs may contribute to the development of SZ and be relevant to the clinical treatment of the disease. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Cancer driver-passenger distinction via sporadic human and dog cancer comparison: a proof-of-principle study with colorectal cancer.

PubMed

Tang, J; Li, Y; Lyon, K; Camps, J; Dalton, S; Ried, T; Zhao, S

2014-02-13

Herein we report a proof-of-principle study illustrating a novel dog-human comparison strategy that addresses a central aim of cancer research, namely cancer driver-passenger distinction. We previously demonstrated that sporadic canine colorectal cancers (CRCs) share similar molecular pathogenesis mechanisms as their human counterparts. In this study, we compared the genome-wide copy number abnormalities between 29 human and 10 canine sporadic CRCs. This led to the identification of 73 driver candidate genes (DCGs), altered in both species, and with 27 from the whole genome and 46 from dog-human genomic rearrangement breakpoint (GRB) regions, as well as 38 passenger candidate genes (PCGs), altered in humans only and located in GRB regions. We noted that DCGs significantly differ from PCGs in every analysis conducted to assess their cancer relevance and biological functions. Importantly, although PCGs are not enriched in any specific functions, DCGs possess significantly enhanced functionality closely associated with cell proliferation and death regulation, as well as with epithelial cell apicobasal polarity establishment/maintenance. These observations support the notion that, in sporadic CRCs of both species, cell polarity genes not only contribute in preventing cancer cell invasion and spreading, but also likely serve as tumor suppressors by modulating cell growth. This pilot study validates our novel strategy and has uncovered four new potential cell polarity and colorectal tumor suppressor genes (RASA3, NUPL1, DENND5A and AVL9). Expansion of this study would make more driver-passenger distinctions for cancers with large genomic amplifications or deletions, and address key questions regarding the relationship between cancer pathogenesis and epithelial cell polarity control in mammals.

Exploring Transcription Factors-microRNAs Co-regulation Networks in Schizophrenia

PubMed Central

Xu, Yong; Yue, Weihua; Yao Shugart, Yin; Li, Sheng; Cai, Lei; Li, Qiang; Cheng, Zaohuo; Wang, Guoqiang; Zhou, Zhenhe; Jin, Chunhui; Yuan, Jianmin; Tian, Lin; Wang, Jun; Zhang, Kai; Zhang, Kerang; Liu, Sha; Song, Yuqing; Zhang, Fuquan

2016-01-01

Background: Transcriptional factors (TFs) and microRNAs (miRNAs) have been recognized as 2 classes of principal gene regulators that may be responsible for genome coexpression changes observed in schizophrenia (SZ). Methods: This study aims to (1) identify differentially coexpressed genes (DCGs) in 3 mRNA expression microarray datasets; (2) explore potential interactions among the DCGs, and differentially expressed miRNAs identified in our dataset composed of early-onset SZ patients and healthy controls; (3) validate expression levels of some key transcripts; and (4) explore the druggability of DCGs using the curated database. Results: We detected a differential coexpression network associated with SZ and found that 9 out of the 12 regulators were replicated in either of the 2 other datasets. Leveraging the differentially expressed miRNAs identified in our previous dataset, we constructed a miRNA–TF–gene network relevant to SZ, including an EGR1–miR-124-3p–SKIL feed-forward loop. Our real-time quantitative PCR analysis indicated the overexpression of miR-124-3p, the under expression of SKIL and EGR1 in the blood of SZ patients compared with controls, and the direction of change of miR-124-3p and SKIL mRNA levels in SZ cases were reversed after a 12-week treatment cycle. Our druggability analysis revealed that many of these genes have the potential to be drug targets. Conclusions: Together, our results suggest that coexpression network abnormalities driven by combinatorial and interactive action from TFs and miRNAs may contribute to the development of SZ and be relevant to the clinical treatment of the disease. PMID:26609121

USAF Posture Statement 2013

DTIC Science & Technology

2013-04-12

request maintains investments in the DCGS, the MQ-1 Predator, the RC-135 Rivet Joint, the RQ-4 Global Hawk Block 40, and U-2 programs, and makes internal... electromagnetic jamming. Our potential adversaries are also making advances by electronically linking their own combat capabilities, creating new military

Environmental Assessment Distributed Common Ground System (DCGS) Operations Facility, Beale Air Force Base, California

DTIC Science & Technology

2014-07-01

The following prehistory and history of Beale AFB has been excerpted from the Beale AFB Integrated Cultural Resource Management Plan (ICRMP) (U.S...during all of the defined prehistoric phases. The prevailing trend in the prehistory of the region is from small, highly mobile hunter-gatherer

Analysis of a mutant exhibiting conditional sorting to dense core secretory granules in Tetrahymena thermophila.

PubMed

Bowman, G R; Turkewitz, A P

2001-12-01

The formation of dense core granules (DCGs) requires both the sorting of granule contents from other secretory proteins and a postsorting maturation process. The Tetrahymena thermophila strain SB281 fails to synthesize DCGs, and previous analysis suggested that the defect lay at or near the sorting step. Because this strain represents one of the very few mutants in this pathway, we have undertaken a more complete study of the phenotype. Genetic epistasis analysis places the defect upstream of those in two other characterized Tetrahymena mutants. Using immunofluorescent detection of granule content proteins, as well as GFP tagging, we describe a novel cytoplasmic compartment to which granule contents can be sorted in growing SB281 cells. Cell fusion experiments indicate that this compartment is not a biosynthetic intermediate in DCG synthesis. Sorting in SB281 is strongly conditional with respect to growth. When cells are starved, the storage compartment is degraded and de novo synthesized granule proteins are rapidly secreted. The mutation in SB281 therefore appears to affect DCG synthesis at the level of both sorting and maturation.

Analysis of a mutant exhibiting conditional sorting to dense core secretory granules in Tetrahymena thermophila.

PubMed Central

Bowman, G R; Turkewitz, A P

2001-01-01

The formation of dense core granules (DCGs) requires both the sorting of granule contents from other secretory proteins and a postsorting maturation process. The Tetrahymena thermophila strain SB281 fails to synthesize DCGs, and previous analysis suggested that the defect lay at or near the sorting step. Because this strain represents one of the very few mutants in this pathway, we have undertaken a more complete study of the phenotype. Genetic epistasis analysis places the defect upstream of those in two other characterized Tetrahymena mutants. Using immunofluorescent detection of granule content proteins, as well as GFP tagging, we describe a novel cytoplasmic compartment to which granule contents can be sorted in growing SB281 cells. Cell fusion experiments indicate that this compartment is not a biosynthetic intermediate in DCG synthesis. Sorting in SB281 is strongly conditional with respect to growth. When cells are starved, the storage compartment is degraded and de novo synthesized granule proteins are rapidly secreted. The mutation in SB281 therefore appears to affect DCG synthesis at the level of both sorting and maturation. PMID:11779800

Hazelwood Interim Storage Site: Annual site environment report, Calendar year 1985

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1986-11-01

The Hazelwood Interim Storage Site (HISS) is presently used for the storage of low-level radioactively contaminated soils. Monitoring results show that the HISS is in compliance with DOE Derived Concentration Guides (DCGs) and radiation protection standards. During 1985, annual average radon concentrations ranged from 10 to 23% of the DCG. The highest external dose rate at the HISS was 287 mrem/yr. The measured background dose rate for the HISS area is 99 mrem/yr. The highest average annual concentration of uranium in surface water monitored in the vicinity of the HISS was 0.7% of the DOE DCG; for /sup 226/Ra itmore » was 0.3% of the applicable DCG, and for /sup 230/Th it was 1.7%. In groundwater, the highest annual average concentration of uranium was 12% of the DCG; for /sup 226/Ra it was 3.6% of the applicable DCG, and for /sup 230/Th it was 1.8%. While there are no concentration guides for stream sediments, the highest concentration of total uranium was 19 pCi/g, the highest concentration of /sup 226/Ra was 4 pCi/g, and the highest concentration of /sup 230/Th was 300 pCi/g. Radon concentrations, external gamma dose rates, and radionuclide concentrations in groundwater at the site were lower than those measured in 1984; radionuclide concentrations in surface water were roughly equivalent to 1984 levels. For sediments, a meaningful comparison with 1984 concentrations cannot be made since samples were obtained at only two locations and were only analyzed for /sup 230/Th. The calculated radiation dose to the maximally exposed individual at the HISS, considering several exposure pathways, was 5.4 mrem, which is 5% of the radiation protection standard.« less

New evidence for geothermal controls upon recent basal melting of mid-latitude glaciers on Mars

NASA Astrophysics Data System (ADS)

Butcher, Frances; Gallagher, Colman; Arnold, Neil; Balme, Matthew; Conway, Susan; Lewis, Stephen; Hagerman, Axel

2017-04-01

Diagnostic evidence for past melting of putative debris-covered glaciers (DCGs) in Mars' mid-latitudes [e.g. 1-2] is extremely rare. As such, it is widely believed that these DCGs have been perennially frozen to their beds in cold-based thermal regimes [e.g. 3] since their formation 40 Ma to 1 Ga [4-8]. Here, we present a geomorphic map and propose a landsystem model that challenges this paradigm. We identify a sinuous ridge emerging from the terminus of a DCG in the broad rift zone NE of the Tharsis volcanic province. We interpret this ridge as an esker formed by deposition of sediment within a subglacial meltwater conduit. This is only the second esker-like ridge to be identified in association with a mid-latitude DCG. Recent work [9] identified a complex of esker-like ridges on the foreland of an extant DCG in Phlegra Montes, for which high-resolution analysis is ongoing [10]. Significantly, both candidate eskers are located within graben. Graben are topographic troughs formed by crustal extension and are commonly associated with elevated geothermal heat flux [e.g. 11]. A paucity of meltwater morphologies associated with DCGs elsewhere in Mars' mid-latitudes implies that atmospheric warming alone was insufficient for widespread basal melting. We argue that, during deglaciation, atmospheric warming supplemented enhanced geothermal heat flux within graben such that the basal temperature threshold for basal melting of DCGs was surpassed in these locations [9]. This has implications for the search for recent life on Mars, as it helps constrain the likely regions of recent meltwater production within protected subglacial environments. As eskers are exposed relicts of subglacial drainage systems, they are accessible to landed missions without the high-risk requirement to drill through remnant decametre-thick debris-mantled ice. FEGB is funded by STFC grant ST/N50421X/1 [1] Head, J.W. et al. (2010), Earth Planet. Sc. Lett. 294, 306-320. [2] Levy, J.S. et al. (2014), J. Geophys. Res. Planets 119, 2188-2196. [3] Marchant, D.R., and Head, J.W. (2007), Icarus 192, 187-222. [4] Baker, D.M.H. et al. (2010), Icarus 207, 186-209 [5] Hartmann, W.K. et al. (2014) Icarus 228, 96-120. [6] Levy, J.S. et al. (2007), J. Geophys. Res. Planets 112, E08004. [7] Berman, D.C., et al. (2012), LPSC XLIII, Abstract #1593. [8] Baker, D.M.H. and Head, J.W. (2015), Icarus 260, 269-288. [9] Gallagher, C., and Balme, M.R. (2015), Earth Planet Sc. Lett. 431, 96-109. [10] Butcher, F.E.G. et al. (2016), LPSC XLVIII, Abstract #1238 [11] Meixner, J. et al. (2016), J. Struct. Geol. 82, 1-15.

Creative Design of Digital Cognitive Games: Application of Cognitive Toys and Isomorphism

ERIC Educational Resources Information Center

Sedig, Kamran; Haworth, Robert

2012-01-01

Digital cognitive games (DCGs) are games whose primary purpose is to mediate (i.e., support, develop, and enhance) cognitive activities such as problem solving, decision making, planning, and critical reasoning. As these games increase in popularity and usage, more attention should be paid to their design. Currently, there is a lack of design…

Environmental Assessment for Construction of the Distributed Common Ground Station (DCGS) at Langley Air Force Base, Virginia

DTIC Science & Technology

2007-03-01

located in the north-central part of the base and includes the areas occupied by the golf course clubhouse , maintenance building, and the driving range...foreseeable future actions regardless of what agency or person undertakes such other actions” (40 CFR 1508.7). Recent CEQ guidance in Considering

Secretagogue-triggered Transfer of Membrane Proteins from Neuroendocrine Secretory Granules to Synaptic-like Microvesicles

PubMed Central

Strasser, Jane E.; Arribas, Monica; Blagoveshchenskaya, Anastasia D.; Cutler, Daniel F.

1999-01-01

The membrane proteins of all regulated secretory organelles (RSOs) recycle after exocytosis. However, the recycling of those membrane proteins that are targeted to both dense core granules (DCGs) and synaptic-like microvesicles (SLMVs) has not been addressed. Since neuroendocrine cells contain both RSOs, and the recycling routes that lead to either organelle overlap, transfer between the two pools of membrane proteins could occur during recycling. We have previously demonstrated that a chimeric protein containing the cytosolic and transmembrane domains of P-selectin coupled to horseradish peroxidase is targeted to both the DCG and the SLMV in PC12 cells. Using this chimera, we have characterized secretagogue-induced traffic in PC12 cells. After stimulation, this chimeric protein traffics from DCGs to the cell surface, internalizes into transferrin receptor (TFnR)-positive endosomes and thence to a population of secretagogue-responsive SLMVs. We therefore find a secretagogue-dependent rise in levels of HRP within SLMVs. In addition, the levels within SLMVs of the endogenous membrane protein, synaptotagmin, as well as a green fluorescent protein-tagged version of vesicle-associated membrane protein (VAMP)/synaptobrevin, also show a secretagogue-dependent increase. PMID:10436017

Differential Connectivity in Colorectal Cancer Gene Expression Network

PubMed

Izadi, Fereshteh

2018-05-30

Colorectal cancer (CRC) is one of the challenging types of cancers; thus, exploring effective biomarkers related to colorectal could lead to significant progresses toward the treatment of this disease. In the present study, CRC gene expression datasets have been reanalyzed. Mutual differentially expressed genes across 294 normal mucosa and adjacent tumoral samples were then utilized in order to build two independent transcriptional regulatory networks. By analyzing the networks topologically, genes with differential global connectivity related to cancer state were determined for which the potential transcriptional regulators including transcription factors were identified. The majority of differentially connected genes (DCGs) were up-regulated in colorectal transcriptome experiments. Moreover, a number of these genes have been experimentally validated as cancer or CRC-associated genes. The DCGs, including GART, TGFB1, ITGA2, SLC16A5, SOX9, and MMP7, were investigated across 12 cancer types. Functional enrichment analysis followed by detailed data mining exhibited that these candidate genes could be related to CRC by mediating in metastatic cascade in addition to shared pathways with 12 cancer types by triggering the inflammatory events Our study uncovered correlated alterations in gene expression related to CRC susceptibility and progression that the potent candidate biomarkers could provide a link to disease.

Performance of comorbidity, risk adjustment, and functional status measures in expenditure prediction for patients with diabetes.

PubMed

Maciejewski, Matthew L; Liu, Chuan-Fen; Fihn, Stephan D

2009-01-01

To compare the ability of generic comorbidity and risk adjustment measures, a diabetes-specific measure, and a self-reported functional status measure to explain variation in health care expenditures for individuals with diabetes. This study included a retrospective cohort of 3,092 diabetic veterans participating in a multisite trial. Two comorbidity measures, four risk adjusters, a functional status measure, a diabetes complication count, and baseline expenditures were constructed from administrative and survey data. Outpatient, inpatient, and total expenditure models were estimated using ordinary least squares regression. Adjusted R(2) statistics and predictive ratios were compared across measures to assess overall explanatory power and explanatory power of low- and high-cost subgroups. Administrative data-based risk adjusters performed better than the comorbidity, functional status, and diabetes-specific measures in all expenditure models. The diagnostic cost groups (DCGs) measure had the greatest predictive power overall and for the low- and high-cost subgroups, while the diabetes-specific measure had the lowest predictive power. A model with DCGs and the diabetes-specific measure modestly improved predictive power. Existing generic measures can be useful for diabetes-specific research and policy applications, but more predictive diabetes-specific measures are needed.

Advanced algorithms for distributed fusion

NASA Astrophysics Data System (ADS)

Gelfand, A.; Smith, C.; Colony, M.; Bowman, C.; Pei, R.; Huynh, T.; Brown, C.

2008-03-01

The US Military has been undergoing a radical transition from a traditional "platform-centric" force to one capable of performing in a "Network-Centric" environment. This transformation will place all of the data needed to efficiently meet tactical and strategic goals at the warfighter's fingertips. With access to this information, the challenge of fusing data from across the batttlespace into an operational picture for real-time Situational Awareness emerges. In such an environment, centralized fusion approaches will have limited application due to the constraints of real-time communications networks and computational resources. To overcome these limitations, we are developing a formalized architecture for fusion and track adjudication that allows the distribution of fusion processes over a dynamically created and managed information network. This network will support the incorporation and utilization of low level tracking information within the Army Distributed Common Ground System (DCGS-A) or Future Combat System (FCS). The framework is based on Bowman's Dual Node Network (DNN) architecture that utilizes a distributed network of interlaced fusion and track adjudication nodes to build and maintain a globally consistent picture across all assets.

Identification of Transcriptional Modules and Key Genes in Chickens Infected with Salmonella enterica Serovar Pullorum Using Integrated Coexpression Analyses.

PubMed

Liu, Bao-Hong; Cai, Jian-Ping

2017-01-01

Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA) and differential coexpression analysis (DCEA) to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S. enterica infection. A total of 19 modules from 13,538 genes were associated with the Jak-STAT signaling pathway, the extracellular matrix, cytoskeleton organization, the regulation of the actin cytoskeleton, G-protein coupled receptor activity, Toll-like receptor signaling pathways, and immune system processes; among them, 14 differentially coexpressed modules (DCMs) and 2,856 differentially coexpressed genes (DCGs) were identified. The global expression of module genes between infected and uninfected chickens showed slight differences but considerable changes for global coexpression. Furthermore, DCGs were consistently linked to the hubs of the modules. These results will help prioritize candidate genes for future studies of Salmonella infection.

Impact of comorbidities on stroke rehabilitation outcomes: does the method matter?

PubMed

Berlowitz, Dan R; Hoenig, Helen; Cowper, Diane C; Duncan, Pamela W; Vogel, W Bruce

2008-10-01

To examine the impact of comorbidities in predicting stroke rehabilitation outcomes and to examine differences among 3 commonly used comorbidity measures--the Charlson Index, adjusted clinical groups (ACGs), and diagnosis cost groups (DCGs)--in how well they predict these outcomes. Inception cohort of patients followed for 6 months. Department of Veterans Affairs (VA) hospitals. A total of 2402 patients beginning stroke rehabilitation at a VA facility in 2001 and included in the Integrated Stroke Outcomes Database. Not applicable. Three outcomes were evaluated: 6-month mortality, 6-month rehospitalization, and change in FIM score. During 6 months of follow-up, 27.6% of patients were rehospitalized and 8.6% died. The mean FIM score increased an average of 20 points during rehabilitation. Addition of comorbidities to the age and sex models improved their performance in predicting these outcomes based on changes in c statistics for logistic and R(2) values for linear regression models. While ACG and DCG models performed similarly, the best models, based on DCGs, had a c statistic of .74 for 6-month mortality and .63 for 6-month rehospitalization, and an R(2) of .111 for change in FIM score. Comorbidities are important predictors of stroke rehabilitation outcomes. How they are classified has important implications for models that may be used in assessing quality of care.

Revisiting Traditional Risk Factors for Rejection and Graft Loss after Kidney Transplantation

PubMed Central

Dunn, TB; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O. Goruroglu; Pruett, TL; Bray, RA; Gebel, HM; Matas, AJ

2011-01-01

Single antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and SAB testing of day of transplant serum as 1) unsensitized; PRA=0 (n= 178), 2) 3rd party sensitized; no DSA (n=363), or 3) donor sensitized; with DSA (n=46), and studied rejection rates, death censored graft survival (DCGS), and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p<0.0001), but not with PRA in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p<0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p=0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. PMID:21812918

Gene expression profiling combined with bioinformatics analysis identify biomarkers for Parkinson disease.

PubMed

Diao, Hongyu; Li, Xinxing; Hu, Sheng; Liu, Yunhui

2012-01-01

Parkinson disease (PD) progresses relentlessly and affects approximately 4% of the population aged over 80 years old. It is difficult to diagnose in its early stages. The purpose of our study is to identify molecular biomarkers for PD initiation using a computational bioinformatics analysis of gene expression. We downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in PD patients compared to controls. Besides, we built a regulatory network by mapping the DCGs to known regulatory data between transcription factors (TFs) and target genes and calculated the regulatory impact factor of each transcription factor. As the results, a total of 1004 genes associated with PD initiation were identified. Pathway enrichment of these genes suggests that biological processes of protein turnover were impaired in PD. In the regulatory network, HLF, E2F1 and STAT4 were found have altered expression levels in PD patients. The expression levels of other transcription factors, NKX3-1, TAL1, RFX1 and EGR3, were not found altered. However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result.

Performance of Comorbidity, Risk Adjustment, and Functional Status Measures in Expenditure Prediction for Patients With Diabetes

PubMed Central

Maciejewski, Matthew L.; Liu, Chuan-Fen; Fihn, Stephan D.

2009-01-01

OBJECTIVE—To compare the ability of generic comorbidity and risk adjustment measures, a diabetes-specific measure, and a self-reported functional status measure to explain variation in health care expenditures for individuals with diabetes. RESEARCH DESIGN AND METHODS—This study included a retrospective cohort of 3,092 diabetic veterans participating in a multisite trial. Two comorbidity measures, four risk adjusters, a functional status measure, a diabetes complication count, and baseline expenditures were constructed from administrative and survey data. Outpatient, inpatient, and total expenditure models were estimated using ordinary least squares regression. Adjusted R2 statistics and predictive ratios were compared across measures to assess overall explanatory power and explanatory power of low- and high-cost subgroups. RESULTS—Administrative data–based risk adjusters performed better than the comorbidity, functional status, and diabetes-specific measures in all expenditure models. The diagnostic cost groups (DCGs) measure had the greatest predictive power overall and for the low- and high-cost subgroups, while the diabetes-specific measure had the lowest predictive power. A model with DCGs and the diabetes-specific measure modestly improved predictive power. CONCLUSIONS—Existing generic measures can be useful for diabetes-specific research and policy applications, but more predictive diabetes-specific measures are needed. PMID:18945927

Identification of Transcriptional Modules and Key Genes in Chickens Infected with Salmonella enterica Serovar Pullorum Using Integrated Coexpression Analyses

PubMed Central

2017-01-01

Salmonella enterica Pullorum is one of the leading causes of mortality in poultry. Understanding the molecular response in chickens in response to the infection by S. enterica is important in revealing the mechanisms of pathogenesis and disease progress. There have been studies on identifying genes associated with Salmonella infection by differential expression analysis, but the relationships among regulated genes have not been investigated. In this study, we employed weighted gene coexpression network analysis (WGCNA) and differential coexpression analysis (DCEA) to identify coexpression modules by exploring microarray data derived from chicken splenic tissues in response to the S. enterica infection. A total of 19 modules from 13,538 genes were associated with the Jak-STAT signaling pathway, the extracellular matrix, cytoskeleton organization, the regulation of the actin cytoskeleton, G-protein coupled receptor activity, Toll-like receptor signaling pathways, and immune system processes; among them, 14 differentially coexpressed modules (DCMs) and 2,856 differentially coexpressed genes (DCGs) were identified. The global expression of module genes between infected and uninfected chickens showed slight differences but considerable changes for global coexpression. Furthermore, DCGs were consistently linked to the hubs of the modules. These results will help prioritize candidate genes for future studies of Salmonella infection. PMID:28529955

Gene Expression Profiling Combined with Bioinformatics Analysis Identify Biomarkers for Parkinson Disease

PubMed Central

Diao, Hongyu; Li, Xinxing; Hu, Sheng; Liu, Yunhui

2012-01-01

Parkinson disease (PD) progresses relentlessly and affects approximately 4% of the population aged over 80 years old. It is difficult to diagnose in its early stages. The purpose of our study is to identify molecular biomarkers for PD initiation using a computational bioinformatics analysis of gene expression. We downloaded the gene expression profile of PD from Gene Expression Omnibus and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in PD patients compared to controls. Besides, we built a regulatory network by mapping the DCGs to known regulatory data between transcription factors (TFs) and target genes and calculated the regulatory impact factor of each transcription factor. As the results, a total of 1004 genes associated with PD initiation were identified. Pathway enrichment of these genes suggests that biological processes of protein turnover were impaired in PD. In the regulatory network, HLF, E2F1 and STAT4 were found have altered expression levels in PD patients. The expression levels of other transcription factors, NKX3-1, TAL1, RFX1 and EGR3, were not found altered. However, they regulated differentially expressed genes. In conclusion, we suggest that HLF, E2F1 and STAT4 may be used as molecular biomarkers for PD; however, more work is needed to validate our result. PMID:23284986

U.S. Army Workshop on Exploring Enterprise, System of Systems, System, and Software Architectures

DTIC Science & Technology

2009-03-01

state of a net-centric intelligence /surveillance/reconnaissance (ISR) capability featuring DCGS by the middle of the next decade.5 In some situations...boundaries. The DoDAF has a relatively long history. It started as a Command, Control, Communications, Computers, Surveillance and Intelligence ...Army have needed to perform tasks such as: col- lect and analyze intelligence information; maneuver the force; target and provide fire support; conduct

Occupational Burnout and Retention of Air Force Distributed Common Ground System (DCGS) Intelligence Personnel

DTIC Science & Technology

2012-01-01

Leiter, 2001) emotional exhaustion “is the central quality of burnout and the most obvious manifestation of this complex syndrome .” Because...2012 2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Occupational Burnout and Retention of Air Force Distributed...supervised, reviewed, and approved by the graduate fellow’s faculty committee. PARDEE RAND GRADUATE SCHOOL Occupational Burnout and Retention of Air Force

Distributed Common Ground System Army Increment 1 (DCGS-A Inc 1)

DTIC Science & Technology

2016-03-01

Acquisition Executive DoD - Department of Defense DoDAF - DoD Architecture Framework FD - Full Deployment FDD - Full Deployment Decision FY - Fiscal...updated prior to the FDD ITAB in December 2012 and provided additional COA analysis/validation referenced in the FDD ADM (December 14, 2012) and FDD ...required by 10 U.S.C. 2334(a)(6). The Army Cost Review Board developed the FDD Army Cost Position (ACP), dated October 19, 2012, through the update of

Knowledge Visualizations: A Tool to Achieve Optimized Operational Decision Making and Data Integration

DTIC Science & Technology

2015-06-01

Hadoop Distributed File System (HDFS) without any integration with Accumulo-based Knowledge Stores based on OWL/RDF. 4. Cloud Based The Apache Software...BTW, 7(12), pp. 227–241. Godin, A. & Akins, D. (2014). Extending DCGS-N naval tactical clouds from in-storage to in-memory for the integrated fires...VISUALIZATIONS: A TOOL TO ACHIEVE OPTIMIZED OPERATIONAL DECISION MAKING AND DATA INTEGRATION by Paul C. Hudson Jeffrey A. Rzasa June 2015 Thesis

Transcription Factor Binding Site Enrichment Analysis in Co-Expression Modules in Celiac Disease

PubMed Central

Romero-Garmendia, Irati; Jauregi-Miguel, Amaia; Plaza-Izurieta, Leticia; Cros, Marie-Pierre; Legarda, Maria; Irastorza, Iñaki; Herceg, Zdenko; Fernandez-Jimenez, Nora

2018-01-01

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gliadin was observed. Using transcriptome-wide co-expression analyses we are able to propose novel genes involved in CD pathogenesis that respond upon gliadin stimulation, also in non-celiac models. PMID:29748492

Activity-dependent release of tissue plasminogen activator from the dendritic spines of hippocampal neurons revealed by live-cell imaging.

PubMed

Lochner, Janis E; Honigman, Leah S; Grant, Wilmon F; Gessford, Sarah K; Hansen, Alexis B; Silverman, Michael A; Scalettar, Bethe A

2006-05-01

Tissue plasminogen activator (tPA) has been implicated in a variety of important cellular functions, including learning-related synaptic plasticity and potentiating N-methyl-D-aspartate (NMDA) receptor-dependent signaling. These findings suggest that tPA may localize to, and undergo activity-dependent secretion from, synapses; however, conclusive data supporting these hypotheses have remained elusive. To elucidate these issues, we studied the distribution, dynamics, and depolarization-induced secretion of tPA in hippocampal neurons, using fluorescent chimeras of tPA. We found that tPA resides in dense-core granules (DCGs) that traffic to postsynaptic dendritic spines and that can remain in spines for extended periods. We also found that depolarization induced by high potassium levels elicits a slow, partial exocytotic release of tPA from DCGs in spines that is dependent on extracellular Ca(+2) concentrations. This slow, partial release demonstrates that exocytosis occurs via a mechanism, such as fuse-pinch-linger, that allows partial release and reuse of DCG cargo and suggests a mechanism that hippocampal neurons may rely upon to avoid depleting tPA at active synapses. Our results also demonstrate release of tPA at a site that facilitates interaction with NMDA-type glutamate receptors, and they provide direct confirmation of fundamental hypotheses about tPA localization and release that bear on its neuromodulatory functions, for example, in learning and memory.

Transcription Factor Binding Site Enrichment Analysis in Co-Expression Modules in Celiac Disease.

PubMed

Romero-Garmendia, Irati; Garcia-Etxebarria, Koldo; Hernandez-Vargas, Hector; Santin, Izortze; Jauregi-Miguel, Amaia; Plaza-Izurieta, Leticia; Cros, Marie-Pierre; Legarda, Maria; Irastorza, Iñaki; Herceg, Zdenko; Fernandez-Jimenez, Nora; Bilbao, Jose Ramon

2018-05-10

The aim of this study was to construct celiac co-expression patterns at a whole genome level and to identify transcription factors (TFs) that could drive the gliadin-related changes in coordination of gene expression observed in celiac disease (CD). Differential co-expression modules were identified in the acute and chronic responses to gliadin using expression data from a previous microarray study in duodenal biopsies. Transcription factor binding site (TFBS) and Gene Ontology (GO) annotation enrichment analyses were performed in differentially co-expressed genes (DCGs) and selection of candidate regulators was performed. Expression of candidates was measured in clinical samples and the activation of the TFs was further characterized in C2BBe1 cells upon gliadin challenge. Enrichment analyses of the DCGs identified 10 TFs and five were selected for further investigation. Expression changes related to active CD were detected in four TFs, as well as in several of their in silico predicted targets. The activation of TFs was further characterized in C2BBe1 cells upon gliadin challenge, and an increase in nuclear translocation of CAMP Responsive Element Binding Protein 1 (CREB1) and IFN regulatory factor-1 (IRF1) in response to gliadin was observed. Using transcriptome-wide co-expression analyses we are able to propose novel genes involved in CD pathogenesis that respond upon gliadin stimulation, also in non-celiac models.

Environmental surveillance data report for the second quarter of 1990

DOE Office of Scientific and Technical Information (OSTI.GOV)

Goldberg, P.Y.; Horwedel, B.M.; Osborne-Lee, A.E.

1991-02-01

Each section of this report consists of a program description; results for the quarter; and an analysis of trends over the previous two years, depending upon the availability of data. Emissions of tritium to the atmosphere returned to levels consistent with the latter part of 1989. Osmium-191 releases were down by a factor of fifty due to changes in operations. Ambient air sampling around ORNL and the reservation showed that I-131 and H-3 continue to be at concentrations of less than 0.01% of the derived concentration guides (DCG) for these isotopes. Tritium and strontium concentrations at White Oak Dam weremore » at 11% and 22% of their DCGs for the quarter respectively. All of the other radionuclides that were evaluated at the dam were at 2% or less of their DCGs. The NPDES compliance ratio for this quarter was 97% due to 20 noncompliances. Twelve of the exceedences were due to Category outfalls. Total radioactive strontium in milk was detected at two of the stations. The concentrations were less than 1% of the DCG for Sr-90. Samples from the perimeter wells of SWSA 6 were consistent with the data collected during the assessment phase with the exception of one well that showed twice the concentration of tritium previously seen (920 Bq/L versus 530 Bq/L). 20 figs., 39 tabs.« less

Functional Gap Analysis of the Maritime Operations Centers

DTIC Science & Technology

2009-12-01

Messaging Services TBMCS , DJC2 MI.1.3.5 Manage Suspense Control Capability Gap MI.1.3.6 Provide Component IM Cell Services Capability Gap MI.1.4 Provide...Admin Support MSRT MI.1.3.3 Manage Electronic File Plan Capability Gap MI.1.3.4 Manage Messaging Services TBMCS , DJC2 MI.1.3.5 Manage Suspense...1.5.9 Execute C4 Policies & Procedures for the Joint Operations Area GCCS-J, DCGS-N, TBMCS , CENTRIX-M EHQ.1.11 Sub Component Interagency

Environmental monitoring at Mound: 1987 report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carfagno, D.G.; Farmer, B.M.

1988-04-25

The local environment around Mound as monitored primarily for tritium and plutonium-238. The results are reported for 1987. Environmental media analyzed included air, water, vegetation, food-stuffs, and sediment. The average concentrations of plutonium 238 and tritium were within the DOE interim air and water Derived Concentration Guides (DCG) for these radionuclides. The average incremental concentrations of plutonium-238 and tritium oxide in air measured at all offsite locations during 1987 were 4.6 x 10/sup -18/ ..mu..Ci/mL and 12.9 x 10/sup -12/ ..mu..Ci/mL, respectively. These correspond to 0.02% and 0.01%, respectively, of the DOE DCGs for uncontrolled areas. The average incremental concentrationmore » of plutonium-238 measured at all locations in the Great Miami River during 1987 was 1.4 x 10/sup - 12/ ..mu..Ci/mL which is 0.0004% of the DOE DCG. The average incremental concentration of tritium measured at all locations in the Great Miami River during 1987 was 0.07 x 10/sup -6/ ..mu..Ci/mL which is 0.004% of the DOE DCG. The dose equivalent estimates for the average air, water, and foodstuff concentrations indicate that the levels are 1% of the DOE standard of 100 mrem. 23 refs., 5 figs., 34 tabs.« less

The effects of body mass index on graft survival in adult recipients transplanted with single pediatric kidneys.

PubMed

Balamuthusamy, Saravanan; Paramesh, Anil; Zhang, Rubin; Florman, Sander; Shenava, Rajesh; Islam, Tareq; Wagner, Janis; Killackey, Mary; Alper, Brent; Simon, Eric E; Slakey, Douglas

2009-01-01

There is insufficient data on the impact of recipient body mass index (BMI) on the long-term graft survival of adult patients transplanted with single pediatric kidneys. We performed a retrospective analysis of adult patients transplanted with single pediatric kidneys at our center. The recipients were classified into 2 groups: group 1 (BMI > or =30) and group 2 (BMI <30). Donor/recipient demographics, postoperative outcomes and survival rates were compared between the 2 groups. There was no significant difference in donor/recipient demographics between the 2 groups. In group 1, the death-censored graft survival (DCGS) at 1, 3 and 5 years was 90% at all 3 time points, and in group 2 it was 86, 68 and 60%, respectively (p = 0.05). The mean glomerular filtration rate (with standard deviation in parentheses) at 1, 3 and 5 years was, respectively, 55 (15), 59 (19) and 55 (28) ml/min for group 1, compared to 65 (28), 69 (23) and 67 (20) ml/min in group 2 (p = NS). Multivariate analysis revealed a hazard ratio of 5.12 (95% confidence interval 1.06-24.7; p = 0.04) for graft loss in nonobese patients when compared to obese patients. Obese patients had an increased risk for acute rejections within the first month of transplant (p = 0.02). Patients with a BMI > or =30 transplanted with single pediatric kidneys have better DCGS rates when compared to nonobese patients. Copyright (c) 2008 S. Karger AG, Basel.

Acute cellular rejection with isolated v-lesions is not associated with more favorable outcomes than vascular rejection with more tubulointerstitial inflammations.

PubMed

Wu, K Y; Budde, K; Schmidt, D; Neumayer, H H; Rudolph, B

2014-04-01

The impact of isolated v-lesions on clinical outcome in biopsies with acute cellular rejection (ACR) is unclear. Two hundred and sixty-five biopsies showing the highest ACR severity for each patient were recruited and classified into four groups: (i) acute interstitial rejection (AIR) I with minimal tubulointerstitial inflammation (TI), (ii) AIR II with intensive TI, (iii) acute vascular rejection (AVR) I with minimal TI, and (iv) AVR II with intensive TI. The complete reversal rates of AIR I and AIR II groups were marginally higher than AVR I and AVR II groups (p = 0.16). At eight yr of transplantation, the death-censored graft survival (DCGS) rate of AIR I group (93.3%) was significantly higher compared with the AVR I (72.7%) or AVR II (72.9%) group. AVR I group had a similar DCGS rate with AVR II group (72.7% vs. 74.1%), whereas AVR with v1-lesion showed significantly higher graft survival (GS) rate than those with v2-lesion (70.2% vs. 45.5%). The t-lesion of AIR and v-lesion of AVR group were associated with graft loss. The extent of TI is non-specifically associated with graft loss in biopsies with AVR; the higher grade v-lesion predicts the lower complete reversal rate and poorer long-term graft survival. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Isolated v-lesion represents a benign phenotype of vascular rejection of the kidney allograft- a retrospective study.

PubMed

Novotny, Marek; Hruba, Petra; Vichova, Petra; Maluskova, Jana; Honsova, Eva; Viklicky, Ondrej; Wohlfahrtova, Mariana

2018-05-31

While the detrimental impact of the humoral acute vascular rejection (AVR) phenotype is recognized, the prognostic significance of isolated v-lesion (IV) remains unclear. In this retrospective single-centre study, AVR was found in 98 out of 1015 patients (9.7%) who had undergone kidney transplantation in 2010-2014, with donor-specific antibodies (DSA) evaluated in all of them. The outcome of four AVR phenotypes was evaluated during median follow-up of 59 months; in 25 patients with IV, 18 with T cell-mediated vascular rejection (TCMRV), 19 with antibody-mediated vascular rejection (AMRV) and 36 with suspected antibody-mediated rejection (sAMRV). AVR was diagnosed mainly by for-cause biopsy (81%) early after transplantation (median 19 POD) and appeared as mild grade intimal arteritis. IV occurred in low sensitized patients after the first transplantation (96%) in the absence of DSA. IV responded satisfactorily to treatment (88%), showed no persistence of rejection in surveillance biopsy, had stable graft function, minimal proteinuria and excellent DCGS (96%). Contrary to that, Kaplan-Meier estimate of 3-year DCGS of AMRV was 66% (log rank=0.0004). Early IV represents a benign phenotype of AVR with a favourable outcome. This study prompts further research to evaluate the nature of IV before considering any change in the classification and management. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Revisiting traditional risk factors for rejection and graft loss after kidney transplantation.

PubMed

Dunn, T B; Noreen, H; Gillingham, K; Maurer, D; Ozturk, O G; Pruett, T L; Bray, R A; Gebel, H M; Matas, A J

2011-10-01

Single-antigen bead (SAB) testing permits reassessment of immunologic risk for kidney transplantation. Traditionally, high panel reactive antibody (PRA), retransplant and deceased donor (DD) grafts have been associated with increased risk. We hypothesized that this risk was likely mediated by (unrecognized) donor-specific antibody (DSA). We grouped 587 kidney transplants using clinical history and single-antigen bead (SAB) testing of day of transplant serum as (1) unsensitized; PRA = 0 (n = 178), (2) third-party sensitized; no DSA (n = 363) or (3) donor sensitized; with DSA (n = 46), and studied rejection rates, death-censored graft survival (DCGS) and risk factors for rejection. Antibody-mediated rejection (AMR) rates were increased with DSA (p < 0.0001), but not with panel reactive antibody (PRA) in the absence of DSA. Cell-mediated rejection (CMR) rates were increased with DSA (p < 0.005); with a trend to increased rates when PRA>0 in the absence of DSA (p = 0.08). Multivariate analyses showed risk factors for AMR were DSA, worse HLA matching, and female gender; for CMR: DSA, PRA>0 and worse HLA matching. AMR and CMR were associated with decreased DCGS. The presence of DSA is an important predictor of rejection risk, in contrast to traditional risk factors. Further development of immunosuppressive protocols will be facilitated by stratification of rejection risk by donor sensitization. ©2011 The Authors Journal compilation©2011 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides.

PubMed

Montero-Hadjadje, Maité; Elias, Salah; Chevalier, Laurence; Benard, Magalie; Tanguy, Yannick; Turquier, Valérie; Galas, Ludovic; Yon, Laurent; Malagon, Maria M; Driouich, Azeddine; Gasman, Stéphane; Anouar, Youssef

2009-05-01

Chromogranin A (CgA) has been proposed to play a major role in the formation of dense-core secretory granules (DCGs) in neuroendocrine cells. Here, we took advantage of unique features of the frog CgA (fCgA) to assess the role of this granin and its potential functional determinants in hormone sorting during DCG biogenesis. Expression of fCgA in the constitutively secreting COS-7 cells induced the formation of mobile vesicular structures, which contained cotransfected peptide hormones. The fCgA and the hormones coexpressed in the newly formed vesicles could be released in a regulated manner. The N- and C-terminal regions of fCgA, which exhibit remarkable sequence conservation with their mammalian counterparts were found to be essential for the formation of the mobile DCG-like structures in COS-7 cells. Expression of fCgA in the corticotrope AtT20 cells increased pro-opiomelanocortin levels in DCGs, whereas the expression of N- and C-terminal deletion mutants provoked retention of the hormone in the Golgi area. Furthermore, fCgA, but not its truncated forms, promoted pro-opiomelanocortin sorting to the regulated secretory pathway. These data demonstrate that CgA has the intrinsic capacity to induce the formation of mobile secretory granules and to promote the sorting and release of peptide hormones. The conserved terminal peptides are instrumental for these activities of CgA.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients.

PubMed

Serrano, Oscar K; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog; Kayler, Liise K

2015-11-06

Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003-2005, 2006-2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003-2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006-2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009-2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. Copyright © 2015 by the American Society of Nephrology.

Outcomes Associated with Steroid Avoidance and Alemtuzumab among Kidney Transplant Recipients

PubMed Central

Serrano, Oscar K.; Friedmann, Patricia; Ahsanuddin, Sayeeda; Millan, Carlos; Ben-Yaacov, Almog

2015-01-01

Background and objectives Alemtuzumab is a humanized anti-CD52 monoclonal antibody used as induction in kidney transplantation (KTX) since 2003. Few studies have evaluated long-term outcomes of this agent or changes in outcomes over time. Design, setting, participants, & measurements A retrospective cohort study was performed examining United States registry data from 2003 to 2014 of primary KTX recipients receiving induction with alemtuzumab (AZ; n=5521) or antithymocyte globulin (ATG; n=8504) and maintenance immunosuppression with tacrolimus and mycophenolate mofetil and early withdrawal of steroids. The primary outcome was overall death-censored graft survival (DCGS), and secondary outcomes were overall patient survival and 1-year acute rejection. Multivariate models were fit with donor, recipient, and transplant covariates. Because poorer outcomes with AZ may occur from a learning curve impact with the use of a new medication, transplant year was categorized into three time periods to evaluate outcomes over time (2003–2005, 2006–2008, ≥2009), and an interaction term of induction type with transplant year category was included in all models to test for era impacts. Results On multivariate analysis of DCGS there was a significant interaction between AZ and era (P<0.001). AZ was significantly associated with inferior DCGS in the earliest 2003–2005 era (adjusted hazard ratio [aHR], 2.21; 95% confidence interval [95% CI], 1.72 to 2.84) but not in the middle 2006–2008 era (aHR, 1.14; 95% CI, 0.96 to 1.36) or the most recent 2009–2014 era (aHR, 1.08; 95% CI, 0.90 to 1.29) compared with ATG. Risk-adjusted patient survival (aHR, 1.32; 95% CI, 1.08 to 1.61; aHR, 1.26; 95% CI, 1.09 to 1.46; and aHR, 1.10; 95% CI, 0.93 to 1.29 by era, respectively) and acute rejection (adjusted odds ratio [aOR], 1.17; 95% CI, 0.96 to 1.42; aOR, 0.94; 95% CI, 0.82 to 1.07; aOR, 0.89; 95% CI, 0.81 to 0.98 by era, respectively) with AZ was comparable with ATG in the most recent era; however, there was no significant interaction with time (P=0.13 and P=0.06, respectively). Conclusions Current alemtuzumab utilization is associated with comparable graft and patient survival and acute rejection compared with ATG. Graft survival with alemtuzumab has improved over time. PMID:26342042

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Quarterly Environmental Data Summary (QEDS) for the fourth quarter of 1997 is prepared in support of the Weldon Spring Site Remedial Action Project Federal Facilities Agreement. The data presented constitute the QEDS. The data were received from the contract laboratories, verified by the Weldon Spring Site verification group and, except for air monitoring data and site KPA generated data (uranium analyses), merged into the data base during the fourth quarter of 1997. Air monitoring data presented are the most recent complete sets of quarterly data. Air data are not stored in the data base and KPA data are notmore » merged into the regular data base. Significant data, defined as data values that have exceeded defined ``above normal`` level 2 values, are discussed in this letter for Environmental Monitoring Plan (EMP) generated data only. Above normal level 2 values are based, in ES and H procedures, on historical high values, DOE Derived Concentration Guides (DCGs), NPDES limits and other guidelines. The procedures also establish actions to be taken in response to such data. Data received and verified during the fourth quarter were within a permissible range of variability except for those which are detailed.« less

Weldon Spring Site Remedial Action Project Federal Facilities Agreement: Quarterly environmental data summary for third quarter 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-11-06

In support of the Weldon Spring Site Remedial Action Project Federal Facilities Agreement, a copy of the Quarterly Environmental Data Summary (QEDS) for the third quarter of 1998 is enclosed. The data presented in this letter and attachment constitute the QEDS. The data, except for air monitoring data and site KPA generated data (uranium analyses), were received from the contract laboratories, verified by the Weldon Spring Site verification group, and merged into the database during the third quarter of 1998. Air monitoring data presented are the most recent complete sets of quarterly data. Significant data, defined as data values thatmore » have exceeded defined above normal Level 2 values, are discussed in this letter for Environmental Monitoring Plan (EMP) generated data only. Above normal Level 2 values are based, in ES and H procedures, on historical high values, DOE Derived Concentration Guides (DCGs), NPDES limits, and other guidelines. The procedures also establish actions to be taken in the event that above normal data occur.« less

Determining Intelligence, Surveillance and Reconnaissance (ISR) System Effectiveness, and Integration as Part of Force Protection and System Survivability

DTIC Science & Technology

2013-09-01

Infantry Fighting Vehicle (Bradley M2A3 ) – The Bradley fighting vehicle is designed for the mobility; it also protects infantry troops when...Persistence Latency of Info Endurance Outgoing Communication Links Sensors Detection Infantry Soldiers X X Bradley Infantry Soldiers X X Bradley M2A3 X...IndustryAdvisoryGroupIAG/Documents/OUSDI%20DCGS%20IAG%20Kick- off%20Presentation%206–23–09.pdf Military Analysis Network. M2A3 and M3A3 Bradley Fighting

Diagnostic cost groups (DCGs) and concurrent utilization among patients with substance abuse disorders.

PubMed

Rosen, Amy K; Loveland, Susan A; Anderson, Jennifer J; Hankin, Cheryl S; Breckenridge, James N; Berlowitz, Dan R

2002-08-01

To assess the performance of Diagnostic Cost Groups (DCGs) in explaining variation in concurrent utilization for a defined subgroup, patients with substance abuse (SA) disorders, within the Department of Veterans Affairs (VA). A 60 percent random sample of veterans who used health care services during Fiscal Year (FY) 1997 was obtained from VA administrative databases. Patients with SA disorders (13.3 percent) were identified from primary and secondary ICD-9-CM diagnosis codes. Concurrent risk adjustment models were fitted and tested using the DCG/HCC model. Three outcome measures were defined: (1) "service days" (the sum of a patient's inpatient and outpatient visit days), (2) mental health/substance abuse (MH/SA) service days, and (3) ambulatory provider encounters. To improve model performance, we ran three DCG/HCC models with additional indicators for patients with SA disorders. To create a single file of veterans who used health care services in FY 1997, we merged records from all VA inpatient and outpatient files. Adding indicators for patients with mild/moderate SA disorders did not appreciably improve the R-squares for any of the outcome measures. When indicators were added for patients with severe SA who were in the most costly category, the explanatory ability of the models was modestly improved for all three outcomes. Modifying the DCG/HCC model with additional markers for SA modestly improved homogeneity and model prediction. Because considerable variation still remained after modeling, we conclude that health care systems should evaluate "off-the-shelf" risk adjustment systems before applying them to their own populations.

Maywood Interim Storage Site: Annual environmental report for calendar year 1990, Maywood, New Jersey

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-09-01

Environmental monitoring of the US Department of Energy's (DOE) Maywood Interim Storage Site (MISS) and surrounding area began in 1984. MISS is part of the Formerly Utilized Sites Remedial Action Program (FUSRAP), a DOE program to decontaminate or otherwise control sites where residual radioactive materials remain from the early years of the nation's atomic energy program or from commercial operations causing conditions that Congress has authorized DOE to remedy. The MISS Environmental monitoring programs was established to accommodate facility characteristics, applicable regulations, hazard potential, quantities and concentrations of materials released, extent and use of affected land and water, and localmore » public interest or concern. The environmental monitoring program at MISS includes sampling networks for radon concentrations in air; external gamma radiation exposure; and total uranium, radium-226, and thorium-232 concentrations in surface water, sediment, and groundwater. Additionally, several nonradiological parameters are measured in surface water, sediment, and groundwater. Monitoring results are compared with applicable Environmental Protection Agency (EPA) standards; federal, state, and local applicable or relevant and appropriate requirements (ARARs); and/or DOE derived concentration guidelines (DCGs). Environmental standards, ARARs, and DCGs are established to protect public health and the environment. Results from the 1990 environmental monitoring program show that concentrations of the contaminants of concern were all below applicable standards. Because the site is used only for interim storage and produces no processing effluents, all monitoring, except for radon and direct gamma radiation, was done on a quarterly basis. 18 refs., 17 figs., 28 tabs.« less

Evaluating diagnosis-based case-mix measures: how well do they apply to the VA population?

PubMed

Rosen, A K; Loveland, S; Anderson, J J; Rothendler, J A; Hankin, C S; Rakovski, C C; Moskowitz, M A; Berlowitz, D R

2001-07-01

Diagnosis-based case-mix measures are increasingly used for provider profiling, resource allocation, and capitation rate setting. Measures developed in one setting may not adequately capture the disease burden in other settings. To examine the feasibility of adapting two such measures, Adjusted Clinical Groups (ACGs) and Diagnostic Cost Groups (DCGs), to the Department of Veterans Affairs (VA) population. A 60% random sample of veterans who used health care services during FY 1997 was obtained from VA inpatient and outpatient administrative databases. A split-sample technique was used to obtain a 40% sample (n = 1,046,803) for development and a 20% sample (n = 524,461) for validation. Concurrent ACG and DCG risk adjustment models, using 1997 diagnoses and demographics to predict FY 1997 utilization (ambulatory provider encounters, and service days-the sum of a patient's inpatient and outpatient visit days), were fitted and cross-validated. Patients were classified into groupings that indicated a population with multiple psychiatric and medical diseases. Model R-squares explained between 6% and 32% of the variation in service utilization. Although reparameterized models did better in predicting utilization than models with external weights, none of the models was adequate in characterizing the entire population. For predicting service days, DCGs were superior to ACGs in most categories, whereas ACGs did better at discriminating among veterans who had the lowest utilization. Although "off-the-shelf" case-mix measures perform moderately well when applied to another setting, modifications may be required to accurately characterize a population's disease burden with respect to the resource needs of all patients.

Recurrence of IgA nephropathy after kidney transplantation in steroid continuation versus early steroid-withdrawal regimens: a retrospective analysis of the UNOS/OPTN database.

PubMed

Leeaphorn, Napat; Garg, Neetika; Khankin, Eliyahu V; Cardarelli, Francesca; Pavlakis, Martha

2018-02-01

In the past 20 years, there has been an increase in use of steroid-withdrawal regimens in kidney transplantation. However, steroid withdrawal may be associated with an increased risk of recurrent IgA nephropathy (IgAN). Using United Network of (Organ Sharing/Organ Procurement and Transplantation Network) UNOS/OPTN data, we analyzed adult patients with end-stage renal disease (ESRD) due to IgAN who received their first kidney transplant between 2000 and 2014. For the primary outcome, we used a competing risk analysis to compare the cumulative incidence of graft loss due to IgAN recurrence between early steroid-withdrawal (ESW) and steroid continuation groups. The secondary outcomes were patient survival and death-censored graft survival (DCGS). A total of 9690 recipients were included (2831 in ESW group and 6859 in steroid continuation group). In total, 1238 recipients experienced graft loss, of which 191 (15.43%) were due to IgAN recurrence. In multivariable analysis, steroid use was associated with a decreased risk of recurrence (subdistribution hazard ratio 0.666, 95% CI 0.482-0.921; P = 0.014). Patient survival and DCGS were not different between the two groups. In the USA, ESW in transplant for ESRD due to IgAN is associated with a higher risk of graft loss due to disease recurrence. Future prospective studies are warranted to further address which patients with IgAN would benefit from steroid continuation. © 2017 Steunstichting ESOT.

Long-Range Reduced Predictive Information Transfers of Autistic Youths in EEG Sensor-Space During Face Processing.

PubMed

Khadem, Ali; Hossein-Zadeh, Gholam-Ali; Khorrami, Anahita

2016-03-01

The majority of previous functional/effective connectivity studies conducted on the autistic patients converged to the underconnectivity theory of ASD: "long-range underconnectivity and sometimes short-rang overconnectivity". However, to the best of our knowledge the total (linear and nonlinear) predictive information transfers (PITs) of autistic patients have not been investigated yet. Also, EEG data have rarely been used for exploring the information processing deficits in autistic subjects. This study is aimed at comparing the total (linear and nonlinear) PITs of autistic and typically developing healthy youths during human face processing by using EEG data. The ERPs of 12 autistic youths and 19 age-matched healthy control (HC) subjects were recorded while they were watching upright and inverted human face images. The PITs among EEG channels were quantified using two measures separately: transfer entropy with self-prediction optimality (TESPO), and modified transfer entropy with self-prediction optimality (MTESPO). Afterwards, the directed differential connectivity graphs (dDCGs) were constructed to characterize the significant changes in the estimated PITs of autistic subjects compared with HC ones. By using both TESPO and MTESPO, long-range reduction of PITs of ASD group during face processing was revealed (particularly from frontal channels to right temporal channels). Also, it seemed the orientation of face images (upright or upside down) did not modulate the binary pattern of PIT-based dDCGs, significantly. Moreover, compared with TESPO, the results of MTESPO were more compatible with the underconnectivity theory of ASD in the sense that MTESPO showed no long-range increase in PIT. It is also noteworthy that to the best of our knowledge it is the first time that a version of MTE is applied for patients (here ASD) and it is also its first use for EEG data analysis.

Identification of genes associated with renal cell carcinoma using gene expression profiling analysis.

PubMed

Yao, Ting; Wang, Qinfu; Zhang, Wenyong; Bian, Aihong; Zhang, Jinping

2016-07-01

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for ~80% of all kidney cancer cases. However, the pathogenesis of RCC has not yet been fully elucidated. To interpret the pathogenesis of RCC at the molecular level, gene expression data and bio-informatics methods were used to identify RCC associated genes. Gene expression data was downloaded from Gene Expression Omnibus (GEO) database and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in RCC patients compared with controls. In addition, a regulatory network was constructed using the known regulatory data between transcription factors (TFs) and target genes in the University of California Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu) and the regulatory impact factor of each TF was calculated. A total of 258,0427 pairs of DCGs were identified. The regulatory network contained 1,525 pairs of regulatory associations between 126 TFs and 1,259 target genes and these genes were mainly enriched in cancer pathways, ErbB and MAPK. In the regulatory network, the 10 most strongly associated TFs were FOXC1, GATA3, ESR1, FOXL1, PATZ1, MYB, STAT5A, EGR2, EGR3 and PELP1. GATA3, ERG and MYB serve important roles in RCC while FOXC1, ESR1, FOXL1, PATZ1, STAT5A and PELP1 may be potential genes associated with RCC. In conclusion, the present study constructed a regulatory network and screened out several TFs that may be used as molecular biomarkers of RCC. However, future studies are needed to confirm the findings of the present study.

Healthcare costs and utilization for Medicare beneficiaries with Alzheimer's.

PubMed

Zhao, Yang; Kuo, Tzu-Chun; Weir, Sharada; Kramer, Marilyn S; Ash, Arlene S

2008-05-22

Alzheimer's disease (AD) is a neurodegenerative disorder incurring significant social and economic costs. This study uses a US administrative claims database to evaluate the effect of AD on direct healthcare costs and utilization, and to identify the most common reasons for AD patients' emergency room (ER) visits and inpatient admissions. Demographically matched cohorts age 65 and over with comprehensive medical and pharmacy claims from the 2003-2004 MEDSTAT MarketScan Medicare Supplemental and Coordination of Benefits (COB) Database were examined: 1) 25,109 individuals with an AD diagnosis or a filled prescription for an exclusively AD treatment; and 2) 75,327 matched controls. Illness burden for each person was measured using Diagnostic Cost Groups (DCGs), a comprehensive morbidity assessment system. Cost distributions and reasons for ER visits and inpatient admissions in 2004 were compared for both cohorts. Regression was used to quantify the marginal contribution of AD to health care costs and utilization, and the most common reasons for ER and inpatient admissions, using DCGs to control for overall illness burden. Compared with controls, the AD cohort had more co-morbid medical conditions, higher overall illness burden, and higher but less variable costs ($13,936 s. $10,369; Coefficient of variation = 181 vs. 324). Significant excess utilization was attributed to AD for inpatient services, pharmacy, ER visits, and home health care (all p < 0.05). In particular, AD patients were far more likely to be hospitalized for infections, pneumonia and falls (hip fracture, syncope, collapse). Patients with AD have significantly more co-morbid medical conditions and higher healthcare costs and utilization than demographically-matched Medicare beneficiaries. Even after adjusting for differences in co-morbidity, AD patients incur excess ER visits and inpatient admissions.

Identification of genes associated with renal cell carcinoma using gene expression profiling analysis

PubMed Central

YAO, TING; WANG, QINFU; ZHANG, WENYONG; BIAN, AIHONG; ZHANG, JINPING

2016-01-01

Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and accounts for ~80% of all kidney cancer cases. However, the pathogenesis of RCC has not yet been fully elucidated. To interpret the pathogenesis of RCC at the molecular level, gene expression data and bio-informatics methods were used to identify RCC associated genes. Gene expression data was downloaded from Gene Expression Omnibus (GEO) database and identified differentially coexpressed genes (DCGs) and dysfunctional pathways in RCC patients compared with controls. In addition, a regulatory network was constructed using the known regulatory data between transcription factors (TFs) and target genes in the University of California Santa Cruz (UCSC) Genome Browser (http://genome.ucsc.edu) and the regulatory impact factor of each TF was calculated. A total of 258,0427 pairs of DCGs were identified. The regulatory network contained 1,525 pairs of regulatory associations between 126 TFs and 1,259 target genes and these genes were mainly enriched in cancer pathways, ErbB and MAPK. In the regulatory network, the 10 most strongly associated TFs were FOXC1, GATA3, ESR1, FOXL1, PATZ1, MYB, STAT5A, EGR2, EGR3 and PELP1. GATA3, ERG and MYB serve important roles in RCC while FOXC1, ESR1, FOXL1, PATZ1, STAT5A and PELP1 may be potential genes associated with RCC. In conclusion, the present study constructed a regulatory network and screened out several TFs that may be used as molecular biomarkers of RCC. However, future studies are needed to confirm the findings of the present study. PMID:27347102

Health-adjusted premium subsidies in the Netherlands.

PubMed

van de Ven, Wynand P M M; van Vliet, René C J A; Lamers, Leida M

2004-01-01

The Dutch government has decided to proceed with managed competition in health care. In this paper we report on progress made with health-based risk adjustment, a key issue in managed competition. In 2004 both Diagnostic Cost Groups (DCGs) computed from hospital diagnoses only and Pharmacy-based Cost Groups (PCGs) computed from out-patient prescription drugs are used to set the premium subsidies for competing risk-bearing sickness funds. These health-based risk adjusters appear to be effective and complementary. Risk selection is not a major problem in the Netherlands. Despite the progress made, we are still faced with a full research agenda for risk adjustment in the coming years.

PHYSIOLOGICAL EFFECTS OF DEUTERIUM ON DOGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Czajka, D.M.; Finkel, A.J.; Fischer, C.S.

1961-08-01

The physiological consequences of the deuterium isotope effect in lange mammals were studied in two dogs, one of which was maintained at 20% concentration of D/sub 2/0 in the bcdy fluids for 50 days, and the other at the toxic range of 33-35% for a brief pericd. Deuteration of the dcgs was effected by replacement of ordinary water with deuterium oxide in both focd and drink. Hemoglobin, hematocrit, and red blood cell count dropped but the white blood cell count was essentially unaffected although there was a progressive lymphopenia and granulocytosis. Serum glucose was decreased, especially at higher deuterium levels.more » Total serum cholesterol values were also diminished although the esters were essentially unchanged. Serum sodium and both NPN and BUN were within normal limits except for a terminal elevation of the latter. Serum potassium was slightly lowered for a brief period after 3 weeks. Electrocardiograms showed ST segment coving and elevation and an increase in the QT ratio that suggested nonspecific myocardial damage; these changes reverted to normal while the dog was still deuterated at a level of 20%. Both dogs exhibited neuromuscular disturbances, in one case definite weakness of the hind legs and in the other, fine muscle tremors. (auth)« less

Photopolymer based VPHGs: from materials to sky results

NASA Astrophysics Data System (ADS)

Zanutta, A.; Orselli, E.; Fäcke, T.; Bianco, A.

2016-07-01

Volume Phase Holographic Gratings cover a relevant position as transmission dispersing elements in astronomical spectrographs and each astronomical observation could take advantage of specific dispersive elements with features tailored for achieving the best performances. The design and manufacturing of high efficiency and reliable VPHGs require photosensitive materials where it is possible to control both the refractive index modulation and the film thickness. By means of Bayfol® HX photopolymers, we designed and manufactured six VPHGs for astronomical instrumentation in a GRISM configuration. We demonstrated how photopolymers are reliable holographic materials for making astronomical VPHGs with performances comparable to those provided by VPHGs based on Dichromated Gelatins (DCGs), but with a much simpler production process.

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

10 CFR 20.1207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for minors. 20.1207 Section 20.1207 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1207 Occupational dose limits for minors. The annual occupational dose limits for minors are...

Comparison of the predictive validity of diagnosis-based risk adjusters for clinical outcomes.

PubMed

Petersen, Laura A; Pietz, Kenneth; Woodard, LeChauncy D; Byrne, Margaret

2005-01-01

Many possible methods of risk adjustment exist, but there is a dearth of comparative data on their performance. We compared the predictive validity of 2 widely used methods (Diagnostic Cost Groups [DCGs] and Adjusted Clinical Groups [ACGs]) for 2 clinical outcomes using a large national sample of patients. We studied all patients who used Veterans Health Administration (VA) medical services in fiscal year (FY) 2001 (n = 3,069,168) and assigned both a DCG and an ACG to each. We used logistic regression analyses to compare predictive ability for death or long-term care (LTC) hospitalization for age/gender models, DCG models, and ACG models. We also assessed the effect of adding age to the DCG and ACG models. Patients in the highest DCG categories, indicating higher severity of illness, were more likely to die or to require LTC hospitalization. Surprisingly, the age/gender model predicted death slightly more accurately than the ACG model (c-statistic of 0.710 versus 0.700, respectively). The addition of age to the ACG model improved the c-statistic to 0.768. The highest c-statistic for prediction of death was obtained with a DCG/age model (0.830). The lowest c-statistics were obtained for age/gender models for LTC hospitalization (c-statistic 0.593). The c-statistic for use of ACGs to predict LTC hospitalization was 0.783, and improved to 0.792 with the addition of age. The c-statistics for use of DCGs and DCG/age to predict LTC hospitalization were 0.885 and 0.890, respectively, indicating the best prediction. We found that risk adjusters based upon diagnoses predicted an increased likelihood of death or LTC hospitalization, exhibiting good predictive validity. In this comparative analysis using VA data, DCG models were generally superior to ACG models in predicting clinical outcomes, although ACG model performance was enhanced by the addition of age.

Risk-adjusted capitation based on the Diagnostic Cost Group Model: an empirical evaluation with health survey information.

PubMed Central

Lamers, L M

1999-01-01

OBJECTIVE: To evaluate the predictive accuracy of the Diagnostic Cost Group (DCG) model using health survey information. DATA SOURCES/STUDY SETTING: Longitudinal data collected for a sample of members of a Dutch sickness fund. In the Netherlands the sickness funds provide compulsory health insurance coverage for the 60 percent of the population in the lowest income brackets. STUDY DESIGN: A demographic model and DCG capitation models are estimated by means of ordinary least squares, with an individual's annual healthcare expenditures in 1994 as the dependent variable. For subgroups based on health survey information, costs predicted by the models are compared with actual costs. Using stepwise regression procedures a subset of relevant survey variables that could improve the predictive accuracy of the three-year DCG model was identified. Capitation models were extended with these variables. DATA COLLECTION/EXTRACTION METHODS: For the empirical analysis, panel data of sickness fund members were used that contained demographic information, annual healthcare expenditures, and diagnostic information from hospitalizations for each member. In 1993, a mailed health survey was conducted among a random sample of 15,000 persons in the panel data set, with a 70 percent response rate. PRINCIPAL FINDINGS: The predictive accuracy of the demographic model improves when it is extended with diagnostic information from prior hospitalizations (DCGs). A subset of survey variables further improves the predictive accuracy of the DCG capitation models. The predictable profits and losses based on survey information for the DCG models are smaller than for the demographic model. Most persons with predictable losses based on health survey information were not hospitalized in the preceding year. CONCLUSIONS: The use of diagnostic information from prior hospitalizations is a promising option for improving the demographic capitation payment formula. This study suggests that diagnostic information from outpatient utilization is complementary to DCGs in predicting future costs. PMID:10029506

Evaluating diagnosis-based risk-adjustment methods in a population with spinal cord dysfunction.

PubMed

Warner, Grace; Hoenig, Helen; Montez, Maria; Wang, Fei; Rosen, Amy

2004-02-01

To examine performance of models in predicting health care utilization for individuals with spinal cord dysfunction. Regression models compared 2 diagnosis-based risk-adjustment methods, the adjusted clinical groups (ACGs) and diagnostic cost groups (DCGs). To improve prediction, we added to our model: (1) spinal cord dysfunction-specific diagnostic information, (2) limitations in self-care function, and (3) both 1 and 2. Models were replicated in 3 populations. Samples from 3 populations: (1) 40% of veterans using Veterans Health Administration services in fiscal year 1997 (FY97) (N=1,046,803), (2) veteran sample with spinal cord dysfunction identified by codes from the International Statistical Classification of Diseases, 9th Revision, Clinical Modifications (N=7666), and (3) veteran sample identified in Veterans Affairs Spinal Cord Dysfunction Registry (N=5888). Not applicable. Inpatient, outpatient, and total days of care in FY97. The DCG models (R(2) range,.22-.38) performed better than ACG models (R(2) range,.04-.34) for all outcomes. Spinal cord dysfunction-specific diagnostic information improved prediction more in the ACG model than in the DCG model (R(2) range for ACG,.14-.34; R(2) range for DCG,.24-.38). Information on self-care function slightly improved performance (R(2) range increased from 0 to.04). The DCG risk-adjustment models predicted health care utilization better than ACG models. ACG model prediction was improved by adding information.

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External Exposure § 835.207 Occupational dose limits for minors. The dose limits for minors occupationally exposed...

Dacryocystography using cone beam CT in patients with lacrimal drainage system obstruction.

PubMed

Tschopp, Markus; Bornstein, Michael M; Sendi, Pedram; Jacobs, Reinhilde; Goldblum, David

2014-01-01

To assess the usefulness of cone beam CT (CBCT) for dacryocystography (DCG) using either direct syringing or passive application of contrast medium. Ten consecutive patients with epiphora who had CBCT-DCG in a sitting position were retrospectively analyzed. CBCT-DCGs were performed using 2 techniques: direct syringing with contrast medium or using the passive technique, where patients received 3 drops of contrast medium into the conjunctival sac before CBCT-DCG. Clinical and radiologic diagnoses were compared for both groups. The 10 patients (men = 3) had a mean age of 63.2 years. Both techniques proved to be simple procedures with good delineation of the bone, soft tissue, and the contrast medium in the lacrimal system. No side effects were noted. CBCT-DCG is a useful alternative to determine the localization of stenosis in patients with chronic epiphora.

Space radiation risk limits and Earth-Moon-Mars environmental models

NASA Astrophysics Data System (ADS)

Cucinotta, Francis A.; Hu, Shaowen; Schwadron, Nathan A.; Kozarev, K.; Townsend, Lawrence W.; Kim, Myung-Hee Y.

2010-12-01

We review NASA's short-term and career radiation limits for astronauts and methods for their application to future exploration missions outside of low Earth orbit. Career limits are intended to restrict late occurring health effects and include a 3% risk of exposure-induced death from cancer and new limits for central nervous system and heart disease risks. Short-term dose limits are used to prevent in-flight radiation sickness or death through restriction of the doses to the blood forming organs and to prevent clinically significant cataracts or skin damage through lens and skin dose limits, respectively. Large uncertainties exist in estimating the health risks of space radiation, chiefly the understanding of the radiobiology of heavy ions and dose rate and dose protraction effects, and the limitations in human epidemiology data. To protect against these uncertainties NASA estimates the 95% confidence in the cancer risk projection intervals as part of astronaut flight readiness assessments and mission design. Accurate organ dose and particle spectra models are needed to ensure astronauts stay below radiation limits and to support the goal of narrowing the uncertainties in risk projections. Methodologies for evaluation of space environments, radiation quality, and organ doses to evaluate limits are discussed, and current projections for lunar and Mars missions are described.

76 FR 53847 - New International Commission on Radiological Protection; Recommendations on the Annual Dose Limit...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

... Radiological Protection; Recommendations on the Annual Dose Limit to the Lens of the Eye AGENCY: Nuclear... Protection (ICRP) recommendations for the limitation of annual dose to the lens of the eye. This significant... might be lower than previously considered. For the lens of the eye, the threshold in absorbed dose for...

[SUBSTANTIATION OF DOSE LIMITS FOR A NEW NORMATIVE DOCUMENT ON RADIATION SAFETY OF LONG-DURATION SPACE MISSIONS AT ORBIT ALTITUDES OF UP TO 500 KM].

PubMed

Ushakov, I B; Grigoriev, Yu G; Shafirkin, A V; Shurshakov, V A

2016-01-01

Review of the data of experimental radiobiology and epidemiological follow-up of large groups of people subjected to radiation exposures on Earth has been undertaken to substantiate dose limits for critical organs of cosmonauts in order to ensure good performance and vitality while on long-duration orbital missions. The career dose limits for cosmonauts and astronauts established earlier in the USSR and USA amounted to nothing more but banning the risk of cancer death increase to 3%. To apply more rigorous criteria of delayed radiation risks, the Russian limits for cosmonauts were revised to substantiate a 4-fold reduction of the average tissue equivalent dose maximum to 1 Sv. The total of cancer and non-cancer radiation risks over lifetime and probable reduction of mean life expectancy (MLE) were calculated using the model of radiation-induced mortality for mammals and taken as the main damage to health. The established dose limit is equal to the career dose for nuclear industry personnel set forth by Russian standard document NRB 99/2009. For better agreement of admissible threshold doses to critical human organs (bone marrow, lens and skin) in the revised radiation limits for long-duration space missions and radiation safety limits on Earth, reduction of dose limits for the critical organs were substantiated additionally; these limits comply with those for planned over-exposure on Earth in document NRB 99/2009.

Occupational radiation dose to eyes from endoscopic retrograde cholangiopancreatography procedures in light of the revised eye lens dose limit from the International Commission on Radiological Protection.

PubMed

O'Connor, U; Gallagher, A; Malone, L; O'Reilly, G

2013-02-01

Endoscopic retrograde cholangiopancreatography (ERCP) is a common procedure that combines the use of X-ray fluoroscopy and endoscopy for examination of the bile duct. Published data on ERCP doses are limited, including staff eye dose from ERCP. Occupational eye doses are of particular interest now as the International Commission on Radiological Protection (ICRP) has recommended a reduction in the dose limit to the lens of the eye. The aim of this study was to measure occupational eye doses obtained from ERCP procedures. A new eye lens dosemeter (EYE-D(™), Radcard, Krakow, Poland) was used to measure the ERCP eye dose, H(p)(3), at two endoscopy departments in Ireland. A review of radiation protection practice at the two facilities was also carried out. The mean equivalent dose to the lens of the eye of a gastroenterologist is 0.01 mSv per ERCP procedure with an undercouch X-ray tube and 0.09 mSv per ERCP procedure with an overcouch X-ray tube. Staff eye dose normalised to patient kerma area product is also presented. Staff eye doses in ERCP have the potential to exceed the revised ICRP limit of 20 mSv per annum when an overcouch X-ray tube is used. The EYE-D dosemeter was found to be a convenient method for measuring lens dose. Eye doses in areas outside of radiology departments should be kept under review, particularly in light of the new ICRP eye dose limit. Occupational eye lens doses from ERCP procedures have been established using a new commercially available dedicated H(p)(3) dosemeter.

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

10 CFR 20.1302 - Compliance with dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... public. 20.1302 Section 20.1302 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation Dose Limits for Individual Members of the Public § 20.1302 Compliance with dose limits..., surveys of radiation levels in unrestricted and controlled areas and radioactive materials in effluents...

Analysis of Exposure-Dose Variation of Inhaled Particles in Adult Subjects.

EPA Science Inventory

Although internal dose is a key factor for determining the health risk of inhaled pollutant particles, available dose information is largely limited to young healthy adults under a few typical exposure conditions. Extrapolation of the limited dose information to different populat...

Dose limits to the lens of the eye: International Basic Safety Standards and related guidance.

PubMed

Boal, T J; Pinak, M

2015-06-01

The International Atomic Energy Agency (IAEA) safety requirements: 'General Safety Requirements Part 3--Radiation protection and safety of radiation sources: International Basic Safety Standards' (BSS) was approved by the IAEA Board of Governors at its meeting in September 2011, and was issued as General Safety Requirements Part 3 in July 2014. The equivalent dose limit for the lens of the eye for occupational exposure in planned exposure situations was reduced from 150 mSv year(-1) to 20 mSv year(-1), averaged over defined periods of 5 years, with no annual dose in a single year exceeding 50 mSv. This reduction in the dose limit for the lens of the eye followed the recommendation of the International Commission on Radiological Protection in its statement on tissue reactions of 21 April 2011. IAEA has developed guidance on the implications of the new dose limit for the lens of the eye. This paper summarises the process that led to the inclusion of the new dose limit for the lens of the eye in the BSS, and the implications of the new dose limit. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

ICPP environmental monitoring report CY-1995

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1996-04-01

Summarized in this report are the data collected through Environmental Monitoring programs conducted at the Idaho Chemical Processing Plant (ICPP) by the Environmental Protection Department. The ICPP is responsible for complying with all applicable Federal, State, Local and DOE Rules, Regulations and Orders. Radiological effluent and emissions are regulated by the DOE in accordance with the Derived Concentration Guides (DCGs). The State of Idaho regulates nonradiological waste resulting from the ICPP operations including airborne, liquid, and solid waste. The Environmental Department updated the Quality Assurance (QA) Project Plan for Environmental Monitoring activities during the third quarter of 1992. QA activitiesmore » have resulted in the ICPP`s implementation of the Environmental Protection Agency (EPA) rules and guidelines pertaining to the collection, analyses, and reporting of environmentally related samples. Where no EPA methods for analyses existed for radionuclides, Lockheed Idaho Technologies Company (LITCO) methods were used.« less

Determining population based mortality risk in the Department of Veterans Affairs.

PubMed

Stefos, Theodore; Lehner, Laura; Render, Marta; Moran, Eileen; Almenoff, Peter

2012-06-01

We develop a patient level hierarchical regression model using administrative claims data to assess mortality outcomes for a national VA population. This model, which complements more traditional process driven performance measures, includes demographic variables and disease specific measures of risk classified by Diagnostic Cost Groups (DCGs). Results indicate some ability to discriminate survivors and non-survivors with an area under the Receiver Operating Characteristic Curve (C-statistic) of .86. Observed to expected mortality ranges from .86 to 1.12 across predicted mortality deciles while Risk Standardized Mortality Rates (RSMRs) range from .76 to 1.29 across 145 VA hospitals. Further research is necessary to understand mortality variation which persists even after adjusting for case mix differences. Future work is also necessary to examine the role of personal behaviors on patient outcomes and the potential impact on population survival rates from changes in treatment policy and infrastructure investment.

ICPP environmental monitoring report for CY-1996

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neff, J.K.

1997-06-01

Summarized in this report are the data collected through Environmental Monitoring programs conducted at the Idaho Chemical Processing Plant (ICPP) by the Environmental Affairs Department. This report is published in response to DOE Order 5400.1. The ICPP is responsible for complying with all applicable Federal, State, Local and DOE Rules, Regulations and Orders. Radiological effluent and emissions are regulated by the DOE in accordance with the Derived Concentration Guides (DCGs) as presented in DOE Order 5400.5. The State of Idaho regulates nonradiological waste resulting from the ICPP operations including airborne, liquid, and solid waste. Quality Assurance activities have resulted inmore » the ICPP`s implementation of the Environmental Protection Agency (EPA) rules and guidelines pertaining to the collection, analyses, and reporting of environmentally related samples. Where no EPA methods for analyses existed for radionuclides, Lockheed Martin Idaho Technologies Company (LMITCO) methods were used.« less

ICPP environmental monitoring report CY-1994

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1995-05-01

Summarized in this report are the data collected through Environmental Monitoring programs conducted at the Idaho Chemical Processing Plant (ICPP) by the Environmental Protection Department. The ICPP is responsible for complying with all applicable Federal, State, Local and DOE Rules, Regulations and Orders. Radiological effluent and emissions are regulated by the DOE in accordance with the Derived Concentration Guides (DCGs) as presented in DOE Order 5400.5. The State of Idaho regulates nonradiological waste resulting from the ICPP operations including airborne, liquid, and solid waste. The Environmental Department updated the Quality Assurance (QA) Project Plan for Environmental Monitoring activities during themore » third quarter of 1992. QA activities have resulted in the ICPP`s implementation of the Environmental Protection Agency (EPA) rules and guidelines pertaining to the collection, analyses, and reporting of environmentally related samples. Where no EPA methods for analyses existed for radionuclides, LITCO methods were used.« less

Second Breakdown of 18V Grounded Gate NMOS induced by the Kirk Effect under Electrostatic Discharge

NASA Astrophysics Data System (ADS)

Jeon, Byung-Chul; Lee, Seung-Chul; Han, Min-Koo

2003-09-01

Electrostatic Discharge (ESD) failure mechanisms of 18V grounded gate NMOS (GGNMOS) for liquid crystal display driver IC (LDI) applications are investigated and effects of layout design parameters on the ESD immunity level are analyzed. Experimental results show that 18V GGNMOS exhibits snapback characteristics and the ESD immunity level is rather high when XO (N-drift overlap over n+ source/drain) is sufficiently large, while GGNMOS does not exhibit the sustaining region and is very vulnerable to ESD stress when XO is relatively small. Simulation results show that the ESD failure mechanism of 18V GGNMOS could be the low-temperature second breakdown induced by the Kirk effect. It is inferred that a certain amount of XO is indispensable to ensure snapback characteristics and high ESD immunity level. Simulation results also show that the ESD immunity level is increased as drain contact to gate space (DCGS) is increased.

Classification of radiation effects for dose limitation purposes: history, current situation and future prospects

PubMed Central

Hamada, Nobuyuki; Fujimichi, Yuki

2014-01-01

Radiation exposure causes cancer and non-cancer health effects, each of which differs greatly in the shape of the dose–response curve, latency, persistency, recurrence, curability, fatality and impact on quality of life. In recent decades, for dose limitation purposes, the International Commission on Radiological Protection has divided such diverse effects into tissue reactions (formerly termed non-stochastic and deterministic effects) and stochastic effects. On the one hand, effective dose limits aim to reduce the risks of stochastic effects (cancer/heritable effects) and are based on the detriment-adjusted nominal risk coefficients, assuming a linear-non-threshold dose response and a dose and dose rate effectiveness factor of 2. On the other hand, equivalent dose limits aim to avoid tissue reactions (vision-impairing cataracts and cosmetically unacceptable non-cancer skin changes) and are based on a threshold dose. However, the boundary between these two categories is becoming vague. Thus, we review the changes in radiation effect classification, dose limitation concepts, and the definition of detriment and threshold. Then, the current situation is overviewed focusing on (i) stochastic effects with a threshold, (ii) tissue reactions without a threshold, (iii) target organs/tissues for circulatory disease, (iv) dose levels for limitation of cancer risks vs prevention of non-life-threatening tissue reactions vs prevention of life-threatening tissue reactions, (v) mortality or incidence of thyroid cancer, and (vi) the detriment for tissue reactions. For future discussion, one approach is suggested that classifies radiation effects according to whether effects are life threatening, and radiobiological research needs are also briefly discussed. PMID:24794798

Modeling adverse event counts in phase I clinical trials of a cytotoxic agent.

PubMed

Muenz, Daniel G; Braun, Thomas M; Taylor, Jeremy Mg

2018-05-01

Background/Aims The goal of phase I clinical trials for cytotoxic agents is to find the maximum dose with an acceptable risk of severe toxicity. The most common designs for these dose-finding trials use a binary outcome indicating whether a patient had a dose-limiting toxicity. However, a patient may experience multiple toxicities, with each toxicity assigned an ordinal severity score. The binary response is then obtained by dichotomizing a patient's richer set of data. We contribute to the growing literature on new models to exploit this richer toxicity data, with the goal of improving the efficiency in estimating the maximum tolerated dose. Methods We develop three new, related models that make use of the total number of dose-limiting and low-level toxicities a patient experiences. We use these models to estimate the probability of having at least one dose-limiting toxicity as a function of dose. In a simulation study, we evaluate how often our models select the true maximum tolerated dose, and we compare our models with the continual reassessment method, which uses binary data. Results Across a variety of simulation settings, we find that our models compare well against the continual reassessment method in terms of selecting the true optimal dose. In particular, one of our models which uses dose-limiting and low-level toxicity counts beats or ties the other models, including the continual reassessment method, in all scenarios except the one in which the true optimal dose is the highest dose available. We also find that our models, when not selecting the true optimal dose, tend to err by picking lower, safer doses, while the continual reassessment method errs more toward toxic doses. Conclusion Using dose-limiting and low-level toxicity counts, which are easily obtained from data already routinely collected, is a promising way to improve the efficiency in finding the true maximum tolerated dose in phase I trials.

Occupational radiation dose to eyes from interventional radiology procedures in light of the new eye lens dose limit from the International Commission on Radiological Protection

PubMed Central

Walsh, C; Gallagher, A; Dowling, A; Guiney, M; Ryan, J M; McEniff, N; O'Reilly, G

2015-01-01

Objective: In 2011, the International Commission on Radiological Protection (ICRP) recommended a substantial reduction in the equivalent dose limit for the lens of the eye, in line with a reduced threshold of absorbed dose for radiation-induced cataracts. This is of particular relevance in interventional radiology (IR) where it is well established that staff doses can be significant, however, there is a lack of data on IR eye doses in terms of Hp(3). Hp(3) is the personal dose equivalent at a depth of 3 mm in soft tissue and is used for measuring lens dose. We aimed to obtain a reliable estimate of eye dose to IR operators. Methods: Lens doses were measured for four interventional radiologists over a 3-month period using dosemeters specifically designed to measure Hp(3). Results: Based on their typical workloads, two of the four interventional radiologists would exceed the new ICRP dose limit with annual estimated doses of 31 and 45 mSv to their left eye. These results are for an “unprotected” eye, and for IR staff who routinely wear lead glasses, the dose beneath the glasses is likely to be significantly lower. Staff eye dose normalized to patient kerma–area product and eye dose per procedure have been included in the analysis. Conclusion: Eye doses to IR operators have been established using a dedicated Hp(3) dosemeter. Estimated annual doses have the potential to exceed the new ICRP limit. Advances in knowledge: We have estimated lens dose to interventional radiologists in terms of Hp(3) for the first time in an Irish hospital setting. PMID:25761211

Liquid Medication Dosing Errors by Hispanic Parents: Role of Health Literacy and English Proficiency

PubMed Central

Harris, Leslie M.; Dreyer, Benard; Mendelsohn, Alan; Bailey, Stacy C.; Sanders, Lee M.; Wolf, Michael S.; Parker, Ruth M.; Patel, Deesha A.; Kim, Kwang Youn A.; Jimenez, Jessica J.; Jacobson, Kara; Smith, Michelle; Yin, H. Shonna

2016-01-01

Objective Hispanic parents in the US are disproportionately affected by low health literacy and limited English proficiency (LEP). We examined associations between health literacy, LEP, and liquid medication dosing errors in Hispanic parents. Methods Cross-sectional analysis of data from a multisite randomized controlled experiment to identify best practices for the labeling/dosing of pediatric liquid medications (SAFE Rx for Kids study); 3 urban pediatric clinics. Analyses were limited to Hispanic parents of children <8 years, with health literacy and LEP data (n=1126). Parents were randomized to 5 groups that varied by pairing of units of measurement on the label/dosing tool. Each parent measured 9 doses [3 amounts (2.5,5,7.5 mL) using 3 tools (2 syringes (0.2,0.5 mL increment), 1 cup)] in random order. Dependent variable: Dosing error=>20% dose deviation. Predictor variables: health literacy (Newest Vital Sign) [limited=0–3; adequate=4–6], LEP (speaks English less than “very well”). Results 83.1% made dosing errors (mean(SD) errors/parent=2.2(1.9)). Parents with limited health literacy and LEP had the greatest odds of making a dosing error compared to parents with adequate health literacy who were English proficient (% trials with errors/parent=28.8 vs. 12.9%; AOR=2.2[1.7–2.8]). Parents with limited health literacy who were English proficient were also more likely to make errors (% trials with errors/parent=18.8%; AOR=1.4[1.1–1.9]). Conclusion Dosing errors are common among Hispanic parents; those with both LEP and limited health literacy are at particular risk. Further study is needed to examine how the redesign of medication labels and dosing tools could reduce literacy and language-associated disparities in dosing errors. PMID:28477800

New Stochastic Annual Limits on Intake for Selected Radionuclides

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carbaugh, Eugene H.

Annual limits on intake (ALI) have historically been tabulated by the International Commission on Radiological Protection (e.g., ICRP 1979, 1961) and also by the Environmental Protection Agency (EPA 1988). These compilations have been rendered obsolete by more recent ICRP dosimetry methods, and, rather than provide new ALIs, the ICRP has opted instead to provide committed dose coefficients from which an ALI can be determined by a user for a specific set of conditions. The U.S. Department of Energy historically has referenced compilations of ALIs and has defined their method of calculation in its radiation protection regulation (10 CFDR 835), butmore » has never provided a specific compilation. Under June 2007 amendments to 10 CFR 835, ALIs can be calculated by dividing an appropriate dose limit, either 5-rem (0.05 Sv) effective dose or 50 rem (0.5 Sv) equivalent dose to an individual organ or tissue, by an appropriate committed dose coefficient. When based on effective dose, the ALI is often referred to as a stochastic annual limit on intake (SALI), and when based on the individual organ or tissue equivalent limit, it has often been called a deterministic annual limit on intake (DALI).« less

Assessment of the benefits and impacts in the U.S. Nuclear Power Industry of hypothesized lower occupational dose limits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Andersen, R.L.; Schmitt, J.F.

1995-03-01

The International Commission on Radiological Protection and the National Council on Radiation Protection and Measurements have issued recommendations that would limit occupational exposure of individuals to doses lower than regulatory limits contained in the Nuclear Regulatory Commission`s 10 CFR Part 20, {open_quotes}Standards for Protection Against Radiation{close_quotes}. Because of this situation, there is interest in the potential benefits and impacts that would be associated with movement of the NRC regulatory limits toward the advisory bodies recommendations. The records of occupational worker doses in the U.S. commercial nuclear power industry show that the vast majority of these workers have doses that aremore » significantly below the regulatory limit of 50 mSv (5 rem) per year. Some workers doses do approach the limits, however. This is most common in the case of specially skilled workers, especially those with skills utilized in support of plant outage work. Any consideration of the potential benefits and impacts of hypothesized lower dose limits must address these workers as an important input to the overall assessment. There are also, of course, many other areas in which the benefits and impacts must be evaluated. To prepare to provide valid, constructive input on this matter, the U.S. nuclear power industry is undertaking an assessment, facilitated by the Nuclear Energy Institute (NEI), of the potential benefits and impacts at its facilities associated with hypothesized lower occupational dose limits. Some preliminary results available to date from this assessment are provided.« less

A Phase I Trial and Pharmacokinetic Study of Aflibercept (VEGF Trap) in Children with Refractory Solid Tumors: A Children’s Oncology Group Phase I Consortium Report

PubMed Central

Bender, Julia Glade; Blaney, Susan M.; Borinstein, Scott; Reid, Joel M.; Baruchel, Sylvain; Ahern, Charlotte; Ingle, Ashish M.; Yamashiro, Darrell J.; Chen, Alice; Weigel, Brenda; Adamson, Peter C.; Park, Julie R.

2012-01-01

Background Aflibercept is a novel decoy receptor that efficiently neutralizes circulating vascular endothelial growth factor (VEGF). A pediatric phase 1 trial was performed to define the dose limiting toxicities (DLT), maximum tolerated dose (MTD) and pharmacokinetics (PK) of aflibercept. Methods Cohorts of 3–6 children with refractory solid tumors received aflibercept intravenously over 60 minutes every 14 days, at 2.0, 2.5 or 3.0 mg/kg/dose. PK sampling and analysis of peripheral blood biomarkers were performed with the initial dose. Results 21 eligible patients were enrolled; 18 were fully evaluable for toxicity. One of 6 patients receiving 2.0 mg/kg/dose developed dose-limiting intra-tumoral hemorrhage and 2 of 6 receiving 3.0 mg/kg/dose developed either dose-limiting tumor pain or tissue necrosis. None of the 6 patients receiving 2.5 mg/kg/dose developed DLT, defining this as the MTD. The most common non-dose limiting toxicities were hypertension and fatigue. Three patients with hepatocellular carcinoma, hepatoblastoma and clear cell sarcoma had stable disease for >13 weeks. At the MTD, the ratio of free to bound aflibercept serum concentration was 2.10 on day 8, but only 0.44 by day 15. A rapid decrease in VEGF (p<0.05) and increase in PlGF (p<0.05) from baseline was observed in response to aflibercept by day 2. Conclusion The aflibercept MTD in children of 2.5 mg/kg/dose every 14 days is lower that the adult recommended dose of 4.0 mg/kg. This dose achieves, but does not sustain, free aflibercept concentrations in excess of bound. Tumor pain and hemorrhage may be evidence of anti-tumor activity, but were dose-limiting. PMID:22791883

Decreasing Irradiated Rat Lung Volume Changes Dose-Limiting Toxicity From Early to Late Effects

DOE Office of Scientific and Technical Information (OSTI.GOV)

Veen, Sonja J. van der; Faber, Hette; Ghobadi, Ghazaleh

2016-01-01

Purpose: Technological developments in radiation therapy result in smaller irradiated volumes of normal tissue. Because the risk of radiation therapy-induced toxicity generally depends on irradiated volume, changing volume could change the dose-limiting toxicity of a treatment. Recently, in our rat model, we found that early radiation-induced lung dysfunction (RILD) was closely related to irradiated volume dependent vascular remodeling besides inflammation. The exact relationship between early and late RILD is still unknown. Therefore, in this preclinical study we investigated the dose-volume relationship of late RILD, assessed its dependence on early and late pathologies and studied if decreasing irradiated volume changed themore » dose-limiting toxicity. Methods and Materials: A volume of 25%, 32%, 50%, 63%, 88%, or 100% of the rat lung was irradiated using protons. Until 26 weeks after irradiation, respiratory rates were measured. Macrovascular remodeling, pulmonary inflammation, and fibrosis were assessed at 26 weeks after irradiation. For all endpoints dose-volume response curves were made. These results were compared to our previously published early lung effects. Results: Early vascular remodeling and inflammation correlated significantly with early RILD. Late RILD correlated with inflammation and fibrosis, but not with vascular remodeling. In contrast to the early effects, late vascular remodeling, inflammation and fibrosis showed a primarily dose but not volume dependence. Comparison of respiratory rate increases early and late after irradiation for the different dose-distributions indicated that with decreasing irradiated volumes, the dose-limiting toxicity changed from early to late RILD. Conclusions: In our rat model, different pathologies underlie early and late RILD with different dose-volume dependencies. Consequently, the dose-limiting toxicity changed from early to late dysfunction when the irradiated volume was reduced. In patients, early and late RILD are also due to different pathologies. As such, new radiation techniques reducing irradiated volume might change the dose-limiting toxicity of the radiation therapy treatment.« less

A phase I study of LY317615 (enzastaurin) and temozolomide in patients with gliomas (EORTC trial 26054)

PubMed Central

Rampling, Roy; Sanson, Marc; Gorlia, Thiery; Lacombe, Denis; Lai, Christina; Gharib, Myriam; Taal, Walter; Stoffregen, Clemens; Decker, Rodney; van den Bent, Martin J.

2012-01-01

We report a phase 1 study to examine the safety and recommended dose of the oral protein kinase C-beta inhibitor (anti-angiogenic) enzastaurin in combination with single-agent temozolomide. The study was conducted in patients with recurrent glioblastoma or newly diagnosed disease that was not treatable with standard (chemo)radiotherapy. Patients were treated with standard dose temozolomide (200 mg/m2 for 5 days every 4 weeks) together with daily oral enzastaurin. Three dose levels of enzastaurin were investigated: 250 mg daily (OD), 500 mg OD, and 250 mg twice daily (BID). Dose-limiting toxicity was determined in the first 2 cycles, but treatment continued until limiting toxicity or disease progression was identified. Twenty-eight patients were enrolled. No dose-limiting toxicity was noted at 250 mg OD or 500 mg OD. However, at 250 mg BID, 2 dose-limiting episodes of thrombocytopenia were noted. The recommended dose for enzastaurin in combination with standard 4-weekly temozolomide is therefore 500 mg OD. The pharmacokinetics of enzastaurin in combination with temozolomide was evaluated. Temozolomide did not appear to effect enzastaurin exposures at the 250 mg or 500 mg OD dose levels. PMID:22291006

Environmental monitoring at Mound: 1986 report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Carfagno, D.G.; Farmer, B.M.

1987-05-11

The local environment around Mound was monitored for tritium and plutonium-238. The results are reported for 1986. Environmental media analyzed included air, water, vegetation, foodstuffs, and sediment. The average concentrations of plutonium-238 and tritium were within the DOE interim air and water Derived Concentration Guides (DCG) for these radionuclides. The average incremental concentrations of plutonium-238 and tritium oxide in air measured at all offsite locations during 1986 were 0.03% and 0.01%, respectively, of the DOE DCGs for uncontrolled areas. The average incremental concentration of plutonium-238 measured at all locations in the Great Miami River during 1986 was 0.0005% of themore » DOE DCG. The average incremental concentration of tritium measured at all locations in the Great Miami River during 1986 was 0.005% of the DOE DCG. The average incremental concentrations of plutonium-238 found during 1986 in surface and area drinking water were less than 0.00006% of the DOE DCG. The average incremental concentration of tritium in surface water was less than 0.005% of the DOE DCG. All tritium in drinking water data is compared to the US EPA Drinking Water Standard. The average concentrations in local private and municipal drinking water systems were less than 25% and 1.5%, respectively. Although no DOE DCG is available for foodstuffs, the average concentrations are a small fraction of the water DCG (0.04%). The concentrations of sediment samples obtained at offsite surface water sampling locations were extremely low and therefore represent no adverse impact to the environment. The dose equivalent estimates for the average air, water, and foodstuff concentrations indicate that the levels are within 1% of the DOE standard of 100 mrem. None of these exceptions, however, had an adverse impact on the water quality of the Great Miami River or caused the river to exceed Ohio Stream Standards. 20 refs., 5 figs., 31 tabs.« less

Characterization of MOSFET dosimeters for low-dose measurements in maxillofacial anthropomorphic phantoms.

PubMed

Koivisto, Juha H; Wolff, Jan E; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-07-08

The aims of this study were to characterize reinforced metal-oxide-semiconductor field-effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low-dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50-90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point-dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k = 2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low-dose limit. The sensitivity was 3.09 ± 0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was -8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD-comparable low-dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low.

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2010-01-01 2010-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2014-01-01 2014-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2012-01-01 2012-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2013-01-01 2013-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 835.202 - Occupational dose limits for general employees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... tissue other than the skin or the lens of the eye of 50 rems (0.5 Sv); (3) An equivalent dose to the lens of the eye of 15 rems (0.15 Sv); and (4) The sum of the equivalent dose to the skin or to any... 10 Energy 4 2011-01-01 2011-01-01 false Occupational dose limits for general employees. 835.202...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

10 CFR 20.1201 - Occupational dose limits for adults.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Occupational dose limits for adults. 20.1201 Section 20.1201 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose... surveys or other radiation measurements for the purpose of demonstrating compliance with the occupational...

Absorbed dose thresholds and absorbed dose rate limitations for studies of electron radiation effects on polyetherimides

NASA Technical Reports Server (NTRS)

Long, Edward R., Jr.; Long, Sheila Ann T.; Gray, Stephanie L.; Collins, William D.

1989-01-01

The threshold values of total absorbed dose for causing changes in tensile properties of a polyetherimide film and the limitations of the absorbed dose rate for accelerated-exposure evaluation of the effects of electron radiation in geosynchronous orbit were studied. Total absorbed doses from 1 kGy to 100 MGy and absorbed dose rates from 0.01 MGy/hr to 100 MGy/hr were investigated, where 1 Gy equals 100 rads. Total doses less than 2.5 MGy did not significantly change the tensile properties of the film whereas doses higher than 2.5 MGy significantly reduced elongation-to-failure. There was no measurable effect of the dose rate on the tensile properties for accelerated electron exposures.

Radiation-induced cataracts: the Health Protection Agency's response to the ICRP statement on tissue reactions and recommendation on the dose limit for the eye lens.

PubMed

Bouffler, Simon; Ainsbury, Elizabeth; Gilvin, Phil; Harrison, John

2012-12-01

This paper presents the response of the Health Protection Agency (HPA) to the 2011 statement from the International Commission on Radiological Protection (ICRP) on tissue reactions and recommendation of a reduced dose limit for the lens of the eye. The response takes the form of a brief review of the most recent epidemiological and mechanistic evidence. This is presented together with a discussion of dose limits in the context of the related risk and the current status of eye dosimetry, which is relevant for implementation of the limits. It is concluded that although further work is desirable to quantify better the risk at low doses and following protracted exposures, along with research into the mechanistic basis for radiation cataractogenesis to inform selection of risk projection models, the HPA endorses the conclusion reached by the ICRP in their 2011 statement that the equivalent dose limit for the lens of the eye should be reduced from 150 to 20 mSv per year, averaged over a five year period, with no year's dose exceeding 50 mSv.

Assessment of the occupational eye lens dose for clinical staff in interventional radiology, cardiology and neuroradiology.

PubMed

Omar, Artur; Kadesjö, Nils; Palmgren, Charlotta; Marteinsdottir, Maria; Segerdahl, Tony; Fransson, Annette

2017-03-20

In accordance with recommendations by the International Commission on Radiological Protection, the current European Basic Safety Standards has adopted a reduced occupational eye lens dose limit of 20 mSv yr -1 . The radiation safety implications of this dose limit is of concern for clinical staff that work with relatively high dose x-ray angiography and interventional radiology. Presented in this work is a thorough assessment of the occupational eye lens dose based on clinical measurements with active personal dosimeters worn by staff during various types of procedures in interventional radiology, cardiology and neuroradiology. Results are presented in terms of the estimated equivalent eye lens dose for various medical professions. In order to compare the risk of exceeding the regulatory annual eye lens dose limit for the widely different clinical situations investigated in this work, the different medical professions were separated into categories based on their distinct work pattern: staff that work (a) regularly beside the patient, (b) in proximity to the patient and (c) typically at a distance from the patient. The results demonstrate that the risk of exceeding the annual eye lens dose limit is of concern for staff category (a), i.e. mainly the primary radiologist/cardiologist. However, the results also demonstrate that the risk can be greatly mitigated if radiation protection shields are used in the clinical routine. The results presented in this work cover a wide range of clinical situations, and can be used as a first indication of the risk of exceeding the annual eye lens dose limit for staff at other medical centres.

Regulating exposure of the lens of the eye to ionising radiations.

PubMed

Thorne, M C

2012-06-01

The International Commission on Radiological Protection (ICRP) has reviewed recent epidemiological evidence suggesting that, for the lens of the eye, the threshold in absorbed dose for the induction of deleterious health effects is about 0.5 Gy. On this basis, the Commission recommends that for occupational exposure in planned exposure situations, the equivalent dose limit for the lens of the eye should be 20 mSv in a year, averaged over defined periods of 5 yr, with exposure not exceeding 50 mSv in any single year. This paper summarises the data that have been taken into account by the ICRP and critically examines whether the proposed downward revision of the dose limit is justified. Overall, it is concluded that the accumulating radiobiological and epidemiological evidence makes it more appropriate to treat cataract induction as a stochastic rather than a deterministic effect. Within this framework, it is illogical to have the same dose limit for the lens of the eye as for the whole body irradiated uniformly. This could be addressed either by removing the special dose limit for the lens of the eye, assigning it an appropriate tissue weighting factor and including it in the computation of the effective dose, or through a composite approach involving the use of a tissue weighting factor for effective dose computations together with a special limit on the equivalent dose to the lens of the eye to ensure that no individual was subject to an unacceptably high risk of induction of clinically significant cataracts.

User Guide for GoldSim Model to Calculate PA/CA Doses and Limits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, F.

2016-10-31

A model to calculate doses for solid waste disposal at the Savannah River Site (SRS) and corresponding disposal limits has been developed using the GoldSim commercial software. The model implements the dose calculations documented in SRNL-STI-2015-00056, Rev. 0 “Dose Calculation Methodology and Data for Solid Waste Performance Assessment (PA) and Composite Analysis (CA) at the Savannah River Site”.

Accuracy and Radiation Dose Reduction of Limited-Range CT in the Evaluation of Acute Appendicitis in Pediatric Patients.

PubMed

Jin, Michael; Sanchez, Thomas R; Lamba, Ramit; Fananapazir, Ghaneh; Corwin, Michael T

2017-09-01

The purpose of this article is to determine the accuracy and radiation dose reduction of limited-range CT prescribed from the top of L2 to the top of the pubic symphysis in children with suspected acute appendicitis. We performed a retrospective study of 210 consecutive pediatric patients from December 11, 2012, through December 11, 2014, who underwent abdominopelvic CT for suspected acute appendicitis. Two radiologists independently reviewed the theoretic limited scans from the superior L2 vertebral body to the top of the pubic symphysis, to assess for visualization of the appendix, acute appendicitis, alternative diagnoses, and incidental findings. Separately, the same parameters were assessed on the full scan by the same two reviewers. Whole-body effective doses were determined for the full- and limited-range scans and were compared using the paired t test. The appendix or entire cecum was visualized on the limited scan in all cases, and no cases of acute appendicitis were missed on the simulated limited scan compared with the full scan. Two alternative diagnoses were missed with the limited scan: one case of hydronephrosis and one of acute acalculous cholecystitis. The mean effective dose for the original scan was 5.6 mSv and that for the simulated limited scan was 3.0 mSv, resulting in a dose reduction of 46.4% (p < 0.001). A limited-range CT examination performed from the top of L2 to the top of the pubic symphysis is as accurate as a full-range abdominopelvic CT in evaluating pediatric patients with suspected appendicitis and reduces the dose by approximately 46%.

Browns Ferry Nuclear Plant radiological impact assessment report, January-June 1988

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, B.E.

1988-01-01

Potential doses to maximum individuals and the population around Browns Ferry are calcuated for each quarter. Measured plant releases for the reporting period are used to estimate these doses. Dispersion of radioactive effluents in the environment is estimated in accordance with the guidance provided and measuring during the period. Using dose calculation methodologies which are described in detail in the Browns Ferry Offsite Dose Calculation Manual, the doses are calculated and used to determine compliance with the dose limits contained in Browns Ferry's Operating License. In this report, the doses resulting from releases are described and compared to quarterly andmore » annual limits established for Browns Ferry.« less

Characterization of MOSFET dosimeters for low‐dose measurements in maxillofacial anthropomorphic phantoms

PubMed Central

Wolff, Jan E.; Kiljunen, Timo; Schulze, Dirk; Kortesniemi, Mika

2015-01-01

The aims of this study were to characterize reinforced metal‐oxide‐semiconductor field‐effect transistor (MOSFET) dosimeters to assess the measurement uncertainty, single exposure low‐dose limit with acceptable accuracy, and the number of exposures required to attain the corresponding limit of the thermoluminescent dosimeters (TLD). The second aim was to characterize MOSFET dosimeter sensitivities for two dental photon energy ranges, dose dependency, dose rate dependency, and accumulated dose dependency. A further aim was to compare the performance of MOSFETs with those of TLDs in an anthropomorphic phantom head using a dentomaxillofacial CBCT device. The uncertainty was assessed by exposing 20 MOSFETs and a Barracuda MPD reference dosimeter. The MOSFET dosimeter sensitivities were evaluated for two photon energy ranges (50–90 kVp) using a constant dose and polymethylmethacrylate backscatter material. MOSFET and TLD comparative point‐dose measurements were performed on an anthropomorphic phantom that was exposed with a clinical CBCT protocol. The MOSFET single exposure low dose limit (25% uncertainty, k=2) was 1.69 mGy. An averaging of eight MOSFET exposures was required to attain the corresponding TLD (0.3 mGy) low‐dose limit. The sensitivity was 3.09±0.13 mV/mGy independently of the photon energy used. The MOSFET dosimeters did not present dose or dose rate sensitivity but, however, presented a 1% decrease of sensitivity per 1000 mV for accumulated threshold voltages between 8300 mV and 17500 mV. The point doses in an anthropomorphic phantom ranged for MOSFETs between 0.24 mGy and 2.29 mGy and for TLDs between 0.25 and 2.09 mGy, respectively. The mean difference was −8%. The MOSFET dosimeters presented statistically insignificant energy dependency. By averaging multiple exposures, the MOSFET dosimeters can achieve a TLD‐comparable low‐dose limit and constitute a feasible method for diagnostic dosimetry using anthropomorphic phantoms. However, for single in vivo measurements (<1.7 mGy) the sensitivity is too low. PACS number: 87.50.wj PMID:26219008

Occupational Radiation Exposure to the Extremities of Medical Staff during Hysterosalpingography and Radionuclide Bone Scan Procedures in Several Nigerian Hospitals.

PubMed

Jibiri, Nnamdi Norbert; Akintunde, Tawakalitu Oluwatoyin; Dambele, Musa Yusuf; Olowookere, Christopher Jimoh

2016-10-05

The practice of regular dose measurement helps to ascertain the level of occupational dose delivered to the staff involved in diagnostic procedures. This study was carried out to evaluate the dose exposed to the hands of radiologists and a radiologic technologist carrying out HSG and radionuclide bone scan examinations in several hospitals in Nigeria. Radiation doses exposed to the hands of radiologists and a technician carrying out hysterosalpingography (HSG) and bone scan procedures were measured using calibrated thermo-luminescent dosimeters. Five radiologists and a radiologic technologist were included in the study for dose measurement. The study indicates that each radiologist carried out approximately 2 examinations per week with the mean dose ranging between 0.49-0.62 mSv per week, resulting in an annual dose of 191 mSv. Similarly, the occupational dose delivered to both the left and right hands of a radiologic technologist administering 99mTc-methylene diphosphonate (MDP) without cannula and with cannula were 10.68 (720.2) and 13.82 (556.4) mSv per week (and per annum), respectively. It was determined that the left hand of the personnel received higher doses than their right hand. The estimated annual dose during HSG is far below the annual dose limit for deterministic effects, however, it is greater than 10% of the applicable annual dose limit. Hence, routine monitoring is required to ensure adequate protection of the personnel. The total annual dose received during the bone scan exceeds the annual dose limit for both hands, and the dose to either left or right hand is greater than the dose limit of 500 mSv/yr. The radiologists monitored are not expected to incur any deterministic effects during HSG examinations, however, accumulated doses arising from the scattered radiation to the eyes, legs, and neck could be substantial and might lead to certain effects. More staff are required to administer 99mTc-MDP in Nigerian institutions to prevent excessive doses to personnel.

Occupational Radiation Exposure to the Extremities of Medical Staff during Hysterosalpingography and Radionuclide Bone Scan Procedures in Several Nigerian Hospitals

PubMed Central

Jibiri, Nnamdi Norbert; Akintunde, Tawakalitu Oluwatoyin; Dambele, Musa Yusuf; Olowookere, Christopher Jimoh

2016-01-01

Objective: The practice of regular dose measurement helps to ascertain the level of occupational dose delivered to the staff involved in diagnostic procedures. This study was carried out to evaluate the dose exposed to the hands of radiologists and a radiologic technologist carrying out HSG and radionuclide bone scan examinations in several hospitals in Nigeria. Methods: Radiation doses exposed to the hands of radiologists and a technician carrying out hysterosalpingography (HSG) and bone scan procedures were measured using calibrated thermo-luminescent dosimeters. Five radiologists and a radiologic technologist were included in the study for dose measurement. Results: The study indicates that each radiologist carried out approximately 2 examinations per week with the mean dose ranging between 0.49-0.62 mSv per week, resulting in an annual dose of 191 mSv. Similarly, the occupational dose delivered to both the left and right hands of a radiologic technologist administering 99mTc-methylene diphosphonate (MDP) without cannula and with cannula were 10.68 (720.2) and 13.82 (556.4) mSv per week (and per annum), respectively. It was determined that the left hand of the personnel received higher doses than their right hand. Conclusion: The estimated annual dose during HSG is far below the annual dose limit for deterministic effects, however, it is greater than 10% of the applicable annual dose limit. Hence, routine monitoring is required to ensure adequate protection of the personnel. The total annual dose received during the bone scan exceeds the annual dose limit for both hands, and the dose to either left or right hand is greater than the dose limit of 500 mSv/yr. The radiologists monitored are not expected to incur any deterministic effects during HSG examinations, however, accumulated doses arising from the scattered radiation to the eyes, legs, and neck could be substantial and might lead to certain effects. More staff are required to administer 99mTc-MDP in Nigerian institutions to prevent excessive doses to personnel. PMID:27751973

A comparison of quantum limited dose and noise equivalent dose

NASA Astrophysics Data System (ADS)

Job, Isaias D.; Boyce, Sarah J.; Petrillo, Michael J.; Zhou, Kungang

2016-03-01

Quantum-limited-dose (QLD) and noise-equivalent-dose (NED) are performance metrics often used interchangeably. Although the metrics are related, they are not equivalent unless the treatment of electronic noise is carefully considered. These metrics are increasingly important to properly characterize the low-dose performance of flat panel detectors (FPDs). A system can be said to be quantum-limited when the Signal-to-noise-ratio (SNR) is proportional to the square-root of x-ray exposure. Recent experiments utilizing three methods to determine the quantum-limited dose range yielded inconsistent results. To investigate the deviation in results, generalized analytical equations are developed to model the image processing and analysis of each method. We test the generalized expression for both radiographic and fluoroscopic detectors. The resulting analysis shows that total noise content of the images processed by each method are inherently different based on their readout scheme. Finally, it will be shown that the NED is equivalent to the instrumentation-noise-equivalent-exposure (INEE) and furthermore that the NED is derived from the quantum-noise-only method of determining QLD. Future investigations will measure quantum-limited performance of radiographic panels with a modified readout scheme to allow for noise improvements similar to measurements performed with fluoroscopic detectors.

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

10 CFR 835.206 - Limits for the embryo/fetus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 4 2010-01-01 2010-01-01 false Limits for the embryo/fetus. 835.206 Section 835.206... Exposure § 835.206 Limits for the embryo/fetus. (a) The equivalent dose limit for the embryo/fetus from the... provided in § 835.206(a) shall be avoided. (c) If the equivalent dose to the embryo/fetus is determined to...

A phase I dose escalation study of TTI-237 in patients with advanced malignant solid tumors.

PubMed

Wang-Gillam, Andrea; Arnold, Susanne M; Bukowski, Ronald M; Rothenberg, Mace L; Cooper, Wendy; Wang, Kenneth K; Gauthier, Eric; Lockhart, A Craig

2012-02-01

This study was to determine the maximum tolerated dose, dose-limiting toxicities, and pharmacokinetic profile of TTI-237, a novel anti-tubulin drug, administered weekly in patients with refractory solid tumors. Using an accelerated dose escalation design, patients with refractory solid tumors were enrolled in this study and treated with TTI-237 intravenously on days 1, 8 and 15 of a 28-day cycle. The starting dose was 4.5 mg/m(2). Pharmacokinetic studies were performed in patients at all dose levels. Twenty-eight patients were enrolled and treated with TTI-237 at dose of 4.5, 9, 15, 22.5 and 31.5 mg/m(2). One dose-limiting toxicity neutropenia fever was observed at 31.5 mg/m(2), and all seven patients developed grade 3 or 4 neutropenia at that dose level. TTI-237 dosage was de-escalated to 22.5 and 18 mg/m(2). Six patients were treated at the 18 mg/m(2) dose level without dose-limiting toxicity prior to trial termination. The mean terminal-phase elimination half-life (t(1/2)) for TTI-237 was 25-29 h, and the mean area under the concentration time curve at 31.5 mg/m(2) was 2,768 ng•h/mL. A protocol defined maximum tolerated dose was not determined because of early termination of the TTI-237 trial by the sponsor. 18 mg/m(2) may be a tolerable dose of TTI-237.

Current situations and discussions in Japan in relation to the new occupational equivalent dose limit for the lens of the eye.

PubMed

Yokoyama, Sumi; Hamada, Nobuyuki; Hayashida, Toshiyuki; Tsujimura, Norio; Tatsuzaki, Hideo; Kurosawa, Tadahiro; Nabatame, Kuniaki; Ohguchi, Hiroyuki; Ohno, Kazuko; Yamauchi-Kawaura, Chiyo; Iimoto, Takeshi; Ichiji, Takeshi; Hotta, Yutaka; Iwai, Satoshi; Akahane, Keiichi

2017-09-25

Since the International Commission on Radiological Protection recommended reducing the occupational equivalent dose limit for the lens of the eye in 2011, there have been extensive discussions in various countries. This paper reviews the current situation in radiation protection of the ocular lens and the discussions on the potential impact of the new lens dose limit in Japan. Topics include historical changes to the lens dose limit, the current situation with occupational lens exposures (e.g., in medical workers, nuclear workers, and Fukushima nuclear power plant workers) and measurements, and the current status of biological studies and epidemiological studies on radiation cataracts. Our focus is on the situation in Japan, but we believe such information sharing will be useful in many other countries.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mayo, Charles, E-mail: charles.mayo@umassmemorial.or; Yorke, Ellen; Merchant, Thomas E.

Publications relating brainstem radiation toxicity to quantitative dose and dose-volume measures derived from three-dimensional treatment planning were reviewed. Despite the clinical importance of brainstem toxicity, most studies reporting brainstem effects after irradiation have fewer than 100 patients. There is limited evidence relating toxicity to small volumes receiving doses above 60-64 Gy using conventional fractionation and no definitive criteria regarding more subtle dose-volume effects or effects after hypofractionated treatment. On the basis of the available data, the entire brainstem may be treated to 54 Gy using conventional fractionation using photons with limited risk of severe or permanent neurological effects. Smaller volumesmore » of the brainstem (1-10 mL) may be irradiated to maximum doses of 59 Gy for dose fractions <=2 Gy; however, the risk appears to increase markedly at doses >64 Gy.« less

Prediction of non-linear pharmacokinetics in humans of an antibody-drug conjugate (ADC) when evaluation of higher doses in animals is limited by tolerability: Case study with an anti-CD33 ADC.

PubMed

Figueroa, Isabel; Leipold, Doug; Leong, Steve; Zheng, Bing; Triguero-Carrasco, Montserrat; Fourie-O'Donohue, Aimee; Kozak, Katherine R; Xu, Keyang; Schutten, Melissa; Wang, Hong; Polson, Andrew G; Kamath, Amrita V

2018-05-14

For antibody-drug conjugates (ADCs) that carry a cytotoxic drug, doses that can be administered in preclinical studies are typically limited by tolerability, leading to a narrow dose range that can be tested. For molecules with non-linear pharmacokinetics (PK), this limited dose range may be insufficient to fully characterize the PK of the ADC and limits translation to humans. Mathematical PK models are frequently used for molecule selection during preclinical drug development and for translational predictions to guide clinical study design. Here, we present a practical approach that uses limited PK and receptor occupancy (RO) data of the corresponding unconjugated antibody to predict ADC PK when conjugation does not alter the non-specific clearance or the antibody-target interaction. We used a 2-compartment model incorporating non-specific and specific (target mediated) clearances, where the latter is a function of RO, to describe the PK of anti-CD33 ADC with dose-limiting neutropenia in cynomolgus monkeys. We tested our model by comparing PK predictions based on the unconjugated antibody to observed ADC PK data that was not utilized for model development. Prospective prediction of human PK was performed by incorporating in vitro binding affinity differences between species for varying levels of CD33 target expression. Additionally, this approach was used to predict human PK of other previously tested anti-CD33 molecules with published clinical data. The findings showed that, for a cytotoxic ADC with non-linear PK and limited preclinical PK data, incorporating RO in the PK model and using data from the corresponding unconjugated antibody at higher doses allowed the identification of parameters to characterize monkey PK and enabled human PK predictions.

EMP Attachment 3 DOE-SC PNNL Site Dose Assessment Guidance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Snyder, Sandra F.

2011-12-21

This Dose Assessment Guidance (DAG) describes methods to use to determine the Maximally-Exposed Individual (MEI) location and to estimate dose impact to that individual under the U.S. Department of Energy Office of Science (DOE-SC) Pacific Northwest National Laboratory (PNNL) Site Environmental Monitoring Plan (EMP). This guidance applies to public dose from radioactive material releases to the air from PNNL Site operations. This document is an attachment to the Pacific Northwest National Laboratory (PNNL) Environmental Monitoring Plan (EMP) and describes dose assessment guidance for radiological air emissions. The impact of radiological air emissions from the U.S. Department of Energy Office ofmore » Science (DOE-SC) PNNL Site is indicated by dose estimates to a maximally exposed member of the public, referred to as the maximally exposed individual (MEI). Reporting requirements associated with dose to members of the public from radiological air emissions are in 40 CFR Part 61.94, WAC 246-247-080, and DOE Order 458.1. The DOE Order and state standards for dose from radioactive air emissions are consistent with U.S. Environmental Protection Agency (EPA) dose standards in 40 CFR 61.92 (i.e., 10 mrem/yr to a MEI). Despite the fact that the current Contract Requirements Document (CRD) for the DOE-SC PNNL Site operations does not include the requirement to meet DOE CRD 458.1, paragraph 2.b, public dose limits, the DOE dose limits would be met when EPA limits are met.« less

Dose planning management of patients undergoing salvage whole brain radiation therapy after radiosurgery

DOE Office of Scientific and Technical Information (OSTI.GOV)

Saw, Cheng B., E-mail: cheng.saw@aol.com; Battin, Frank; McKeague, Janice

2016-01-01

Dose or treatment planning management is necessary for the re-irradiation of intracranial relapses after focal irradiation, radiosurgery, or stereotactic radiotherapy. The current clinical guidelines for metastatic brain tumors are the use of focal irradiation if the patient presents with 4 lesions or less. Salvage treatments with the use of whole brain radiation therapy (WBRT) can then be used to limit disease progression if there is an intracranial relapse. However, salvage WBRT poses a number of challenges in dose planning to limit disease progression and preserve neurocognitive function. This work presents the dose planning management that addresses a method of delineatingmore » previously treated volumes, dose level matching, and the dose delivery techniques for WBRT.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Thompson, Reid F.; Zhai, Huifang; Both, Stefan

Purpose: Uncontrolled local growth is the cause of death in ∼30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. Methods: The authors compared DS, PBS, andmore » IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Results: Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6–53.8 and 34.9–52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Conclusions: Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.« less

TU-D-201-05: Validation of Treatment Planning Dose Calculations: Experience Working with MPPG 5.a

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xue, J; Park, J; Kim, L

2016-06-15

Purpose: Newly published medical physics practice guideline (MPPG 5.a.) has set the minimum requirements for commissioning and QA of treatment planning dose calculations. We present our experience in the validation of a commercial treatment planning system based on MPPG 5.a. Methods: In addition to tests traditionally performed to commission a model-based dose calculation algorithm, extensive tests were carried out at short and extended SSDs, various depths, oblique gantry angles and off-axis conditions to verify the robustness and limitations of a dose calculation algorithm. A comparison between measured and calculated dose was performed based on validation tests and evaluation criteria recommendedmore » by MPPG 5.a. An ion chamber was used for the measurement of dose at points of interest, and diodes were used for photon IMRT/VMAT validations. Dose profiles were measured with a three-dimensional scanning system and calculated in the TPS using a virtual water phantom. Results: Calculated and measured absolute dose profiles were compared at each specified SSD and depth for open fields. The disagreement is easily identifiable with the difference curve. Subtle discrepancy has revealed the limitation of the measurement, e.g., a spike at the high dose region and an asymmetrical penumbra observed on the tests with an oblique MLC beam. The excellent results we had (> 98% pass rate on 3%/3mm gamma index) on the end-to-end tests for both IMRT and VMAT are attributed to the quality beam data and the good understanding of the modeling. The limitation of the model and the uncertainty of measurement were considered when comparing the results. Conclusion: The extensive tests recommended by the MPPG encourage us to understand the accuracy and limitations of a dose algorithm as well as the uncertainty of measurement. Our experience has shown how the suggested tests can be performed effectively to validate dose calculation models.« less

Status of NCRP Scientific Committee 1-23 Commentary on Guidance on Radiation Dose Limits for the Lens of the Eye.

PubMed

Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Don; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A

2016-02-01

Previous National Council on Radiation Protection and Measurements (NCRP) publications have addressed the issues of risk and dose limitation in radiation protection and included guidance on specific organs and the lens of the eye. NCRP decided to prepare an updated commentary intended to enhance the previous recommendations provided in earlier reports. The NCRP Scientific Committee 1-23 (SC 1-23) is charged with preparing a commentary that will evaluate recent studies on the radiation dose response for the development of cataracts and also consider the type and severity of the cataracts as well as the dose rate; provide guidance on whether existing dose limits to the lens of the eye should be changed in the United States; and suggest research needs regarding radiation effects on and dose limits to the lens of the eye. A status of the ongoing work of SC 1-23 was presented at the Annual Meeting, "Changing Regulations and Radiation Guidance: What Does the Future Hold?" The following represents a synopsis of a few main points in the current draft commentary. It is likely that several changes will be forthcoming as SC 1-23 responds to subject matter expert review and develops a final document, expected by mid 2016.

Limitations of current dosimetry for intracavitary accelerated partial breast irradiation with high dose rate iridium-192 and electronic brachytherapy sources

NASA Astrophysics Data System (ADS)

Raffi, Julie A.

Intracavitary accelerated partial breast irradiation (APBI) is a method of treating early stage breast cancer using a high dose rate (HDR) brachytherapy source positioned within the lumpectomy cavity. An expandable applicator stretches the surrounding tissue into a roughly spherical or elliptical shape and the dose is prescribed to 1 cm beyond the edge of the cavity. Currently, dosimetry for these treatments is most often performed using the American Association of Physicists in Medicine Task Group No. 43 (TG-43) formalism. The TG-43 dose-rate equation determines the dose delivered to a homogeneous water medium by scaling the measured source strength with standardized parameters that describe the radial and angular features of the dose distribution. Since TG-43 parameters for each source model are measured or calculated in a homogeneous water medium, the dosimetric effects of the patient's dimensions and composition are not accounted for. Therefore, the accuracy of TG-43 calculations for intracavitary APBI is limited by the presence of inhomogeneities in and around the target volume. Specifically, the breast is smaller than the phantoms used to determine TG-43 parameters and is surrounded by air, ribs, and lung tissue. Also, the composition of the breast tissue itself can affect the dose distribution. This dissertation is focused on investigating the limitations of TG-43 dosimetry for intracavitary APBI for two HDR brachytherapy sources: the VariSource TM VS2000 192Ir source and the AxxentRTM miniature x-ray source. The dose for various conditions was determined using thermoluminescent dosimeters (TLDs) and Monte Carlo (MC) calculations. Accurate measurements and calculations were achieved through the implementation of new measurement and simulation techniques and a novel breast phantom was developed to enable anthropomorphic phantom measurements. Measured and calculated doses for phantom and patient geometries were compared with TG-43 calculated doses to illustrate the limitations of TG-43 dosimetry for intracavitary APBI. TG-43 dose calculations overestimate the dose for regions approaching the lung and breast surface and underestimate the dose for regions in and beyond less-attenuating media such as lung tissue, and for lower energies, breast tissue as well.

Vocal Dose Measures: Quantifying Accumulated Vibration Exposure in Vocal Fold Tissues

PubMed Central

Titze, Ingo R.; Švec, Jan G.; Popolo, Peter S.

2011-01-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses. PMID:12959470

Vocal dose measures: quantifying accumulated vibration exposure in vocal fold tissues.

PubMed

Titze, Ingo R; Svec, Jan G; Popolo, Peter S

2003-08-01

To measure the exposure to self-induced tissue vibration in speech, three vocal doses were defined and described: distance dose, which accumulates the distance that tissue particles of the vocal folds travel in an oscillatory trajectory; energy dissipation dose, which accumulates the total amount of heat dissipated over a unit volume of vocal fold tissues; and time dose, which accumulates the total phonation time. These doses were compared to a previously used vocal dose measure, the vocal loading index, which accumulates the number of vibration cycles of the vocal folds. Empirical rules for viscosity and vocal fold deformation were used to calculate all the doses from the fundamental frequency (F0) and sound pressure level (SPL) values of speech. Six participants were asked to read in normal, monotone, and exaggerated speech and the doses associated with these vocalizations were calculated. The results showed that large F0 and SPL variations in speech affected the dose measures, suggesting that accumulation of phonation time alone is insufficient. The vibration exposure of the vocal folds in normal speech was related to the industrial limits for hand-transmitted vibration, in which the safe distance dose was derived to be about 500 m. This limit was found rather low for vocalization; it was related to a comparable time dose of about 17 min of continuous vocalization, or about 35 min of continuous reading with normal breathing and unvoiced segments. The voicing pauses in normal speech and dialogue effectively prolong the safe time dose. The derived safety limits for vocalization will likely require refinement based on a more detailed knowledge of the differences in hand and vocal fold tissue morphology and their response to vibrational stress, and on the effect of recovery of the vocal fold tissue during voicing pauses.

Incidental irradiation of mediastinal and hilar lymph node stations during 3D-conformal radiotherapy for non-small cell lung cancer.

PubMed

Kepka, Lucyna; Bujko, Krzysztof; Zolciak-Siwinska, Agnieszka; Garmol, Dariusz

2008-01-01

To estimate the doses of incidental irradiation in particular lymph node stations (LNS) in different extents of elective nodal irradiation (ENI) in 3D-conformal radiotherapy (3D-CRT) for non-small cell lung cancer (NSCLC). METHODS; Doses of radiotherapy were estimated for particular LNS delineated according to the recommendations of the University of Michigan in 220 patients treated using 3D-CRT with different (extended, limited and omitted) extents of ENI. Minimum doses and volumes of LNS receiving 40 Gy or more (V40) were compared for omitted vs. limited+ extended ENI and limited vs. extended ENI. For omission of the ENI the minimum doses and V40 for particular LNS were significantly lower than for patients treated with ENI. For the limited ENI group, the minimum doses for LNS 5, 6 lower parts of 3A and 3P (not included in the elective area) did not differ significantly from doses given to respective LNS for extended ENI group. When the V40 values for extended and limited ENI were compared, no significant differences were seen for any LNS, except for group 1/2R, 1/2L. Incidental irradiation of untreated LNS seems play a part in case of limited ENI, but not in cases without ENI. For subclinical disease the delineation of uninvolved LNS 5, 6, and lower parts of 3A, 3P may be not necessary, because these stations receive the substantial part of irradiation incidentally, if LNS 4R, 4L, 7, and ipsilateral hilum are included in the elective area while this is not case for stations 1 and 2.

10 CFR 20.1208 - Dose equivalent to an embryo/fetus.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Dose equivalent to an embryo/fetus. 20.1208 Section 20.1208 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1208 Dose equivalent to an embryo/fetus. (a) The licensee shall ensure that the dose...

10 CFR 20.1208 - Dose equivalent to an embryo/fetus.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Dose equivalent to an embryo/fetus. 20.1208 Section 20.1208 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1208 Dose equivalent to an embryo/fetus. (a) The licensee shall ensure that the dose...

10 CFR 20.1208 - Dose equivalent to an embryo/fetus.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Dose equivalent to an embryo/fetus. 20.1208 Section 20.1208 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1208 Dose equivalent to an embryo/fetus. (a) The licensee shall ensure that the dose...

10 CFR 20.1208 - Dose equivalent to an embryo/fetus.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Dose equivalent to an embryo/fetus. 20.1208 Section 20.1208 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1208 Dose equivalent to an embryo/fetus. (a) The licensee shall ensure that the dose...

10 CFR 20.1208 - Dose equivalent to an embryo/fetus.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Dose equivalent to an embryo/fetus. 20.1208 Section 20.1208 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1208 Dose equivalent to an embryo/fetus. (a) The licensee shall ensure that the dose...

Spatial frequency performance limitations of radiation dose optimization and beam positioning

NASA Astrophysics Data System (ADS)

Stewart, James M. P.; Stapleton, Shawn; Chaudary, Naz; Lindsay, Patricia E.; Jaffray, David A.

2018-06-01

The flexibility and sophistication of modern radiotherapy treatment planning and delivery methods have advanced techniques to improve the therapeutic ratio. Contemporary dose optimization and calculation algorithms facilitate radiotherapy plans which closely conform the three-dimensional dose distribution to the target, with beam shaping devices and image guided field targeting ensuring the fidelity and accuracy of treatment delivery. Ultimately, dose distribution conformity is limited by the maximum deliverable dose gradient; shallow dose gradients challenge techniques to deliver a tumoricidal radiation dose while minimizing dose to surrounding tissue. In this work, this ‘dose delivery resolution’ observation is rigorously formalized for a general dose delivery model based on the superposition of dose kernel primitives. It is proven that the spatial resolution of a delivered dose is bounded by the spatial frequency content of the underlying dose kernel, which in turn defines a lower bound in the minimization of a dose optimization objective function. In addition, it is shown that this optimization is penalized by a dose deposition strategy which enforces a constant relative phase (or constant spacing) between individual radiation beams. These results are further refined to provide a direct, analytic method to estimate the dose distribution arising from the minimization of such an optimization function. The efficacy of the overall framework is demonstrated on an image guided small animal microirradiator for a set of two-dimensional hypoxia guided dose prescriptions.

Organ biodistribution of Germanium-68 in rat in the presence and absence of [68Ga]Ga-DOTA-TOC for the extrapolation to the human organ and whole-body radiation dosimetry

PubMed Central

Velikyan, Irina; Antoni, Gunnar; Sörensen, Jens; Estrada, Sergio

2013-01-01

Positron Emission Tomography (PET) and in particular gallium-68 (68Ga) applications are growing exponentially worldwide contributing to the expansion of nuclear medicine and personalized management of patients. The significance of 68Ga utility is reflected in the implementation of European Pharmacopoeia monographs. However, there is one crucial point in the monographs that might limit the use of the generators and consequently expansion of 68Ga applications and that is the limit of 0.001% of Germanium-68 (68Ge(IV)) radioactivity content in a radiopharmaceutical. We have investigated the organ distribution of 68Ge(IV) in rat and estimated human dosimetry parameters in order to provide experimental evidence for the determination and justification of the 68Ge(IV) limit. Male and female rats were injected in the tail vein with formulated [68Ge]GeCl4 in the absence or presence of [68Ga]Ga-DOTA-TOC. The tissue radioactivity distribution data was extrapolated for the estimation of human organ equivalent doses and total effective dose using Organ Level Internal Dose Assessment Code software (OLINDA/EXM). 68Ge(IV) was evenly distributed among the rat organs and fast renal excretion prevailed. Human organ equivalent dose and total effective dose estimates indicated that the kidneys were the dose-limiting organs (185±54 μSv/MBq for female and 171±38 μSv/MBq for male) and the total effective dose was 15.5±0.1 and 10.7±1.2 μSv/MBq, respectively for female and male. The results of this dosimetry study conclude that the 68Ge(IV) limit currently recommended by monographs could be increased considerably (>100 times) without exposing the patient to harm given the small absorbed doses to normal organs and fast excretion. PMID:23526484

Eye doses to staff in a nuclear medicine department.

PubMed

Summers, Elizabeth C; Brown, Janis L E; Bownes, Peter J; Anderson, Shona E

2012-05-01

Occupational radiation doses to the Nuclear Medicine Department staff at Mount Vernon Hospital are routinely measured using optically stimulated luminescence dosemeters for whole-body effective dose and ring thermoluminescence dosemeters (TLDs) for finger dose. In 2002, a project was carried out using LiF:Mg,Cu,P Chinese TLDs to measure the dose to the lens of the eye received by staff during normal working procedures. Separate pairs of TLDs were worn by staff on their forehead between their eyes while dispensing and releasing in the radiopharmacy, injecting, and when administering I-131 capsules to patients. The dose received was calculated using calibration data from identical TLDs irradiated with Tc-99m, I-131, and the Ir-192 source of a Gammamed High Dose Rate (HDR) treatment unit. Data were collected over a 5-month period and the mean dose to the eye was calculated for each procedure. Using a typical yearly workload, the annual dose to the eye for a single member of staff was calculated and found to be 4.5 mSv. The occupational eye dose limit was, at the time, 150 mSv; therefore, staff were well below the level (3/10th of this limit) that would have required them to be classified. However, there have been large increases in radiopharmacy production and I-131 therapies administered at Mount Vernon in subsequent years. It is therefore expected that the eye dose received by staff will have increased to be significantly higher than 4.5 mSv and will in fact be greater than 6 mSv, which is 3/10th of the proposed new dose limit and would require these staff to become classified workers.

Hydrogen peroxide kinetics in water radiolysis

NASA Astrophysics Data System (ADS)

Iwamatsu, Kazuhiro; Sundin, Sara; LaVerne, Jay A.

2018-04-01

The kinetics of the formation and reaction of hydrogen peroxide in the long time γ- radiolysis of water is examined using a combination of experiment with model calculations. Escape yields of hydrogen peroxide on the microsecond time scale are easily measured with added radical scavengers even with substantial amounts of initial added hydrogen peroxide. The γ-radiolysis of aqueous hydrogen peroxide solutions without added radical scavengers reach a steady state limiting concentration of hydrogen peroxide with increasing dose, and that limit is directly proportional to the initial concentration of added hydrogen peroxide. The dose necessary to reach that limiting hydrogen peroxide concentration is also proportional to the initial concentration, but dose rate has a very small effect. The addition of molecular hydrogen to aqueous solutions of hydrogen peroxide leads to a decrease in the high dose limiting hydrogen peroxide concentration that is linear with the initial hydrogen concentration, but the amount of decrease is not stoichiometric. Proton irradiations of solutions with added hydrogen peroxide and hydrogen are more difficult to predict because of the decreased yields of radicals; however, with a substantial increase in dose rate there is a sufficient decrease in radical yields that hydrogen addition has little effect on hydrogen peroxide decay.

Radiation Hormesis: Historical Perspective and Implications for Low-Dose Cancer Risk Assessment

PubMed Central

Vaiserman, Alexander M.

2010-01-01

Current guidelines for limiting exposure of humans to ionizing radiation are based on the linear-no-threshold (LNT) hypothesis for radiation carcinogenesis under which cancer risk increases linearly as the radiation dose increases. With the LNT model even a very small dose could cause cancer and the model is used in establishing guidelines for limiting radiation exposure of humans. A slope change at low doses and dose rates is implemented using an empirical dose and dose rate effectiveness factor (DDREF). This imposes usually unacknowledged nonlinearity but not a threshold in the dose-response curve for cancer induction. In contrast, with the hormetic model, low doses of radiation reduce the cancer incidence while it is elevated after high doses. Based on a review of epidemiological and other data for exposure to low radiation doses and dose rates, it was found that the LNT model fails badly. Cancer risk after ordinarily encountered radiation exposure (medical X-rays, natural background radiation, etc.) is much lower than projections based on the LNT model and is often less than the risk for spontaneous cancer (a hormetic response). Understanding the mechanistic basis for hormetic responses will provide new insights about both risks and benefits from low-dose radiation exposure. PMID:20585444

Introduction to benchmark dose methods and U.S. EPA's benchmark dose software (BMDS) version 2.1.1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Davis, J. Allen, E-mail: davis.allen@epa.gov; Gift, Jeffrey S.; Zhao, Q. Jay

2011-07-15

Traditionally, the No-Observed-Adverse-Effect-Level (NOAEL) approach has been used to determine the point of departure (POD) from animal toxicology data for use in human health risk assessments. However, this approach is subject to substantial limitations that have been well defined, such as strict dependence on the dose selection, dose spacing, and sample size of the study from which the critical effect has been identified. Also, the NOAEL approach fails to take into consideration the shape of the dose-response curve and other related information. The benchmark dose (BMD) method, originally proposed as an alternative to the NOAEL methodology in the 1980s, addressesmore » many of the limitations of the NOAEL method. It is less dependent on dose selection and spacing, and it takes into account the shape of the dose-response curve. In addition, the estimation of a BMD 95% lower bound confidence limit (BMDL) results in a POD that appropriately accounts for study quality (i.e., sample size). With the recent advent of user-friendly BMD software programs, including the U.S. Environmental Protection Agency's (U.S. EPA) Benchmark Dose Software (BMDS), BMD has become the method of choice for many health organizations world-wide. This paper discusses the BMD methods and corresponding software (i.e., BMDS version 2.1.1) that have been developed by the U.S. EPA, and includes a comparison with recently released European Food Safety Authority (EFSA) BMD guidance.« less

A dosimetric comparison of proton and photon therapy in unresectable cancers of the head of pancreas.

PubMed

Thompson, Reid F; Mayekar, Sonal U; Zhai, Huifang; Both, Stefan; Apisarnthanarax, Smith; Metz, James M; Plastaras, John P; Ben-Josef, Edgar

2014-08-01

Uncontrolled local growth is the cause of death in ∼ 30% of patients with unresectable pancreatic cancers. The addition of standard-dose radiotherapy to gemcitabine has been shown to confer a modest survival benefit in this population. Radiation dose escalation with three-dimensional planning is not feasible, but high-dose intensity-modulated radiation therapy (IMRT) has been shown to improve local control. Still, dose-escalation remains limited by gastrointestinal toxicity. In this study, the authors investigate the potential use of double scattering (DS) and pencil beam scanning (PBS) proton therapy in limiting dose to critical organs at risk. The authors compared DS, PBS, and IMRT plans in 13 patients with unresectable cancer of the pancreatic head, paying particular attention to duodenum, small intestine, stomach, liver, kidney, and cord constraints in addition to target volume coverage. All plans were calculated to 5500 cGy in 25 fractions with equivalent constraints and normalized to prescription dose. All statistics were by two-tailed paired t-test. Both DS and PBS decreased stomach, duodenum, and small bowel dose in low-dose regions compared to IMRT (p < 0.01). However, protons yielded increased doses in the mid to high dose regions (e.g., 23.6-53.8 and 34.9-52.4 Gy for duodenum using DS and PBS, respectively; p < 0.05). Protons also increased generalized equivalent uniform dose to duodenum and stomach, however these differences were small (<5% and 10%, respectively; p < 0.01). Doses to other organs-at-risk were within institutional constraints and placed no obvious limitations on treatment planning. Proton therapy does not appear to reduce OAR volumes receiving high dose. Protons are able to reduce the treated volume receiving low-intermediate doses, however the clinical significance of this remains to be determined in future investigations.

The regulated secretory pathway and human disease: insights from gene variants and single nucleotide polymorphisms.

PubMed

Lin, Wei-Jye; Salton, Stephen R

2013-01-01

The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs), where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs), with neuropsychiatric, endocrine, and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the human brain-derived neurotrophic factor gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired.

SCORPION persistent surveillance system with universal gateway

NASA Astrophysics Data System (ADS)

Coster, Michael; Chambers, Jon; Winters, Michael; Belesi, Joe

2008-04-01

This paper addresses benefits derived from the universal gateway utilized in Northrop Grumman Systems Corporation's (NGSC) SCORPION, a persistent surveillance and target recognition system produced by the Xetron campus in Cincinnati, Ohio. SCORPION is currently deployed in Operations Iraqi Freedom (OIF) and Enduring Freedom (OEF). The SCORPION universal gateway is a flexible, field programmable system that provides integration of over forty Unattended Ground Sensor (UGS) types from a variety of manufacturers, multiple visible and thermal electro-optical (EO) imagers, and numerous long haul satellite and terrestrial communications links, including the Army Research Lab (ARL) Blue Radio. Xetron has been integrating best in class sensors with this universal gateway to provide encrypted data exfiltration and remote sensor command and control since 1998. SCORPION data can be distributed point to point, or to multiple Common Operational Picture (COP) systems, including Command and Control Personal Computer (C2PC), Common Data Interchange Format for the Situational Awareness Display (CDIF/SAD), Force XXI Battle Command Brigade and Below (FBCB2), Defense Common Ground Systems (DCGS), and Remote Automated Position Identification System (RAPIDS).

The Regulated Secretory Pathway and Human Disease: Insights from Gene Variants and Single Nucleotide Polymorphisms

PubMed Central

Lin, Wei-Jye; Salton, Stephen R.

2013-01-01

The regulated secretory pathway provides critical control of peptide, growth factor, and hormone release from neuroendocrine and endocrine cells, and neurons, maintaining physiological homeostasis. Propeptides and prohormones are packaged into dense core granules (DCGs), where they frequently undergo tissue-specific processing as the DCG matures. Proteins of the granin family are DCG components, and although their function is not fully understood, data suggest they are involved in DCG formation and regulated protein/peptide secretion, in addition to their role as precursors of bioactive peptides. Association of gene variation, including single nucleotide polymorphisms (SNPs), with neuropsychiatric, endocrine, and metabolic diseases, has implicated specific secreted proteins and peptides in disease pathogenesis. For example, a SNP at position 196 (G/A) of the human brain-derived neurotrophic factor gene dysregulates protein processing and secretion and leads to cognitive impairment. This suggests more generally that variants identified in genes encoding secreted growth factors, peptides, hormones, and proteins involved in DCG biogenesis, protein processing, and the secretory apparatus, could provide insight into the process of regulated secretion as well as disorders that result when it is impaired. PMID:23964269

ICPP environmental monitoring report CY-1993: Environmental characterization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1994-05-01

Summarized in this report are the data collected through Environmental Monitoring programs conducted at the Idaho Chemical Processing Plant (ICPP) by the Environmental Safety & Health (ES&H) Department. This report is published in response to DOE Order 5400.1. This report covers the period from December 21, 1992 through December 20, 1993. The ICPP is responsible for complying with all applicable Federal, State, Local and DOE Rules, Regulations and Orders. Radiological effluent and emissions are regulated by the DOE in accordance with the Derived Concentration Guides (DCGs) as presented in DOE Order 5400.5. The State of Idaho regulates all nonradiological wastemore » resulting from the ICPP operations including all airborne, liquid, and solid waste. The ES&H Department updated the Quality Assurance (QA) Project Plan for Environmental Monitoring activities during the third quarter of 1992. QA activities have resulted in the ICPP`s implementation of the Environmental Protection Agency (EPA) rules and guidelines pertaining to the collection, analyses, and reporting of environmentally related samples. Where no EPA methods for analyses existed for radionuclides, WINCO methods were used.« less

76 FR 40755 - Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment

Federal Register 2010, 2011, 2012, 2013, 2014

2011-07-11

... NUCLEAR REGULATORY COMMISSION [NRC-2009-0279] Impact of Reduced Dose Limits on NRC Licensed Activities; Solicitation of Public Comment AGENCY: Nuclear Regulatory Commission. ACTION: Solicitation of public comment. SUMMARY: The U.S. Nuclear Regulatory Commission (NRC or Commission) is seeking public...

10 CFR 20.2205 - Reports to individuals of exceeding dose limits.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Reports to individuals of exceeding dose limits. 20.2205 Section 20.2205 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Reports..., or an identified member of the public, to radiation or radioactive material, the licensee shall also...

10 CFR 20.2205 - Reports to individuals of exceeding dose limits.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Reports to individuals of exceeding dose limits. 20.2205 Section 20.2205 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Reports..., or an identified member of the public, to radiation or radioactive material, the licensee shall also...

10 CFR 20.2205 - Reports to individuals of exceeding dose limits.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Reports to individuals of exceeding dose limits. 20.2205 Section 20.2205 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Reports..., or an identified member of the public, to radiation or radioactive material, the licensee shall also...

10 CFR 20.2205 - Reports to individuals of exceeding dose limits.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Reports to individuals of exceeding dose limits. 20.2205 Section 20.2205 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Reports..., or an identified member of the public, to radiation or radioactive material, the licensee shall also...

Dose-Response Analysis of RNA-Seq Profiles in Archival Formalin-fixed paraffin-embedded (FFPE) Samples

EPA Science Inventory

Formalin-fixed paraffin-embedded (FFPE) samples provide a vast untapped resource for chemical safety and translational science. To date, genomic profiling of FFPE samples has been limited by poor RNA quality and inconsistent results with limited utility in dose-response assessmen...

MPC and ALI: their basis and their comparison

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kennedy, W.E. Jr.; Watson, E.C.

Radiation protection regulations in the United States have evolved from the recommendations of the International Commission on Radiological Protection (ICRP) and the National Council on Radiation Protection and Measurements (NCRP). In 1959, the ICRP issued Publication 2 which contained specific recommendations on dose rate limits, permissible body burdens, metabolic data for radionuclides, and maximum permissible concentrations (MPC) in air or water. Over the next 20 years, new information became available concerning the effects of radiation, the uptake and retention of radionuclides, and the radioactive decay schemes of parent radionuclides. To include this newer information, the ICRP issued Publication 30 inmore » 1978 to supersede Publication 2. One of the secondary limits defined in Publication 30 is the annual limit of intake (ALI). Radionuclide specific ALI values are intended to replace MPC values in determining whether or not ambient air and water concentrations are sufficiently low to maintain the dose to workers within accepted dose rate limits. In this paper, we discuss the derivation of MPC and ALI values, compare inhalation committed dose equivalent factors derived from ICRP Publications 2 and 30, and discuss the practical implications of using either MPC or ALI in determining compliance with occupational exposure limits. 6 references.« less

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2014 CFR

2014-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2010 CFR

2010-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2013 CFR

2013-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1301 - Dose limits for individual members of the public.

Code of Federal Regulations, 2012 CFR

2012-01-01

... Section 20.1301 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Radiation..., exclusive of the dose contributions from background radiation, from any medical administration the....75, to receive a radiation dose greater than 0.1 rem (1 mSv) if— (1) The radiation dose received does...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

10 CFR 20.1203 - Determination of external dose from airborne radioactive material.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Determination of external dose from airborne radioactive material. 20.1203 Section 20.1203 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1203 Determination of external dose from airborne radioactive...

Characterization of a commercial multileaf collimator used for intensity modulated radiation therapy.

PubMed

Low, D A; Sohn, J W; Klein, E E; Markman, J; Mutic, S; Dempsey, J F

2001-05-01

The characteristics of a commercial multileaf collimator (MLC) to deliver static and dynamic multileaf collimation (SMLC and DMLC, respectively) were investigated to determine their influence on intensity modulated radiation therapy (IMRT) treatment planning and quality assurance. The influence of MLC leaf positioning accuracy on sequentially abutted SMLC fields was measured by creating abutting fields with selected gaps and overlaps. These data were also used to measure static leaf positioning precision. The characteristics of high leaf-velocity DMLC delivery were measured with constant velocity leaf sequences starting with an open field and closing a single leaf bank. A range of 1-72 monitor units (MU) was used providing a range of leaf velocities. The field abutment measurements yielded dose errors (as a percentage of the open field max dose) of 16.7+/-0.7% mm(-1) and 12.8+/-0.7% mm(-1) for 6 MV and 18 MV photon beams, respectively. The MLC leaf positioning precision was 0.080+/-0.018 mm (single standard deviation) highlighting the excellent delivery hardware tolerances for the tested beam delivery geometry. The high leaf-velocity DMLC measurements showed delivery artifacts when the leaf sequence and selected monitor units caused the linear accelerator to move the leaves at their maximum velocity while modulating the accelerator dose rate to deliver the desired leaf and MU sequence (termed leaf-velocity limited delivery). According to the vendor, a unique feature to their linear accelerator and MLC is that the dose rate is reduced to provide the correct cm MU(-1) leaf velocity when the delivery is leaf-velocity limited. However, it was found that the system delivered roughly 1 MU per pulse when the delivery was leaf-velocity limited causing dose profiles to exhibit discrete steps rather than a smooth dose gradient. The root mean square difference between the steps and desired linear gradient was less than 3% when more than 4 MU were used. The average dose per MU was greater and less than desired for closing and opening leaf patterns, respectively, when the delivery was leaf-velocity limited. The results indicated that the dose delivery artifacts should be minor for most clinical cases, but limit the assumption of dose linearity when significantly reducing the delivered dose for dosimeter characterization studies or QA measurements.

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2010 CFR

2010-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2011 CFR

2011-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2013 CFR

2013-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2012 CFR

2012-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

10 CFR 60.136 - Preclosure controlled area.

Code of Federal Regulations, 2014 CFR

2014-01-01

... limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The eye dose equivalent shall not exceed 0.15 Sv (15 rem), and the shallow dose...

Prophylactic G-CSF and antibiotics enable a significant dose-escalation of triplet-chemotherapy in non-small cell lung cancer.

PubMed

Timmer-Bonte, J N H; Punt, C J A; vd Heijden, H F M; van Die, C E; Bussink, J; Beijnen, J H; Huitema, A D R; Tjan-Heijnen, V C G

2008-05-01

In advanced non-small cell lung cancer (NSCLC) the clinical benefit of a platinum-based doublet is only modest, therefore, attenuated dosed three-drug combinations are investigated. We hypothesized that with adequate support a full dosed chemotherapy triplet is feasible. The study was designed as a dose finding study of paclitaxel in chemotherapy-naive patients. Paclitaxel was given as a 3-h infusion on day 1, followed by fixed doses of teniposide (or etoposide) 100mg/m(2) days 1, 3, 5 and cisplatin 80 mg/m(2) day 1 every 3 weeks. As myelotoxicity was expected to be the dose-limiting toxicity, prophylactic G-CSF and antibiotic support was evaluated. Indeed, paclitaxel 120 mg/m(2) resulted in dose-limiting neutropenia, despite G-CSF support. Teniposide/etoposide day 1, 3, 5 was less myelotoxic compared to day 1, 2, 3. G-CSF support allowed paclitaxel dose-escalation to 250 mg/m(2). The addition of prophylactic antibiotics enabled dose-escalation to 275 mg/m(2) without reaching MTD. In conclusion, G-CSF and antibiotics prophylaxis enables the delivery of a full dosed chemotherapy triplet in previously untreated NSCLC patients.

Dose-Response Relationship between Cumulative Occupational Lead Exposure and the Associated Health Damages: A 20-Year Cohort Study of a Smelter in China

PubMed Central

Wu, Yue; Gu, Jun-Ming; Huang, Yun; Duan, Yan-Ying; Huang, Rui-Xue; Hu, Jian-An

2016-01-01

Long-term airborne lead exposure, even below official occupational limits, has been found to cause lead poisoning at higher frequencies than expected, which suggests that China’s existing occupational exposure limits should be reexamined. A retrospective cohort study was conducted on 1832 smelting workers from 1988 to 2008 in China. These were individuals who entered the plant and came into continuous contact with lead at work for longer than 3 months. The dose-response relationship between occupational cumulative lead exposure and lead poisoning, abnormal blood lead, urinary lead and erythrocyte zinc protoporphyrin (ZPP) were analyzed and the benchmark dose lower bound confidence limits (BMDLs) were calculated. Statistically significant positive correlations were found between cumulative lead dust and lead fumes exposures and workplace seniority, blood lead, urinary lead and ZPP values. A dose-response relationship was observed between cumulative lead dust or lead fumes exposure and lead poisoning (p < 0.01). The BMDLs of the cumulative occupational lead dust and fumes doses were 0.68 mg-year/m3 and 0.30 mg-year/m3 for lead poisoning, respectively. The BMDLs of workplace airborne lead concentrations associated with lead poisoning were 0.02 mg/m3 and 0.01 mg/m3 for occupational exposure lead dust and lead fume, respectively. In conclusion, BMDLs for airborne lead were lower than occupational exposure limits, suggesting that the occupational lead exposure limits need re-examination and adjustment. Occupational cumulative exposure limits (OCELs) should be established to better prevent occupational lead poisoning. PMID:26999177

Soil contamination standards for protection of personnel

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rittmann, P.D.

1998-04-16

The objective of this report is to recommend soil contamination levels that will ensure that radionuclide intakes by unprotected workers are likely to give internal doses below selected dose limits during the working year. The three internal dose limits are 1, 100, and 500 mrem per year. In addition, photon, beta, and alpha instrument readings are estimated for these soil concentration limits. Two exposure pathways are considered: the first is inhalation of resuspended dust and the second is ingestion of trace amounts of soil. In addition, radioactive decay and ingrowth of progeny during the year of exposure is included. Externalmore » dose from the soil contamination is not included because monitoring and control of external exposures is carried out independently from internal exposures, which are the focus of this report. The methods used are similar to those used by Carbaugh and Bihl (1993) to set bioassay criteria for such workers.« less

Phase I Trial Using Patupilone (Epothilone B) and Concurrent Radiotherapy for Central Nervous System Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fogh, Shannon; Machtay, Mitchell; Werner-Wasik, Maria

Purpose: Based on preclinical data indicating the radiosensitizing potential of epothilone B, the present study was designed to evaluate the toxicity and response rate of patupilone, an epothilone B, with concurrent radiotherapy (RT) for the treatment of central nervous system malignancies. Methods and Materials: The present Phase I study evaluated the toxicities associated with patupilone combined with RT to establish the maximal tolerated dose. Eligible patients had recurrent gliomas (n = 10) primary (n = 5) or metastatic (n = 17) brain tumors. Dose escalation occurred if no dose-limiting toxicities, defined as any Grade 4-5 toxicity or Grade 3 toxicitymore » requiring hospitalization, occurred during treatment. Results: Of 14 patients, 5 were treated with weekly patupilone at 1.5 mg/m{sup 2}, 4 at 2.0 mg/m{sup 2}, 4 at 2.5 mg/m{sup 2}, and 1 at 4 mg/m{sup 2}. Of 18 patients, 7 were treated in the 6-mg/m{sup 2} group, 6 in the 8-mg/m{sup 2} group, and 5 in the 10-mg/m{sup 2} group. Primary central nervous system malignancies received RT to a median dose of 60 Gy. Central nervous system metastases received whole brain RT to a median dose of 37.4 Gy, and patients with recurrent gliomas underwent stereotactic RT to a median dose of 37.5 Gy. One dose-limiting toxicity (pneumonia) was observed in group receiving 8-mg/m{sup 2} every 3 weeks. At the subsequent dose level (10 mg/m{sup 2}), two Grade 4 dose-limiting toxicities occurred (renal failure and pulmonary hemorrhage); thus, 8 mg/m{sup 2} every 3 weeks was the maximal tolerated dose and the recommended Phase II dose. Conclusion: Combined with a variety of radiation doses and fractionation schedules, concurrent patupilone was well tolerated and safe, with a maximal tolerated dose of 8 mg/m{sup 2} every 3 weeks.« less

Occupational radiation doses during interventional procedures

NASA Astrophysics Data System (ADS)

Nuraeni, N.; Hiswara, E.; Kartikasari, D.; Waris, A.; Haryanto, F.

2016-03-01

Digital subtraction angiography (DSA) is a type of fluoroscopy technique used in interventional radiology to clearly visualize blood vessels in a bony or dense soft tissue environment. The use of DSA procedures has been increased quite significantly in the Radiology departments in various cities in Indonesia. Various reports showed that both patients and medical staff received a noticeable radiation dose during the course of this procedure. A study had been carried out to measure these doses among interventionalist, nurse and radiographer. The results show that the interventionalist and the nurse, who stood quite close to the X-ray beams compared with the radiographer, received radiation higher than the others. The results also showed that the radiation dose received by medical staff were var depending upon the duration and their position against the X-ray beams. Compared tothe dose limits, however, the radiation dose received by all these three medical staff were still lower than the limits.

Development of a point-of-care HIV/AIDS medication dosing support system using the Android mobile platform.

PubMed

Sadasivam, Rajani S; Gathibandhe, Vaibhav; Tanik, Murat M; Willig, James H

2012-06-01

Medication dosing errors can greatly reduce HIV treatment effectiveness as incorrect dosing leads to drug resistance and non-adherence. In order to dose correctly, HIV therapy providers must balance several patient characteristics such as renal functions and weight. In developing countries and other resource-limited settings, dosing errors are more likely because treatment is provided by mid-level providers with only basic training in HIV therapy. These providers also typically lack electronic tools informing medical decisions. Widespread adoption of mobile phones in developing nations offers an opportunity to implement a point-of-care system to help providers reduce dosing errors. We discuss the development of the mHIV-Dr system prototype using the new Android mobile platform. mHIV-Dr is being designed to provide dosing recommendations for front-line providers in developing countries. We also discuss the additional challenges in the implementation of the mHIV-Dr system in a resource limited setting.

IV busulfan dose individualization in children undergoing hematopoietic stem cell transplant: limited sampling strategies.

PubMed

Dupuis, L Lee; Sibbald, Cathryn; Schechter, Tal; Ansari, Marc; Gassas, Adam; Théorêt, Yves; Kassir, Nastya; Champagne, Martin A; Doyle, John

2008-05-01

We currently calculate area under the busulfan concentration time curve (AUC) using 7 plasma busulfan concentrations (AUC7) drawn after the first of 16 i.v. busulfan doses given as a 2-hour infusion every 6 hours. The aim of this study was to develop and validate limited sampling strategies (LSSs) using 3 or fewer busulfan concentration values with which to reliably calculate AUC in children undergoing hematopoietic stem cell transplant (HSCT). Children in the development group (44) received i.v. busulfan at Sick Kids; the validation group consisted of 35 children who received care at CHU Ste-Justine. Busulfan doses given and subsequent plasma busulfan concentrations were recorded. LSSs using 1 to 3 concentration-time points were developed using multiple linear regression. LSS were considered to be acceptable when adjusted r(2) > 0.9, mean bias <15% and precision <15%. Extent of agreement between the AUC7 values and the LSS AUC was assessed by the intraclass correlation coefficient (ICC) and Bland-Altman (BA) analysis. Agreement was considered to be excellent when the lower limit of the 95% confidence limit of the ICC exceeded 0.9 and when the limits of agreement in the BA analysis were +/-15% for both AUC and dose. Administration of the theoretic adjusted busulfan doses based on each LSS was simulated and cases where the resulting AUC was >1500 or <900 microM x min were noted. LSSs using 1, 2, or 3 plasma busulfan concentrations were developed that showed excellent agreement with AUC7 and adjusted busulfan doses. In the validation sample, only the 2- and 3-point LSSs demonstrated acceptable precision and lack of bias. LSSs using 2 or 3 plasma busulfan concentrations can be used to reliably estimate busulfan AUC after IV administration in children undergoing HSCT.

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 4 2014-01-01 2014-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 4 2012-01-01 2012-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 4 2013-01-01 2013-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

10 CFR 835.207 - Occupational dose limits for minors.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 4 2011-01-01 2011-01-01 false Occupational dose limits for minors. 835.207 Section 835.207 Energy DEPARTMENT OF ENERGY OCCUPATIONAL RADIATION PROTECTION Standards for Internal and External... to radiation and/or radioactive materials at a DOE activity are 0.1 rem (0.001 Sv) total effective...

Celecoxib interferes to a limited extent with aspirin‐mediated inhibition of platelets aggregation

PubMed Central

Ruzov, Mark; Rimon, Gilad; Pikovsky, Oleg

2015-01-01

Aims The aim of the study was to analyze the interaction between celecoxib and low dose aspirin for COX‐1 binding and its consequences on the aspirin‐mediated antiplatelet effects. Methods We investigated ex vivo the interaction between celecoxib and aspirin for COX‐1 binding and measured the resulting antiplatelet effects. We applied mechanism‐based pharmacokinetic−pharmacodynamic (PKPD) modelling to analyze these data and to predict in vivo platelet aggregation for different doses and administration schedules of aspirin and celecoxib. Results The predictions of the PK‐PD model were consistent with results from previous studies that investigated interaction between aspirin and celecoxib. The modelling results indicate that celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. The extent of this interaction can be substantial (up to 15% increase in platelet aggregation by 200 mg day−1 celecoxib when combined with low dose aspirin) during the first days of aspirin administration in patients who are already treated with celecoxib, and it cannot be prevented by separate administration of the interacting drugs. Conclusions At the recommended therapeutic doses, celecoxib can attenuate to a limited extent the in vivo antiplatelet effects of low dose aspirin. Patients receiving a combination of low dose aspirin and the recommended doses of celecoxib were not identified to have increased risk of cardiovascular and cerebrovascular events due to competition between these drugs for COX‐1 binding. Interaction between low dose aspirin and other COX‐2 inhibitors and its clinical consequences requires further investigation. PMID:26456703

Photons, protons or carbon ions for stage I non-small cell lung cancer - Results of the multicentric ROCOCO in silico study.

PubMed

Wink, Krista C J; Roelofs, Erik; Simone, Charles B; Dechambre, David; Santiago, Alina; van der Stoep, Judith; Dries, Wim; Smits, Julia; Avery, Stephen; Ammazzalorso, Filippo; Jansen, Nicolas; Jelen, Urszula; Solberg, Timothy; de Ruysscher, Dirk; Troost, Esther G C

2018-03-12

To compare dose to organs at risk (OARs) and dose-escalation possibility for 24 stage I non-small cell lung cancer (NSCLC) patients in a ROCOCO (Radiation Oncology Collaborative Comparison) trial. For each patient, 3 photon plans [Intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT) and CyberKnife], a double scattered proton (DSP) and an intensity-modulated carbon-ion (IMIT) therapy plan were created. Dose prescription was 60 Gy (equivalent) in 8 fractions. The mean dose and dose to 2% of the clinical target volume (CTV) were lower for protons and ions compared with IMRT (p < 0.01). Doses to the lungs, heart, and mediastinal structures were lowest with IMIT (p < 0.01), doses to the spinal cord were lowest with DSP (p < 0.01). VMAT and CyberKnife allowed for reduced doses to most OARs compared with IMRT. Dose escalation was possible for 8 patients. Generally, the mediastinum was the primary dose-limiting organ. On average, the doses to the OARs were lowest using particles, with more homogenous CTV doses. Given the ability of VMAT and CyberKnife to limit doses to OARs compared with IMRT, the additional benefit of particles may only be clinically relevant in selected patients and thus should be carefully weighed for every individual patient. Copyright © 2018 Elsevier B.V. All rights reserved.

[An investigation of ionizing radiation dose in a manufacturing enterprise of ion-absorbing type rare earth ore].

PubMed

Zhang, W F; Tang, S H; Tan, Q; Liu, Y M

2016-08-20

Objective: To investigate radioactive source term dose monitoring and estimation results in a manufacturing enterprise of ion-absorbing type rare earth ore and the possible ionizing radiation dose received by its workers. Methods: Ionizing radiation monitoring data of the posts in the control area and supervised area of workplace were collected, and the annual average effective dose directly estimated or estimated using formulas was evaluated and analyzed. Results: In the control area and supervised area of the workplace for this rare earth ore, α surface contamination activity had a maximum value of 0.35 Bq/cm 2 and a minimum value of 0.01 Bq/cm 2 ; β radioactive surface contamination activity had a maximum value of 18.8 Bq/cm 2 and a minimum value of 0.22 Bq/cm 2 . In 14 monitoring points in the workplace, the maximum value of the annual average effective dose of occupational exposure was 1.641 mSv/a, which did not exceed the authorized limit for workers (5 mSv/a) , but exceeded the authorized limit for general personnel (0.25 mSv/a) . The radionuclide specific activity of ionic mixed rare earth oxides was determined to be 0.9. Conclusion: The annual average effective dose of occupational exposure in this enterprise does not exceed the authorized limit for workers, but it exceeds the authorized limit for general personnel. We should pay attention to the focus of the radiation process, especially for public works radiation.

Tolerance limits and methodologies for IMRT measurement-based verification QA: Recommendations of AAPM Task Group No. 218.

PubMed

Miften, Moyed; Olch, Arthur; Mihailidis, Dimitris; Moran, Jean; Pawlicki, Todd; Molineu, Andrea; Li, Harold; Wijesooriya, Krishni; Shi, Jie; Xia, Ping; Papanikolaou, Nikos; Low, Daniel A

2018-04-01

Patient-specific IMRT QA measurements are important components of processes designed to identify discrepancies between calculated and delivered radiation doses. Discrepancy tolerance limits are neither well defined nor consistently applied across centers. The AAPM TG-218 report provides a comprehensive review aimed at improving the understanding and consistency of these processes as well as recommendations for methodologies and tolerance limits in patient-specific IMRT QA. The performance of the dose difference/distance-to-agreement (DTA) and γ dose distribution comparison metrics are investigated. Measurement methods are reviewed and followed by a discussion of the pros and cons of each. Methodologies for absolute dose verification are discussed and new IMRT QA verification tools are presented. Literature on the expected or achievable agreement between measurements and calculations for different types of planning and delivery systems are reviewed and analyzed. Tests of vendor implementations of the γ verification algorithm employing benchmark cases are presented. Operational shortcomings that can reduce the γ tool accuracy and subsequent effectiveness for IMRT QA are described. Practical considerations including spatial resolution, normalization, dose threshold, and data interpretation are discussed. Published data on IMRT QA and the clinical experience of the group members are used to develop guidelines and recommendations on tolerance and action limits for IMRT QA. Steps to check failed IMRT QA plans are outlined. Recommendations on delivery methods, data interpretation, dose normalization, the use of γ analysis routines and choice of tolerance limits for IMRT QA are made with focus on detecting differences between calculated and measured doses via the use of robust analysis methods and an in-depth understanding of IMRT verification metrics. The recommendations are intended to improve the IMRT QA process and establish consistent, and comparable IMRT QA criteria among institutions. © 2018 American Association of Physicists in Medicine.

Phase I Trial Using Proteasome Inhibitor Bortezomib and Concurrent Temozolomide and Radiotherapy for Central Nervous System Malignancies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kubicek, Gregory J.; Werner-Wasik, Maria; Machtay, Mitchell

Purpose: To evaluate the toxicity and response rate of bortezomib with concurrent radiotherapy and temozolomide in the treatment of patients with central nervous system malignancies. Patients and Methods: This open-label, dose-escalation, Phase I clinical study evaluated the safety of three dose levels of intravenously administered bortezomib (0.7, 1.0, and 1.3 mg/m{sup 2}/dose) on Days 1, 4, 8, and 11 of a 21-day cycle, in addition to concurrent radiotherapy and temozolomide at a daily dose of 75 mg/m{sup 2} starting on Day 1. The primary endpoint was dose-limiting toxicity, defined as any Grade 4-5 toxicity or Grade 3 toxicity directly attributablemore » to protocol treatment, requiring hospitalization and/or radiotherapy interruption. The secondary endpoints included feasibility, non-dose-limiting toxicity, and treatment response. Results: A total of 27 patients were enrolled, 23 of whom had high-grade glioma (10 recurrent and 13 newly diagnosed). No dose-limiting toxicities were noted in any dose group, including the highest (1.3 mg/m{sup 2}/dose). The most frequent toxicities were Grade 1 and 2 stomatitis, erythema, and alopecia. All 27 patients were evaluable for response. At a median follow-up of 15.0 months, 9 patients were still alive, with a median survival of 17.4 months for all patients and 15.0 months for patients with high-grade glioma. Conclusion: Bortezomib administered at its typical 'systemic' dose (1.3 mg/m{sup 2}) is well tolerated and safe combined with temozolomide and radiotherapy when used in the treatment of central nervous system malignancies. A Phase II study to characterize efficacy is warranted.« less

Radiation dose to workers due to the inhalation of dust during granite fabrication.

PubMed

Zwack, L M; McCarthy, W B; Stewart, J H; McCarthy, J F; Allen, J G

2014-03-01

There has been very little research conducted to determine internal radiation doses resulting from worker exposure to ionising radiation in granite fabrication shops. To address this issue, we estimated the effective radiation dose of granite workers in US fabrication shops who were exposed to the maximum respirable dust and silica concentrations allowed under current US regulations, and also to concentrations reported in the literature. Radiation doses were calculated using standard methods developed by the International Commission on Radiological Protection. The calculated internal doses were very low, and below both US occupational standards (50 mSv yr(-1)) and limits applicable to the general public (1 mSv yr(-1)). Workers exposed to respirable granite dust concentrations at the US Occupational Safety and Health Administration (OSHA) respirable dust permissible exposure limit (PEL) of 5 mg m(-3) over a full year had an estimated radiation dose of 0.062 mSv yr(-1). Workers exposed to respirable granite dust concentrations at the OSHA silica PEL and at the American Conference of Governmental Industrial Hygienists Threshold Limit Value for a full year had expected radiation doses of 0.007 mSv yr(-1) and 0.002 mSv yr(-1), respectively. Using data from studies of respirable granite dust and silica concentrations measured in granite fabrication shops, we calculated median expected radiation doses that ranged from <0.001 to 0.101 mSv yr(-1).

Study of natural radioactivity in Mansehra granite, Pakistan: environmental concerns.

PubMed

Qureshi, Aziz Ahmed; Jadoon, Ishtiaq Ahmed Khan; Wajid, Ali Abbas; Attique, Ahsan; Masood, Adil; Anees, Muhammad; Manzoor, Shahid; Waheed, Abdul; Tubassam, Aneela

2014-03-01

A part of Mansehra Granite was selected for the assessment of radiological hazards. The average activity concentrations of (226)Ra, (232)Th and (40)K were found to be 27.32, 50.07 and 953.10 Bq kg(-1), respectively. These values are in the median range when compared with the granites around the world. Radiological hazard indices and annual effective doses were estimated. All of these indices were found to be within the criterion limits except outdoor external dose (82.38 nGy h(-1)) and indoor external dose (156.04 nGy h(-1)), which are higher than the world's average background levels of 51 and 55 nGy h(-1), respectively. These values correspond to an average annual effective dose of 0.867 mSv y(-1), which is less than the criterion limit of 1 mSv y(-1) (ICRP-103). Some localities in the Mansehra city have annual effective dose higher than the limit of 1 mSv y(-1). Overall, the Mansehra Granite does not pose any significant radiological health hazard in the outdoor or indoor.

Performance Characteristics of an Independent Dose Verification Program for Helical Tomotherapy

PubMed Central

Chang, Isaac C. F.; Chen, Jeff; Yartsev, Slav

2017-01-01

Helical tomotherapy with its advanced method of intensity-modulated radiation therapy delivery has been used clinically for over 20 years. The standard delivery quality assurance procedure to measure the accuracy of delivered radiation dose from each treatment plan to a phantom is time-consuming. RadCalc®, a radiotherapy dose verification software, has released specifically for beta testing a module for tomotherapy plan dose calculations. RadCalc®'s accuracy for tomotherapy dose calculations was evaluated through examination of point doses in ten lung and ten prostate clinical plans. Doses calculated by the TomoHDA™ tomotherapy treatment planning system were used as the baseline. For lung cases, RadCalc® overestimated point doses in the lung by an average of 13%. Doses within the spinal cord and esophagus were overestimated by 10%. Prostate plans showed better agreement, with overestimations of 6% in the prostate, bladder, and rectum. The systematic overestimation likely resulted from limitations of the pencil beam dose calculation algorithm implemented by RadCalc®. Limitations were more severe in areas of greater inhomogeneity and less prominent in regions of homogeneity with densities closer to 1 g/cm3. Recommendations for RadCalc® dose calculation algorithms and anatomical representation were provided based on the results of the study. PMID:28974862

High-Dose Atomoxetine Treatment of ADHD in Youths with Limited Response to Standard Doses

ERIC Educational Resources Information Center

Kratochvil, Christopher J.; Michelson, David; Newcorn, Jeffrey H.; Weiss, Margaret D.; Busner, Joan; Moore, Rodney J.; Ruff, Dustin D.; Ramsey, Janet; Dickson, Ruth; Turgay, Atilla; Saylor, Keith E.; Luber, Stephen; Vaughan, Brigette; Allen, Albert J.

2007-01-01

Objective: To assess the utility and tolerability of higher than standard atomoxetine doses to treat attention-deficit/hyperactivity disorder (ADHD). Method: Two randomized, double-blind trials of atomoxetine nonresponders ages 6 to 16 years were conducted comparing continued treatment with same-dose atomoxetine to treatment using greater than…

Systematic influences of gamma-ray spectrometry data near the decision threshold for radioactivity measurements in the environment.

PubMed

Zorko, Benjamin; Korun, Matjaž; Mora Canadas, Juan Carlos; Nicoulaud-Gouin, Valerie; Chyly, Pavol; Blixt Buhr, Anna Maria; Lager, Charlotte; Aquilonius, Karin; Krajewski, Pawel

2016-07-01

Several methods for reporting outcomes of gamma-ray spectrometric measurements of environmental samples for dose calculations are presented and discussed. The measurement outcomes can be reported as primary measurement results, primary measurement results modified according to the quantification limit, best estimates obtained by the Bayesian posterior (ISO 11929), best estimates obtained by the probability density distribution resembling shifting, and the procedure recommended by the European Commission (EC). The annual dose is calculated from the arithmetic average using any of these five procedures. It was shown that the primary measurement results modified according to the quantification limit could lead to an underestimation of the annual dose. On the other hand the best estimates lead to an overestimation of the annual dose. The annual doses calculated from the measurement outcomes obtained according to the EC's recommended procedure, which does not cope with the uncertainties, fluctuate between an under- and overestimation, depending on the frequency of the measurement results that are larger than the limit of detection. In the extreme case, when no measurement results above the detection limit occur, the average over primary measurement results modified according to the quantification limit underestimates the average over primary measurement results for about 80%. The average over best estimates calculated according the procedure resembling shifting overestimates the average over primary measurement results for 35%, the average obtained by the Bayesian posterior for 85% and the treatment according to the EC recommendation for 89%. Copyright © 2016 Elsevier Ltd. All rights reserved.

EPA's Benchmark Dose Modeling Software

EPA Science Inventory

The EPA developed the Benchmark Dose Software (BMDS) as a tool to help Agency risk assessors facilitate applying benchmark dose (BMD) method’s to EPA’s human health risk assessment (HHRA) documents. The application of BMD methods overcomes many well know limitations ...

Dosimetric quality, accuracy, and deliverability of modulated radiotherapy treatments for spinal metastases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kairn, Tanya, E-mail: t.kairn@gmail.com; School of Chemistry, Physics, and Mechanical Engineering, Queensland University of Technology, Brisbane; Papworth, Daniel

2016-10-01

Cancer often metastasizes to the vertebra, and such metastases can be treated successfully using simple, static posterior or opposed-pair radiation fields. However, in some cases, including when re-irradiation is required, spinal cord avoidance becomes necessary and more complex treatment plans must be used. This study evaluated 16 sample intensity-modulated radiation therapy (IMRT) and volumetric-modulated arc therapy (VMAT) treatment plans designed to treat 6 typical vertebral and paraspinal volumes using a standard prescription, with the aim of investigating the advantages and limitations of these treatment techniques and providing recommendations for their optimal use in vertebral treatments. Treatment plan quality and beammore » complexity metrics were evaluated using the Treatment And Dose Assessor (TADA) code. A portal-imaging–based quality assurance (QA) system was used to evaluate treatment delivery accuracy, and radiochromic film measurements were used to provide high-resolution verification of treatment plan dose accuracy, especially in the steep dose gradient regions between each vertebral target and spinal cord. All treatment modalities delivered approximately the same doses and the same levels of dose heterogeneity to each planning target volume (PTV), although the minimum PTV doses in the vertebral plans were substantially lower than the prescription, because of the requirement that the plans meet a strict constraint on the dose to the spinal cord and cord planning risk volume (PRV). All plans met required dose constraints on all organs at risk, and all measured PTV-cord dose gradients were steeper than planned. Beam complexity analysis suggested that the IMRT treatment plans were more deliverable (less complex, leading to greater QA success) than the VMAT treatment plans, although the IMRT plans also took more time to deliver. The accuracy and deliverability of VMAT treatment plans were found to be substantially increased by limiting the number of monitor units (MU) per beam at the optimization stage, and thereby limiting beam modulation complexity. The VMAT arcs that were optimized with MU limitation had higher QA pass rates as well as higher modulation complexity scores (less complexity), lower modulation indices (less modulation), lower MU per beam, larger beam segments, and fewer small apertures than the VMAT arcs that were optimized without MU limitation. It is recommended that VMAT treatments for vertebral volumes, where the PTV abuts or surrounds the spinal cord, should be optimized with MU limitation. IMRT treatments may be preferable to the VMAT treatments, for dosimetry and deliverability reasons, but may be inappropriate for some patients because of their increased treatment delivery time.« less

Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

PubMed

Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

2014-08-01

Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cost of goods sold and total cost of delivery for oral and parenteral vaccine packaging formats.

PubMed

Sedita, Jeff; Perrella, Stefanie; Morio, Matt; Berbari, Michael; Hsu, Jui-Shan; Saxon, Eugene; Jarrahian, Courtney; Rein-Weston, Annie; Zehrung, Darin

2018-03-14

Despite limitations of glass packaging for vaccines, the industry has been slow to implement alternative formats. Polymer containers may address many of these limitations, such as breakage and delamination. However, the ability of polymer containers to achieve cost of goods sold (COGS) and total cost of delivery (TCOD) competitive with that of glass containers is unclear, especially for cost-sensitive low- and lower-middle-income countries. COGS and TCOD models for oral and parenteral vaccine packaging formats were developed based on information from subject matter experts, published literature, and Kenya's comprehensive multiyear plan for immunization. Rotavirus and inactivated poliovirus vaccines (IPV) were used as representative examples of oral and parenteral vaccines, respectively. Packaging technologies evaluated included glass vials, blow-fill-seal (BFS) containers, preformed polymer containers, and compact prefilled auto-disable (CPAD) devices in both BFS and preformed formats. For oral vaccine packaging, BFS multi-monodose (MMD) ampoules were the least expensive format, with a COGS of $0.12 per dose. In comparison, oral single-dose glass vials had a COGS of $0.40. BFS MMD ampoules had the lowest TCOD of oral vaccine containers at $1.19 per dose delivered, and ten-dose glass vials had a TCOD of $1.61 per dose delivered. For parenteral vaccines, the lowest COGS was achieved with ten-dose glass vials at $0.22 per dose. In contrast, preformed CPAD devices had the highest COGS at $0.60 per dose. Ten-dose glass vials achieved the lowest TCOD of the parenteral vaccine formats at $1.56 per dose delivered. Of the polymer containers for parenteral vaccines, BFS MMD ampoules achieved the lowest TCOD at $1.89 per dose delivered, whereas preformed CPAD devices remained the most expensive format, at $2.25 per dose delivered. Given their potential to address the limitations of glass and reduce COGS and TCOD, polymer containers deserve further consideration as alternative approaches for vaccine packaging. Copyright © 2018 PATH. Published by Elsevier Ltd.. All rights reserved.

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the geant4 Monte Carlo code

PubMed Central

Guan, Fada; Peeler, Christopher; Bronk, Lawrence; Geng, Changran; Taleei, Reza; Randeniya, Sharmalee; Ge, Shuaiping; Mirkovic, Dragan; Grosshans, David; Mohan, Radhe; Titt, Uwe

2015-01-01

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the geant 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from geant 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LETt and dose-averaged LET, LETd) using geant 4 for different tracking step size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LETt and LETd of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LETt but significant for LETd. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in geant 4 can result in incorrect LETd calculation results in the dose plateau region for small step limits. The erroneous LETd results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in geant 4. The incorrect LETd values lead to substantial differences in the calculated RBE. Conclusions: When the geant 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LETt in the dose plateau region and LETd around the Bragg peak. For a large step limit, i.e., 500 μm, LETd is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LETd and LETt becomes positive. PMID:26520716

Safety and pharmacokinetics of ramucirumab in combination with docetaxel in Japanese patients with locally advanced or metastatic breast cancer: a Phase Ib study.

PubMed

Masuda, Norikazu; Iwata, Hiroji; Aogi, Kenjiro; Xu, Yihuan; Ibrahim, Ayman; Gao, Ling; Dalal, Rita; Yoshikawa, Reigetsu; Sasaki, Yasutsuna

2016-12-01

The primary objective of this study was to investigate the safety and tolerability and to confirm the recommended dose of the anti-vascular endothelial growth factor receptor 2 monoclonal antibody ramucirumab in combination with docetaxel in Japanese patients with metastatic/locally advanced breast cancer. In this multicenter, single-arm, Phase Ib trial, eligibility criteria included: 20 years or older, Eastern Cooperative Oncology Group performance status of 0/1 and confirmed diagnosis of human epidermal growth factor receptor 2-negative metastatic/locally recurrent inoperable breast adenocarcinoma. Patients received docetaxel (75 mg/m 2 ) followed by ramucirumab (10 mg/kg) on Day 1 of 21-day cycles. Recommended dose was defined as <33% dose-limiting toxicities in dose-limiting toxicity-evaluable patients in Cycle 1. The safety, pharmacokinetics, immunogenicity and antitumor activity were examined. Seven patients were treated. Most adverse events were mild to moderate. Two patients during Cycle 1 experienced a dose-limiting toxicity; one patient each experienced Grade 3 febrile neutropenia and Grade 3 gingivitis. Both dose-limiting toxicities subsequently resolved. No patients discontinued study therapies during Cycle 1. Four serious adverse events were possibly related to ramucirumab in combination with docetaxel. Anti-ramucirumab antibodies were not detected. Pharmacokinetic analysis revealed low total body clearance and long apparent terminal elimination half-life (~7-12 days). Partial response was reported in four patients. The combination of ramucirumab and docetaxel was tolerable in female Japanese patients with breast cancer. Ramucirumab 10 mg/kg in combination with docetaxel (75 mg/m 2 ) was confirmed as the recommended dose among Japanese patients, supporting its use in future studies. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A Phase I study of bizelesin (NSC 615291) in patients with advanced solid tumors.

PubMed

Pitot, Henry C; Reid, Joel M; Sloan, Jeff A; Ames, Matthew M; Adjei, Alex A; Rubin, Joseph; Bagniewski, Pamela G; Atherton, Pamela; Rayson, Daniel; Goldberg, Richard M; Erlichman, Charles

2002-03-01

To evaluate the toxicities, characterize the pharmacokinetics, and determine the maximum-tolerated dose of bizelesin administered once every 4 weeks. Patients with advanced solid tumors received escalating doses of bizelesin as an i.v. push every 4 weeks. Pharmacokinetic studies were performed with the first treatment cycle. Nineteen eligible patients received a total of 54 courses of bizelesin at doses ranging from 0.1 to 1 microg/m(2). Dose-limiting toxicity of neutropenia was seen in 2 of 4 patients treated at the 1 microg/m(2) dose level. Nonhematological toxicity was generally mild with maximum toxicity being

Combination of romidepsin with cyclophosphamide, doxorubicin, vincristine, and prednisone in previously untreated patients with peripheral T-cell lymphoma: a non-randomised, phase 1b/2 study.

PubMed

Dupuis, Jehan; Morschhauser, Franck; Ghesquières, Hervé; Tilly, Hervé; Casasnovas, Olivier; Thieblemont, Catherine; Ribrag, Vincent; Bossard, Céline; Le Bras, Fabien; Bachy, Emmanuel; Hivert, Bénédicte; Nicolas-Virelizier, Emmanuelle; Jardin, Fabrice; Bastie, Jean-Noel; Amorim, Sandy; Lazarovici, Julien; Martin, Antoine; Coiffier, Bertrand

2015-04-01

Romidepsin is a histone deacetylase inhibitor approved in the USA for patients with recurrent or refractory peripheral T-cell lymphoma and has shown activity in this setting with mainly haematological and gastrointestinal toxicity. Although it has limited efficacy, cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy is widely used for treatment of de-novo peripheral T-cell lymphoma. We aimed to assess the safety, tolerability, and activity of romidepsin combined with CHOP in patients with previously untreated disease. We enrolled patients aged 18-80 years with histologically proven, previously untreated, peripheral T-cell lymphoma (Eastern Cooperative Oncology Group performance status ≤2) into a dose-escalation (phase 1b) and expansion (phase 2) study at nine Lymphoma Study Association centres in France. In the dose-escalation phase, we allocated consecutive blocks of three participants to receive eight 3 week cycles of CHOP (intravenous cyclophosphamide 750 mg/m(2), doxorubicin 50 mg/m(2), and vincristine 1.4 mg/m(2) [maximum 2 mg] on day 1 and oral prednisone 40 mg/m(2) on days 1-5) in association with varying doses of romidepsin. The starting dose was 10 mg/m(2) intravenously on days 1 and 8 of each cycle, and we used a 3 + 3 design. We assessed dose-limiting toxicities only during the first two cycles. The primary endpoint was to determine the recommended dose for the combination. For the phase 2 study, we aimed to increase the cohort of patients receiving the recommended dose to a total of 25 patients. Patients were assessed for safety outcomes at least twice per cycle according to the Common Terminology Criteria for Adverse Events, version 4.0. Safety analyses included all patients who received at least one dose of romidepsin and CHOP. This trial is registered at the European Clinical Trials Database (EudraCT), number 2010-020962-91 and ClinicalTrials.gov, number NCT01280526. Between Jan 13, 2011, and May 21, 2013, we enrolled 37 patients (18 treated in phase 1b and 19 patients in phase 2). Three of six patients initially treated at 10 mg/m(2) had a dose-limiting toxicity. The dose-escalation committee decided to modify the study protocol to redefine dose-limiting toxicities with regard to haematological toxicity. Three patients were treated with 8 mg/m(2) of romidepsin, an additional three at 10 mg/m(2) (one dose-limiting toxicity), and six patients at 12 mg/m(2) (three dose-limiting toxicities). We chose romidepsin 12 mg/m(2) as the recommended dose for phase 2. Of the 37 patients treated, three had early cardiac events (two myocardial infarctions and one acute cardiac failure). No deaths were attributable to toxicity. 25 (68%) of 37 patients had at least one serious adverse event. Overall, the most frequent serious adverse events were febrile neutropenia (five [14%] of 37 patients), physical health deterioration (five [14%]), lung infection (four [11%]), and vomiting (three [8%]). 33 (89%) of patients had grade 3-4 neutropenia, and 29 (78%) had grade 3-4 thrombocytopenia. Romidepsin can be combined with CHOP but this combination should now be tested in comparison to CHOP alone in a randomised trial. Celgene. Copyright © 2015 Elsevier Ltd. All rights reserved.

Dose Equivalents for Second-Generation Antipsychotic Drugs: The Classical Mean Dose Method

PubMed Central

Leucht, Stefan; Samara, Myrto; Heres, Stephan; Patel, Maxine X.; Furukawa, Toshi; Cipriani, Andrea; Geddes, John; Davis, John M.

2015-01-01

Background: The concept of dose equivalence is important for many purposes. The classical approach published by Davis in 1974 subsequently dominated textbooks for several decades. It was based on the assumption that the mean doses found in flexible-dose trials reflect the average optimum dose which can be used for the calculation of dose equivalence. We are the first to apply the method to second-generation antipsychotics. Methods: We searched for randomized, double-blind, flexible-dose trials in acutely ill patients with schizophrenia that examined 13 oral second-generation antipsychotics, haloperidol, and chlorpromazine (last search June 2014). We calculated the mean doses of each drug weighted by sample size and divided them by the weighted mean olanzapine dose to obtain olanzapine equivalents. Results: We included 75 studies with 16 555 participants. The doses equivalent to 1 mg/d olanzapine were: amisulpride 38.3 mg/d, aripiprazole 1.4 mg/d, asenapine 0.9 mg/d, chlorpromazine 38.9 mg/d, clozapine 30.6 mg/d, haloperidol 0.7 mg/d, quetiapine 32.3mg/d, risperidone 0.4mg/d, sertindole 1.1 mg/d, ziprasidone 7.9 mg/d, zotepine 13.2 mg/d. For iloperidone, lurasidone, and paliperidone no data were available. Conclusions: The classical mean dose method is not reliant on the limited availability of fixed-dose data at the lower end of the effective dose range, which is the major limitation of “minimum effective dose methods” and “dose-response curve methods.” In contrast, the mean doses found by the current approach may have in part depended on the dose ranges chosen for the original trials. Ultimate conclusions on dose equivalence of antipsychotics will need to be based on a review of various methods. PMID:25841041

Statistical analysis of radioimmunoassay. In comparison with bioassay (in Japanese)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nakano, R.

1973-01-01

Using the data of RIA (radioimmunoassay), statistical procedures for dealing with two problems of the linearization of dose response curve and calculation of relative potency were described. There were three methods for linearization of dose response curve of RIA. In each method, the following parameters were shown on the horizontal and vertical axis: dose x, (B/T)/sup -1/; c/x + c, B/T (C: dose which makes B/T 50%); log x, logit B/T. Among them, the last method seems to be most practical. The statistical procedures for bioassay were employed for calculating the relative potency of unknown samples compared to the standardmore » samples from dose response curves of standand and unknown samples using regression coefficient. It is desirable that relative potency is calculated by plotting more than 5 points in the standard curve and plotting more than 2 points in unknow samples. For examining the statistical limit of precision of measuremert, LH activity of gonadotropin in urine was measured and relative potency, precision coefficient and the upper and lower limits of relative potency at 95% confidence limit were calculated. On the other hand, bioassay (by the ovarian ascorbic acid reduction method and anteriol lobe of prostate weighing method) was done in the same samples, and the precision was compared with that of RIA. In these examinations, the upper and lower limits of the relative potency at 95% confidence limit were near each other, while in bioassay, a considerable difference was observed between the upper and lower limits. The necessity of standardization and systematization of the statistical procedures for increasing the precision of RIA was pointed out. (JA)« less

Severe neuropathy after high dose carboplatin in three patients receiving multidrug chemotherapy

PubMed Central

Heinzlef, O.; Lotz, J.; Roullet, E.

1998-01-01

Three patients are described who developed a severe neuropathy after chemotherapy with high dose cis-diamine-(1,1-cyclobutane dicarboxylato) platinum (carboplatin). This toxic side effect, which is unusual at conventional doses, might become more frequent as increasing doses are administered to overcome drug resistance in cancer treatment, and might limit its use at very high doses before haematopoietic stem cell transplantation. 

 PMID:9598687

Impact of reduced dose limits on NRC licensed activities. Major issues in the implementation of ICRP/NCRP dose limit recommendations: Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Meinhold, C.B.

This report summarizes information required to estimate, at least qualitatively, the potential impacts of reducing occupational dose limits below those given in 10 CFR 20 (Revised). For this study, a questionnaire was developed and widely distributed to the radiation protection community. The resulting data together with data from existing surveys and sources were used to estimate the impact of three dose-limit options; 10 mSv yr{sup {minus}1} (1 rem yr{sup {minus}1}), 20 mSv yr{sup {minus}1} (2 rem yr{sup {minus}1}), and a combination of an annual limit of 50 mSv yr{sup {minus}1} (5 rem yr{sup {minus}1}) coupled with a cumulative limit, inmore » rem, equal to age in years. Due to the somewhat small number of responses and the lack of data in some specific areas, a working committee of radiation protection experts from a variety of licensees was employed to ensure the exposure data were representative. The following overall conclusions were reached: (1) although 10 mSv yr{sup {minus}1} is a reasonable limit for many licensees, such a limit could be extraordinarily difficult to achieve and potentially destructive to the continued operation of some licensees, such as nuclear power, fuel fabrication, and medicine; (2) twenty mSv yr{sup {minus}1} as a limit is possible for some of these groups, but for others it would prove difficult. (3) fifty mSv yr{sup {minus}1} and age in 10s of mSv appear reasonable for all licensees, both in terms of the lifetime risk of cancer and severe genetic effects to the most highly exposed workers, and the practicality of operation.« less

Limited Margin Radiation Therapy for Children and Young Adults With Ewing Sarcoma Achieves High Rates of Local Tumor Control

DOE Office of Scientific and Technical Information (OSTI.GOV)

Talleur, Aimee C.; Navid, Fariba; Spunt, Sheri L.

Purpose: To determine the rate of local failure using focal conformal, limited margin radiation therapy (RT) and dose escalation for tumors ≥8 cm (greatest dimension at diagnosis) in children and young adults with Ewing sarcoma (EWS). Methods and Materials: Eligible patients with EWS were treated on a phase 2 institutional trial of focal conformal, limited margin RT using conformal or intensity modulated techniques. The treatment volume incorporated a 1-cm constrained margin around the gross tumor. Unresected tumors, <8 cm at diagnosis, received a standard dose of 55.8 Gy and tumors ≥8 cm, an escalated dose to 64.8 Gy. Patients with microscopic residual disease after resectionmore » received adjuvant RT to 50.4 Gy. Adjuvant brachytherapy was permitted in selected patients. Results: Forty-five patients were enrolled: 26 with localized and 19 with metastatic disease. Median (range) age, tumor size, and follow-up were 13.0 years (2.9-24.7 years), 9.0 cm (2.4-17.0 cm), and 54.5 months (1.9-122.2 months), respectively. All patients received systemic chemotherapy. The median (range) RT dose for all patients was 56.1 Gy (45-65.5 Gy). Seventeen patients received adjuvant, 16 standard-dose, and 12 escalated-dose RT. Failures included 1 local, 10 distant, and 1 local/distant. The estimated 10-year cumulative incidence of local failure was 4.4% ± 3.1%, with no statistical difference seen between RT treatment groups and no local failures in the escalated-dose RT treatment group. Conclusions: Treatment with focal conformal, limited margin RT, including dose escalation for larger tumors, provides favorable local tumor control in EWS.« less

Comparative Benchmark Dose Modeling as a Tool to Make the First Estimate of Safe Human Exposure Levels to Lunar Dust

NASA Technical Reports Server (NTRS)

James, John T.; Lam, Chiu-wing; Scully, Robert R.

2013-01-01

Brief exposures of Apollo Astronauts to lunar dust occasionally elicited upper respiratory irritation; however, no limits were ever set for prolonged exposure ot lunar dust. Habitats for exploration, whether mobile of fixed must be designed to limit human exposure to lunar dust to safe levels. We have used a new technique we call Comparative Benchmark Dose Modeling to estimate safe exposure limits for lunar dust collected during the Apollo 14 mission.

Radiation Exposure to Relatives of Patients Treated with Iodine-131 for Thyroid Cancer at Siriraj Hospital.

PubMed

Tonnonchiang, Siriporn; Sritongkul, Nopamon; Chaudakshetrin, Pachee; Tuntawiroon, Malulee

2016-02-01

Thyroid cancer patients treated with 1-131 are potential source of radiation exposure to relatives who are knowingly and willingly exposed to ionizing radiation as a result of providing comfort to patients undergoing I-131 therapy. This study aims to determine radiation dose received by relatives who care for non self-supporting 1-131 patients at Siriraj Hospital. Twenty caregivers of 20 patients underwent I-131 therapy for thyroid cancer with a standard protocol were given specific instructions with regard to radiation safety and provided with electronic digital dosimeter to continuously measure radiation dose received on daily basis, three days in the hospital. On the day patient is released, thyroid uptake estimates were performed to assess internal radiation dose received by caregivers. The 3-day accumulative doses to caregivers to patients receiving 150 mCi (n = 11) and 200 mCi (n = 9) of I-131 ranged from 37 to 333 uSv and 176 to 1,920 pSv respectively depending on the level of supports required. Thyroid uptake estimates in all caregivers were undetectable. Dosimeter indicated a maximum whole-body dose of1.92 mSv was more than the public dose limit of] mSv but within the dose constraint of 5 mSv for caregivers. Radiation dose to caregivers of a non self-supporting hospitalized patient undergoing 1-131 therapy were well below the limits recommended by the ICRP. The patients can be comforted with confidence that dose to caregivers will be less than the limit. This study provides guidance for medical practitioners to obtain practical radiation safety concerns associated with hospitalized patients receiving I-131 therapy especially when patient needs assistance.

Revisiting the definition of dose-limiting toxicities in paediatric oncology phase I clinical trials: An analysis from the Innovative Therapies for Children with Cancer Consortium.

PubMed

Bautista, Francisco; Moreno, Lucas; Marshall, Lynley; Pearson, Andrew D J; Geoerger, Birgit; Paoletti, Xavier

2017-11-01

Dose-escalation trials aim to identify the maximum tolerated dose and, importantly, the recommended phase II dose (RP2D) and rely on the occurrence of dose-limiting toxicities (DLTs) during the first treatment cycle. Molecularly targeted agents (MTAs) often follow continuous and prolonged administrations, displaying a distinct toxicity profile compared to conventional chemotherapeutics, and classical DLT criteria might not be appropriate to evaluate MTAs' toxicity. We investigated this issue in children. The Innovative Therapies for Children with Cancer Consortium (ITCC) phase I trials of novel anticancer agents between 2004 and 2015 were analysed. Data from investigational product, trial design, items defining DLT/RP2D were extracted. A survey on dose-escalation process, DLTs and RP2D definition was conducted among the ITCC clinical trials committee members. Thirteen phase I trials with 15 dose-escalation cohorts were analysed. They explored 11 MTAs and 2 novel cytotoxics; 12 evaluated DLT during cycle 1. Definition of DLT was heterogeneous: Grade III-IV haematologic toxicities that were transient or asymptomatic and grade III-IV non-haematological toxicities manageable with adequate supportive care were often excluded, whereas some included dose intensity or grade II toxicities into DLT. None of the studies considered delayed toxicity into the RP2D definition. DLTs should be homogeneously defined across trials, limiting the number of exceptions due to specific toxicities. Dose escalation should still be based on safety data from cycle 1, but delayed and overall toxicities, pharmacokinetic parameters and pharmacodynamic data should be considered to refine the final RP2D. The evaluation of long-term toxicity in the developing child cannot be adequately addressed in early trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Comparing Hp(3) evaluated from the conversion coefficients from air kerma to personal dose equivalent for eye lens dosimetry calibrated on a new cylindrical PMMA phantom

NASA Astrophysics Data System (ADS)

Esor, J.; Sudchai, W.; Monthonwattana, S.; Pungkun, V.; Intang, A.

2017-06-01

Based on a new occupational dose limit recommended by ICRP (2011), the annual dose limit for the lens of the eye for workers should be reduced from 150 mSv/y to 20 mSv/y averaged over 5 consecutive years in which no single year exceeding 50 mSv. This new dose limit directly affects radiologists and cardiologists whose work involves high radiation exposure over 20 mSv/y. Eye lens dosimetry (Hp(3)) has become increasingly important and should be evaluated directly based on dosimeters that are worn closely to the eye. Normally, Hp(3) dose algorithm was carried out by the combination of Hp(0.07) and Hp(10) values while dosimeters were calibrated on slab PMMA phantom. Recently, there were three reports from European Union that have shown the conversion coefficients from air kerma to Hp(3). These conversion coefficients carried out by ORAMED, PTB and CEA Saclay projects were performed by using a new cylindrical head phantom. In this study, various delivered doses were calculated using those three conversion coefficients while nanoDot, small OSL dosimeters, were used for Hp(3) measurement. These calibrations were performed with a standard X-ray generator at Secondary Standard Dosimetry Laboratory (SSDL). Delivered doses (Hp(3)) using those three conversion coefficients were compared with Hp(3) from nanoDot measurements. The results showed that percentage differences between delivered doses evaluated from the conversion coefficient of each project and Hp(3) doses evaluated from the nanoDots were found to be not exceeding -11.48 %, -8.85 % and -8.85 % for ORAMED, PTB and CEA Saclay project, respectively.

Energy spectrum control for modulated proton beams.

PubMed

Hsi, Wen C; Moyers, Michael F; Nichiporov, Dmitri; Anferov, Vladimir; Wolanski, Mark; Allgower, Chris E; Farr, Jonathan B; Mascia, Anthony E; Schreuder, Andries N

2009-06-01

In proton therapy delivered with range modulated beams, the energy spectrum of protons entering the delivery nozzle can affect the dose uniformity within the target region and the dose gradient around its periphery. For a cyclotron with a fixed extraction energy, a rangeshifter is used to change the energy but this produces increasing energy spreads for decreasing energies. This study investigated the magnitude of the effects of different energy spreads on dose uniformity and distal edge dose gradient and determined the limits for controlling the incident spectrum. A multilayer Faraday cup (MLFC) was calibrated against depth dose curves measured in water for nonmodulated beams with various incident spectra. Depth dose curves were measured in a water phantom and in a multilayer ionization chamber detector for modulated beams using different incident energy spreads. Some nozzle entrance energy spectra can produce unacceptable dose nonuniformities of up to +/-21% over the modulated region. For modulated beams and small beam ranges, the width of the distal penumbra can vary by a factor of 2.5. When the energy spread was controlled within the defined limits, the dose nonuniformity was less than +/-3%. To facilitate understanding of the results, the data were compared to the measured and Monte Carlo calculated data from a variable extraction energy synchrotron which has a narrow spectrum for all energies. Dose uniformity is only maintained within prescription limits when the energy spread is controlled. At low energies, a large spread can be beneficial for extending the energy range at which a single range modulator device can be used. An MLFC can be used as part of a feedback to provide specified energy spreads for different energies.

Phase I Study of Vandetanib With Radiotherapy and Temozolomide for Newly Diagnosed Glioblastoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drappatz, Jan; Norden, Andrew D.; Division of Cancer Neurology, Department of Neurology, Brigham and Women's Hospital, Boston, MA

Purpose: Increasing evidence has suggested that angiogenesis inhibition might potentiate the effects of radiotherapy and chemotherapy in patients with glioblastoma (GBM). In addition, epidermal growth factor receptor inhibition might be of therapeutic benefit, because the epidermal growth factor receptor is upregulated in GBM and contributes to radiation resistance. We conducted a Phase I study of vandetanib, an inhibitor of vascular endothelial growth factor receptor 2 and epidermal growth factor receptor, in patients with newly diagnosed GBM combined with RT and temozolomide (TMZ). Methods and Materials: A total of 13 GBM patients were treated with vandetanib, radiotherapy, and concurrent and adjuvantmore » TMZ, using a standard '3 + 3' dose escalation. The maximal tolerated dose was defined as the dose with <1 of 6 dose-limiting toxicities during the first 12 weeks of therapy. The eligible patients were adults with newly diagnosed GBM, Karnofsky performance status of {>=}60, normal organ function, who were not taking enzyme-inducing antiepileptic drugs. Results: Of the 13 patients, 6 were treated with vandetanib at a dose of 200mg daily. Of the 6 patients, 3 developed dose-limiting toxicities within the first 12 weeks, including gastrointestinal hemorrhage and thrombocytopenia in 1 patient, neutropenia in 1 patient, and diverticulitis with gastrointestinal perforation in 1 patient. The other 7 patients were treated with 100 mg daily, with no dose-limiting toxicities observed, establishing this dose as the maximal tolerated dose combined with TMZ and RT. Conclusion: Vandetanib can be safely combined with RT and TMZ in GBM patients. A Phase II study in which patients are randomized to vandetanib 100 mg daily with RT and TMZ or RT and TMZ alone is underway.« less

Opioid needs of patients with advanced cancer and the morphine dose-limiting law in Egypt.

PubMed

Alsirafy, Samy A; El-Mesidi, Salah M; El-Sherief, Wesam A; Galal, Khaled M; Abou-Elela, Enas N; Aklan, Nahla A

2011-01-01

Morphine is the drug of choice for moderate to severe cancer pain management. The Egyptian Narcotics Control Law limits the amount of morphine prescribed in a single prescription to a maximum of 420 mg for tablets and 60 mg for ampoules. The usual practice in Egypt is to provide that limited amount of morphine on a weekly basis. The aim of this study is to estimate the extent to which Egyptian patients may be undertreated because of this law. We reviewed the medical records of advanced cancer patients referred to the first palliative care unit in Egypt over a seven-month period. Cancer pain was managed following the WHO guidelines. After modifying the internal institutional policy, patients received adequate amounts of the available opioids without any violations of the law. From 117 eligible advanced cancer patients, 58 (50%) patients required strong opioids, 32 (27%) required weak opioids, and 27 (23%) required no regular opioids. The mean last prescribed opioid dose for those who required strong opioids was 194 mg of oral morphine equivalent/24 h (± 180). For this group of patients, a single weekly prescription would supply enough oral morphine for only 26% of them. In the case of parenteral morphine, none of these patients would receive an adequate supply. In view of the current morphine dose-limiting law and practices in Egypt, the majority of patients suffering severe cancer pain would not have access to adequate morphine doses. That dose-limiting law and other restrictive regulations represent an obstacle to cancer pain control in Egypt and should be revised urgently.

Evaluation and optimization of occupational eye lens dosimetry during positron emission tomography (PET) procedures.

PubMed

Guiu-Souto, Jacobo; Sánchez-García, Manuel; Vázquez-Vázquez, Rubén; Otero, Carlos; Luna, Victor; Mosquera, Javier; Busto, Ramón Lobato; Aguiar, Pablo; Ruibal, Álvaro; Pardo-Montero, Juan; Pombar-Cameán, Miguel

2016-06-01

The last recommendations of the International Commission on Radiological Protection for eye lens dose suggest an important reduction on the radiation limits associated with early and late tissue reactions. The aim of this work is to quantify and optimize the eye lens dose associated to nurse staff during positron emission tomography (PET) procedures. PET is one of the most important diagnostic methods of oncological and neurological cancer disease involving an important number of workers exposed to the high energy isotope F-18. We characterize the relevant stages as preparation and administration of monodose syringes in terms of occupational dose. A direct reading silicon dosimeter was used to measure the lens dose to staff. The highest dose of radiation was observed during preparation of the fluorodesoxyglucose (FDG) syringes. By optimizing a suitable vials' distribution of FDG we find an important reduction in occupational doses. Extrapolation of our data to other clinical scenarios indicates that, depending on the work load and/or syringes activity, safety limits of the dose might be exceeded.

Radionuclides in bats using a contaminated pond on the Nevada National Security Site, USA

DOE Office of Scientific and Technical Information (OSTI.GOV)

Warren, Ronald W.; Hall, Derek B.; Greger, Paul D.

In this study, perched groundwater percolating through radionuclide contamination in the E Tunnel Complex on the Nevada National Security Site, formerly the Nevada Test Site, emerges and is stored in a series of ponds making it available to wildlife, including bats. Since many bat species using the ponds are considered sensitive or protected/regulated and little information is available on dose to bats from radioactive water sources, bats were sampled to determine if the dose they were receiving exceeded the United States Department of Energy dose limit of 1.0E-3 Gy/day. Radionuclide concentrations in water, sediment, and flying insects were also measuredmore » as input parameters to the dose rate model and to examine trophic level relationships. The RESRAD-Biota model was used to calculate dose rates to bats using different screening levels. Efficacy of RESRAD-Biota and suggested improvements are discussed. Finally, dose to bats foraging and drinking at these ponds is well below the dose limit set to protect terrestrial biota populations.« less

Radionuclides in bats using a contaminated pond on the Nevada National Security Site, USA

DOE PAGES

Warren, Ronald W.; Hall, Derek B.; Greger, Paul D.

2014-01-03

In this study, perched groundwater percolating through radionuclide contamination in the E Tunnel Complex on the Nevada National Security Site, formerly the Nevada Test Site, emerges and is stored in a series of ponds making it available to wildlife, including bats. Since many bat species using the ponds are considered sensitive or protected/regulated and little information is available on dose to bats from radioactive water sources, bats were sampled to determine if the dose they were receiving exceeded the United States Department of Energy dose limit of 1.0E-3 Gy/day. Radionuclide concentrations in water, sediment, and flying insects were also measuredmore » as input parameters to the dose rate model and to examine trophic level relationships. The RESRAD-Biota model was used to calculate dose rates to bats using different screening levels. Efficacy of RESRAD-Biota and suggested improvements are discussed. Finally, dose to bats foraging and drinking at these ponds is well below the dose limit set to protect terrestrial biota populations.« less

DOSE-DEPENDENT TRANSITIONS IN MECHANISMS OF TOXICITY: CASE STUDIES

EPA Science Inventory

Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed ...

Psychopharmacology of theobromine in healthy volunteers.

PubMed

Baggott, Matthew J; Childs, Emma; Hart, Amy B; de Bruin, Eveline; Palmer, Abraham A; Wilkinson, Joy E; de Wit, Harriet

2013-07-01

Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, current evidence for this is limited. We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1,000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Caffeine had the expected effects on mood including feelings of alertness and cardiovascular parameters. Theobromine responses differed according to dose; it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses, we also examined individual differences in the drug's effects in relation to genes related to their target receptors, but few associations were detected. This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes, effects become negative.

Psychopharmacology of theobromine in healthy volunteers

PubMed Central

Baggott, Matthew J.; Childs, Emma; Hart, Amy B.; de Bruin, Eveline; Palmer, Abraham A.; Wilkinson, Joy E.; de Wit, Harriet

2013-01-01

Background Theobromine, a methylxanthine related to caffeine and present in high levels in cocoa, may contribute to the appeal of chocolate. However, currently evidence for this is limited. Objectives We conducted a within-subjects placebo-controlled study of a wide range of oral theobromine doses (250, 500, and 1000 mg) using an active control dose of caffeine (200 mg) in 80 healthy participants. Results Caffeine had the expected effects on mood including feelings of alertness, and cardiovascular parameters. Theobromine responses differed according to dose: it showed limited subjective effects at 250 mg and negative mood effects at higher doses. It also dose-dependently increased heart rate. In secondary analyses we also examined individual differences in the drugs' effects in relation to genes related to their target receptors, but few associations were detected. Conclusions This study represents the highest dose of theobromine studied in humans. We conclude that theobromine at normal intake ranges may contribute to the positive effects of chocolate, but at higher intakes effects become negative. PMID:23420115

21 CFR 520.2380c - Thiabendazole bolus.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) Limitations. As a single oral dose; may repeat once in 2 to 3 weeks; do not treat animals within 3 days of...) Chemical name. 2-(4-Thiazolyl) benzimidazole. (b) Specifications. Conforms to N.F. XII. (c) Sponsor. See No...) Limitations. As a single oral dose; as a drench or bolus; may repeat once in 2 to 3 weeks; do not treat...

21 CFR 520.2380c - Thiabendazole bolus.

Code of Federal Regulations, 2011 CFR

2011-04-01

...) Limitations. As a single oral dose; may repeat once in 2 to 3 weeks; do not treat animals within 3 days of...) Chemical name. 2-(4-Thiazolyl) benzimidazole. (b) Specifications. Conforms to N.F. XII. (c) Sponsor. See No...) Limitations. As a single oral dose; as a drench or bolus; may repeat once in 2 to 3 weeks; do not treat...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2012 CFR

2012-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2014 CFR

2014-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2011 CFR

2011-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2013 CFR

2013-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

10 CFR 72.106 - Controlled area of an ISFSI or MRS.

Code of Federal Regulations, 2010 CFR

2010-01-01

... controlled area may not receive from any design basis accident the more limiting of a total effective dose equivalent of 0.05 Sv (5 rem), or the sum of the deep-dose equivalent and the committed dose equivalent to any individual organ or tissue (other than the lens of the eye) of 0.5 Sv (50 rem). The lens dose...

Guidance on radiation dose limits for the lens of the eye: overview of the recommendations in NCRP Commentary No. 26.

PubMed

Dauer, Lawrence T; Ainsbury, Elizabeth A; Dynlacht, Joseph; Hoel, David; Klein, Barbara E K; Mayer, Donald; Prescott, Christina R; Thornton, Raymond H; Vano, Eliseo; Woloschak, Gayle E; Flannery, Cynthia M; Goldstein, Lee E; Hamada, Nobuyuki; Tran, Phung K; Grissom, Michael P; Blakely, Eleanor A

2017-10-01

This review summarizes the conclusions and recommendations of the new National Council on Radiation Protection and Measurements (NCRP) Commentary No. 26 guidance on radiation dose limits for the lens of the eye. The NCRP addressed radiation protection principles in respect to the lens of the eye, discussed the current understanding of eye biology and lens effects, reviewed and evaluated epidemiology, and assessed exposed populations with the potential for significant radiation exposures to the lens while suggesting monitoring and protection practices. Radiation-induced damage to the lens of the eye can include the loss of clarity resulting in opacification or clouding several years after exposure. The impact is highly dependent on the type of radiation, how the exposure of the lens was delivered, the genetic susceptibilities of the individual exposed, and the location of the opacity relative to the visual axis of the individual. The preponderance of epidemiological evidence suggests that lens damage could occur at lower doses than previously considered and the NCRP has determined that it is prudent to reduce the recommended annual lens of the eye occupational dose limit from an equivalent dose of 150 mSv to an absorbed dose of 50 mGy. Significant additional research is still needed in the following areas: comprehensive evaluation of the overall effects of ionizing radiation on the eye, dosimetry methodology and dose-sparing optimization techniques, additional high quality epidemiology studies, and a basic understanding of the mechanisms of cataract development.

Role of particle radiotherapy in the management of head and neck cancer.

PubMed

Laramore, George E

2009-05-01

Modern imaging techniques and powerful computers allow a radiation oncologist to design treatments delivering higher doses of radiation than previously possible. Dose distributions imposed by the physics of 'standard' photon and electron beams limit further dose escalation. Hadron radiotherapy offers advantages in either dose distribution and/or improved radiobiology that may significantly improve the treatment of certain head and neck malignancies. Clinical studies support the effectiveness of fast-neutron radiotherapy in the treatment of major and minor salivary gland tumors. Data show highly favorable outcomes with proton radiotherapy for skull-base malignancies and tumors near highly critical normal tissues compared with that expected with standard radiotherapy. Heavy-ion radiotherapy clinical studies are mainly being conducted with fully stripped carbon ions, and limited data seem to indicate a possible improvement over proton radiotherapy for the same subset of radioresistant tumors where neutrons show a benefit over photons. Fast-neutron radiotherapy has different radiobiological properties compared with standard radiotherapy but similar depth dose distributions. Its role in the treatment of head and neck cancer is currently limited to salivary gland malignancies and certain radioresistant tumors such as sarcomas. Protons have the same radiobiological properties as standard radiotherapy beams but more optimal depth dose distributions, making it particularly advantageous when treating tumors adjacent to highly critical structures. Heavy ions combine the radiobiological properties of fast neutrons with the physical dose distributions of protons, and preliminary data indicate their utility for radioresistant tumors adjacent to highly critical structures.

Assessment of national dosimetry quality audits results for teletherapy machines from 1989 to 2015.

PubMed

Muhammad, Wazir; Ullah, Asad; Mahmood, Khalid; Matiullah

2016-01-01

The purpose of this study was to ensure accuracy in radiation dose delivery, external dosimetry quality audit has an equal importance with routine dosimetry performed at clinics. To do so, dosimetry quality audit was organized by the Secondary Standard Dosimetry Laboratory (SSDL) of Pakistan Institute of Nuclear Science and Technology (PINSTECH) at the national level to investigate and minimize uncertainties involved in the measurement of absorbed dose, and to improve the accuracy of dose measurement at different radiotherapy hospitals. A total of 181 dosimetry quality audits (i.e., 102 of Co-60 and 79 of linear accelerators) for teletherapy units installed at 22 different sites were performed from 1989 to 2015. The percent deviation between users’ calculated/stated dose and evaluated dose (in the result of on-site dosimetry visits) were calculated and the results were analyzed with respect to the limits of ± 2.5% (ICRU "optimal model") ± 3.0% (IAEA on-site dosimetry visits limit) and ± 5.0% (ICRU minimal or "lowest acceptable" model). The results showed that out of 181 total on-site dosimetry visits, 20.44%, 16.02%, and 4.42% were out of acceptable limits of ± 2.5% ± 3.0%, and ± 5.0%, respectively. The importance of a proper ongoing quality assurance program, recommendations of the followed protocols, and properly calibrated thermometers, pressure gauges, and humidity meters at radiotherapy hospitals are essential in maintaining consistency and uniformity of absorbed dose measurements for precision in dose delivery.

Robust EM Continual Reassessment Method in Oncology Dose Finding

PubMed Central

Yuan, Ying; Yin, Guosheng

2012-01-01

The continual reassessment method (CRM) is a commonly used dose-finding design for phase I clinical trials. Practical applications of this method have been restricted by two limitations: (1) the requirement that the toxicity outcome needs to be observed shortly after the initiation of the treatment; and (2) the potential sensitivity to the prespecified toxicity probability at each dose. To overcome these limitations, we naturally treat the unobserved toxicity outcomes as missing data, and use the expectation-maximization (EM) algorithm to estimate the dose toxicity probabilities based on the incomplete data to direct dose assignment. To enhance the robustness of the design, we propose prespecifying multiple sets of toxicity probabilities, each set corresponding to an individual CRM model. We carry out these multiple CRMs in parallel, across which model selection and model averaging procedures are used to make more robust inference. We evaluate the operating characteristics of the proposed robust EM-CRM designs through simulation studies and show that the proposed methods satisfactorily resolve both limitations of the CRM. Besides improving the MTD selection percentage, the new designs dramatically shorten the duration of the trial, and are robust to the prespecification of the toxicity probabilities. PMID:22375092

Status of eye lens radiation dose monitoring in European hospitals.

PubMed

Carinou, Eleftheria; Ginjaume, Merce; O'Connor, Una; Kopec, Renata; Sans Merce, Marta

2014-12-01

A questionnaire was developed by the members of WG12 of EURADOS in order to establish an overview of the current status of eye lens radiation dose monitoring in hospitals. The questionnaire was sent to medical physicists and radiation protection officers in hospitals across Europe. Specific topics were addressed in the questionnaire such as: knowledge of the proposed eye lens dose limit; monitoring and dosimetry issues; training and radiation protection measures. The results of the survey highlighted that the new eye lens dose limit can be exceeded in interventional radiology procedures and that eye lens protection is crucial. Personnel should be properly trained in how to use protective equipment in order to keep eye lens doses as low as reasonably achievable. Finally, the results also highlighted the need to improve the design of eye dosemeters in order to ensure satisfactory use by workers.

Radiation and cataract.

PubMed

Rehani, Madan M; Vano, Eliseo; Ciraj-Bjelac, Olivera; Kleiman, Norman J

2011-09-01

When this paper was about to go to press, the International Commission on Radiological Protection released a statement recommending a change in the threshold dose for the eye lens and dose limits for eye for occupationally exposed persons. It is clear that the earlier published threshold for radiation cataract is no longer valid. Epidemiological studies among Chernobyl clean-up workers, A bomb survivors, astronauts, residents of contaminated buildings, radiological technicians and recent surveys of staff in interventional rooms indicate that there is an increased incidence of lens opacities at doses below 1 Gy. Nevertheless, eye lens dosimetry is at a primitive stage and needs to be developed further. Despite uncertainties concerning dose threshold and dosimetry, it is possible to significantly reduce the risk of radiation cataract through the use of appropriate eye protection. By increasing awareness among those at risk and better adoption and increased usage of protective measures, radiation cataract can become preventable despite lowering of dose limits.

Phase I dose-escalation study of afatinib, an ErbB family blocker, plus docetaxel in patients with advanced cancer.

PubMed

Marshall, John; Shapiro, Geoffrey I; Uttenreuther-Fischer, Martina; Ould-Kaci, Mahmoud; Stopfer, Peter; Gordon, Michael S

2013-02-01

To determine the maximum tolerated dose (MTD), safety and anti-tumor activity of afatinib combined with docetaxel in advanced cancer. The MTD was determined from dose-limiting toxicities in the first cycle. Thirty-one patients received 10, 20 and 30 mg oral afatinib, plus 60 and 75 mg/m(2) intravenous docetaxel (six cohorts; 3-week cycles). The MTD of afatinib was 20 mg/day (days 2-21) with 75 mg/m(2) docetaxel (day 1). Dose-limiting toxicities were grade 3/4 diarrhea (n = 3) and febrile neutropenia (n = 6). Most frequently occurring adverse events were diarrhea, neutropenia and rash. Disease stabilization occurred in 14 patients. Afatinib 20 mg/day plus docetaxel was suboptimal and the study could not yield Phase II dose recommendations. The combination resulted in a manageable safety profile.

Dose Assessment of Los Alamos National Laboratory-Derived Residual Radionuclides in Soils within Tract A-18-2 for Land Conveyance and Transfer Decisions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ruedig, Elizabeth; Whicker, Jeffrey Jay

In 2017, soil sampling for radiological materials was conducted within Tract A-18-2 specifically for land conveyance decisions. Measurements of radionuclides in soil samples were evaluated against a recreational use scenario, and all measurements were below screening action levels for each radionuclide. The total estimated dose was less than 1 mrem/y (< 10 μSv/y) for a hypothetical recreational user (compared to a dose limit of 25 mrem/y (250 μSv/y)). Dose estimates were based on the 95% upper confidence limits for radionuclide concentrations within the Tract. Additionally, dose estimates less than 3 mrem/y are considered to be As Low As Reasonably Achievable,more » so no follow-up analysis was conducted. Release of this property is consistent with the requirements of DOE Order 458.1 and Policy 412.« less

[The dose estimation to the population as a result of radioactive contamination of the Semipalatinsk Test area].

PubMed

Spiridonova, S I; Mukusheva, M K; Shubina, O A; Solomatin, V M; Epifanova, I E

2008-01-01

The results are presented from estimation of spatial distribution of 137Cs and 90Sr contamination densities in the areas of horses and sheep grazing within the Semipalatinsk Test Site. Dose burdens to various cohorts of the population living within the STS and consuming contaminated animal products are predicted. Doses of shepherds in the most contaminated pasture areas have been found to exceed the accepted limit (1 mSv/y). The conclusion is made about the need for further studies on the risk assessment of the STS population exposure above the accepted limits.

The Impact of a One-Dose versus Two-Dose Oral Cholera Vaccine Regimen in Outbreak Settings: A Modeling Study

PubMed Central

Azman, Andrew S.; Luquero, Francisco J.; Ciglenecki, Iza; Grais, Rebecca F.; Sack, David A.; Lessler, Justin

2015-01-01

Background In 2013, a stockpile of oral cholera vaccine (OCV) was created for use in outbreak response, but vaccine availability remains severely limited. Innovative strategies are needed to maximize the health impact and minimize the logistical barriers to using available vaccine. Here we ask under what conditions the use of one dose rather than the internationally licensed two-dose protocol may do both. Methods and Findings Using mathematical models we determined the minimum relative single-dose efficacy (MRSE) at which single-dose reactive campaigns are expected to be as or more effective than two-dose campaigns with the same amount of vaccine. Average one- and two-dose OCV effectiveness was estimated from published literature and compared to the MRSE. Results were applied to recent outbreaks in Haiti, Zimbabwe, and Guinea using stochastic simulations to illustrate the potential impact of one- and two-dose campaigns. At the start of an epidemic, a single dose must be 35%–56% as efficacious as two doses to avert the same number of cases with a fixed amount of vaccine (i.e., MRSE between 35% and 56%). This threshold decreases as vaccination is delayed. Short-term OCV effectiveness is estimated to be 77% (95% CI 57%–88%) for two doses and 44% (95% CI −27% to 76%) for one dose. This results in a one-dose relative efficacy estimate of 57% (interquartile range 13%–88%), which is above conservative MRSE estimates. Using our best estimates of one- and two-dose efficacy, we projected that a single-dose reactive campaign could have prevented 70,584 (95% prediction interval [PI] 55,943–86,205) cases in Zimbabwe, 78,317 (95% PI 57,435–100,150) in Port-au-Prince, Haiti, and 2,826 (95% PI 2,490–3,170) cases in Conakry, Guinea: 1.1 to 1.2 times as many as a two-dose campaign. While extensive sensitivity analyses were performed, our projections of cases averted in past epidemics are based on severely limited single-dose efficacy data and may not fully capture uncertainty due to imperfect surveillance data and uncertainty about the transmission dynamics of cholera in each setting. Conclusions Reactive vaccination campaigns using a single dose of OCV may avert more cases and deaths than a standard two-dose campaign when vaccine supplies are limited, while at the same time reducing logistical complexity. These findings should motivate consideration of the trade-offs between one- and two-dose campaigns in resource-constrained settings, though further field efficacy data are needed and should be a priority in any one-dose campaign. PMID:26305226

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chau, Ricky; Teo, Peter; Kam, Michael

The aim of this study is to evaluate the deficiencies in target coverage and organ protection of 2-dimensional radiation therapy (2DRT) in the treatment of advanced T-stage (T3-4) nasopharyngeal carcinoma (NPC), and assess the extent of improvement that could be achieved with intensity modulated radiation therapy (IMRT), with special reference to of the dose to the planning organ-at-risk volume (PRV) of the brainstem and spinal cord. A dosimetric study was performed on 10 patients with advanced T-stage (T3-4 and N0-2) NPC. Computer tomography (CT) images of 2.5-mm slice thickness of the head and neck were acquired with the patient immobilizedmore » in semi-extended-head position. A 2D plan based on Ho's technique, and an IMRT plan based on a 7-coplanar portals arrangement, were established for each patient. 2DRT was planned with the field borders and shielding drawn on the simulator radiograph with reference to bony landmarks, digitized, and entered into a planning computer for reconstruction of the 3D dose distribution. The 2DRT and IMRT treatment plans were evaluated and compared with respect to the dose-volume histograms (DVHs) of the targets and the organs-at-risk (OARs), tumor control probability (TCP), and normal tissue complication probabilities (NTCPs). With IMRT, the dose coverage of the target was superior to that of 2DRT. The mean minimum dose of the GTV and PTV were increased from 33.7 Gy (2DRT) to 62.6 Gy (IMRT), and 11.9 Gy (2DRT) to 47.8 Gy (IMRT), respectively. The D{sub 95} of the GTV and PTV were also increased from 57.1 Gy (2DRT) to 67 Gy (IMRT), and 45 Gy (2DRT) to 63.6 Gy (IMRT), respectively. The TCP was substantially increased to 78.5% in IMRT. Better protection of the critical normal organs was also achieved with IMRT. The mean maximum dose delivered to the brainstem and spinal cord were reduced significantly from 61.8 Gy (2DRT) to 52.8 Gy (IMRT) and 56 Gy (2DRT) to 43.6 Gy (IMRT), respectively, which were within the conventional dose limits of 54 Gy for brainstem and of 45 Gy for spinal cord. The mean maximum doses deposited on the PRV of the brainstem and spinal cord were 60.7 Gy and 51.6 Gy respectively, which were above the conventional dose limits. For the chiasm, the mean dose maximum and the dose to 5% of its volume were reduced from 64.3 Gy (2DRT) to 53.7 Gy (IMRT) and from 62.8 Gy (2DRT) to 48.7 Gy (IMRT), respectively, and the corresponding NTCP was reduced from 18.4% to 2.1%. For the temporal lobes, the mean dose to 10% of its volume (about 4.6 cc) was reduced from 63.8 Gy (2DRT) to 55.4 Gy (IMRT) and the NTCP was decreased from 11.7% to 3.4%. The therapeutic ratio for T3-4 NPC tumors can be significantly improved with IMRT treatment technique due to improvement both in target coverage and the sparing of the critical normal organ. Although the maximum doses delivered to the brainstem and spinal cord in IMRT can be kept at or below their conventional dose limits, the maximum doses deposited on the PRV often exceed these limits due to the close proximity between the target and OARs. In other words, ideal dosimetric considerations cannot be fulfilled in IMRT planning for T3-4 NPC tumors. A compromise of the maximal dose limit to the PRV of the brainstem and spinal cord would need be accepted if dose coverage to the targets is not to be unacceptably compromised. Dosimetric comparison with 2DRT plans show that these dose limits to PRV were also frequently exceeded in 2DRT plans for locally advanced NPC. A dedicated retrospective study on the incidence of clinical injury to neurological organs in a large series of patients with T3-4 NPC treated by 2DRT may provide useful reference data in exploring how far the PRV dose constraints may be relaxed, to maximize the target coverage without compromising the normal organ function.« less

Analysis of the track- and dose-averaged LET and LET spectra in proton therapy using the GEANT4 Monte Carlo code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Guan, Fada; Peeler, Christopher; Taleei, Reza

Purpose: The motivation of this study was to find and eliminate the cause of errors in dose-averaged linear energy transfer (LET) calculations from therapeutic protons in small targets, such as biological cell layers, calculated using the GEANT 4 Monte Carlo code. Furthermore, the purpose was also to provide a recommendation to select an appropriate LET quantity from GEANT 4 simulations to correlate with biological effectiveness of therapeutic protons. Methods: The authors developed a particle tracking step based strategy to calculate the average LET quantities (track-averaged LET, LET{sub t} and dose-averaged LET, LET{sub d}) using GEANT 4 for different tracking stepmore » size limits. A step size limit refers to the maximally allowable tracking step length. The authors investigated how the tracking step size limit influenced the calculated LET{sub t} and LET{sub d} of protons with six different step limits ranging from 1 to 500 μm in a water phantom irradiated by a 79.7-MeV clinical proton beam. In addition, the authors analyzed the detailed stochastic energy deposition information including fluence spectra and dose spectra of the energy-deposition-per-step of protons. As a reference, the authors also calculated the averaged LET and analyzed the LET spectra combining the Monte Carlo method and the deterministic method. Relative biological effectiveness (RBE) calculations were performed to illustrate the impact of different LET calculation methods on the RBE-weighted dose. Results: Simulation results showed that the step limit effect was small for LET{sub t} but significant for LET{sub d}. This resulted from differences in the energy-deposition-per-step between the fluence spectra and dose spectra at different depths in the phantom. Using the Monte Carlo particle tracking method in GEANT 4 can result in incorrect LET{sub d} calculation results in the dose plateau region for small step limits. The erroneous LET{sub d} results can be attributed to the algorithm to determine fluctuations in energy deposition along the tracking step in GEANT 4. The incorrect LET{sub d} values lead to substantial differences in the calculated RBE. Conclusions: When the GEANT 4 particle tracking method is used to calculate the average LET values within targets with a small step limit, such as smaller than 500 μm, the authors recommend the use of LET{sub t} in the dose plateau region and LET{sub d} around the Bragg peak. For a large step limit, i.e., 500 μm, LET{sub d} is recommended along the whole Bragg curve. The transition point depends on beam parameters and can be found by determining the location where the gradient of the ratio of LET{sub d} and LET{sub t} becomes positive.« less

Risk-adjusted capitation funding models for chronic disease in Australia: alternatives to casemix funding.

PubMed

Antioch, K M; Walsh, M K

2002-01-01

Under Australian casemix funding arrangements that use Diagnosis-Related Groups (DRGs) the average price is policy based, not benchmarked. Cost weights are too low for State-wide chronic disease services. Risk-adjusted Capitation Funding Models (RACFM) are feasible alternatives. A RACFM was developed for public patients with cystic fibrosis treated by an Australian Health Maintenance Organization (AHMO). Adverse selection is of limited concern since patients pay solidarity contributions via Medicare levy with no premium contributions to the AHMO. Sponsors paying premium subsidies are the State of Victoria and the Federal Government. Cost per patient is the dependent variable in the multiple regression. Data on DRG 173 (cystic fibrosis) patients were assessed for heteroskedasticity, multicollinearity, structural stability and functional form. Stepwise linear regression excluded non-significant variables. Significant variables were 'emergency' (1276.9), 'outlier' (6377.1), 'complexity' (3043.5), 'procedures' (317.4) and the constant (4492.7) (R(2)=0.21, SE=3598.3, F=14.39, Prob<0.0001. Regression coefficients represent the additional per patient costs summed to the base payment (constant). The model explained 21% of the variance in cost per patient. The payment rate is adjusted by a best practice annual admission rate per patient. The model is a blended RACFM for in-patient, out-patient, Hospital In The Home, Fee-For-Service Federal payments for drugs and medical services; lump sum lung transplant payments and risk sharing through cost (loss) outlier payments. State and Federally funded home and palliative services are 'carved out'. The model, which has national application via Coordinated Care Trials and by Australian States for RACFMs may be instructive for Germany, which plans to use Australian DRGs for casemix funding. The capitation alternative for chronic disease can improve equity, allocative efficiency and distributional justice. The use of Diagnostic Cost Groups (DCGs) is a promising alternative classification system for capitation arrangements.

Quarterly environmental data summary for first quarter 1998

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

1998-05-01

In support of the Weldon Spring Site Remedial Action Project Federal Facilities Agreement, a copy of the Quarterly Environmental Data Summary (QEDS) for the first quarter of 1998 is enclosed. The data presented in this letter and attachment constitute the QEDS. The data were received from the contract laboratories, verified by the Weldon Spring Site verification group and, except for air monitoring data and site KPA generated data (uranium analyses), merged into the data base during the first quarter of 1998. Air monitoring data presented are the most recent complete sets of quarterly data. Air data are not stored inmore » the data base, and KPA data are not merged into the regular data base. Significant data, defined as data values that have exceeded defined {open_quotes}above normal{close_quotes} Level 2 values, are discussed in this letter for Environmental Monitoring Plan (EMP) generated data only. Above normal Level 2 values are based, in ES&H procedures, on historical high values, DOE Derived Concentration Guides (DCGs), NPDES limits and other guidelines. The procedures also establish actions to be taken in the event that {open_quotes}above normal{close_quotes} data occur. All data received and verified during the first quarter were within a permissible range of variability except for those detailed below. Above normal occurrences are cited for groundwater, air, and NPDES data. There were none for springs or surface water. The following discussion offers a brief summary of the data merged during the first quarter that exceeded the above normal criteria and updates on past reported above normal data. The attached tables present the most recent data for air and the data merged into the data base during the first quarter 1998 for groundwater, NPDES, surface water, and springs. Graphs showing concentrations of selected contaminants of concern at some of the critical locations have also been included in this QEDS. The graphs are discussed in the separate sections.« less

Study of runaway electrons using dosimetry of hard x-ray radiations in Damavand tokamak

NASA Astrophysics Data System (ADS)

Rasouli, C.; Pourshahab, B.; Hosseini Pooya, S. M.; Orouji, T.; Rasouli, H.

2014-05-01

In this work several studies have been conducted on hard x-ray emissions of Damavand tokamak based on radiation dosimetry using the Thermoluminescence method. The goal was to understand interactions of runaway electrons with plasma particles, vessel wall, and plasma facing components. Total of 354 GR-200 (LiF:Mg,Cu,P) thermoluminescence dosimeter (TLD) crystals have been placed on 118 points - three TLDs per point - to map hard x-ray radiation doses on the exterior of the vacuum vessel. Results show two distinctive levels of x-ray radiations doses on the exterior of the vessel. The low-dose area on which measured dose is about 0.5 mSv/shot. In the low-dose area there is no particular component inside the vessel. On the contrary, on high-dose area of the vessel, x-ray radiations dose exceeds 30 mSv/shot. The high-dose area coincides with the position of limiters, magnetic probe ducts, and vacuum vessel intersections. Among the high-dose areas, the highest level of dose is measured in the position of the limiter, which could be due to its direct contact with the plasma column and with runaway electrons. Direct collisions of runaway electrons with the vessel wall and plasma facing components make a major contribution for production of hard x-ray photons in Damavand tokamak.

Study of runaway electrons using dosimetry of hard x-ray radiations in Damavand tokamak.

PubMed

Rasouli, C; Pourshahab, B; Hosseini Pooya, S M; Orouji, T; Rasouli, H

2014-05-01

In this work several studies have been conducted on hard x-ray emissions of Damavand tokamak based on radiation dosimetry using the Thermoluminescence method. The goal was to understand interactions of runaway electrons with plasma particles, vessel wall, and plasma facing components. Total of 354 GR-200 (LiF:Mg,Cu,P) thermoluminescence dosimeter (TLD) crystals have been placed on 118 points--three TLDs per point--to map hard x-ray radiation doses on the exterior of the vacuum vessel. Results show two distinctive levels of x-ray radiations doses on the exterior of the vessel. The low-dose area on which measured dose is about 0.5 mSv/shot. In the low-dose area there is no particular component inside the vessel. On the contrary, on high-dose area of the vessel, x-ray radiations dose exceeds 30 mSv/shot. The high-dose area coincides with the position of limiters, magnetic probe ducts, and vacuum vessel intersections. Among the high-dose areas, the highest level of dose is measured in the position of the limiter, which could be due to its direct contact with the plasma column and with runaway electrons. Direct collisions of runaway electrons with the vessel wall and plasma facing components make a major contribution for production of hard x-ray photons in Damavand tokamak.

Evaluation of effective dose with chest digital tomosynthesis system using Monte Carlo simulation

NASA Astrophysics Data System (ADS)

Kim, Dohyeon; Jo, Byungdu; Lee, Youngjin; Park, Su-Jin; Lee, Dong-Hoon; Kim, Hee-Joung

2015-03-01

Chest digital tomosynthesis (CDT) system has recently been introduced and studied. This system offers the potential to be a substantial improvement over conventional chest radiography for the lung nodule detection and reduces the radiation dose with limited angles. PC-based Monte Carlo program (PCXMC) simulation toolkit (STUK, Helsinki, Finland) is widely used to evaluate radiation dose in CDT system. However, this toolkit has two significant limits. Although PCXMC is not possible to describe a model for every individual patient and does not describe the accurate X-ray beam spectrum, Geant4 Application for Tomographic Emission (GATE) simulation describes the various size of phantom for individual patient and proper X-ray spectrum. However, few studies have been conducted to evaluate effective dose in CDT system with the Monte Carlo simulation toolkit using GATE. The purpose of this study was to evaluate effective dose in virtual infant chest phantom of posterior-anterior (PA) view in CDT system using GATE simulation. We obtained the effective dose at different tube angles by applying dose actor function in GATE simulation which was commonly used to obtain the medical radiation dosimetry. The results indicated that GATE simulation was useful to estimate distribution of absorbed dose. Consequently, we obtained the acceptable distribution of effective dose at each projection. These results indicated that GATE simulation can be alternative method of calculating effective dose in CDT applications.

A Commentary on: "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008".

PubMed

Brooks, Antone L

2015-04-01

This commentary provides a very brief overview of the book "A History of the United States Department of Energy (DOE) Low Dose Radiation Research Program: 1998-2008" ( http://lowdose.energy.gov ). The book summarizes and evaluates the research progress, publications and impact of the U.S. Department of Energy Low Dose Radiation Research Program over its first 10 years. The purpose of this book was to summarize the impact of the program's research on the current thinking and low-dose paradigms associated with the radiation biology field and to help stimulate research on the potential adverse and/or protective health effects of low doses of ionizing radiation. In addition, this book provides a summary of the data generated in the low dose program and a scientific background for anyone interested in conducting future research on the effects of low-dose or low-dose-rate radiation exposure. This book's exhaustive list of publications coupled with discussions of major observations should provide a significant resource for future research in the low-dose and dose-rate region. However, because of space limitations, only a limited number of critical references are mentioned. Finally, this history book provides a list of major advancements that were accomplished by the program in the field of radiation biology, and these bulleted highlights can be found in last part of chapters 4-10.

Effects of dose scaling on delivery quality assurance in tomotherapy

PubMed Central

Nalichowski, Adrian; Burmeister, Jay

2012-01-01

Delivery quality assurance (DQA) of tomotherapy plans is routinely performed with silver halide film which has a limited range due to the effects of saturation. DQA plans with dose values exceeding this limit require the dose of the entire plan to be scaled downward if film is used, to evaluate the dose distribution in two dimensions. The potential loss of fidelity between scaled and unscaled DQA plans as a function of dose scaling is investigated. Three treatment plans for 12 Gy fractions designed for SBRT of the lung were used to create DQA procedures that were scaled between 100% and 10%. The dose was measured with an ionization chamber array and compared to values from the tomotherapy treatment planning system. Film and cylindrical ion chamber measurements were also made for one patient for scaling factors of 50% to 10% to compare with the ionization chamber array measurements. The array results show the average gamma pass rate is ≥99% from 100% to 30% scaling. The average gamma pass rate falls to 93.6% and 51.1% at 20% and 10% scaling, respectively. Film analysis yields similar pass rates. Cylindrical ion chambers did not exhibit significant variation with dose scaling, but only represent points in the low gradient region of the dose distribution. Scaling the dose changes the mechanics of the radiation delivery, as well as the signal‐to‐noise ratio. Treatment plans which exhibit parameters that differ significantly from those common to DQA plans studied in this paper may exhibit different behavior. Dose scaling should be limited to the smallest degree possible. Planar information, such as that from film or a detector array, is required. The results show that it is not necessary to perform both a scaled and unscaled DQA plan for the treatment plans considered here. PACS numbers: 87.55.km, 87.55.Qr PMID:22231213

Impact of the introduction of rotavirus vaccine on the timeliness of other scheduled vaccines: the Australian experience.

PubMed

Hull, Brynley P; Menzies, Robert; Macartney, Kristine; McIntyre, Peter B

2013-04-08

Strict age limits for receipt of rotavirus vaccines and simultaneous use of vaccines requiring two (Rotarix(®)) and three (RotaTeq(®)) doses in Australia may impact on coverage and timeliness of other vaccines in the infant schedule. Using data from the Australian Childhood Immunisation Register (ACIR), coverage and timeliness of rotavirus vaccines and changes in timeliness of other infant vaccines following rotavirus vaccine introduction was examined, with particular emphasis on Indigenous infants in whom coverage is less optimal. Final dose rotavirus coverage reached 83% within 21 months of program commencement but remained 7% lower than other vaccines due in infancy. Coverage was 11-17% lower in Indigenous infants. Adherence to the first dose upper age limits for rotavirus vaccine was high with >97% of children vaccinated by the recommended age, but for subsequent rotavirus doses, receipt beyond the upper age limits was more common, especially in Indigenous children. Following rotavirus vaccine introduction, there were improvements in timeliness of receipt of all doses of DTPa-containing and 7-valent pneumococcal conjugate vaccines. High population coverage can be attained with rotavirus vaccines, even with adherence to strict upper age restrictions for vaccine dose administration. Rotavirus vaccine introduction appears to have impacted upon the timeliness of other concomitantly scheduled vaccines. These factors should be considered when rotavirus programs are introduced. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dosing Accuracy of Insulin Aspart FlexPens After Transport Through the Pneumatic Tube System.

PubMed

Ward, Leah G; Heckman, Michael G; Warren, Amy I; Tran, Kimberly

2013-01-01

The purpose of this study was to evaluate whether transporting insulin aspart FlexPens via a pneumatic tube system affects the dosing accuracy of the pens. A total of 115 Novo Nordisk FlexPens containing insulin aspart were randomly assigned to be transported via a pneumatic tube system (n = 92) or to serve as the control (n = 23). Each pen was then randomized to 10 international unit (IU) doses (n = 25) or 30 IU doses (n = 67), providing 600 and 603 doses, respectively, for the pneumatic tube group. The control group also received random assignment to 10 IU doses (n = 6) or 30 IU doses (n = 17), providing 144 and 153 doses, respectively. Each dose was expelled using manufacturer instructions. Weights were recorded, corrected for specific gravity, and evaluated based on acceptable International Organization for Standardization (ISO) dosing limits. In the group of pens transported through the pneumatic tube system, none of the 600 doses of 10 IU (0.0%; 95% CI, 0.0 to 0.6) and none of the 603 doses of 30 IU (0.0%; 95% CI, 0.0 to 0.6) fell outside of the range of acceptable weights. Correspondingly, in the control group, none of the 144 doses at 10 IU (0.0%; 95% CI, 0.0 to 2.5) and none of the 153 doses at 30 IU (0.0%; 95% CI, 0.0 to 2.4) were outside of acceptable ISO limits. Transportation via pneumatic tube system does not appear to compromise dosing accuracy. Hospital pharmacies may rely on the pneumatic tube system for timely and accurate transport of insulin aspart FlexPens.

High-Dose Vitamin C (PDQ®)—Health Professional Version

Cancer.gov

High-dose vitamin C, with and without conventional cancer therapies, appeared promising in early studies and was well tolerated. However, these studies have several limitations due to lack of rigor in trial design. Get detailed information about high-dose vitamin C in cancer in this clinician summary.

BENCHMARK DOSES FOR CHEMICAL MIXTURES: EVALUATION OF A MIXTURE OF 18 PHAHS.

EPA Science Inventory

Benchmark doses (BMDs), defined as doses of a substance that are expected to result in a pre-specified level of "benchmark" response (BMR), have been used for quantifying the risk associated with exposure to environmental hazards. The lower confidence limit of the BMD is used as...

Analysis and evaluation for consumer goods containing NORM in Korea.

PubMed

Jang, Mee; Chung, Kun Ho; Lim, Jong Myoung; Ji, Young Yong; Kim, Chang Jong; Kang, Mun Ja

2017-08-01

We analyzed the consumer goods containing NORM by ICP-MS and evaluated the external dose. To evaluate the external dose, we assumed the small room model as irradiation scenario and calculated the specific effective dose rate using MCNPX code. The external doses for twenty goods are less than 1 mSv considering the specific effective dose rates and usage quantities. However, some of them have relatively high dose and the activity concentration limits are necessary as a screening tool. Copyright © 2017 Elsevier Ltd. All rights reserved.

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

DOE Office of Scientific and Technical Information (OSTI.GOV)

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.

PubMed

Poet, T S; Schlosser, P M; Rodriguez, C E; Parod, R J; Rodwell, D E; Kirman, C R

2016-04-01

The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Analyses of risks associated with radiation exposure from past major solar particle events

NASA Technical Reports Server (NTRS)

Weyland, Mark D.; Atwell, William; Cucinotta, Francis A.; Wilson, John W.; Hardy, Alva C.

1991-01-01

Radiation exposures and cancer induction/mortality risks were investigated for several major solar particle events (SPE's). The SPE's included are: February 1956, November 1960, August 1972, October 1989, and the September, August, and October 1989 events combined. The three 1989 events were treated as one since all three could affect a single lunar or Mars mission. A baryon transport code was used to propagate particles through aluminum and tissue shield materials. A free space environment was utilized for all calculations. Results show the 30-day blood forming organs (BFO) limit of 25 rem was surpassed by all five events using 10 g/sq cm of shielding. The BFO limit is based on a depth dose of 5 cm of tissue, while a more detailed shield distribution of the BFO's was utilized. A comparison between the 5 cm depth dose and the dose found using the BFO shield distribution shows that the 5 cm depth value slightly higher than the BFO dose. The annual limit of 50 rem was exceeded by the August 1972, October 1989, and the three combined 1989 events with 5 g/sq cm of shielding. Cancer mortality risks ranged from 1.5 to 17 percent at 1 g/sq cm and 0.5 to 1.1 percent behind 10 g/sq cm of shielding for five events. These ranges correspond to those for a 45 year old male. It is shown that secondary particles comprise about 1/3 of the total risk at 10 g/sq cm of shielding. Utilizing a computerized Space Shuttle shielding model to represent a typical spacecraft configuration in free space at the August 1972 SPE, average crew doses exceeded the BFO dose limit.

Low-voltage chest CT: another way to reduce the radiation dose in asbestos-exposed patients.

PubMed

Macía-Suárez, D; Sánchez-Rodríguez, E; Lopez-Calviño, B; Diego, C; Pombar, M

2017-09-01

To assess whether low voltage chest computed tomography (CT) can be used to successfully diagnose disease in patients with asbestos exposure. Fifty-six former employees of the shipbuilding industry, who were candidates to receive a standard-dose chest CT due to their occupational exposure to asbestos, underwent a routine CT. Immediately after this initial CT, they underwent a second acquisition using low-dose chest CT parameters, based on a low potential (80 kV) and limited tube current. The findings of the two CT protocols were compared based on typical diseases associated with asbestos exposure. The kappa coefficient for each parameter and for an overall rating (grouping them based on mediastinal, pleural, and pulmonary findings) were calculated in order to test for correlations between the two protocols. A good correlation between routine and low-dose CT was demonstrated for most parameters with a mean radiation dose reduction of up to 83% of the effective dose based on the dose-length product between protocols. Low-dose chest CT, based on a limited tube potential, is useful for patients with an asbestos exposure background. Low-dose chest CT can be successfully used to minimise the radiation dose received by patients, as this protocol produced an estimated mean effective dose similar to that of an abdominal or pelvis plain film. Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

A GPU-accelerated and Monte Carlo-based intensity modulated proton therapy optimization system.

PubMed

Ma, Jiasen; Beltran, Chris; Seum Wan Chan Tseung, Hok; Herman, Michael G

2014-12-01

Conventional spot scanning intensity modulated proton therapy (IMPT) treatment planning systems (TPSs) optimize proton spot weights based on analytical dose calculations. These analytical dose calculations have been shown to have severe limitations in heterogeneous materials. Monte Carlo (MC) methods do not have these limitations; however, MC-based systems have been of limited clinical use due to the large number of beam spots in IMPT and the extremely long calculation time of traditional MC techniques. In this work, the authors present a clinically applicable IMPT TPS that utilizes a very fast MC calculation. An in-house graphics processing unit (GPU)-based MC dose calculation engine was employed to generate the dose influence map for each proton spot. With the MC generated influence map, a modified least-squares optimization method was used to achieve the desired dose volume histograms (DVHs). The intrinsic CT image resolution was adopted for voxelization in simulation and optimization to preserve spatial resolution. The optimizations were computed on a multi-GPU framework to mitigate the memory limitation issues for the large dose influence maps that resulted from maintaining the intrinsic CT resolution. The effects of tail cutoff and starting condition were studied and minimized in this work. For relatively large and complex three-field head and neck cases, i.e., >100,000 spots with a target volume of ∼ 1000 cm(3) and multiple surrounding critical structures, the optimization together with the initial MC dose influence map calculation was done in a clinically viable time frame (less than 30 min) on a GPU cluster consisting of 24 Nvidia GeForce GTX Titan cards. The in-house MC TPS plans were comparable to a commercial TPS plans based on DVH comparisons. A MC-based treatment planning system was developed. The treatment planning can be performed in a clinically viable time frame on a hardware system costing around 45,000 dollars. The fast calculation and optimization make the system easily expandable to robust and multicriteria optimization.

Phase I Study of Preoperative Chemoradiation With S-1 and Oxaliplatin in Patients With Locally Advanced Resectable Rectal Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Yong Sang; Lee, Jae-Lyun; Park, Jin Hong

Purpose: To perform a Phase I study of preoperative chemoradiation (CRT) with S-1, a novel oral fluoropyrimidine, plus oxaliplatin in patients with locally advanced rectal cancer, to determine the maximum tolerated dose and the recommended dose. Methods and Materials: Radiotherapy was delivered to a total of 45 Gy in 25 fractions and followed by a coned-down boost of 5.4 Gy in 3 fractions. Concurrent chemotherapy consisted of a fixed dose of oxaliplatin (50 mg/m{sup 2}/week) on Days 1, 8, 22, and 29 and escalated doses of S-1 on Days 1-14 and 22-35. The initial dose of S-1 was 50 mg/m{supmore » 2}/day, gradually increasing to 60, 70, and 80 mg/m{sup 2}/day. Surgery was performed within 6 {+-} 2 weeks. Results: Twelve patients were enrolled and tolerated up to Dose Level 4 (3 patients at each dose level) without dose-limiting toxicity. An additional 3 patients were enrolled at Dose Level 4, with 1 experiencing a dose-limiting toxicity of Grade 3 diarrhea. Although maximum tolerated dose was not attained, Dose Level 4 (S-1 80 mg/m{sup 2}/day) was chosen as the recommended dose for further Phase II studies. No Grade 4 toxicity was observed, and Grade 3 toxicities of leukopenia and diarrhea occurred in the same patient (1 of 15, 6.7%). Pathologic complete responses were observed in 2 of 15 patients (13.3%). Conclusions: The recommended dose of S-1 was determined to be 80 mg/m{sup 2}/day when combined with oxaliplatin in preoperative CRT, and a Phase II trial is now ongoing.« less

BENCHMARK DOSE TECHNICAL GUIDANCE DOCUMENT ...

EPA Pesticide Factsheets

The purpose of this document is to provide guidance for the Agency on the application of the benchmark dose approach in determining the point of departure (POD) for health effects data, whether a linear or nonlinear low dose extrapolation is used. The guidance includes discussion on computation of benchmark doses and benchmark concentrations (BMDs and BMCs) and their lower confidence limits, data requirements, dose-response analysis, and reporting requirements. This guidance is based on today's knowledge and understanding, and on experience gained in using this approach.

The estimation of galactic cosmic ray penetration and dose rates

NASA Technical Reports Server (NTRS)

Burrell, M. O.; Wright, J. J.

1972-01-01

This study is concerned with approximation methods that can be readily applied to estimate the absorbed dose rate from cosmic rays in rads - tissue or rems inside simple geometries of aluminum. The present work is limited to finding the dose rate at the center of spherical shells or behind plane slabs. The dose rate is calculated at tissue-point detectors or for thin layers of tissue. This study considers cosmic-rays dose rates for both free-space and earth-orbiting missions.

Gene expression analysis of colorectal cancer by bioinformatics strategy.

PubMed

Cui, Meng; Yuan, Junhua; Li, Jun; Sun, Bing; Li, Tao; Li, Yuantao; Wu, Guoliang

2014-10-01

We used bioinformatics technology to analyze gene expression profiles involved in colorectal cancer tissue samples and healthy controls. In this paper, we downloaded the gene expression profile GSE4107 from Gene Expression Omnibus (GEO) database, in which a total of 22 chips were available, including normal colonic mucosa tissue from normal healthy donors (n=10), colorectal cancer tissue samples from colorectal patients (n=33). To further understand the biological functions of the screened DGEs, the KEGG pathway enrichment analysis were conducted. Then we built a transcriptome network to study differentially co-expressed links. A total of 3151 DEGs of CRC were selected. Besides, total 164 DCGs (Differentially Coexpressed Gene, DCG) and 29279 DCLs (Differentially Co-expressed Link, DCL) were obtained. Furthermore, the significantly enriched KEGG pathways were Endocytosis, Calcium signaling pathway, Vascular smooth muscle contraction, Linoleic acid metabolism, Arginine and proline metabolism, Inositol phosphate metabolism and MAPK signaling pathway. Our results show that the generation of CRC involves multiple genes, TFs and pathways. Several signal and immune pathways are linked to CRC and give us more clues in the process of CRC. Hence, our work would pave ways for novel diagnosis of CRC, and provided theoretical guidance into cancer therapy.

ICPP environmental monitoring report, CY 1989

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

1991-01-01

Summarized in this report are the data collected through Environmental Monitoring programs conducted at the Idaho Chemical Processing Plant (ICPP) by the Environmental Assurance (EA) Section of the Environmental Compliance and SIS Operations (EC/SIS) Department. Published in response to DOE Order 5484.1, Chap. 3, this report covers the period from December 20, 1988 through December 19, 1989. The ICPP is responsible for complying with all applicable Federal, State, Local and DOE Rules, Regulations and Orders. Radiological effluent and emissions are regulated by the DOE in accordance with the Derived Concentration Guides (DCGs) as presented in DOE Order 5,400.05, and themore » State of Idaho Maximum Permissible Concentrations (MPCs). The Environmental Protection Agency (EPA) regulates all nonradiological waste resulting from the ICPP operations including all airborne, liquid, and solid waste. The EA Section completed a Quality Assurance (QA) Plan for Environmental Monitoring activities during the third quarter of 1986. QA activities have resulted in the ICPP's implementation of the Environmental Protection Agency rules and guidelines pertaining to the Collection, analyses, and reporting of environmentally related samples. Where no approved methods for analyses existed for radionuclides, currently used methods were submitted for the EPA approval. 17 figs., 11 tabs.« less

Cumulative total effective whole-body radiation dose in critically ill patients.

PubMed

Rohner, Deborah J; Bennett, Suzanne; Samaratunga, Chandrasiri; Jewell, Elizabeth S; Smith, Jeffrey P; Gaskill-Shipley, Mary; Lisco, Steven J

2013-11-01

Uncertainty exists about a safe dose limit to minimize radiation-induced cancer. Maximum occupational exposure is 20 mSv/y averaged over 5 years with no more than 50 mSv in any single year. Radiation exposure to the general population is less, but the average dose in the United States has doubled in the past 30 years, largely from medical radiation exposure. We hypothesized that patients in a mixed-use surgical ICU (SICU) approach or exceed this limit and that trauma patients were more likely to exceed 50 mSv because of frequent diagnostic imaging. Patients admitted into 15 predesignated SICU beds in a level I trauma center during a 30-day consecutive period were prospectively observed. Effective dose was determined using Huda's method for all radiography, CT imaging, and fluoroscopic examinations. Univariate and multivariable linear regressions were used to analyze the relationships between observed values and outcomes. Five of 74 patients (6.8%) exceeded exposures of 50 mSv. Univariate analysis showed trauma designation, length of stay, number of CT scans, fluoroscopy minutes, and number of general radiographs were all associated with increased doses, leading to exceeding occupational exposure limits. In a multivariable analysis, only the number of CT scans and fluoroscopy minutes remained significantly associated with increased whole-body radiation dose. Radiation levels frequently exceeded occupational exposure standards. CT imaging contributed the most exposure. Health-care providers must practice efficient stewardship of radiologic imaging in all critically ill and injured patients. Diagnostic benefit must always be weighed against the risk of cumulative radiation dose.

Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

PubMed

Furman, Wayne L; Crews, Kristine R; Billups, Catherine; Wu, Jianrong; Gajjar, Amar J; Daw, Najat C; Patrick, Christian C; Rodriguez-Galindo, Carlos; Stewart, Clinton F; Dome, Jeffrey S; Panetta, John C; Houghton, Peter J; Santana, Victor M

2006-02-01

Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unkelbach, J; Perko, Z; Wolfgang, J

Purpose: Stereotactic body radiotherapy (SBRT) has become an established treatment option for liver cancer. For patients with large tumors, the prescription dose is often limited by constraints on the mean liver dose, leading to tumor recurrence. In this work, we demonstrate that spatiotemporal fractionation schemes, ie delivering distinct dose distributions in different fractions, may allow for a 10% increase in biologically effective dose (BED) in the tumor compared to current practice where each fraction delivers the same dose distribution. Methods: We consider rotation therapy delivered with x-ray beams. Treatment plan optimization is performed using objective functions evaluated for the cumulativemore » BED delivered at the end of treatment. This allows for simultaneously optimizing multiple distinct treatment plans for different fractions. Results: The treatment that optimally exploits fractionation effects is designed such that each fraction delivers a similar dose bath to the uninvolved liver while delivering high single fraction doses to complementary parts of the target volume. Thereby, partial hypofractionation in the tumor is achieved along with near uniform fractionation in the surrounding liver - leading to an improvement in the therapeutic ratio. The benefit of such spatiotemporal fractionation schemes depends on tumor geometry and location as well as the number of fractions. For 5-fraction treatments (allowing for 5 distinct dose distributions) an improvement in the order of 10% is observed. Conclusion: Delivering distinct dose distributions in different fractions, purely motivated by fractionation effects rather than geometric changes, may improve the therapeutic ratio. For treatment sites where the prescriptions dose is limited by mean dose constraints in the surrounding organ, such as liver cancer, this approach may facilitate biological dose escalation and improved cure rates.« less

Dose rate constants for the quantity Hp(3) for frequently used radionuclides in nuclear medicine.

PubMed

Szermerski, Bastian; Bruchmann, Iris; Behrens, Rolf; Geworski, Lilli

2016-12-01

According to recent studies, the human eye lens is more sensitive to ionising radiation than previously assumed. Therefore, the dose limit for personnel occupationally exposed to ionising radiation will be lowered from currently 150 mSv to 20 mSv per year. Currently, no data base for a reliable estimation of the dose to the lens of the eye is available for nuclear medicine. Furthermore, the dose is usually not monitored. The aim of this work was to determine dose rate constants for the quantity H p (3), which is supposed to estimate the dose to the lens of the eye. For this, H p (3)-dosemeters were fixed to an Alderson Phantom at different positions. The dosemeters were exposed to radiation from nuclides typically used in nuclear medicine in their geometries analog to their application in nuclear medicine, e.g. syringe or vial. The results show that the handling of high-energy beta (i.e. electron or positron) emitters may lead to a relevant dose to the lens of the eye. For low-energy beta emitters and gamma emitters, an exceeding of the lowered dose limit seems to be unlikely. Copyright © 2015. Published by Elsevier GmbH.

A procedure to determine the planar integral spot dose values of proton pencil beam spots

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anand, Aman; Sahoo, Narayan; Zhu, X. Ronald

2012-02-15

Purpose: Planar integral spot dose (PISD) of proton pencil beam spots (PPBSs) is a required input parameter for beam modeling in some treatment planning systems used in proton therapy clinics. The measurement of PISD by using commercially available large area ionization chambers, like the PTW Bragg peak chamber (BPC), can have large uncertainties due to the size limitation of these chambers. This paper reports the results of our study of a novel method to determine PISD values from the measured lateral dose profiles and peak dose of the PPBS. Methods: The PISDs of 72.5, 89.6, 146.9, 181.1, and 221.8 MeVmore » energy PPBSs were determined by area integration of their planar dose distributions at different depths in water. The lateral relative dose profiles of the PPBSs at selected depths were measured by using small volume ion chambers and were investigated for their angular anisotropies using Kodak XV films. The peak spot dose along the beam's central axis (D{sub 0}) was determined by placing a small volume ion chamber at the center of a broad field created by the superposition of spots at different locations. This method allows eliminating positioning uncertainties and the detector size effect that could occur when measuring it in single PPBS. The PISD was then calculated by integrating the measured lateral relative dose profiles for two different upper limits of integration and then multiplying it with corresponding D{sub 0}. The first limit of integration was set to radius of the BPC, namely 4.08 cm, giving PISD{sub RBPC}. The second limit was set to a value of the radial distance where the profile dose falls below 0.1% of the peak giving the PISD{sub full}. The calculated values of PISD{sub RBPC} obtained from area integration method were compared with the BPC measured values. Long tail dose correction factors (LTDCFs) were determined from the ratio of PISD{sub full}/PISD{sub RBPC} at different depths for PPBSs of different energies. Results: The spot profiles were found to have angular anisotropy. This anisotropy in PPBS dose distribution could be accounted in a reasonable approximate manner by taking the average of PISD values obtained using the in-line and cross-line profiles. The PISD{sub RBPC} values fall within 3.5% of those measured by BPC. Due to inherent dosimetry challenges associated with PPBS dosimetry, which can lead to large experimental uncertainties, such an agreement is considered to be satisfactory for validation purposes. The PISD{sub full} values show differences ranging from 1 to 11% from BPC measured values, which are mainly due to the size limitation of the BPC to account for the dose in the long tail regions of the spots extending beyond its 4.08 cm radius. The dose in long tail regions occur both for high energy beams such as 221.8 MeV PPBS due to the contributions of nuclear interactions products in the medium, and for low energy PPBS because of their larger spot sizes. The calculated LTDCF values agree within 1% with those determined by the Monte Carlo (MC) simulations. Conclusions: The area integration method to compute the PISD from PPBS lateral dose profiles is found to be useful both to determine the correction factors for the values measured by the BPC and to validate the results from MC simulations.« less

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2014 CFR

2014-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2013 CFR

2013-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

21 CFR 361.1 - Radioactive drugs for certain research uses.

Code of Federal Regulations, 2012 CFR

2012-04-01

... following: Whole body, active blood-forming organs, lens of the eye, and gonads: Rems Single dose 3 Annual... body, active blood-forming organs, lens of the eye, gonads, and other organ doses from the administered... set forth in paragraph (d) of this section, that: (i) The pharmacological dose is within the limits...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2011 CFR

2011-01-01

... 10 Energy 1 2011-01-01 2011-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 10 Energy 1 2014-01-01 2014-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2013 CFR

2013-01-01

... 10 Energy 1 2013-01-01 2013-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2012 CFR

2012-01-01

... 10 Energy 1 2012-01-01 2012-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

10 CFR 20.1202 - Compliance with requirements for summation of external and internal doses.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 10 Energy 1 2010-01-01 2010-01-01 false Compliance with requirements for summation of external and internal doses. 20.1202 Section 20.1202 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Occupational Dose Limits § 20.1202 Compliance with requirements for summation of...

Subacute toxicity of the mycotoxin cyclopiazonic acid.

PubMed

van Rensburg, S J

1984-12-01

Cyclopiazonic acid (CA) is known to contaminate processed foods, maize and peanuts. Since previously available toxicity data were limited to the effects of single doses, Wistar-derived rats were given weekly doses of 0, 12 or 21 mg CA/kg body weight in 1 N-sodium bicarbonate, using a dosage volume of 2.5 ml/kg body weight, and subgroups of eight were killed 1 wk after doses 2, 5, 9 and 14. Males on the highest dose level showed mild growth retardation initially and 25% died suddenly during wk 4. No abnormal signs were observed in the surviving males or in any of the females throughout the 15 wk of the experiment. CA induced mild cellular degenerative changes in the myocardium and in several other organs where ballooning of nuclei, especially in ductal epithelia, was also characteristic. The changes were only weakly related to dose level, sex and the number of doses given. The findings suggest that CA is probably a metabolic inhibitor requiring considerable concentrations to exert toxicity. The limited data currently available do not elicit concern in terms of human risk or warrant any particular control procedures.

Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

PubMed Central

Li, Zijian; Jennings, Aaron A.

2017-01-01

Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

Are Recommended Doses of Acetaminophen Effective for Children Aged 2 to 3 Years? A Pharmacokinetic Modeling Answer.

PubMed

Abourbih, Daniel Asher; Gosselin, Sophie; Villeneuve, Eric; Kazim, Sara

2016-01-01

Acetaminophen (APAP) elixir is a widely used pediatric antipyretic medication. It has been shown that up to 30% of febrile children presenting to a large urban pediatric emergency department received inadequate APAP dosages at home with errors primarily due to age-based dosing. Parental education material in the form of weight-based dosing guides has been proposed; however, validation of current recommended APAP dosages using pharmacokinetic models is needed. This study used a mathematical model of APAP absorption to predict plasma concentrations and to compare them with the range required to reach and achieve antipyresis (10-20 μg/mL). A common APAP preparation (Children's Tylenol Elixir) was tested (children aged 2-3 years, 10.9-15.9 kg). The manufacturer's suggested dose of 160 mg was compared with the standard 10 to 15 mg/kg dose range. The model predicts a peak plasma concentration between 6.38 and 8.55 μg/mL for 10 mg/kg dose and 9.57 and 12.8 μg/mL for 15 mg/kg dose. The manufacturer's suggested dose of 160 mg was tested across the limits of the weight range (10.9-15.9 kg). A peak plasma concentration between 9.36 and 12.6 μg/mL was found for the lower weight limit (10.9 kg child) and 6.42 to 8.61 μg/mL for the upper weight limit (15.9 kg child). With the use of this model, the 10 mg/kg dose does not reach the plasma concentration value for antipyresis (10-20 μg/mL), whereas 15 mg/kg is adequate only if assuming a greater absorption constant. The 160 mg dose is effective only for children weighing 10.9 kg. Individual differences in drug bioavailability, volume of distribution, and absorption/elimination constants undoubtedly exist, and future studies directly measuring plasma APAP concentration and pharmacokinetics are needed. However, these results indicate that dosages for APAP in children should be weight based and manufacturers should review their dosing recommendations.

Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc.

PubMed

Hou, X; Tanguay, J; Vuckovic, M; Buckley, K; Schaffer, P; Bénard, F; Ruth, T J; Celler, A

2016-12-07

Cyclotron-produced 99m Tc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99m Tc. However, the small amount of 92-98 Mo in the irradiation of enriched 100 Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

Imaging study of using radiopharmaceuticals labeled with cyclotron-produced 99mTc

NASA Astrophysics Data System (ADS)

Hou, X.; Tanguay, J.; Vuckovic, M.; Buckley, K.; Schaffer, P.; Bénard, F.; Ruth, T. J.; Celler, A.

2016-12-01

Cyclotron-produced 99mTc (CPTc) has been recognized as an attractive and practical substitution of reactor/generator based 99mTc. However, the small amount of 92-98Mo in the irradiation of enriched 100Mo could lead to the production of other radioactive technetium isotopes (Tc-impurities) which cannot be chemically separated. Thus, these impurities could contribute to patient dose and affect image quality. The potential radiation dose caused by these Tc-impurities produced using different targets, irradiation conditions, and corresponding to different injection times have been investigated, leading us to create dose-based limits of these parameters for producing clinically acceptable CPTc. However, image quality has been not considered. The aim of the present work is to provide a comprehensive and quantitative analysis of image quality for CPTc. The impact of Tc-impurities in CPTc on image resolution, background noise, and contrast is investigated by performing both Monte-Carlo simulations and phantom experiments. Various targets, irradiation, and acquisition conditions are employed for investigating the image-based limits of CPTc production parameters. Additionally, the relationship between patient dose and image quality of CPTc samples is studied. Only those samples which meet both dose- and image-based limits should be accepted in future clinical studies.

Dose and risk in diagnostic radiology: How big How little Lecture Number 16

DOE Office of Scientific and Technical Information (OSTI.GOV)

Webster, E.W.

1992-01-01

This lecture is divided into two parts: dose and risk. The dose segment is technical and noncontroversial since it deals with straightforward measurements or calculations which do not depend on unproven hypotheses. Some conflicting contributions of low dose epidemiological studies to the appraisal of risk are briefly presented. Attention is focused on the following: dose reduction in radiography; dose reduction in fluoroscopy; limitations of dose reduction; estimated radiation risks for diagnostic radiology examinations; excess breast cancer following X-ray examinations for scoliosis; dose-response relation for human mammary cancer; lung cancer from protracted X-irradiation; leukemia and diagnostic X-ray exposure; and thyroid cancermore » after diagnostic dose of I-131.« less

Phase I North Central Cancer Treatment Group Trial-N9923 of escalating doses of twice-daily thoracic radiation therapy with amifostine and with alternating chemotherapy in limited stage small-cell lung cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garces, Yolanda I.; Okuno, Scott H.; Schild, Steven E.

Purpose: The primary goal was to identify the maximum tolerable dose (MTD) of thoracic radiation therapy (TRT) that can be given with chemotherapy and amifostine for patients with limited-stage small-cell lung cancer (LSCLC). Methods and Materials: Treatment began with two cycles of topotecan (1 mg/m{sup 2}) Days 1 to 5 and paclitaxel (175 mg/m{sup 2}) Day 5 (every 3 weeks) given before and after TRT. The TRT began at 6 weeks. The TRT was given in 120 cGy fractions b.i.d. and the dose escalation (from 4,800 cGy, dose level 1, to 6,600 cGy, dose level 4) followed the standard 'cohortsmore » of 3' design. The etoposide (E) (50 mg/day) and cisplatin (C) (3 mg/m{sup 2}) were given i.v. before the morning TRT and amifostine (500 mg/day) was given before the afternoon RT. This was followed by prophylactic cranial irradiation (PCI). The dose-limiting toxicities (DLTs) were defined as Grade {>=}4 hematologic, febrile neutropenia, esophagitis, or other nonhematologic toxicity, Grade {>=}3 dyspnea, or Grade {>=}2 pneumonitis. Results: Fifteen patients were evaluable for the Phase I portion of the trial. No DLTs were seen at dose levels 1 and 2. Two patients on dose level 4 experienced DLTs: 1 patient had a Grade 4 pneumonitis, dyspnea, fatigue, hypokalemia, and anorexia, and 1 patient had a Grade 5 hypoxia attributable to TRT. One of 6 patients on dose level 3 had a DLT, Grade 3 esophagitis. The Grade {>=}3 toxicities seen in at least 10% of patients during TRT were esophagitis (53%), leukopenia (33%), dehydration (20%), neutropenia (13%), and fatigue (13%). The median survival was 14.5 months. Conclusion: The MTD of b.i.d. TRT was 6000 cGy (120 cGy b.i.d.) with EP and amifostine.« less

A group sequential adaptive treatment assignment design for proof of concept and dose selection in headache trials.

PubMed

Hall, David B; Meier, Ulrich; Diener, Hans-Cristoph

2005-06-01

The trial objective was to test whether a new mechanism of action would effectively treat migraine headaches and to select a dose range for further investigation. The motivation for a group sequential, adaptive, placebo-controlled trial design was (1) limited information about where across the range of seven doses to focus attention, (2) a need to limit sample size for a complicated inpatient treatment and (3) a desire to reduce exposure of patients to ineffective treatment. A design based on group sequential and up and down designs was developed and operational characteristics were explored by trial simulation. The primary outcome was headache response at 2 h after treatment. Groups of four treated and two placebo patients were assigned to one dose. Adaptive dose selection was based on response rates of 60% seen with other migraine treatments. If more than 60% of treated patients responded, then the next dose was the next lower dose; otherwise, the dose was increased. A stopping rule of at least five groups at the target dose and at least four groups at that dose with more than 60% response was developed to ensure that a selected dose would be statistically significantly (p=0.05) superior to placebo. Simulations indicated good characteristics in terms of control of type 1 error, sufficient power, modest expected sample size and modest bias in estimation. The trial design is attractive for phase 2 clinical trials when response is acute and simple, ideally binary, placebo comparator is required, and patient accrual is relatively slow allowing for the collection and processing of results as a basis for the adaptive assignment of patients to dose groups. The acute migraine trial based on this design was successful in both proof of concept and dose range selection.

A phase I, pharmacokinetic and pharmacodynamic study on vorinostat in combination with 5-fluorouracil, leucovorin, and oxaliplatin in patients with refractory colorectal cancer.

PubMed

Fakih, Marwan G; Pendyala, Lakshmi; Fetterly, Gerald; Toth, Karoli; Zwiebel, James A; Espinoza-Delgado, Igor; Litwin, Alan; Rustum, Youcef M; Ross, Mary Ellen; Holleran, Julianne L; Egorin, Merrill J

2009-05-01

We conducted a phase I study to determine the maximum tolerated dose of vorinostat in combination with fixed doses of 5-fluorouracil (FU), leucovorin, and oxaliplatin (FOLFOX). Vorinostat was given orally twice daily for 1 week every 2 weeks. FOLFOX was given on days 4 and 5 of vorinostat. The vorinostat starting dose was 100 mg twice daily. Escalation occurred in cohorts of three to six patients. Pharmacokinetics of vorinostat, FU, and oxaliplatin were studied. Twenty-one patients were enrolled. Thrombocytopenia, neutropenia, gastrointestinal toxicities, and fatigue increased in frequency and severity at higher dose levels of vorinostat. Two of 4 evaluable patients at dose level 4 (vorinostat 400 mg orally twice daily) developed dose-limiting fatigue. One of 10 evaluable patients at dose level 3 (vorinostat 300 mg orally twice daily) had dose-limiting fatigue, anorexia, and dehydration. There were significant relationships between vorinostat dose and the area under the curve on days 1 and 5 (Pearson, < 0.001). The vorinostat area under the curve increased (P = 0.005) and clearance decreased (P = 0.003) on day 5 compared with day 1. The median C(max) of FU at each dose level increased significantly with increasing doses of vorinostat, suggesting a pharmacokinetic interaction between FU and vorinostat. Vorinostat-induced thymidylate synthase (TS) modulation was not consistent; only two of six patients had a decrease in intratumoral TS expression by reverse transcription-PCR. The maximum tolerated dose of vorinostat in combination with FOLFOX is 300 mg orally twice daily x 1 week every 2 weeks. Alternative vorinostat dosing schedules may be needed for optimal down-regulation of TS expression.

A novel method for the evaluation of uncertainty in dose-volume histogram computation.

PubMed

Henríquez, Francisco Cutanda; Castrillón, Silvia Vargas

2008-03-15

Dose-volume histograms (DVHs) are a useful tool in state-of-the-art radiotherapy treatment planning, and it is essential to recognize their limitations. Even after a specific dose-calculation model is optimized, dose distributions computed by using treatment-planning systems are affected by several sources of uncertainty, such as algorithm limitations, measurement uncertainty in the data used to model the beam, and residual differences between measured and computed dose. This report presents a novel method to take them into account. To take into account the effect of associated uncertainties, a probabilistic approach using a new kind of histogram, a dose-expected volume histogram, is introduced. The expected value of the volume in the region of interest receiving an absorbed dose equal to or greater than a certain value is found by using the probability distribution of the dose at each point. A rectangular probability distribution is assumed for this point dose, and a formulation that accounts for uncertainties associated with point dose is presented for practical computations. This method is applied to a set of DVHs for different regions of interest, including 6 brain patients, 8 lung patients, 8 pelvis patients, and 6 prostate patients planned for intensity-modulated radiation therapy. Results show a greater effect on planning target volume coverage than in organs at risk. In cases of steep DVH gradients, such as planning target volumes, this new method shows the largest differences with the corresponding DVH; thus, the effect of the uncertainty is larger.

The relationship between ovarian function and ovarian limited dose in radiotherapy postoperation of ovarian transposition in young patients with cervical cancer.

PubMed

Du, Zhenhua; Qu, Hui

2017-03-01

In this study, the relationship between ovarian function and ovarian limited dose in radiotherapy was evaluated in young patients with cervical cancer who underwent ovarian transposition (Fig1B). Moreover, the novel ovarian dose limit for a better preservation of ovarian function in intensity-modulated radiation therapy (IMRT) was determined. We retrospectively analyzed data from 86 patients with cervical cancer who received radical hysterectomy and ovarian transposition from January 2013 to June 2015. In agreement with the National Comprehensive Cancer Network Guidelines (NCCN) for Cervical Cancer Version 2.2015, 65 patients with pathological high-risk factors were administered adjuvant radiotherapy-20 of them received three-dimensional conformal radiotherapy (Observation Group A), 24 patients received IMRT with no limitation on radiation dose to ovaries (Observation Group B), and 21 patients underwent IMRT with limited radiation dose(V 10 <20%) to ovaries (Observation Group C). Twenty-one patients without any predetermined high-risk factors did not received radiation therapy (Control Group D). Patients from all four groups were followed up, and sex hormone levels (E 2 , P, follicle-stimulating hormone [FSH], LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy were measured by electrochemiluminescence immunoassay. Subsequently, changes in sex hormone levels in all four groups of patients at various time points were analyzed. The levels of sexual hormones (E 2 , P, FSH, LH) before radiation, postradiation, 3 month, and 6 month after the radiation therapy in patients from all three observation groups were significantly lower than those in patients of the control group (P < 0.05). There was no statistically significant difference in the levels of sex hormones in patients of the control group at different time points (P > 0.05). Within each observation group, there was a statistically significant difference in the sex hormone levels in patients before the radiation and after the radiation (P < 0.05); however, when data from all three observation groups were compared, only the difference in the levels of FSH and LH between the patients from Group A and Group C was statistically significant (P < 0.05). The results of receiver-operating characteristic (ROC) curve analysis suggested that limiting ovarian radiation dose to V 7.5  < 26% in IMRT prevents the disruption of ovarian function (area under ROC curve was 0.740, confidence interval [CI] = 0.606-0.874). In young patients with cervical cancer who underwent radical hysterectomy and ovarian transposition without receiving adjuvant radiotherapy, ovarian endocrine function was well preserved. In patients who received any type of postoperative radiotherapy, ovarian function was affected, suggesting that the standard ovarian limited dose used in IMRT disrupted ovarian function. The results of the ROC curve analysis suggested that the new optimal dose limit of V 7.5  < 26% should be used in IMRT to preserve ovarian function (P = 0.003). © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

OCCUPATIONAL DOSE DURING ADULT INTERVENTIONAL CARDIOLOGY: FIRST VALUES WITH PERSONAL ACTIVE DOSIMETERS IN CHILE.

PubMed

Ubeda, Carlos; Morales, Claudio; Gutiérrez, Diego; Oliveira, Marcus; Manterola, Carlos

2018-05-11

The objective of this article is to present initial occupational dose values using digital active personal dosimeters for medical staff during adult interventional cardiology procedures in a public hospital in Chile. Personal dose equivalent Hp(10) over the lead apron of physician, nurse and radiographer were measured during 59 procedures. Mean values of occupational dose Hp(10) per procedure were 47.6, 6.2 and 4.3 μSv for physician, nurse and radiographer, respectively. If no protective tools are used, physician dose can exceed the new eye lens dose limit.

Quality and efficiency of statin prescribing across countries with a special focus on South Africa: findings and future implications.

PubMed

Godman, Brian; Bishop, Iain; Campbell, Stephen M; Malmström, Rickard E; Truter, Ilse

2015-04-01

Statins are recommended first-line treatment for hyperlipidemia, with published studies suggesting limited differences between them. However, there are reports of under-dosing. South Africa has introduced measures to enhance generic utilization. Part one documents prescribed doses of statins in 2011. Part two determines the extent of generics versus originator and single-sourced statins in 2011 and their costs. Underdosing of simvastatin in 2011 with average prescribed dose of 23.7 mg; however, not for atorvastatin (20.91 mg) or rosuvastatin (15.02 mg). High utilization of generics versus originators at 93-99% for atorvastatin and simvastatin, with limited utilization of single-sourced statins (22% of total statins - defined daily dose basis), mirroring Netherlands, Sweden and UK. Generics priced 33-51% below originator prices. Opportunity to increase simvastatin dosing through education, prescribing targets and incentives. Opportunity to lower generic prices with generic simvastatin 96-98% below single-sourced prices in some European countries.

A compact in vivo neutron activation analysis system to quantify manganese in human hand bone

NASA Astrophysics Data System (ADS)

Liu, Yingzi

As an urgent issue of correlating cumulative manganese (Mn) exposure to neurotoxicity, bone has emerged as an attractive biomarker for long-term Mn deposition and storage. A novel Deuterium-Deuterium (DD) neutron generator irradiation system has been simulated and constructed, incorporating moderator, reflector and shielding. This neutron activation analysis (NAA) irradiation assembly presents several desirable features, including high neutron flux, improved detection limit and acceptable neutron & photon dose, which would allow it be ready for clinical measurement. Key steps include simulation modeling and verifying, irradiation system design, detector characterization, and neutron flux and dose assessment. Activation foils were also analyzed to reveal the accurate neutron spectrum in the irradiation cave. The detection limit with this system is 0.428 ppm with 36 mSv equivalent hand dose and 52 microSv whole body effective dose.

Generalised photon skyshine calculations.

PubMed

Hayes, Robert

2004-01-01

The energy-dependent dose contributions from monoenergetic photon source points located 1.5 m above the ground have been tabulated. These values are intended to be used for regulatory compliance with site boundary dose limitations and as such are all presented in effective dose units. Standard air and soil are modelled where the air has vertical density gradient approximation. Energies from 0.05 up to 10 MeV are evaluated for dose transport up to 40 mean free paths.

Evaluation of multiple institutions' models for knowledge-based planning of volumetric modulated arc therapy (VMAT) for prostate cancer.

PubMed

Ueda, Yoshihiro; Fukunaga, Jun-Ichi; Kamima, Tatsuya; Adachi, Yumiko; Nakamatsu, Kiyoshi; Monzen, Hajime

2018-03-20

The aim of this study was to evaluate the performance of a commercial knowledge-based planning system, in volumetric modulated arc therapy for prostate cancer at multiple radiation therapy departments. In each institute, > 20 cases were assessed. For the knowledge-based planning, the estimated dose (ED) based on geometric and dosimetric information of plans was generated in the model. Lower and upper limits of estimated dose were saved as dose volume histograms for each organ at risk. To verify whether the models performed correctly, KBP was compared with manual optimization planning in two cases. The relationships between the EDs in the models and the ratio of the OAR volumes overlapping volume with PTV to the whole organ volume (V overlap /V whole ) were investigated. There were no significant dosimetric differences in OARs and PTV between manual optimization planning and knowledge-based planning. In knowledge-based planning, the difference in the volume ratio of receiving 90% and 50% of the prescribed dose (V90 and V50) between institutes were more than 5.0% and 10.0%, respectively. The calculated doses with knowledge-based planning were between the upper and lower limits of ED or slightly under the lower limit of ED. The relationships between the lower limit of ED and V overlap /V whole were different among the models. In the V90 and V50 for the rectum, the maximum differences between the lower limit of ED among institutes were 8.2% and 53.5% when V overlap /V whole for the rectum was 10%. In the V90 and V50 for the bladder, the maximum differences of the lower limit of ED among institutes were 15.1% and 33.1% when V overlap /V whole for the bladder was 10%. Organs' upper and lower limits of ED in the models correlated closely with the V overlap /V whole . It is important to determine whether the models in KBP match a different institute's plan design before the models can be shared.

Beta-carotene conversion to vitamin A decreases as the dietary dose increases in humans

USDA-ARS?s Scientific Manuscript database

It has been suggested that high doses of B-carotene limit its conversion to vitamin A, yet this effect has not been well established in humans. A feeding study was conducted in which volunteers consumed two doses of deuterium labeled B-carotene on two occasions, with B-carotene and vitamin A respon...

Risk equivalent of exposure versus dose of radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bond, V.P.

This report describes a risk analysis study of low-dose irradiation and the resulting biological effects on a cell. The author describes fundamental differences between the effects of high-level exposure (HLE) and low-level exposure (LLE). He stresses that the concept of absorbed dose to an organ is not a dose but a level of effect produced by a particular number of particles. He discusses the confusion between a linear-proportional representation of dose limits and a threshold-curvilinear representation, suggesting that a LLE is a composite of both systems. (TEM)

Initial Dosing and Taper Complexity of Methadone and Morphine for Treatment of Neonatal Abstinence Syndrome

PubMed Central

Ibach, Bethany W.; Johnson, Peter N.; Ernst, Kimberly D.; Harrison, Donald; Miller, Jamie L.

2016-01-01

Background: Methadone and morphine are commonly used to treat neonatal abstinence syndrome (NAS). Limited data exist to describe the most appropriate initial doses and taper regimens of these agents. Objectives: Describe the median initial dose and frequency of methadone and morphine for NAS. Compare dose adjustments, time to symptom relief, and taper complexity between groups. Methods: Retrospective study of neonates receiving enteral methadone or morphine for NAS over a 4-year period. Data collection included medication regimen, abstinence scores based on the Modified Finnegan Neonatal Abstinence Scoring Tool, and adverse events. Planned home taper complexity was assessed using the Medication Taper Complexity Score–Revised (MTCS-R). The primary outcome was initial opioid dose. Secondary outcomes included number of dose adjustments, time to symptom relief, and MTCS-R score. Results: Fifty neonates were initially treated for NAS with methadone (n = 36) or morphine (n = 14). The median initial dose was 0.09 mg/kg (range = 0.03-0.2) for methadone and 0.04 mg/kg (range = 0.03-0.4) for morphine. The most common initial dosing interval was q8h for methadone versus q3h for morphine. Number of dose adjustments and time to symptom relief were similar between groups. Median MTCS-R scores were similar between groups. There was no difference in adverse events between groups. Limitations included small sample size, preference toward methadone use, and variability of initial opioid dosing and titration. Conclusions: There was significant variability in initial doses of both agents. Neonates receiving methadone required less frequent dosing than morphine, which may result in easier administration and may allow for safer outpatient administration.

Phase I Study of Conformal Radiotherapy and Concurrent Full-Dose Gemcitabine With Erlotinib for Unresected Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Robertson, John M., E-mail: jrobertson@beaumont.edu; Margolis, Jeffrey; Jury, Robert P.

2012-02-01

Purpose: To determine the recommended dose of radiotherapy when combined with full-dose gemcitabine and erlotinib for unresected pancreas cancer. Methods and Materials: Patients with unresected pancreatic cancer (Zubrod performance status 0-2) were eligible for the present study. Gemcitabine was given weekly for 7 weeks (1,000 mg/m{sup 2}) with erlotinib daily for 8 weeks (100 mg). A final toxicity assessment was performed in Week 9. Radiotherapy (starting at 30 Gy in 2-Gy fractions, 5 d/wk) was given to the gross tumor plus a 1-cm margin starting with the first dose of gemcitabine. A standard 3 plus 3 dose escalation (an additionalmore » 4 Gy within 2 days for each dose level) was used, except for the starting dose level, which was scheduled to contain 6 patients. In general, Grade 3 or greater gastrointestinal toxicity was considered a dose-limiting toxicity, except for Grade 3 anorexia or Grade 3 fatigue alone. Results: A total of 20 patients were treated (10 men and 10 women). Nausea, vomiting, and infection were significantly associated with the radiation dose (p = .01, p = .03, and p = .03, respectively). Of the 20 patients, 5 did not complete treatment and were not evaluable for dose-escalation purposes (3 who developed progressive disease during treatment and 2 who electively discontinued it). Dose-limiting toxicity occurred in none of 6 patients at 30 Gy, 2 of 6 at 34 Gy, and 1 of 3 patients at 38 Gy. Conclusion: The results of the present study have indicated that the recommended Phase II dose is 30 Gy in 15 fractions.« less

Phase 1 study of ombrabulin in combination with cisplatin (CDDP) in Japanese patients with advanced solid tumors.

PubMed

Takahashi, Shunji; Nakano, Kenji; Yokota, Tomoya; Shitara, Kohei; Muro, Kei; Sunaga, Yoshinori; Ecstein-Fraisse, Evelyne; Ura, Takashi

2016-08-27

In clinical studies in Western countries, the recommended dose of combination ombrabulin a vascular disrupting agent, with cisplatin is 25 mg/m 2 ombrabulin with 75 mg/m 2 cisplatin every 3 weeks. Here, we report the first Phase 1 study of this treatment regimen in Japanese patients with advanced solid tumors. This was an open-label, multicenter, sequential cohort, dose-escalation Phase 1 study of ombrabulin with cisplatin administered once every 3 weeks. The study used a 3 + 3 design without intrapatient dose escalation. The investigated dose levels of ombrabulin were 15.5 and 25 mg/m 2 combined with cisplatin 75 mg/m 2 . The latter dose level was regarded as the maximum administered dose if more than one patient experienced dose-limiting toxicities. Ten patients were treated, but no dose-limiting toxicity was observed at both dose levels. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 was the maximum administered dose and regarded as the recommended dose in the combination regimen for Japanese patients with cancer. The most frequently reported drug-related adverse events were neutropenia, decreased appetite, constipation, nausea and fatigue. One partial response and five cases of stable disease were reported as the best overall responses. Pharmacokinetic parameters of ombrabulin and cisplatin were comparable with those in non-Japanese patients. Ombrabulin 25 mg/m 2 with cisplatin 75 mg/m 2 once every 3 weeks was well tolerated and established as the recommended dose in Japanese patients with advanced solid tumors. The safety and pharmacokinetic profiles were comparable between Japanese and Caucasian patients. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Potential impurities in drug substances: Compound-specific toxicology limits for 20 synthetic reagents and by-products, and a class-specific toxicology limit for alkyl bromides.

PubMed

Bercu, J P; Galloway, S M; Parris, P; Teasdale, A; Masuda-Herrera, M; Dobo, K; Heard, P; Kenyon, M; Nicolette, J; Vock, E; Ku, W; Harvey, J; White, A; Glowienke, S; Martin, E A; Custer, L; Jolly, R A; Thybaud, V

2018-04-01

This paper provides compound-specific toxicology limits for 20 widely used synthetic reagents and common by-products that are potential impurities in drug substances. In addition, a 15 μg/day class-specific limit was developed for monofunctional alkyl bromides, aligning this with the class-specific limit previously defined for monofunctional alkyl chlorides. Both the compound- and class-specific toxicology limits assume a lifetime chronic exposure for the general population (including sensitive subpopulations) by all routes of exposure for pharmaceuticals. Inhalation-specific toxicology limits were also derived for acrolein, formaldehyde, and methyl bromide because of their localized toxicity via that route. Mode of action was an important consideration for a compound-specific toxicology limit. Acceptable intake (AI) calculations for certain mutagenic carcinogens assumed a linear dose-response for tumor induction, and permissible daily exposure (PDE) determination assumed a non-linear dose-response. Several compounds evaluated have been previously incorrectly assumed to be mutagenic, or to be mutagenic carcinogens, but the evidence reported here for such compounds indicates a lack of mutagenicity, and a non-mutagenic mode of action for tumor induction. For non-mutagens with insufficient data to develop a toxicology limit, the ICH Q3A qualification thresholds are recommended. The compound- and class-specific toxicology limits described here may be adjusted for an individual drug substance based on treatment duration, dosing schedule, severity of the disease and therapeutic indication. Copyright © 2018. Published by Elsevier Inc.

Phase I study of carboplatin combined with pemetrexed for elderly patients with advanced non-squamous non-small cell lung cancer.

PubMed

Takeoka, Hiroaki; Yamada, Kazuhiko; Azuma, Koichi; Zaizen, Yoshiaki; Yamashita, Fumie; Yoshida, Tsukasa; Naito, Yoshiko; Okayama, Yusuke; Miyamoto, Maki; Hoshino, Tomoaki

2014-05-01

The primary objective of this study was to evaluate the safety and tolerability of carboplatin plus pemetrexed for elderly patients (≥75 years) with chemotherapy-naïve advanced non-squamous non-small cell lung cancer. Patients received escalated doses of carboplatin at an area under the concentration-time curve of 4 (Level 1) or 5 (Level 2) plus pemetrexed (500 mg/m(2)) every 3 weeks for a maximum of six cycles. Dose escalation was decided according to whether dose-limiting toxicity occurred in the first cycle of chemotherapy. A total of 20 patients (6 at Level 1, 14 at Level 2) were enrolled. No dose-limiting toxicities were observed in patients at Level 1 or the first six patients at Level 2, and therefore the combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was considered to be the recommended dose. Among a total of 14 patients in Level 2, only 1 patient experienced dose-limiting toxicity: Grade 3 febrile neutropenia and urticaria. The major toxicities were neutropenia, thrombocytopenia and anemia. Liver dysfunction, fatigue and anorexia were also common, but generally manageable. Six patients showed partial responses, giving the overall response rate of 30%. The median progression-free survival period was 4.8 months (95% confidence interval 2.9-6.7 months). The combination of carboplatin at an area under the concentration-time curve of 5 plus pemetrexed at 500 mg/m(2) was determined as the recommended dose in chemotherapy-naïve elderly patients (≥75 years) with advanced non-squamous non-small cell lung cancer, in view of overall safety and tolerability.

Space radiation dosimetry in low-Earth orbit and beyond.

PubMed

Benton, E R; Benton, E V

2001-09-01

Space radiation dosimetry presents one of the greatest challenges in the discipline of radiation protection. This is a result of both the highly complex nature of the radiation fields encountered in low-Earth orbit (LEO) and interplanetary space and of the constraints imposed by spaceflight on instrument design. This paper reviews the sources and composition of the space radiation environment in LEO as well as beyond the Earth's magnetosphere. A review of much of the dosimetric data that have been gathered over the last four decades of human space flight is presented. The different factors affecting the radiation exposures of astronauts and cosmonauts aboard the International Space Station (ISS) are emphasized. Measurements made aboard the Mir Orbital Station have highlighted the importance of both secondary particle production within the structure of spacecraft and the effect of shielding on both crew dose and dose equivalent. Roughly half the dose on ISS is expected to come from trapped protons and half from galactic cosmic rays (GCRs). The dearth of neutron measurements aboard LEO spacecraft and the difficulty inherent in making such measurements have led to large uncertainties in estimates of the neutron contribution to total dose equivalent. Except for a limited number of measurements made aboard the Apollo lunar missions, no crew dosimetry has been conducted beyond the Earth's magnetosphere. At the present time we are forced to rely on model-based estimates of crew dose and dose equivalent when planning for interplanetary missions, such as a mission to Mars. While space crews in LEO are unlikely to exceed the exposure limits recommended by such groups as the NCRP, dose equivalents of the same order as the recommended limits are likely over the course of a human mission to Mars. c2001 Elsevier Science B.V. All rights reserved.

The importance of protection glasses during neuroangiographies: A study on radiation exposure at the lens of the primary operator.

PubMed

Tavares, J B; Sacadura-Leite, E; Matoso, T; Neto, L L; Biscoito, L; Campos, J; Sousa-Uva, A

2016-06-01

In interventional neuroradiology, few operators routinely use radiation protection glasses. Moreover, in most centers, radiation dose data only accounts for whole body dose without specific information on lens dose. In 2012, the International Commission on Radiological Protection advised that the threshold limit value for the lens should be 20 mSv/year instead of the previous 150 mSv/year limit. The purpose of this study was to compare the radiation dose in the operator's lens during real diagnostic and interventional neuroangiographies, either using or without lead protection glasses. Using the Educational Direct Dosimeter (EDD30 dosimeter), accumulated radiation dose in the lens was measured in 13 neuroangiographies: seven diagnostic and six interventional. Operators with and without radiation protection glasses were included and the sensor was placed near their left eye, closest to the radiation beam. Without glasses, the corrected mean dose of radiation in the lens was 8.02 µSv for diagnostic procedures and 168.57 µSv for interventional procedures. Using glasses, these values were reduced to 1.74 µSv and 33.24 µSv, respectively. Considering 20 mSv as the suggested annual limit of equivalent dose in the lens, neuroradiologists may perform up to 2,494 diagnostic procedures per year without protecting glasses, a number that increases to 11,494 when glasses are used consistently. Regarding intervention, a maximum of 119 procedures per year is advised if glasses are not used, whereas up to 602 procedures/year may be performed using this protection. Therefore, neuroradiologists should always wear radiation protection glasses. © The Author(s) 2016.

Leaded eyeglasses substantially reduce radiation exposure of the surgeon's eyes during acquisition of typical fluoroscopic views of the hip and pelvis.

PubMed

Burns, Sean; Thornton, Raymond; Dauer, Lawrence T; Quinn, Brian; Miodownik, Daniel; Hak, David J

2013-07-17

Despite recommendations to do so, few orthopaedists wear leaded glasses when performing operative fluoroscopy. Radiation exposure to the ocular lens causes cataracts, and regulatory limits for maximum annual occupational exposure to the eye continue to be revised downward. Using anthropomorphic patient and surgeon phantoms, radiation dose at the surgeon phantom's lens was measured with and without leaded glasses during fluoroscopic acquisition of sixteen common pelvic and hip views. The magnitude of lens dose reduction from leaded glasses was calculated by dividing the unprotected dose by the dose measured behind leaded glasses. On average, the use of leaded glasses reduced radiation to the surgeon phantom's eye by tenfold, a 90% reduction in dose. However, there was widespread variation in the amount of radiation that reached the phantom surgeon's eye among the various radiographic projections we studied. Without leaded glasses, the dose measured at the surgeon's lens varied more than 250-fold among these sixteen different views. In addition to protecting the surgeon's eye from the deleterious effects of radiation, the use of leaded glasses could permit an orthopaedist to perform fluoroscopic views on up to ten times more patients before reaching the annual dose limit of 20 mSv of radiation to the eye recommended by the International Commission on Radiological Protection. Personal safety and adherence to limits of occupational radiation exposure should compel orthopaedists to wear leaded glasses for fluoroscopic procedures if other protective barriers are not in use. Leaded glasses are a powerful tool for reducing the orthopaedic surgeon's lens exposure to radiation during acquisition of common intraoperative fluoroscopic views.

SU-G-JeP3-06: Lower KV Image Dose Are Expected From a Limited-Angle Intra-Fractional Verification (LIVE) System for SBRT Treatments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, G; Yin, F; Ren, L

Purpose: In order to track the tumor movement for patient positioning verification during arc treatment delivery or in between 3D/IMRT beams for stereotactic body radiation therapy (SBRT), the limited-angle kV projections acquisition simultaneously during arc treatment delivery or in-between static treatment beams as the gantry moves to the next beam angle was proposed. The purpose of this study is to estimate additional imaging dose resulting from multiple tomosynthesis acquisitions in-between static treatment beams and to compare with that of a conventional kV-CBCT acquisition. Methods: kV imaging system integrated into Varian TrueBeam accelerators was modeled using EGSnrc Monte Carlo user code,more » BEAMnrc and DOSXYZnrc code was used in dose calculations. The simulated realistic kV beams from the Varian TrueBeam OBI 1.5 system were used to calculate dose to patient based on CT images. Organ doses were analyzed using DVHs. The imaging dose to patient resulting from realistic multiple tomosynthesis acquisitions with each 25–30 degree kV source rotation between 6 treatment beam gantry angles was studied. Results: For a typical lung SBRT treatment delivery much lower (20–50%) kV imaging doses from the sum of realistic six tomosynthesis acquisitions with each 25–30 degree x-ray source rotation between six treatment beam gantry angles were observed compared to that from a single CBCT image acquisition. Conclusion: This work indicates that the kV imaging in this proposed Limited-angle Intra-fractional Verification (LIVE) System for SBRT Treatments has a negligible imaging dose increase. It is worth to note that the MV imaging dose caused by MV projection acquisition in-between static beams in LIVE can be minimized by restricting the imaging to the target region and reducing the number of projections acquired. For arc treatments, MV imaging acquisition in LIVE does not add additional imaging dose as the MV images are acquired from treatment beams directly during the treatment.« less

A Phase I/II Trial of Intensity Modulated Radiation (IMRT) Dose Escalation With Concurrent Fixed-dose Rate Gemcitabine (FDR-G) in Patients With Unresectable Pancreatic Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ben-Josef, Edgar, E-mail: edgar.ben-josef@uphs.upenn.edu; Schipper, Mathew; Francis, Isaac R.

2012-12-01

Purpose: Local failure in unresectable pancreatic cancer may contribute to death. We hypothesized that intensification of local therapy would improve local control and survival. The objectives were to determine the maximum tolerated radiation dose delivered by intensity modulated radiation with fixed-dose rate gemcitabine (FDR-G), freedom from local progression (FFLP), and overall survival (OS). Methods and Materials: Eligibility included pathologic confirmation of adenocarcinoma, radiographically unresectable, performance status of 0-2, absolute neutrophil count of {>=}1500/mm{sup 3}, platelets {>=}100,000/mm{sup 3}, creatinine <2 mg/dL, bilirubin <3 mg/dL, and alanine aminotransferase/aspartate aminotransferase {<=}2.5 Multiplication-Sign upper limit of normal. FDR-G (1000 mg/m{sup 2}/100 min intravenously) wasmore » given on days -22 and -15, 1, 8, 22, and 29. Intensity modulated radiation started on day 1. Dose levels were escalated from 50-60 Gy in 25 fractions. Dose-limiting toxicity was defined as gastrointestinal toxicity grade (G) {>=}3, neutropenic fever, or deterioration in performance status to {>=}3 between day 1 and 126. Dose level was assigned using TITE-CRM (Time-to-Event Continual Reassessment Method) with the target dose-limiting toxicity (DLT) rate set to 0.25. Results: Fifty patients were accrued. DLTs were observed in 11 patients: G3/4 anorexia, nausea, vomiting, and/or dehydration (7); duodenal bleed (3); duodenal perforation (1). The recommended dose is 55 Gy, producing a probability of DLT of 0.24. The 2-year FFLP is 59% (95% confidence interval [CI]: 32-79). Median and 2-year overall survival are 14.8 months (95% CI: 12.6-22.2) and 30% (95% CI 17-45). Twelve patients underwent resection (10 R0, 2 R1) and survived a median of 32 months. Conclusions: High-dose radiation therapy with concurrent FDR-G can be delivered safely. The encouraging efficacy data suggest that outcome may be improved in unresectable patients through intensification of local therapy.« less

Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Madani, Indira; Duthoy, Wim; Derie, Cristina R.N.

2007-05-01

Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was appliedmore » for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

Dose Modeling Evaluations and Technical Support Document For the Authorized Limits Request for the DOE-Owned Property Outside the Limited Area, Paducah Gaseous Diffusion Plant Paducah, Kentucky

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boerner, A. J.; Maldonado, D. G.; Hansen, Tom

2012-09-01

Environmental assessments and remediation activities are being conducted by the U.S. Department of Energy (DOE) at the Paducah Gaseous Diffusion Plant (PGDP), Paducah, Kentucky. The Oak Ridge Institute for Science and Education (ORISE), a DOE prime contractor, was contracted by the DOE Portsmouth/Paducah Project Office (DOE-PPPO) to conduct radiation dose modeling analyses and derive single radionuclide soil guidelines (soil guidelines) in support of the derivation of Authorized Limits (ALs) for 'DOE-Owned Property Outside the Limited Area' ('Property') at the PGDP. The ORISE evaluation specifically included the area identified by DOE restricted area postings (public use access restrictions) and areas licensedmore » by DOE to the West Kentucky Wildlife Management Area (WKWMA). The licensed areas are available without restriction to the general public for a variety of (primarily) recreational uses. Relevant receptors impacting current and reasonably anticipated future use activities were evaluated. In support of soil guideline derivation, a Conceptual Site Model (CSM) was developed. The CSM listed radiation and contamination sources, release mechanisms, transport media, representative exposure pathways from residual radioactivity, and a total of three receptors (under present and future use scenarios). Plausible receptors included a Resident Farmer, Recreational User, and Wildlife Worker. single radionuclide soil guidelines (outputs specified by the software modeling code) were generated for three receptors and thirteen targeted radionuclides. These soil guidelines were based on satisfying the project dose constraints. For comparison, soil guidelines applicable to the basic radiation public dose limit of 100 mrem/yr were generated. Single radionuclide soil guidelines from the most limiting (restrictive) receptor based on a target dose constraint of 25 mrem/yr were then rounded and identified as the derived soil guidelines. An additional evaluation using the derived soil guidelines as inputs into the code was also performed to determine the maximum (peak) dose for all receptors. This report contains the technical basis in support of the DOE?s derivation of ALs for the 'Property.' A complete description of the methodology, including an assessment of the input parameters, model inputs, and results is provided in this report. This report also provides initial recommendations on applying the derived soil guidelines.« less

JOURNAL CLUB: Quantification of Fetal Dose Reduction if Abdominal CT Is Limited to the Top of the Iliac Crests in Pregnant Patients With Trauma.

PubMed

Corwin, Michael T; Seibert, J Anthony; Fananapazir, Ghaneh; Lamba, Ramit; Boone, John M

2016-04-01

The purposes of this study were to correlate fetal z-axis location within the maternal abdomen on CT with gestational age and estimate fetal dose reduction of a study limited to the abdomen only, with its lower aspect at the top of the iliac crests, compared with full abdominopelvic CT in pregnant trauma patients. We performed a study of pregnant patients who underwent CT of the abdomen and pelvis for trauma at a single institution over a 10-year period. The inferior aspect of maternal liver, spleen, gallbladder, pancreas, adrenals, and kidneys was recorded as above or below the iliac crests. The distance from the iliac crest to the top of the fetus or gestational sac was determined. The CT images of the limited and full scanning studies were independently reviewed by two blinded radiologists to identify traumatic injuries. Fetal dose profiles, including both scatter and primary radiation, were computed analytically along the central axis of the patient to estimate fetal dose reduction. Linear regression analysis was performed between gestational age and distance of the fetus to the iliac crests. Thirty-five patients were included (mean age, 26.2 years). Gestational age ranged from 5 to 38 weeks, with 5, 19, and 11 gestations in the first, second, and third trimesters, respectively. All solid organs were above the iliac crests in all patients. In three of six patients, traumatic findings in the pelvis would have been missed with the limited study. There was high correlation between gestational age and distance of the fetus to the iliac crests (R(2) = 0.84). The mean gestational age at which the top of the fetus was at the iliac crest was 17.3 weeks. Using the limited scanning study, fetuses at 5, 20, and 40 weeks of gestation would receive an estimated 4.3%, 26.2%, and 59.9% of the dose, respectively, compared with the dose for the full scanning study. In pregnant patients in our series with a history of trauma, CT of the abdomen only was an effective technique to reduce fetal radiation exposure compared with full abdomen and pelvis CT.

WE-AB-207B-01: Dose Tolerance for SBRT/SABR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grimm, J

Purpose: Stereotactic body radiation therapy (SBRT) / stereotactic ablative body radiotherapy (SABR) is gaining popularity, but quantitative dose tolerance has still been lacking. To improve this, the April 2016 issue of Seminars in Radiation Oncology will have normal tissue complication probability (NTCP) models for 10 critical structures: optic pathway, cochlea, oral mucosa, esophagus, chestwall, aorta, bronchi, duodenum, small bowel, and spinal cord. Methods: The project included more than 1500 treatments in 1–5 fractions using CyberKnife, Gamma Knife, or LINAC, with 60 authors from 15 institutions. NTCP models were constructed from the 97 grade 2–3 complications, predominantly scored using the commonmore » terminology criteria for adverse events (CTCAEv4). Dose volume histogram (DVH) data from each institutional dataset was loaded into the DVH Evaluator software (DiversiLabs, LLC, Huntingdon Valley, Pa) for modeling. The current state of the literature for the critical structures was depicted using DVH Risk Maps: comparative graphs of dose tolerance limits that can include estimated risk levels, reported complications, DVH data for study patients, as well as high- and low-risk dose tolerance limits. Results: For relatively acceptable toxicity like grade 1–3 rib fractures and chestwall pain, the high-risk limits have 50% risk and the low-risk limits have 5% risk. Emami et al (IJROBP 1991 May 15;21(1):109–22) used 50% and 5% risk levels for all structures, whereas this effort used clinically acceptable ranges for each: in structures like aorta or spinal cord where complications must be avoided, the high- and low-risk limits have about 3% and 1% risk, respectively, in this issue of Seminars. These statistically based guidelines can help ensure plan quality for each patient. Conclusion: NTCP for SBRT is now becoming available. Hypofractionated dose tolerance can be dramatically different than extrapolations of conventional fractionation so NTCP analysis of the SBRT/SBRT data is important to ensure safe clinical practice. Dr. Grimm, designed and holds intellectual property rights to the DVH Evaluator software tool which is an FDA-cleared product in commercial use, and was used to analyze the data.« less

Role of the standard deviation in the estimation of benchmark doses with continuous data.

PubMed

Gaylor, David W; Slikker, William

2004-12-01

For continuous data, risk is defined here as the proportion of animals with values above a large percentile, e.g., the 99th percentile or below the 1st percentile, for the distribution of values among control animals. It is known that reducing the standard deviation of measurements through improved experimental techniques will result in less stringent (higher) doses for the lower confidence limit on the benchmark dose that is estimated to produce a specified risk of animals with abnormal levels for a biological effect. Thus, a somewhat larger (less stringent) lower confidence limit is obtained that may be used as a point of departure for low-dose risk assessment. It is shown in this article that it is important for the benchmark dose to be based primarily on the standard deviation among animals, s(a), apart from the standard deviation of measurement errors, s(m), within animals. If the benchmark dose is incorrectly based on the overall standard deviation among average values for animals, which includes measurement error variation, the benchmark dose will be overestimated and the risk will be underestimated. The bias increases as s(m) increases relative to s(a). The bias is relatively small if s(m) is less than one-third of s(a), a condition achieved in most experimental designs.

Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

PubMed

Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

2017-05-01

The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

Annual limits on intake (ALI) values in ICRP 61 and 10 CFR Part 20 (1991)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhu, M.; Kearfott, K.J.

The newest major revision of Nuclear Regulatory Commission`s 10 CFR Part 20 (1991) incorporates the new dose methodology system, revised limits, and improved internal dose computations presented in International Commission on Radiation Protection (ICRP) Publication 30 (1979). A year before the issue of this revised 10 CFR Part 20, the ICRP dispatched Publication 61 (1990). This new ICRP report employed different dose limits, in addition to incorporating more recent biological information and variations in physiological and different tissue weighing factors for various organs. An investigation of the numerical differences in the Annual Limit on Intake (ALI) reported in this moremore » recent international regulations and those of the new regulations was thus undertaken. Overall means, medians, modes, maximum, minimum, and ranges of the percent changes are almost identical for ingestion and inhalation, although the percent difference between 10 CFR and ICRP Publication 61 showed minor differences for individual radionuclides. Approximately 334 of 1,351 radionuclides for inhalation and 173 of 771 radionuclides for ingestion have much less restrictive ALIs in the new ICRP recommendations than in the old, with some of those limits increased by at least a factor of two. Approximately 51% of the radionuclides for ingestion intake and 48% of radionuclides for inhalation intake showed changes of greater than 25%. The radionuclides observed to have much less restrictive ALIs are primarily the radionuclides of thorium, mercury, plutonium, uranium, and americium which have short effective clearance rates. While many countries have already applied the ICRP 61 recommendations to their radiation protection standards, using the ICRP 30 recommendation in the United States does not match the international standards even when the values of the ALIs are adjusted for differences in dose limits.« less

Biological dosimetry in a group of radiologists by the analysis of dicentrics and translocations.

PubMed

Montoro, A; Rodríguez, P; Almonacid, M; Villaescusa, J I; Verdú, G; Caballín, M R; Barrios, L; Barquinero, J F

2005-11-01

The results of a cytogenetic study carried out in a group of nine radiologists are presented. Chromosome aberrations were detected by fluorescence plus Giemsa staining and fluorescence in situ hybridization. Dose estimates were obtained by extrapolating the yield of dicentrics and translocations to their respective dose-effect curves. In seven individuals, the 95% confidence limits of the doses estimated by dicentrics did not include 0 Gy. The 99 dicentrics observed in 17,626 cells gave a collective estimated dose of 115 mGy (95% confidence limits 73-171). For translocations, five individuals had estimated doses that were clearly higher than the total accumulated recorded dose. The 82 total apparently simple translocations observed in 9722 cells gave a collective estimated dose of 275 mGy (132-496). The mean genomic frequencies (x100 +/- SE) of complete and total apparently simple translocations observed in the group of radiologists (1.91 +/- 0.30 and 2.67 +/- 0.34, respectively) were significantly higher than those observed in a matched control group (0.53 +/- 0.10 and 0.87 +/- 0.13, P < 0.01 in both cases) and in another occupationally exposed matched group (0.79 +/- 0.12 and 1.14 +/-0.14, P < 0.03 and P < 0.01, respectively). The discrepancies observed between the physically recorded doses and the biologically estimated doses indicate that the radiologists did not always wear their dosimeters or that the dosimeters were not always in the radiation field.

Radiation exposure to nuclear medicine staffs during 18F-FDG PET/CT procedures at Ramathibodi Hospital

NASA Astrophysics Data System (ADS)

Donmoon, T.; Chamroonrat, W.; Tuntawiroon, M.

2016-03-01

The aim of this study is to estimate the whole body and finger radiation doses per study received by nuclear medicine staff involved in dispensing, administration of 18F-FDG and interacting with radioactive patients during PET/CT imaging procedures in a PET/CT facility. The whole-body doses received by radiopharmacists, technologists and nurses were measured by electronic dosimeter and the finger doses by ring dosimeter during a period of 4 months. In 70 PET/CT studies, the mean whole-body dose per study to radiopharmacist, technologist, and nurse were 1.07±0.09, 1.77±0.46, μSv, and not detectable respectively. The mean finger doses per study received by radiopharmacist, technologist, and nurse were 265.65±107.55, 4.84±1.08 and 19.22±2.59 μSv, respectively. The average time in contact with 18F-FDG was 5.88±0.03, 39.06±1.89 and 1.21±0.02 minutes per study for radiopharmacist, technologist and nurse respectively. Technologists received highest mean effective whole- body dose per study and radiopharmacist received the highest finger dose per study. When compared with the ICRP dose limit, each individual worker can work with many more 18F- FDG PET/CT studies for a whole year without exceeding the occupational dose limits. This study confirmed that low levels of radiation does are received by our medical personnel involved in 18F-FDG PET/CT procedures.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fritz, Brad G.; Dirkes, Roger L.; Napier, Bruce A.

The Hanford Reach National Monument (HRNM) was created by presidential proclamation in 2000. It is located along the Columbia River in south central Washington and consists of five distinct units. The McGee Ranch-Riverlands and the North Slope units are addressed in this report. North Slope refers to two of the HRNM units: the Saddle Mountain Unit and the Wahluke Slope Unit. The Saddle Mountain and Wahluke Slope Units are located north of the Columbia River, while the McGee Ranch-Riverlands Unit is located south of the Columbia River and north and west of Washington State Highway 24. To fulfill internal U.S.more » Department of Energy (DOE) requirements prior to any radiological clearance of land, the DOE must evaluate the potential for residual radioactive contamination on this land and determine compliance with the requirements of DOE Order 5400.5. Authorized limits for residual radioactive contamination were developed based on the DOE annual exposure limit to the public (100 mrem) using future potential land-use scenarios. The DOE Office of Environmental Management approved these authorized limits on March 1, 2004. Historical soil monitoring conducted on and around the HRNM indicated soil concentrations of radionuclides were well below the authorized limits (Fritz et al. 2003). However, the historical sampling was done at a limited number of sampling locations. Therefore, additional soil sampling was conducted to determine if the concentrations of radionuclides in soil on the McGee Ranch-Riverlands and North Slope units were below the authorized limits. Sixty-seven soil samples were collected from the McGee Ranch-Riverlands and North Slope units. A software package (Visual Sample Plan) was used to plan the collection to assure an adequate number of samples were collected. The number of samples necessary to decide with a high level of confidence (99%) that the soil concentrations of radionuclides on the North Slope and McGee Ranch-Riverlands units did not exceed the authorized limits was determined to be 27. Additional soil samples were collected from areas suspected to have a potential for accumulation of radionuclides. This included samples collected from the riparian zone along the Columbia River, Savage Island, and other locations across the North Slope and McGee Ranch-Riverlands units. The 67 soil samples collected from the McGee Ranch-Riverlands and North Slope units all had concentrations of radionuclides far below the authorized limits established by the DOE. Statistical analysis of the results concluded that the Authorized Limits were not exceeded when total uncertainty was considered. The calculated upper confidence limit for each radionuclide measured in this study (which represents the value at which 99% of the measurements reside below with a 99% confidence level) was lower than the Authorized Limit for each radionuclide. The maximum observed soil concentrations for the radionuclides included in the authorized limits would result in a potential annual dose of 0.23 mrem assuming the most probable use scenario, a recreational visitor. This potential dose is well below the DOE 100-mrem/year dose limit for members of the public. Furthermore, the results of the biota dose assessment screen, which used the RESRAD biota code, indicated that the sum of fractions is less than one. This assumed soil concentrations equal to the maximum concentrations of radionuclides measured on the McGee Ranch-Riverlands and North Slope units’ in this study. Since the sum of fractions was less than 1, dose to terrestrial biota will not exceed the recommended biota dose limit for the soil concentrations measured in this study.« less

'Muscle-sparing' statins: preclinical profiles and future clinical use.

PubMed

Pfefferkorn, Jeffrey A

2009-03-01

Coronary heart disease (CHD) is a leading cause of death in the US, and hypercholesterolemia is a key risk factor for this disease. The current standard of care for treating hypercholesterolemia is the use of HMG-CoA reductase inhibitors, also known as statins, which block the rate-limiting step of cholesterol biosynthesis. In widespread clinical use, statins have proven safe and effective for both primary prevention of CHD and secondary prevention of coronary events. Results from several recent clinical trials have demonstrated that increasingly aggressive cholesterol-lowering therapy might offer additional protection against CHD compared with less aggressive treatment standards. While higher doses of current statin therapies are capable of achieving these more aggressive treatment goals, in certain cases statin-induced myalgia, the muscle pain or weakness that sometimes accompanies high-dose statin therapy, limits patient compliance with a treatment regimen. To address this limitation, efforts have been undertaken to develop highly hepatoselective statins that are capable of delivering best-in-class efficacy with minimized risk of dose-limiting myalgia. In this review, the preclinical and early clinical data for these next generation statins are discussed.

X-ray emission as a potential hazard during ultrashort pulse laser material processing

NASA Astrophysics Data System (ADS)

Legall, Herbert; Schwanke, Christoph; Pentzien, Simone; Dittmar, Günter; Bonse, Jörn; Krüger, Jörg

2018-06-01

In laser machining with ultrashort laser pulses unwanted X-ray radiation in the keV range can be generated when a critical laser intensity is exceeded. Even if the emitted X-ray dose per pulse is low, high laser repetition rates can lead to an accumulation of X-ray doses beyond exposure safety limits. For 925 fs pulse duration at a center wavelength of 1030 nm, the X-ray emission was investigated up to an intensity of 2.6 × 1014 W/cm2. The experiments were performed in air with a thin disk laser at a repetition rate of 400 kHz. X-ray spectra and doses were measured for various planar target materials covering a wide range of the periodic table from aluminum to tungsten. Without radiation shielding, the measured radiation doses at this high repetition rate clearly exceed the regulatory limits. Estimations for an adequate radiation shielding are provided.

Low-Dose N,N-Dimethylformamide Exposure and Liver Injuries in a Cohort of Chinese Leather Industry Workers.

PubMed

Qi, Cong; Gu, Yiyang; Sun, Qing; Gu, Hongliang; Xu, Bo; Gu, Qing; Xiao, Jing; Lian, Yulong

2017-05-01

We assessed the risk of liver injuries following low doses of N,N-dimethylformamide (DMF) below threshold limit values (20 mg/m) among leather industry workers and comparison groups. A cohort of 429 workers from a leather factory and 466 non-exposed subjects in China were followed for 4 years. Poisson regression and piece-wise linear regression were used to examine the relationship between DMF and liver injury. Workers exposed to a cumulative dose of DMF were significantly more likely than non-exposed workers to develop liver injury. A nonlinear relationship between DMF and liver injury was observed, and a threshold of the cumulative DMF dose for liver injury was 7.30 (mg/m) year. The findings indicate the importance of taking action to reduce DMF occupational exposure limits for promoting worker health.

Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day.

PubMed

Collins, Natalie D; Barrett, Alan D T

2017-03-01

Live attenuated 17D vaccine is considered one of the safest and efficacious vaccines developed to date. This review highlights what is known and the gaps in knowledge of vaccine-induced protective immunity. Recently, the World Health Organization modifying its guidance from 10-year booster doses to one dose gives lifelong protection in most populations. Nonetheless, there are some data suggesting immunity, though protective, may wane over time in certain populations and more research is needed to address this question. Despite having an effective vaccine to control yellow fever, vaccine shortages were identified during outbreaks in 2016, eventuating the use of a fractional-dosing campaign in the Democratic Republic of the Congo. Limited studies hinder identification of the underlying mechanism(s) of vaccine longevity; however, concurrent outbreaks during 2016 provide an opportunity to evaluate vaccine immunity following fractional dosing and insights into vaccine longevity in populations where there is limited information.

Dose Schedule Optimization and the Pharmacokinetic Driver of Neutropenia

PubMed Central

Patel, Mayankbhai; Palani, Santhosh; Chakravarty, Arijit; Yang, Johnny; Shyu, Wen Chyi; Mettetal, Jerome T.

2014-01-01

Toxicity often limits the utility of oncology drugs, and optimization of dose schedule represents one option for mitigation of this toxicity. Here we explore the schedule-dependency of neutropenia, a common dose-limiting toxicity. To this end, we analyze previously published mathematical models of neutropenia to identify a pharmacokinetic (PK) predictor of the neutrophil nadir, and confirm this PK predictor in an in vivo experimental system. Specifically, we find total AUC and Cmax are poor predictors of the neutrophil nadir, while a PK measure based on the moving average of the drug concentration correlates highly with neutropenia. Further, we confirm this PK parameter for its ability to predict neutropenia in vivo following treatment with different doses and schedules. This work represents an attempt at mechanistically deriving a fundamental understanding of the underlying pharmacokinetic drivers of neutropenia, and provides insights that can be leveraged in a translational setting during schedule selection. PMID:25360756

Radiological protection and medical dosimetry for the Skylab crewmen

NASA Technical Reports Server (NTRS)

Bailey, J. V.; Hoffman, R. A.; English, R. A.

1977-01-01

Dosimetry results for Skylab crewmembers show that the Skylab 4 crewmen received the highest dose equivalents but remained well within the established limits for Skylab missions below the threshold of significant clinical effects. These dose equivalents apply specificially to long term effects such as general life shortening, increased neoplasm incidence, and cataract production. A Skylab crewman could fly a mission comparable to one 84-day Skylab 4 mission per year for 50 years before exceeding these career limits.

Radiation exposure of the radiologist's eye lens during CT-guided interventions.

PubMed

Heusch, Philipp; Kröpil, Patric; Buchbender, Christian; Aissa, Joel; Lanzman, Rotem S; Heusner, Till A; Ewen, Klaus; Antoch, Gerald; Fürst, Günther

2014-02-01

In the past decade the number of computed tomography (CT)-guided procedures performed by interventional radiologists have increased, leading to a significantly higher radiation exposure of the interventionalist's eye lens. Because of growing concern that there is a stochastic effect for the development of lens opacification, eye lens dose reduction for operators and patients should be of maximal interest. To determine the interventionalist's equivalent eye lens dose during CT-guided interventions and to relate the results to the maximum of the recommended equivalent dose limit. During 89 CT-guided interventions (e.g. biopsies, drainage procedures, etc.) measurements of eye lens' radiation doses were obtained from a dedicated dosimeter system for scattered radiation. The sensor of the personal dosimeter system was clipped onto the side of the lead glasses which was located nearest to the CT gantry. After the procedure, radiation dose (µSv), dose rate (µSv/min) and the total exposure time (s) were recorded. For all 89 interventions, the median total exposure lens dose was 3.3 µSv (range, 0.03-218.9 µSv) for a median exposure time of 26.2 s (range, 1.1-94.0 s). The median dose rate was 13.9 µSv/min (range, 1.1-335.5 µSv/min). Estimating 50-200 CT-guided interventions per year performed by one interventionalist, the median dose of the eye lens of the interventional radiologist does not exceed the maximum of the ICRP-recommended equivalent eye lens dose limit of 20 mSv per year.

Esophageal Dose Tolerance in Patients Treated With Stereotactic Body Radiation Therapy.

PubMed

Nuyttens, Joost J; Moiseenko, Vitali; McLaughlin, Mark; Jain, Sheena; Herbert, Scott; Grimm, Jimm

2016-04-01

Mediastinal critical structures such as trachea, bronchus, esophagus, and heart are among the dose-limiting factors for stereotactic body radiation therapy (SBRT) to central lung lesions. The purpose of this study was to characterize the risk of esophagitis for patients treated with SBRT and to develop a statistical dose-response model to assess the equivalent uniform dose, D10%, D5cc, D1cc, and Dmax, to the esophagus and the risk of toxicity. Toxicity outcomes of a dose-escalation study of 56 patients who had taken CyberKnife treatment from 45-60Gy in 3-7 fractions at the Erasmus MC-Daniel den Hoed Cancer Center were utilized to create the dose-response model for esophagus. A total of 5 grade 2 esophageal complications were reported (Common Terminology Criteria for Adverse Events version 3.0); 4 complications were early effects and 1 complication was a late effect. All analyses were performed in terms of 5-fraction equivalent dosing. According to our study, D1cc at a dose of 32.9Gy and Dmax dose of 43.4Gy corresponded to a complication probability of 50% for grade 2 toxicity. In this series of 58 CyberKnife mediastinal lung cases, no grade 3 or higher esophageal toxicity occurred. Our estimates of esophageal toxicity are compared with the data in the literature. Further research needs to be performed to establish more reliable dose limits as longer follow-up and toxicity outcomes are reported in patients treated with SBRT for central lung lesions. Copyright © 2016 Elsevier Inc. All rights reserved.

Optimization of the sensitivity/doses relationship for a bench-top EDXRF system used for in vivo quantification of gold nanoparticles.

PubMed

Santibáñez, M; Saavedra, R; Vásquez, M; Malano, F; Pérez, P; Valente, M; Figueroa, R G

2017-11-01

The present work is devoted to optimizing the sensitivity-doses relationship of a bench-top EDXRF system, with the aim of achieving a detection limit of 0.010mg/ml of gold nanoparticles in tumor tissue (clinical values expected), for doses below 10mGy (value fixed for in vivo application). Tumor phantoms of 0.3cm 3 made of a suspension of gold nanoparticles (15nm AurovistTM, Nanoprobes Inc.) were studied at depths of 0-4mm in a tissue equivalent cylindrical phantom. The optimization process was implemented configuring several tube voltages and aluminum filters, to obtain non-symmetrical narrow spectra with fixed FWHM of 5keV and centered among the 11.2-20.3keV. The used statistical figure of merit was the obtained sensitivity (with each spectrum at each depth) weighted by the delivered surface doses. The detection limit of the system was determined measuring several gold nanoparticles concentrations ranging from 0.0010 to 5.0mg/ml and a blank sample into tumor phantoms, considering a statistical fluctuation within 95% of confidence. The results show the possibility of obtaining a detection limit for gold nanoparticles concentrations around 0.010mg/ml for surface tumor phantoms requiring doses around 2mGy. Copyright © 2017 Elsevier Ltd. All rights reserved.

Assessing endotoxins in equine-derived snake antivenoms: Comparison of the USP pyrogen test and the Limulus Amoebocyte Lysate assay (LAL).

PubMed

Solano, Gabriela; Gómez, Aarón; León, Guillermo

2015-10-01

Snake antivenoms are parenterally administered; therefore, endotoxin content must be strictly controlled. Following international indications to calculate endotoxin limits, it was determined that antivenom doses between 20 mL and 120 mL should not exceed 17.5 Endotoxin Units per milliliter (EU/mL) and 2.9 EU/mL, respectively. The rabbit pyrogen test (RPT) has been used to evaluate endotoxin contamination in antivenoms, but some laboratories have recently implemented the LAL assay. We compared the capability of both tests to evaluate endotoxin contamination in antivenoms, and we found that both methods can detect all endotoxin concentrations in the range of the antivenom specifications. The acceptance criteria of RPT and LAL must be harmonized by calculating the endotoxin limit as the quotient of the threshold pyrogenic dose and the therapeutic dose and the dose administered to rabbits as the quotient of the threshold pyrogenic dose and the endotoxin limit. Since endotoxins from Gram-negative bacteria exert different pyrogenicity, if contamination occurred, antivenom batches that induce pyrogenic reactions may be found in spite of passing LAL specifications. Although LAL assay can be used to assess endotoxin content throughout the antivenom manufacturing process, we recommend that the release of final products be based on the results of both methods. Copyright © 2015 Elsevier Ltd. All rights reserved.

Advances in Inhalation Dosimetry Models and Methods for Occupational Risk Assessment and Exposure Limit Derivation

PubMed Central

Kuempel, Eileen D.; Sweeney, Lisa M.; Morris, John B.; Jarabek, Annie M.

2015-01-01

The purpose of this article is to provide an overview and practical guide to occupational health professionals concerning the derivation and use of dose estimates in risk assessment for development of occupational exposure limits (OELs) for inhaled substances. Dosimetry is the study and practice of measuring or estimating the internal dose of a substance in individuals or a population. Dosimetry thus provides an essential link to understanding the relationship between an external exposure and a biological response. Use of dosimetry principles and tools can improve the accuracy of risk assessment, and reduce the uncertainty, by providing reliable estimates of the internal dose at the target tissue. This is accomplished through specific measurement data or predictive models, when available, or the use of basic dosimetry principles for broad classes of materials. Accurate dose estimation is essential not only for dose-response assessment, but also for interspecies extrapolation and for risk characterization at given exposures. Inhalation dosimetry is the focus of this paper since it is a major route of exposure in the workplace. Practical examples of dose estimation and OEL derivation are provided for inhaled gases and particulates. PMID:26551218

Limited PCB antagonism of TCDD-induced malformations in mice

DOE Office of Scientific and Technical Information (OSTI.GOV)

Morrissey, R.E.; Harris, M.W.; Diliberto, J.J.

1992-01-01

Mice used to model induction of cleft palate and kidney malformations in offspring following maternal treatment with TCDD, were dosed on gestation day with hexachlorobiphenyl (HCB) and/or with tetrachlorodibenzo-p-dioxin (TCDD) to investigate the potential protective effects of HCB against TCDD-induced teratogenicity. At the doses used in the study, there was no effect of either compound on number of live or dead offspring. Fetal body weight was slightly decreased in all groups dosed with = or > 250 mg HCB/kg. HCB did not induce cleft palate at a dose of 1000 mg/kg, but did induce increases in hydronephrosis and hydroureter atmore » 500 and 1000 mg/kg. Combinations of HCB and TCDD decreased the incidence of cleft palate induced by TCDD alone, but only at doses of 15 microgram TCDD/kg combined with 125-500 mg HCB/kg. The window for antagonism of hydronephrosis (incidence and severity) appeared narrower (15 microgram TCDD/kg + 500 mg HCB/kg). HCB induced increases (3 fold) in EROD activity at doses of 500 and 1000 mg/kg, suggesting that the limited antagonism of TCDD teratogenicity by HCB would be consistent with control by Ah receptor. (Copyright (c) 1992 Elsevier Science Publishers B.V.)« less

Vertical Distribution and Estimated Doses from Artificial Radionuclides in Soil Samples around the Chernobyl Nuclear Power Plant and the Semipalatinsk Nuclear Testing Site

PubMed Central

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides (241Am, 134Cs, 137Cs, and 60Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides (241Am, 57Co, 137Cs, 95Zr, 95Nb, 58Co, and 60Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public. PMID:23469013

Vertical distribution and estimated doses from artificial radionuclides in soil samples around the Chernobyl nuclear power plant and the Semipalatinsk nuclear testing site.

PubMed

Taira, Yasuyuki; Hayashida, Naomi; Tsuchiya, Rimi; Yamaguchi, Hitoshi; Takahashi, Jumpei; Kazlovsky, Alexander; Urazalin, Marat; Rakhypbekov, Tolebay; Yamashita, Shunichi; Takamura, Noboru

2013-01-01

For the current on-site evaluation of the environmental contamination and contributory external exposure after the accident at the Chernobyl Nuclear Power Plant (CNPP) and the nuclear tests at the Semipalatinsk Nuclear Testing Site (SNTS), the concentrations of artificial radionuclides in soil samples from each area were analyzed by gamma spectrometry. Four artificial radionuclides ((241)Am, (134)Cs, (137)Cs, and (60)Co) were detected in surface soil around CNPP, whereas seven artificial radionuclides ((241)Am, (57)Co, (137)Cs, (95)Zr, (95)Nb, (58)Co, and (60)Co) were detected in surface soil around SNTS. Effective doses around CNPP were over the public dose limit of 1 mSv/y (International Commission on Radiological Protection, 1991). These levels in a contaminated area 12 km from Unit 4 were high, whereas levels in a decontaminated area 12 km from Unit 4 and another contaminated area 15 km from Unit 4 were comparatively low. On the other hand, the effective doses around SNTS were below the public dose limit. These findings suggest that the environmental contamination and effective doses on the ground definitely decrease with decontamination such as removing surface soil, although the effective doses of the sampling points around CNPP in the present study were all over the public dose limit. Thus, the remediation of soil as a countermeasure could be an extremely effective method not only for areas around CNPP and SNTS but also for areas around the Fukushima Dai-ichi Nuclear Power Plant (FNPP), and external exposure levels will be certainly reduced. Long-term follow-up of environmental monitoring around CNPP, SNTS, and FNPP, as well as evaluation of the health effects in the population residing around these areas, could contribute to radiation safety and reduce unnecessary exposure to the public.

Monitoring the eye lens: which dose quantity is adequate?

NASA Astrophysics Data System (ADS)

Behrens, R.; Dietze, G.

2010-07-01

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity Hp(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity Hp(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of Hp(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of Hp(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of Hp(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

Monitoring the eye lens: which dose quantity is adequate?

PubMed

Behrens, R; Dietze, G

2010-07-21

Recent epidemiological studies suggest a rather low dose threshold (below 0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimized and current dose limits for the eye lens may be reduced in the future. The question of which personal dose equivalent quantity is appropriate for monitoring the dose to the eye lens arises from this situation. While in many countries dosemeters calibrated in terms of the dose equivalent quantity H(p)(0.07) have been seen as being adequate for monitoring the dose to the eye lens, this might be questionable in the case of reduced dose limits and, thus, it may become necessary to use the dose equivalent quantity H(p)(3) for this purpose. To discuss this question, the dose conversion coefficients for the equivalent dose of the eye lens (in the following eye lens dose) were determined for realistic photon and beta radiation fields and compared with the values of the corresponding conversion coefficients for the different operational quantities. The values obtained lead to the following conclusions: in radiation fields where most of the dose comes from photons, especially x-rays, it is appropriate to use dosemeters calibrated in terms of H(p)(0.07) on a slab phantom, while in other radiation fields (dominated by beta radiation or unknown contributions of photon and beta radiation) dosemeters calibrated in terms of H(p)(3) on a slab phantom should be used. As an alternative, dosemeters calibrated in terms of H(p)(0.07) on a slab phantom could also be used; however, in radiation fields containing beta radiation with the end point energy near 1 MeV, an overestimation of the eye lens dose by up to a factor of 550 is possible.

SU-F-P-21: Study of Dosimetry Accuracy of Small Passively Scattered Proton Beam Fields

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Y; Gautam, A; Kerr, M

2016-06-15

Purpose: To study the accuracy of the dose distribution of very small irregular fields of passively scattered proton beams calculated by the analytical pencil beam model of the Eclipse treatment planning system (TPS). Methods: An irregular field with a narrow region (width < 1 cm) that was used for the treatment of a small volume adjacent to a previously treated area were chosen for this investigation. Point doses at different locations inside the field were measured with a small volume ion chamber (A26, Standard Imaging). 2-D dose distributions were measured using a 2-D ion chamber array (MatriXX, IBA). All themore » measurements were done in plastic water phantom. The measured dose distributions were compared with the verification plan dose calculated in a water like phantom for the patient treatment field without the use of the compensator. Results: Point doses measured with the ion chamber in the narrowest section of the field were found to differ as much as 10% from the Eclipse calculated dose at some of the points. The 2-D dose distribution measured with the MatriXX which was validated by comparison with limited film measurement, at the proximal 95%, center of the spread out Bragg Peak and distal 90% depths agreed reasonably well with the TPS calculated dose distribution with more than 92% of the pixels passing the 2% / 2 mm dose distance agreement. Conclusion: The dose calculated by the pencil beam model of the Eclipse TPS for narrow irregular fields may not be accurate within 5% at some locations of the field, especially at the points close to the field edge due to the limitation of the dose calculation model. Overall accuracy of the calculated 2-D dose distribution was found to be acceptable for the 2%/2 mm dose/distance agreement with the measurement.« less

Dose-finding study of intensive weekly alternating schedule of docetaxel, 5-fluorouracil, and oxaliplatin, FD/FOx regimen, in metastatic gastric cancer.

PubMed

Bruera, Gemma; Massacese, Silvia; Galvano, Antonio; Mas, Antonella Dal; Guadagni, Stefano; Calvisi, Giuseppe; Ciacco, Eugenio; Russo, Antonio; Ricevuto, Enrico

2018-04-17

Proper administration timing, dose-intensity, efficacy/toxicity ratio of triplet docetaxel (DTX), 5-fluorouracil (5-FU), and oxaliplatin (OXP) should be improved to safely perform three-drugs intensive first line in advanced gastric cancer (GC). This dose-finding study investigated recommended 5-FU and OXP doses, safety of triplet regimen and preliminary activity. Schedule: 12h-timed-flat-infusion 5-FU 700-1000 mg/m 2 /d 1-2, 8-9, 15-16, 22-23, with 100 mg/m 2 /d increase for dose level; DTX 50 mg/m 2 d 1, 15 fixed dose, OXP at three increasing dose-levels 60-70-80 mg/m 2 d 8, 22, every 4 weeks. Intra- and inter-patients dose-escalation was planned. Ten fit <75 years patients were enrolled: median age 59; young-elderly 4 (40%). From first to fifth dose level, 5 patients (1 per cohort) were enrolled according to intra-patient dose escalation, no dose-limiting toxicity (DLT) were reported. At sixth level, 1 DLT, G2 diarrhea, was reported, thus other 2 patients were enrolled, DLT 1/3 patients (33%). Maximum tolerated dose (MTD) was not reached. 5-FU and OXP recommended doses (RD) were 1000 mg/m 2 /d and 80 mg/m 2 , respectively. To confirm RD, other 3 patients were enrolled, without DLT. Cumulative G3-4 toxicities were: neutropenia 50%, leucopenia 20%, hypoalbuminemia 10%, mucositis 10%, asthenia 20%. Limiting toxicity syndromes were 30%, 25% in young-elderly, all multiple site. Objective response rate intent-to-treat 60%, disease control rate 90%. After 15 months follow-up, progression-free and overall survival, 6 and 17 months, respectively. First line intensive FD/FOx regimen adding DXT/5-FU/OXP can be safely administered at recommended doses in advanced GC, with promising high activity and efficacy.

Ultra-Low-Dose Fetal CT With Model-Based Iterative Reconstruction: A Prospective Pilot Study.

PubMed

Imai, Rumi; Miyazaki, Osamu; Horiuchi, Tetsuya; Asano, Keisuke; Nishimura, Gen; Sago, Haruhiko; Nosaka, Shunsuke

2017-06-01

Prenatal diagnosis of skeletal dysplasia by means of 3D skeletal CT examination is highly accurate. However, it carries a risk of fetal exposure to radiation. Model-based iterative reconstruction (MBIR) technology can reduce radiation exposure; however, to our knowledge, the lower limit of an optimal dose is currently unknown. The objectives of this study are to establish ultra-low-dose fetal CT as a method for prenatal diagnosis of skeletal dysplasia and to evaluate the appropriate radiation dose for ultra-low-dose fetal CT. Relationships between tube current and image noise in adaptive statistical iterative reconstruction and MBIR were examined using a 32-cm CT dose index (CTDI) phantom. On the basis of the results of this examination and the recommended methods for the MBIR option and the known relationship between noise and tube current for filtered back projection, as represented by the expression SD = (milliamperes) -0.5 , the lower limit of the optimal dose in ultra-low-dose fetal CT with MBIR was set. The diagnostic power of the CT images obtained using the aforementioned scanning conditions was evaluated, and the radiation exposure associated with ultra-low-dose fetal CT was compared with that noted in previous reports. Noise increased in nearly inverse proportion to the square root of the dose in adaptive statistical iterative reconstruction and in inverse proportion to the fourth root of the dose in MBIR. Ultra-low-dose fetal CT was found to have a volume CTDI of 0.5 mGy. Prenatal diagnosis was accurately performed on the basis of ultra-low-dose fetal CT images that were obtained using this protocol. The level of fetal exposure to radiation was 0.7 mSv. The use of ultra-low-dose fetal CT with MBIR led to a substantial reduction in radiation exposure, compared with the CT imaging method currently used at our institution, but it still enabled diagnosis of skeletal dysplasia without reducing diagnostic power.

Phase I clinical and pharmacokinetic study of kahalalide F administered weekly as a 1-hour infusion to patients with advanced solid tumors.

PubMed

Pardo, Beatriz; Paz-Ares, Luis; Tabernero, Josep; Ciruelos, Eva; García, Margarita; Salazar, Ramón; López, Ana; Blanco, María; Nieto, Antonio; Jimeno, José; Izquierdo, Miguel Angel; Trigo, José Manuel

2008-02-15

A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available. Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 microg/m(2), and dose escalation proceeded based on the worst toxicity found in the previous cohort. Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 microg/m(2). Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 microg/m(2), and the recommended dose for phase II studies was 650 microg/m(2). No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent. The maximum tolerated dose was 800 microg/m(2). Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 microg/m(2) was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.

Stereotactic body radiation therapy of early-stage non-small-cell lung carcinoma: Phase I study

DOE Office of Scientific and Technical Information (OSTI.GOV)

McGarry, Ronald C.; Papiez, Lech; Williams, Mark

Purpose: A Phase I dose escalation study of stereotactic body radiation therapy to assess toxicity and local control rates for patients with medically inoperable Stage I lung cancer. Methods and Materials: All patients had non-small-cell lung carcinoma, Stage T1a or T1b N0, M0. Patients were immobilized in a stereotactic body frame and treated in escalating doses of radiotherapy beginning at 24 Gy total (3 x 8 Gy fractions) using 7-10 beams. Cohorts were dose escalated by 6.0 Gy total with appropriate observation periods. Results: The maximum tolerated dose was not achieved in the T1 stratum (maximum dose = 60 Gy),more » but within the T2 stratum, the maximum tolerated dose was realized at 72 Gy for tumors larger than 5 cm. Dose-limiting toxicity included predominantly bronchitis, pericardial effusion, hypoxia, and pneumonitis. Local failure occurred in 4/19 T1 and 6/28 T2 patients. Nine local failures occurred at doses {<=}16 Gy and only 1 at higher doses. Local failures occurred between 3 and 31 months from treatment. Within the T1 group, 5 patients had distant or regional recurrence as an isolated event, whereas 3 patients had both distant and regional recurrence. Within the T2 group, 2 patients had solitary regional recurrences, and the 4 patients who failed distantly also failed regionally. Conclusions: Stereotactic body radiation therapy seems to be a safe, effective means of treating early-stage lung cancer in medically inoperable patients. Excellent local control was achieved at higher dose cohorts with apparent dose-limiting toxicities in patients with larger tumors.« less

Dental cone-beam CT reconstruction from limited-angle view data based on compressed-sensing (CS) theory for fast, low-dose X-ray imaging

NASA Astrophysics Data System (ADS)

Je, Uikyu; Cho, Hyosung; Lee, Minsik; Oh, Jieun; Park, Yeonok; Hong, Daeki; Park, Cheulkyu; Cho, Heemoon; Choi, Sungil; Koo, Yangseo

2014-06-01

Recently, reducing radiation doses has become an issue of critical importance in the broader radiological community. As a possible technical approach, especially, in dental cone-beam computed tomography (CBCT), reconstruction from limited-angle view data (< 360°) would enable fast scanning with reduced doses to the patient. In this study, we investigated and implemented an efficient reconstruction algorithm based on compressed-sensing (CS) theory for the scan geometry and performed systematic simulation works to investigate the image characteristics. We also performed experimental works by applying the algorithm to a commercially-available dental CBCT system to demonstrate its effectiveness for image reconstruction in incomplete data problems. We successfully reconstructed CBCT images with incomplete projections acquired at selected scan angles of 120, 150, 180, and 200° with a fixed angle step of 1.2° and evaluated the reconstruction quality quantitatively. Both simulation and experimental demonstrations of the CS-based reconstruction from limited-angle view data show that the algorithm can be applied directly to current dental CBCT systems for reducing the imaging doses and further improving the image quality.

PACKAGING CERTIFICATION PROGRAM METHODOLOGY FOR DETERMINING DOSE RATES FOR SMALL GRAM QUANTITIES IN SHIPPING PACKAGINGS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nathan, S.; Loftin, B.; Abramczyk, G.

The Small Gram Quantity (SGQ) concept is based on the understanding that small amounts of hazardous materials, in this case radioactive materials (RAM), are significantly less hazardous than large amounts of the same materials. This paper describes a methodology designed to estimate an SGQ for several neutron and gamma emitting isotopes that can be shipped in a package compliant with 10 CFR Part 71 external radiation level limits regulations. These regulations require packaging for the shipment of radioactive materials, under both normal and accident conditions, to perform the essential functions of material containment, subcriticality, and maintain external radiation levels withinmore » the specified limits. By placing the contents in a helium leak-tight containment vessel, and limiting the mass to ensure subcriticality, the first two essential functions are readily met. Some isotopes emit sufficiently strong photon radiation that small amounts of material can yield a large dose rate outside the package. Quantifying the dose rate for a proposed content is a challenging issue for the SGQ approach. It is essential to quantify external radiation levels from several common gamma and neutron sources that can be safely placed in a specific packaging, to ensure compliance with federal regulations. The Packaging Certification Program (PCP) Methodology for Determining Dose Rate for Small Gram Quantities in Shipping Packagings provides bounding shielding calculations that define mass limits compliant with 10 CFR 71.47 for a set of proposed SGQ isotopes. The approach is based on energy superposition with dose response calculated for a set of spectral groups for a baseline physical packaging configuration. The methodology includes using the MCNP radiation transport code to evaluate a family of neutron and photon spectral groups using the 9977 shipping package and its associated shielded containers as the base case. This results in a set of multipliers for 'dose per particle' for each spectral group. For a given isotope, the source spectrum is folded with the response for each group. The summed contribution from all isotopes determines the total dose from the RAM in the container.« less

Short communication: a repeated simian human immunodeficiency virus reverse transcriptase/herpes simplex virus type 2 cochallenge macaque model for the evaluation of microbicides.

PubMed

Kenney, Jessica; Derby, Nina; Aravantinou, Meropi; Kleinbeck, Kyle; Frank, Ines; Gettie, Agegnehu; Grasperge, Brooke; Blanchard, James; Piatak, Michael; Lifson, Jeffrey D; Zydowsky, Thomas M; Robbiani, Melissa

2014-11-01

Epidemiological studies suggest that prevalent herpes simplex virus type 2 (HSV-2) infection increases the risk of HIV acquisition, underscoring the need to develop coinfection models to evaluate promising prevention strategies. We previously established a single high-dose vaginal coinfection model of simian human immunodeficiency virus (SHIV)/HSV-2 in Depo-Provera (DP)-treated macaques. However, this model does not appropriately mimic women's exposure. Repeated limiting dose SHIV challenge models are now used routinely to test prevention strategies, yet, at present, there are no reports of a repeated limiting dose cochallenge model in which to evaluate products targeting HIV and HSV-2. Herein, we show that 20 weekly cochallenges with 2-50 TCID50 simian human immunodeficiency virus reverse transcriptase (SHIV-RT) and 10(7) pfu HSV-2 results in infection with both viruses (4/6 SHIV-RT, 6/6 HSV-2). The frequency and level of vaginal HSV-2 shedding were significantly greater in the repeated exposure model compared to the single high-dose model (p<0.0001). We used this new model to test the Council's on-demand microbicide gel, MZC, which is active against SHIV-RT in DP-treated macaques and HSV-2 and human papillomavirus (HPV) in mice. While MZC reduced SHIV and HSV-2 infections in our repeated limiting dose model when cochallenging 8 h after each gel application, a barrier effect of carrageenan (CG) that was not seen in DP-treated animals precluded evaluation of the significance of the antiviral activity of MZC. Both MZC and CG significantly (p<0.0001) reduced the frequency and level of vaginal HSV-2 shedding compared to no gel treatment. This validates the use of this repeated limiting dose cochallenge model for testing products targeting HIV and HSV-2.

Safety of stavudine in the treatment of HIV infection with a special focus on resource-limited settings.

PubMed

Makinson, Alain; Moing, Vincent Le; Kouanfack, Charles; Laurent, Christian; Delaporte, Eric

2008-05-01

Western randomized trials and prospective cohorts in resource-limited settings have proven virological success with stavudine-based highly active antiretroviral therapy. However, stavudine is no longer recommended in first-line treatments in these two settings due to its intrinsic toxicities and side effects. Yet it remains a cornerstone of treatment in resource-limited settings, due to lack of alternatives and its availability in generic fixed-dose combinations. To review the toxic effects of stavudine and their prevention and management strategies, especially in resource-limited settings. Data from clinical and pharmacological trials in Western countries, as well as prospective cohorts in resource-limited settings, were reviewed. Initiating or switching to less toxic nucleoside analogues whenever possible, or lowering stavudine doses to 30 mg b.i.d., is strongly recommended.

Time-resolved dosimetry using a pinpoint ionization chamber as quality assurance for IMRT and VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Louwe, Robert J. W., E-mail: rob.louwe@ccdbh.org.nz; Satherley, Thomas; Day, Rebecca A.

Purpose: To develop a method to verify the dose delivery in relation to the individual control points of intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using an ionization chamber. In addition to more effective problem solving during patient-specific quality assurance (QA), the aim is to eventually map out the limitations in the treatment chain and enable a targeted improvement of the treatment technique in an efficient way. Methods: Pretreatment verification was carried out for 255 treatment plans that included a broad range of treatment indications in two departments using the equipment of different vendors. In-house developed softwaremore » was used to enable calculation of the dose delivery for the individual beamlets in the treatment planning system (TPS), for data acquisition, and for analysis of the data. The observed deviations were related to various delivery and measurement parameters such as gantry angle, field size, and the position of the detector with respect to the field edge to distinguish between error sources. Results: The average deviation of the integral fraction dose during pretreatment verification of the planning target volume dose was −2.1% ± 2.2% (1 SD), −1.7% ± 1.7% (1 SD), and 0.0% ± 1.3% (1 SD) for IMRT at the Radboud University Medical Center (RUMC), VMAT (RUMC), and VMAT at the Wellington Blood and Cancer Centre, respectively. Verification of the dose to organs at risk gave very similar results but was generally subject to a larger measurement uncertainty due to the position of the detector at a high dose gradient. The observed deviations could be related to limitations of the TPS beam models, attenuation of the treatment couch, as well as measurement errors. The apparent systematic error of about −2% in the average deviation of the integral fraction dose in the RUMC results could be explained by the limitations of the TPS beam model in the calculation of the beam penumbra. Conclusions: This study showed that time-resolved dosimetry using an ionization chamber is feasible and can be largely automated which limits the required additional time compared to integrated dose measurements. It provides a unique QA method which enables identification and quantification of the contribution of various error sources during IMRT and VMAT delivery.« less

Avelumab for metastatic or locally advanced previously treated solid tumours (JAVELIN Solid Tumor): a phase 1a, multicohort, dose-escalation trial.

PubMed

Heery, Christopher R; O'Sullivan-Coyne, Geraldine; Madan, Ravi A; Cordes, Lisa; Rajan, Arun; Rauckhorst, Myrna; Lamping, Elizabeth; Oyelakin, Israel; Marté, Jennifer L; Lepone, Lauren M; Donahue, Renee N; Grenga, Italia; Cuillerot, Jean-Marie; Neuteboom, Berend; Heydebreck, Anja von; Chin, Kevin; Schlom, Jeffrey; Gulley, James L

2017-05-01

Avelumab (MSB0010718C) is a human IgG1 monoclonal antibody that binds to PD-L1, inhibiting its binding to PD-1, which inactivates T cells. We aimed to establish the safety and pharmacokinetics of avelumab in patients with solid tumours while assessing biological correlatives for future development. This open-label, single-centre, phase 1a, dose-escalation trial (part of the JAVELIN Solid Tumor trial) assessed four doses of avelumab (1 mg/kg, 3 mg/kg, 10 mg/kg, and 20 mg/kg), with dose-level cohort expansions to provide additional safety, pharmacokinetics, and target occupancy data. This study used a standard 3 + 3 cohort design and assigned patients sequentially at trial entry according to the 3 + 3 dose-escalation algorithm and depending on the number of dose-limiting toxicities during the first 3-week assessment period (the primary endpoint). Patient eligibility criteria included age 18 years or older, Eastern Cooperative Oncology Group performance status 0-1, metastatic or locally advanced previously treated solid tumours, and adequate end-organ function. Avelumab was given as a 1-h intravenous infusion every 2 weeks. Patients in the dose-limiting toxicity analysis set were assessed for the primary endpoint of dose-limiting toxicity, and all patients enrolled in the dose-escalation part were assessed for the secondary endpoints of safety (treatment-emergent and treatment-related adverse events according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0), pharmacokinetic and pharmacodynamic profiles (immunological effects), best overall response by Response Evaluation Criteria, and antidrug antibody formation. The population for the pharmacokinetic analysis included a subset of patients with rich pharmacokinetic samples from two selected disease-specific expansion cohorts at the same study site who had serum samples obtained at multiple early timepoints. This trial is registered with ClinicalTrials.gov, number NCT01772004. Patient recruitment to the dose-escalation part reported here is closed. Between Jan 31, 2013, and Oct 8, 2014, 53 patients were enrolled (four patients at 1 mg/kg, 13 at 3 mg/kg, 15 at 10 mg/kg, and 21 at 20 mg/kg). 18 patients were analysed in the dose-limiting toxicity analysis set: three at dose level 1 (1 mg/kg), three at dose level 2 (3 mg/kg), six at dose level 3 (10 mg/kg), and six at dose level 4 (20 mg/kg). Only one dose-limiting toxicity occurred, at the 20 mg/kg dose, and thus the maximum tolerated dose was not reached. In all 53 enrolled patients (the safety analysis set), common treatment-related adverse events (occurring in >10% of patients) included fatigue (21 patients [40%]), influenza-like symptoms (11 [21%]), fever (8 [15%]), and chills (6 [11%]). Grade 3-4 treatment-related adverse events occurred in nine (17%) of 53 patients, with autoimmune disorder (n=3), increased blood creatine phosphokinase (n=2), and increased aspartate aminotransferase (n=2) each occurring in more than one patient (autoimmune disorder in two patients at 10 mg/kg and one patient at 20 mg/kg, increased blood creatine phosphokinase in two patients at 20 mg/kg, and increased aspartate aminotransferase in one patient at 1 mg/kg, and one patient at 10 mg/kg). Six (11%) of 53 patients had a serious treatment-related adverse event: autoimmune disorder (two [13%]), lower abdominal pain (one [7%]), fatigue (one [7%]), and influenza-like illness (one [7%]) in three patients treated at 10 mg/kg dose level, and autoimmune disorder (one [5%]), increased amylase (one [5%]), myositis (one [5%]), and dysphonia (one [5%]) in three patients who received the 20 mg/kg dose. We recorded some evidence of clinical activity in various solid tumours, with partial confirmed or unconfirmed responses in four (8%) of 53 patients; 30 (57%) additional patients had stable disease. Pharmacokinetic analysis (n=86) showed a dose-proportional exposure between doses of 3 mg/kg and 20 mg/kg and a half-life of 95-99 h (3·9-4·1 days) at the 10 mg/kg and 20 mg/kg doses. Target occupancy was greater than 90% at doses of 3 mg/kg and 10 mg/kg. Antidrug antibodies were detected in two (4%) of 53 patients. No substantial differences were found in absolute lymphocyte count or multiple immune cell subsets, including those expressing PD-L1, after treatment with avelumab. 31 (58%) of 53 patients in the overall safety population died; no deaths were related to treatment on study. Avelumab has an acceptable toxicity profile up to 20 mg/kg and the maximum tolerated dose was not reached. Based on pharmacokinetics, target occupancy, and immunological analysis, we chose 10 mg/kg every 2 weeks as the dose for further development and phase 3 trials are ongoing. National Cancer Institute and Merck KGaA. Copyright © 2017 Elsevier Ltd. All rights reserved.

Radiation exposure of aviation crewmembers and cancer.

PubMed

Bramlitt, Edward T; Shonka, Joseph J

2015-01-01

Crewmembers are exposed to galactic cosmic radiation on every flight and occasionally to solar protons on polar flights. Data are presented showing that the proton occasions are seven times more frequent than generally believed. Crewmembers are also exposed to neutrons and gamma rays from the sun and to gamma rays from terrestrial thunderstorms. Solar neutrons and gamma rays (1) expose the daylight side of Earth, (2) are most intense at lower latitudes, (3) may be as or more frequent than solar protons, and (4) have relativistic energies. The U.S. agency responsible for crewmember safety only considers the galactic component with respect to its recommended 20 mSv y(-1) limit, but it has an estimate for a thunderstorm dose of 30 mSv. In view of overlooked sources, possible over-limit doses, and lack of dosimetry, dose reconstructions are needed. However, using the agency dose estimates and the compensation procedure for U.S. nuclear weapon workers, the probability of crewmember cancers can be at least as likely as not. Ways to improve the quality of dose estimates are suggested, and a worker's compensation program specific to aviation crewmembers is recommended.

Point-of-use chlorination of turbid water: results from a field study in Tanzania.

PubMed

Mohamed, Hussein; Brown, Joe; Njee, Robert M; Clasen, Thomas; Malebo, Hamisi M; Mbuligwe, Steven

2015-06-01

Household-based chlorine disinfection is widely effective against waterborne bacteria and viruses, and may be among the most inexpensive and accessible options for household water treatment. The microbiological effectiveness of chlorine is limited, however, by turbidity. In Tanzania, there are no guidelines on water chlorination at household level, and limited data on whether dosing guidelines for higher turbidity waters are sufficient to produce potable water. This study was designed to assess the effectiveness of chlorination across a range of turbidities found in rural water sources, following local dosing guidelines that recommend a 'double dose' for water that is visibly turbid. We chlorinated water from 43 sources representing a range of turbidities using two locally available chlorine-based disinfectants: WaterGuard and Aquatabs. We determined free available chlorine at 30 min and 24 h contact time. Our data suggest that water chlorination with WaterGuard or Aquatabs can be effective using both single and double doses up to 20 nephelometric turbidity units (NTU), or using a double dose of Aquatabs up to 100 NTU, but neither was effective at turbidities greater than 100 NTU.

The relationship between carbohydrate and the mealtime insulin dose in type 1 diabetes.

PubMed

Bell, Kirstine J; King, Bruce R; Shafat, Amir; Smart, Carmel E

2015-01-01

A primary focus of the nutritional management of type 1 diabetes has been on matching prandial insulin therapy with carbohydrate amount consumed. Different methods exist to quantify carbohydrate including counting in one gram increments, 10g portions or 15g exchanges. Clinicians have assumed that counting in one gram increments is necessary to precisely dose insulin and optimize postprandial control. Carbohydrate estimations in portions or exchanges have been thought of as inadequate because they may result in less precise matching of insulin dose to carbohydrate amount. However, studies examining the impact of errors in carbohydrate quantification on postprandial glycemia challenge this commonly held view. In addition it has been found that a single mealtime bolus of insulin can cover a range of carbohydrate intake without deterioration in postprandial control. Furthermore, limitations exist in the accuracy of the nutrition information panel on a food label. This article reviews the relationship between carbohydrate quantity and insulin dose, highlighting limitations in the evidence for a linear association. These insights have significant implications for patient education and mealtime insulin dose calculations. Copyright © 2015 Elsevier Inc. All rights reserved.

Committed effective dose determination in southern Brazilian cereal flours.

PubMed

Scheibel, V; Appoloni, C R

2013-01-01

The health impact of radionuclide ingestion from foodstuffs was evaluated by the committed effective doses determined in eight commercial samples of South-Brazilian cereal flours (soy, wheat, cornmeal, cassava, rye, oat, barley and rice flours). The radioactivity traces of (228)Th, (228)Ra, (226)Ra, (40)K, (7)Be and (137)Cs were measured by gamma-ray spectrometry employing an HPGe detector of 66 % relative efficiency. The efficiency curve has taken into account the differences in densities and chemical composition between the matrix and the certified sample. The highest concentration levels of (228)Th and (40)K were 3.5±0.4 and 1469±17 Bq kg(-1) for soy flour, respectively, within the 95 % confidence level. The lower limit of detection for (137)Cs ranged from 0.04 to 0.4 Bq kg(-1). The highest committed effective dose was 0.36 μSv.y(-1) for (228)Ra in cassava flour (adults). All committed effective doses determined at the present work were lower than the International Atomic Energy Agency dose limit of 1 mSv.y(-1), to the public exposure.

Report of Task Group on the implications of the implementation of the ICRP recommendations for a revised dose limit to the lens of the eye.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B

2013-12-01

This report was commissioned by the IRPA President to provide an assessment of the impact on members of IRPA Associate Societies of the introduction of ICRP recommendations for a reduced dose limit for the lens of the eye. The report summarises current practice and considers possible changes that may be required. Recommendations for further collaboration, clarification and changes to working practices are suggested.

Finger doses for staff handling radiopharmaceuticals in nuclear medicine.

PubMed

Pant, Gauri S; Sharma, Sanjay K; Rath, Gaura K

2006-09-01

Radiation doses to the fingers of occupational workers handling 99mTc-labeled compounds and 131I for diagnostic and therapeutic procedures in nuclear medicine were measured by thermoluminescence dosimetry. The doses were measured at the base of the ring finger and the index finger of both hands in 2 groups of workers. Group 1 (7 workers) handled 99mTc-labeled radiopharmaceuticals, and group 2 (6 workers) handled 131I for diagnosis and therapy. Radiation doses to the fingertips of 3 workers also were measured. Two were from group 1, and 1 was from group 2. The doses to the base of the fingers for the radiopharmacy staff and physicians from group 1 were observed to be 17+/-7.5 (mean+/-SD) and 13.4+/-6.5 microSv/GBq, respectively. Similarly, the dose to the base of the fingers for the 3 physicians in group 2 was estimated to be 82.0+/-13.8 microSv/GBq. Finger doses for the technologists in both groups could not be calculated per unit of activity because they did not handle the radiopharmaceuticals directly. Their doses were reported in millisieverts that accumulated in 1 wk. The doses to the fingertips of the radiopharmacy worker and the physician in group 1 were 74.3+/-19.8 and 53.5+/-21.9 microSv/GBq, respectively. The dose to the fingertips of the physician in group 2 was 469.9+/-267 microSv/GBq. The radiation doses to the fingers of nuclear medicine staff at our center were measured. The maximum expected annual dose to the extremities appeared to be less than the annual limit (500 mSv/y), except for a physician who handled large quantities of 131I for treatment. Because all of these workers are on rotation and do not constantly handle radioactivity throughout the year, the doses to the base of the fingers or the fingertips should not exceed the prescribed annual limit of 500 mSv.

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2014 CFR

2014-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2011 CFR

2011-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2012 CFR

2012-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2010 CFR

2010-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

Code of Federal Regulations, 2013 CFR

2013-01-01

...) a committed effective dose equivalent of 5 rems (stochastic ALI) or (2) a committed dose equivalent of 50 rems to an organ or tissue (non-stochastic ALI). The stochastic ALIs were derived to result in... equivalent to the whole body of 5 rems. The derivation includes multiplying the committed dose equivalent to...

40 CFR 799.9539 - TSCA mammalian erythrocyte micronucleus test.

Code of Federal Regulations, 2010 CFR

2010-07-01

... peripheral blood). (iv) Limit test. If a test at one dose level of at least 2,000 mg/kg body weight using a... dose is 2,000 mg/kg/body weight/day for treatment up to 14 days, and 1,000 mg/kg/body weight/day for... water test substance concentration parts per million (ppm) to the actual dose (mg/kg body weight/day...

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior

PubMed Central

Thanos, Panayotis K.; Robison, Lisa S.; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M.; Komatsu, David E.; Hadjiargyrou, Michael; Volkow, Nora D.

2015-01-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (i.e. quicker and higher peak concentrations). Here, we evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic the clinical drug delivery profile. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60 mg/kg/day; as well as dual-dosages of 4 and 10 mg/kg/day, 20 and 30 mg/kg/day, or 30 and 60 mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Blood was sampled and plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60 mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30 ng/mL), while the 4/10 mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8 ng/mL). Treatment with the higher dual-dosage (HD: 30/60 mg/kg) resulted in hyperactivity, while the lower (LD: 4/10 mg/kg) had no effect. Next, chronic effects of these dual-dosages were assessed on behavior throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle; decreased exploratory behavior; and increased anxiolytic behavior. These findings suggest that this dual-dosage-drinking-paradigm can be used to examine the effects of clinically relevant pharmacokinetic doses of MP, and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. PMID:25641666

A pharmacokinetic model of oral methylphenidate in the rat and effects on behavior.

PubMed

Thanos, Panayotis K; Robison, Lisa S; Steier, Jessica; Hwang, Yu Fen; Cooper, Thomas; Swanson, James M; Komatsu, David E; Hadjiargyrou, Michael; Volkow, Nora D

2015-04-01

Most animal studies using methylphenidate (MP) do not administer it the same way it is administered clinically (orally), but rather by injection, resulting in an altered pharmacokinetic profile (quicker and higher peak concentrations). We evaluated several oral-dosing regimens in rats, including dual-dose drinking, to mimic clinical drug delivery. Using an 8-hour-limited-access-drinking-paradigm, MP solutions were delivered at different doses (20, 30, or 60mg/kg/day; as well as dual-dosages of 4 and 10mg/kg/day, 20 and 30mg/kg/day, or 30 and 60mg/kg/day, in which the low dose was administered in the first hour of drinking followed by 7 h of drinking the high dose). Plasma was assayed for MP levels at many time points. Results showed that an 8-hour limited drinking of a dual-dosage 30/60mg/kg MP solution achieved a pharmacokinetic profile similar to clinically administered doses of MP at the high end of the spectrum (peaking at ~30ng/mL), while the 4/10mg/kg MP dual-dosage produced plasma levels in the range produced by typically prescribed clinical doses of MP (peaking at ~8ng/mL). Treatment with the higher dual-dosage (HD: 30/60mg/kg) resulted in hyperactivity, while the lower (LD: 4/10mg/kg) had no effect. Chronic effects of these dual-dosages were assessed throughout three months of treatment and one month of abstinence, beginning in adolescence. MP dose-dependently decreased body weight, which remained attenuated throughout abstinence. MP decreased food intake during early treatment, suggesting that MP may be an appetite suppressant and may also speed metabolism and/or suppress growth. Chronic HD MP resulted in hyperactivity limited during the dark cycle, decreased exploratory behavior, and increased anxiolytic behavior. Findings suggest that these dual-dosage-drinking-paradigms can be used to examine the effects of clinically relevant pharmacokinetic doses of MP and that chronic treatment with such dosages can result in long-lasting developmental and behavioral changes. Copyright © 2015 Elsevier Inc. All rights reserved.

Five-year ALARA review of dosimetry results :

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulus, Luke R.

2013-08-01

A review of personnel dosimetry (external and internal) and environmental monitoring results from 1 January 2008 through 31 December 2012 performed at Sandia National Laboratories, New Mexico was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform with the ALARA philosophy. ALARA is the philosophical approach to radiation protection by managing and controlling radiation exposures (individual and collective) to the work force and to the general public to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limitmore » but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

Prevalence of shigellosis in the U.S.: consistency with dose-response information.

PubMed

Crockett, C S; Haas, C N; Fazil, A; Rose, J B; Gerba, C P

1996-06-01

Every year there are estimated 300000 cases of Shigella in the United States (Bennett et al., 1987, Am. J. Prev. Med. 3, 102-114). A beta-poisson model was fit to human dose-response information on pathogenic Shigella using the Maximum Likelihood Estimation technique (Haas, 1983, Am. J. Epidemiol. 118, 573-582). Pooled and separate data sets for the Shigella species were fit to the beta-Poisson model and 95% confidence limits and regions were calculated. Shigella dysentariae and Shigella flexneri confidence regions and limits overlapped with each other and with the pooled data set, suggesting that this model can describe Shigella in general. The pooled Shigella model as well as the upper and lower confidence limits of the three data sets showed average exposures based on the estimated U.S. caseload of pathogenic Shigella of 0.01 to 0.014 organisms (confidence limits 0.001-0.05) for a 7-day per annum period of exposure and ranges from 0.07 to 0.1 organisms (confidence limits 0.006-0.4). for a 1-day per annum period of exposure. The plausibility of the pooled dose-response model was then evaluated by comparison with two known cruise ship outbreaks. The pooled model estimated that the two outbreaks studied could have been due to ingestion of 344 (confidence limits 72-915) Shigella cells per meal and 10.5-12 (confidence limits 1-44) Shigella cells per glass of water by passengers.

10 CFR 835.1 - Scope.

Code of Federal Regulations, 2011 CFR

2011-01-01

... doses received as a patient for the purposes of medical diagnosis or therapy, or radiation doses... OCCUPATIONAL RADIATION PROTECTION General Provisions § 835.1 Scope. (a) General. The rules in this part establish radiation protection standards, limits, and program requirements for protecting individuals from...

TLD measurements of in vivo mammographic exposures and the calculated mean glandular dose across the United States.

PubMed

Gentry, J R; DeWerd, L A

1996-06-01

An analysis is presented of the exposures received by TLDs placed on the breasts of 4400 women obtaining mammograms at 170 institutions across the United States. Mean glandular dose and exposure were examined as a function of compressed breast thickness. The exposure and mean glandular dose were found to increase linearly with breast thickness. The mean glandular dose typically delivered by the institutions was well below the limit of 3.0 mGy for the 4.5-cm breast. However, some institutions tend to uniformly give higher doses. In such institutions approximately 25% of 4.5-cm-thick breasts received a mean glandular dose exceeding 3.0 mGy.

Phase 1 Dose Escalation Study of Accelerated Radiation Therapy With Concurrent Chemotherapy for Locally Advanced Lung Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kelsey, Chris R., E-mail: christopher.kelsey@duke.edu; Das, Shiva; Gu, Lin

2015-12-01

Purpose: To determine the maximum tolerated dose of radiation therapy (RT) given in an accelerated fashion with concurrent chemotherapy using intensity modulated RT. Methods and Materials: Patients with locally advanced lung cancer (non-small cell and small cell) with good performance status and minimal weight loss received concurrent cisplatin and etoposide with RT. Intensity modulated RT with daily image guidance was used to facilitate esophageal avoidance and delivered using 6 fractions per week (twice daily on Fridays with a 6-hour interval). The dose was escalated from 58 Gy to a planned maximum dose of 74 Gy in 4 Gy increments in a standardmore » 3 + 3 trial design. Dose-limiting toxicity (DLT) was defined as acute grade 3-5 nonhematologic toxicity attributed to RT. Results: A total of 24 patients were enrolled, filling all dose cohorts, all completing RT and chemotherapy as prescribed. Dose-limiting toxicity occurred in 1 patient at 58 Gy (grade 3 esophagitis) and 1 patient at 70 Gy (grade 3 esophageal fistula). Both patients with DLTs had large tumors (12 cm and 10 cm, respectively) adjacent to the esophagus. Three additional patients were enrolled at both dose cohorts without further DLT. In the final 74-Gy cohort, no DLTs were observed (0 of 6). Conclusions: Dose escalation and acceleration to 74 Gy with intensity modulated RT and concurrent chemotherapy was tolerable, with a low rate of grade ≥3 acute esophageal reactions.« less

Acute effects of THC on time perception in frequent and infrequent cannabis users.

PubMed

Sewell, R Andrew; Schnakenberg, Ashley; Elander, Jacqueline; Radhakrishnan, Rajiv; Williams, Ashley; Skosnik, Patrick D; Pittman, Brian; Ranganathan, Mohini; D'Souza, D Cyril

2013-03-01

Cannabinoids have been shown to alter time perception, but existing literature has several limitations. Few studies have included both time estimation and production tasks, few control for subvocal counting, most had small sample sizes, some did not record subjects' cannabis use, many tested only one dose, and used either oral or inhaled administration of Δ⁹-tetrahydrocannabinol (THC), leading to variable pharmacokinetics, and some used whole-plant cannabis containing cannabinoids other than THC. Our study attempted to address these limitations. This study aims to characterize the acute effects of THC and frequent cannabis use on seconds-range time perception. THC was hypothesized to produce transient, dose-related time overestimation and underproduction. Frequent cannabis smokers were hypothesized to show blunted responses to these alterations. IV THC was administered at doses from 0.015 to 0.05 mg/kg to 44 subjects who participated in several double-blind, randomized, counterbalanced, crossover, placebo-controlled studies. Visual time estimation and production tasks in the seconds range were presented to subjects three times on each test day. All doses induced time overestimation and underproduction. Chronic cannabis use had no effect on baseline time perception. While infrequent/nonsmokers showed temporal overestimation at medium and high doses and temporal underproduction at all doses, frequent cannabis users showed no differences. THC effects on time perception were not dose related. A psychoactive dose of THC increases internal clock speed as indicated by time overestimation and underproduction. This effect is not dose related and is blunted in chronic cannabis smokers who did not otherwise have altered baseline time perception.

Perception of Radiation Risk by Japanese Radiation Specialists Evaluated as a Safe Dose Before the Fukushima Nuclear Accident.

PubMed

Miura, Miwa; Ono, Koji; Yamauchi, Motohiro; Matsuda, Naoki

2016-06-01

From October to December 2010, just before the radiological accident at the Fukushima Daiichi nuclear power plant, 71 radiation professionals from radiation facilities in Japan were asked what they considered as a "safe dose" of radiation for themselves, their partners, parents, children, siblings, and friends. Although the 'safe dose' they noted varied widely, from less than 1 mSv y to more than 100 mSv y, the average dose was 35.6 mSv y, which is around the middle point between the legal exposure dose limits for the annual average and for any single year. Similar results were obtained from other surveys of members of the Japan Radioisotope Association (36.9 mSv y) and of the Oita Prefectural Hospital (36.8 mSv y). Among family members and friends, the minimum average "safe" dose was 8.5 mSv y for children, for whom 50% of the responders claimed a "safe dose" of less than 1 mSv. Gender, age and specialty of the radiation professional also affected their notion of a "safe dose." These findings suggest that the perception of radiation risk varies widely even for radiation professionals and that the legal exposure dose limits derived from regulatory science may act as an anchor of safety. The different levels of risk perception for different target groups among radiation professionals appear similar to those in the general population. The gap between these characteristics of radiation professionals and the generally accepted picture of radiation professionals might have played a role in the state of confusion after the radiological accident.

Occupational radiation exposure in vascular interventional radiology: A complete evaluation of different body regions.

PubMed

Bacchim Neto, Fernando Antonio; Alves, Allan Felipe Fattori; Mascarenhas, Yvone Maria; Nicolucci, Patrícia; Pina, Diana Rodrigues de

2016-08-01

To perform a complete evaluation on radiation doses, received by primary and assistant medical staff, while performing different vascular interventional radiology procedures. We evaluated dose received in different body regions during three categories of vascular procedures: lower limb angiography (Angiography), lower limb percutaneous transluminal angioplasty (Angioplasty) and stent graft placement for abdominal aortic aneurysm treatment (A. A. A. Treatment). We positioned the dosimeters near the eye lens, thyroid, chest, abdomen, hands, and feet of the interventional physicians. Equivalent dose was compared with annual dose limits for workers in order to determine the maximum number of procedures per year that each physician could perform. We assessed 90 procedures. We found the highest equivalent doses in the A. A. A. Treatment, in which 90% of the evaluations indicated at least one region receiving more than 1mSv per procedure. Angioplasty was the only procedural modality that provided statistically different doses for different professionals, which is an important aspect on regards to radiological protection strategies. In comparison with the dose limits, the most critical region in all procedures was the eye lens. Since each body region of the interventionist is exposed to different radiation levels, dose distribution measurements are essential for radiological protection strategies. These results indicate that dosimeters placed in abdomen instead of chest may represent more accurately the whole body doses received by the medical staff. Additional dosimeters and a stationary shield for the eye lens are strongly recommended. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Phase I trial and pharmacokinetic study of raltitrexed in children with recurrent or refractory leukemia: a pediatric oncology group study.

PubMed

Horton, Terzah M; Blaney, Susan M; Langevin, Anne-Marie; Kuhn, John; Kamen, Barton; Berg, Stacey L; Bernstein, Mark; Weitman, Steven

2005-03-01

To evaluate the toxicity, antileukemic activity, and pharmacology of raltitrexed administered weekly for 3 weeks to patients with refractory or recurrent leukemia. Raltitrexed was administered as a 15-minute infusion for 3 consecutive weeks every 5 weeks, at doses ranging from 1.3 to 2.8 mg/m(2). The first course was used to determine the dose-limiting toxicities and maximum tolerated dose. Correlative studies included an assessment of raltitrexed pharmacokinetics and measurement of plasma 2'-deoxyuridine concentrations, a surrogate measure of thymidylate synthase inhibition. Twenty-one children (18 evaluable) with refractory leukemia received 25 courses of raltitrexed. The dose-limiting toxicity was reversible elevation in liver transaminases at the 2.8-mg/m(2) dose level and the maximum tolerated dose was 2.1 mg/m(2) per dose. Pharmacokinetics were best characterized by a two-compartment model with a clearance of 139 mL/min/m(2) (8.3 L/h/m(2)), a 2.4-L volume of distribution, an initial half-life (t(1/2alpha)) of 6 minutes, and a terminal half-life (t(1/2beta)) of 45 minutes. There were three objective responses. Raltitrexed was well tolerated when administered as a single agent to children with recurrent or refractory leukemia. We observed preliminary evidence of antileukemia activity using this weekly dosing schedule and these observations support further evaluation of raltitrexed in this population.

Phase I trial of combination chemotherapy with docetaxel, cisplatin and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer.

PubMed

Tahara, M; Araki, K; Okano, S; Kiyota, N; Fuse, N; Minashi, K; Yoshino, T; Doi, T; Zenda, S; Kawashima, M; Ogino, T; Hayashi, R; Minami, H; Ohtsu, A

2011-01-01

we investigated the maximum tolerated dose (MTD) of combination therapy with docetaxel, cisplatin, and S-1 (TPS) in patients with locally advanced or recurrent/metastatic head and neck cancer (HNC). treatment consisted of docetaxel (Taxotere) at doses of 50, 60, and 70 mg/m(2); cisplatin at 70 mg·m(2)/day on day 1; and S-1 twice daily on days 1-14 at doses of 40, 60, and 80 mg·m(2)/day, repeated every 3 or 4 weeks. forty patients were enrolled. MTD was not reached until level 4. Subjects at expanded dose were limited to patients with locally advanced disease. Two dose-limiting toxic effects (DLTs) were observed at dose level 5 (TPS: 70/70/80 mg·m(2)/day, every 3 weeks), namely one grade 3 infection and one grade 3 hyperbilirubinemia, establishing this as the MTD. Of 12 patients treated at dose level 6 (TPS: 70/70/60 mg·m(2)/day, every 3 weeks), 2 DLTs were seen. Six achieved a complete response and 22 a partial response, giving a response rate of 70%. TPS was well tolerated. The recommended phase II dose as induction chemotherapy for locally advanced HNC was determined as 70/70/60 mg·m(2)/day every 3 weeks. Antitumor activity was highly promising and warrants further investigation.

[Clinical pharmacist influence at hospital to prevent overdosed prescription of acetaminophen].

PubMed

Viguier, F; Roessle, C; Zerhouni, L; Rouleau, A; Benmelouka, C; Chevallier, A; Chast, F; Conort, O

2016-11-01

The recommended daily dose of acetaminophen is limited to 60mg/kg/day with a maximum of 3g daily dose in adults weighing less than 50kg or in patients undergoing certain risk factors. This study aimed at assessing the fulfillment of those recommendations and the possible impact on the liver dysfunction at supra-therapeutic doses of acetaminophen. This study was performed one day in 9 services. Patients characteristics, acetaminophen dose, daily dose administered, physiopathological aspects, markers of liver damage were collected. Among 542 prescriptions analyzed, 343 of them contained acetaminophen. The median age of patients studied was 81 years and one third weighed less than 50kg. The main risk factor of supra-therapeutic prescriptions was the lack of dose acetaminophen based on weight with 14% patients concerned and this risk raised at 17% when the pathophysiological conditions were included. The presence of pharmacists in medicals departments was more effective than the use of informatics programs limiting the dose systematically to 3g/day, or a distant pharmaceutical validation from care services to reduce the risk of acetaminophen overdose. According to the statement of administrations, only 4 of 49 patients received doses above 60mg/kg/day with a low impact on liver function tests. The continuous presence in pharmaceutical care services was the most effective measure to ensure effective implementation of acetaminophen recommendations. Copyright © 2016 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

A phase I study with neratinib (HKI-272), an irreversible pan ErbB receptor tyrosine kinase inhibitor, in patients with solid tumors.

PubMed

Wong, Kwok-K; Fracasso, Paula M; Bukowski, Ronald M; Lynch, Thomas J; Munster, Pamela N; Shapiro, Geoffrey I; Jänne, Pasi A; Eder, Joseph P; Naughton, Michael J; Ellis, Matthew J; Jones, Suzanne F; Mekhail, Tarek; Zacharchuk, Charles; Vermette, Jennifer; Abbas, Richat; Quinn, Susan; Powell, Christine; Burris, Howard A

2009-04-01

The dose-limiting toxicities, maximum tolerated dose, pharmacokinetic profile, and preliminary antitumor activity of neratinib (HKI-272), an irreversible pan ErbB inhibitor, were determined in patients with advanced solid tumors. Neratinib was administered orally as a single dose, followed by a 1-week observation period, and then once daily continuously. Planned dose escalation was 40, 80, 120, 180, 240, 320, 400, and 500 mg. For pharmacokinetic analysis, timed blood samples were collected after administration of the single dose and after the first 14 days of continuous daily administration. Dose-limiting toxicity was grade 3 diarrhea, which occurred in one patient treated with 180 mg and in four patients treated with 400 mg neratinib; hence, the maximum tolerated dose was determined to be 320 mg. Other common neratinib-related toxicities included nausea, vomiting, fatigue, and anorexia. Exposure to neratinib was dose dependent, and the pharmacokinetic profile of neratinib supports a once-a-day dosing regimen. Partial response was observed for 8 (32%) of the 25 evaluable patients with breast cancer. Stable disease >or=24 weeks was observed in one evaluable breast cancer patient and 6 (43%) of the 14 evaluable non-small cell lung cancer patients. The maximum tolerated dose of once-daily oral neratinib is 320 mg. The most common neratinib-related toxicity was diarrhea. Antitumor activity was observed in patients with breast cancer who had previous treatment with trastuzumab, anthracyclines, and taxanes, and tumors with a baseline ErbB-2 immunohistochemical staining intensity of 2+ or 3+. The antitumor activity, tolerable toxicity profile, and pharmacokinetic properties of neratinib warrant its further evaluation.

A phase I/II study of carfilzomib 2-10-min infusion in patients with advanced solid tumors.

PubMed

Papadopoulos, Kyriakos P; Burris, Howard A; Gordon, Michael; Lee, Peter; Sausville, Edward A; Rosen, Peter J; Patnaik, Amita; Cutler, Richard E; Wang, Zhengping; Lee, Susan; Jones, Suzanne F; Infante, Jeffery R

2013-10-01

Tolerability, pharmacokinetics (PK), pharmacodynamics, and antitumor activity of carfilzomib, a selective proteasome inhibitor, administered twice weekly by 2-10-min intravenous (IV) infusion on days 1, 2, 8, 9, 15, and 16 in 28-day cycles, were assessed in patients with advanced solid tumors in this phase I/II study. Adult patients with solid tumors progressing after ≥1 prior therapies were enrolled. The dose was 20 mg/m(2) in week 1 of cycle 1 and 20, 27, or 36 mg/m(2) thereafter. The maximum tolerated dose or protocol-defined maximum planned dose (MPD) identified during dose escalation was administered to an expansion cohort and to patients with small cell lung, non-small cell lung, ovarian, and renal cancer in phase II tumor-specific cohorts. Fourteen patients received carfilzomib during dose escalation. The single dose-limiting toxicity at 20/36 mg/m(2) was grade 3 fatigue, establishing the MPD as the expansion and phase II dose. Sixty-five additional patients received carfilzomib at the MPD. Adverse events included fatigue, nausea, anorexia, and dyspnea. Carfilzomib PK was dose proportional with a half-life <1 h. All doses resulted in at least 80 % proteasome inhibition in blood. Partial responses occurred in two patients in phase I, with 21.5 % stable disease after four cycles in evaluable patients in the expansion and phase II cohorts. Carfilzomib 20/36 mg/m(2) was well tolerated when administered twice weekly by 2-10-min IV infusion. At this dose and infusion rate, carfilzomib inhibited the proteasome in blood but demonstrated limited antitumor activity in patients with advanced solid tumors.

Improvements in Critical Dosimetric Endpoints Using the Contura Multilumen Balloon Breast Brachytherapy Catheter to Deliver Accelerated Partial Breast Irradiation: Preliminary Dosimetric Findings of a Phase IV Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Arthur, Douglas W., E-mail: darthur@mcvh-vcu.ed; Vicini, Frank A.; Todor, Dorin A.

2011-01-01

Purpose: Dosimetric findings in patients treated with the Contura multilumen balloon (MLB) breast brachytherapy catheter to deliver accelerated partial breast irradiation (APBI) on a multi-institutional Phase IV registry trial are presented. Methods and Materials: Computed tomography-based three-dimensional planning with dose optimization was performed. For the trial, new ideal dosimetric goals included (1) {>=}95% of the prescribed dose (PD) covering {>=}90% of the target volume, (2) a maximum skin dose {<=}125% of the PD, (3) maximum rib dose {<=}145% of the PD, and (4) the V150 {<=}50 cc and V200 {<=}10 cc. The ability to concurrently achieve these dosimetric goals usingmore » the Contura MLB was analyzed. Results: 144 cases were available for review. Using the MLB, all dosimetric criteria were met in 76% of cases. Evaluating dosimetric criteria individually, 92% and 89% of cases met skin and rib dose criteria, respectively. In 93% of cases, ideal target volume coverage goals were met, and in 99%, dose homogeneity criteria (V150 and V200) were satisfied. When skin thickness was {>=}5 mm to <7 mm, the median skin dose was limited to 120.1% of the PD, and when skin thickness was <5 mm, the median skin dose was 124.2%. When rib distance was <5 mm, median rib dose was reduced to 136.5% of the PD. When skin thickness was <7 mm and distance to rib was <5 mm, median skin and rib doses were jointly limited to 120.6% and 142.1% of the PD, respectively. Conclusion: The Contura MLB catheter provided the means of achieving the imposed higher standard of dosimetric goals in the majority of clinical scenarios encountered.« less

Safety, pharmacokinetics, and pharmacodynamic properties of oral DEBIO1143 (AT-406) in patients with advanced cancer: results of a first-in-man study.

PubMed

Hurwitz, Herbert I; Smith, David C; Pitot, Henry C; Brill, Jeffrey M; Chugh, Rashmi; Rouits, Elisabeth; Rubin, Joseph; Strickler, John; Vuagniaux, Gregoire; Sorensen, J Mel; Zanna, Claudio

2015-04-01

To assess safety/tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and antitumor activity of DEBIO1143, an antagonist of inhibitor apoptosis proteins. This first-in-man study in patients with advanced cancer used an accelerated dose titration design. DEBIO1143 was given orally once daily on days 1-5 every 2 or 3 weeks until disease progressed or patients dropped out. The starting dose of 5 mg was escalated by 100% in single patients until related grade 2 toxicity occurred. This triggered expansion to cohorts of three and subsequently six patients and reduction in dose increments to 50%. Maximum tolerated dose (MTD) was exceeded when any two patients within the same cohort experienced dose-limiting toxicity (DLT). On days 1 and 5, PK and PD samples were taken. Thirty-one patients received doses from 5 to 900 mg. Only one DLT was reported at 180 mg. No MTD was found. Most common adverse drug reactions were fatigue (26%), nausea (23%), and vomiting (13%). Average t max and T 1/2 was about 1 and 6 h, respectively. Exposure increased proportionally with doses from 80 to 900 mg, without accumulation over 5 days. Plasma CCL2 increased at 3-6 h postdose and epithelial apoptosis marker M30 on day 5; cIAP-1 levels in PBMCs decreased at all doses >80 mg. Five patients (17%) had stable disease as the best treatment response. DEBIO1143 was well tolerated at doses up to 900 mg and elicited PD effects at doses greater 80 mg. Limited antitumor activity may suggest development rather as adjunct treatment.

The evaluation the magnitude radiation exposure dose rate in digital radiography room design

NASA Astrophysics Data System (ADS)

Dwiyanto, Agung; Setia Budi, Wahyu; Hardiman, Gagoek

2017-12-01

This study discusses the dose rate in digital radiography room, buit according to meet the provisions of KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation of BAPETEN No. 8 / 2011. The provisions primary concern of radiation safety, not comfort, by considering the space design. There are five aspects to consider in designing the space: functionality, comfort, security, movement activities and aesthetics. However provisions only met three aspects of the design, which are a function, security and movement activity. Therefore, it is necessary to evaluate digital radiography room in terms of its ability to control external radiation exposure to be safe and comfortable The dose rate is measured by the range of primary and secondary radiation in the observation points by using Surveymeter. All data are obtained by the preliminary survey prior to the study. Furthermore, the review of digital radiography room is done based on architectural design theory. The dose rate for recommended improvement room is recalculated using the same method as the actual room with the help of computer modeling. The result of dose rate calculation at the inner and outer part of digital radiography observation room shows that in-room dose for a week at each measuring point exceeds the allowable dose limit both for staff and public. During a week of observation, the outdoor dose at some measuring points exceeds the dose limit set by the KEMENKES No.1014 / Menkes / SK / XI / 2008 and Regulation BEPETEN No 8/2011. Meanwhile, the result of dose rate calculation in the inner and outer part of the improved digital radiography room can meet the applicable regulations better.

A Phase I and Pharmacokinetic Study of the Oral Histone Deacetylase Inhibitor, MS-275, in Patients with Refractory Solid Tumors and Lymphomas

PubMed Central

Gore, Lia; Rothenberg, Mace L.; O'Bryant, Cindy L.; Schultz, Mary Kay; Sandler, Alan B.; Coffin, Denise; McCoy, Candice; Schott, Astrid; Scholz, Catherine; Eckhardt, S. Gail

2010-01-01

Purpose To evaluate the toxicity profile, pharmacologic, and biological properties of 3-pyridylmethyl N-{4-[(2-aminophenyl)carbamoyl]benzyl}carbamate (MS-275), a histone deacetylase inhibitor, when administered orally on three different dosing schedules. Experimental Design Patients with advanced solid malignancies and lymphomas were treated on three dose schedules: once every other week, twice weekly for 3 weeks every 28 days, and once weekly for 3 weeks every 28 days. First-cycle plasma pharmacokinetics and peripheral blood mononuclear cell histone acetylation were determined. Results Twenty-seven patients received ≥149 courses of treatment. Hypophosphatemia and asthenia were dose limiting on the weekly and twice-weekly dosing schedules; there was no dose-limiting toxicity on the every other week schedule. Pharmacokinetic variables revealed dose-dependent and dose-proportional increases. Two of 27 patients showed partial remissions, including one patient with metastatic melanoma who had a partial response and has remained on study for >5 years. Six patients showed prolonged disease stabilization. Levels of histone H3 and H4 acetylation in peripheral blood mononuclear cells increased qualitatively but with a high degree of interpatient variation. Conclusions MS-275 is well tolerated at doses up to 6 mg/m2 every other week or 4 mg/m2 weekly for 3 weeks followed by 1 week of rest and results in biologically relevant plasma concentrations and antitumor activity. Twice-weekly dosing was not tolerable due to asthenia, and further evaluation of this schedule was halted. The recommended dose for further disease-focused studies is 4 mg/m2 given weekly for 3 weeks every 28 days or 2 to 6 mg/m2 given once every other week. PMID:18579665

Five-Year ALARA Review of Dosimetry Results 1 January 2009 through 31 December 2013.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulus, Luke R

2014-08-01

A review of dosimetry results from 1 January 2009 through 31 December 2013 was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform to the ALARA philosophy. This included a review and evaluation of personnel dosimetry (external and internal) results at Sandia National Laboratories, New Mexico as well as at Sandia National Laboratories, California. Additionally, results of environmental monitoring efforts at Sandia National Laboratories, New Mexico were reviewed. ALARA is a philosophical approach to radiation protection by managing and controlling radiation exposures (individual and collective) to the work force and to the general publicmore » to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limit but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

Five-Year ALARA Review of Dosimetry Results 1 January 2010 through 31 December 2014.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Paulus, Luke R.

2015-06-01

A review of dosimetry results from 1 January 2010 through 31 December 2014 was conducted to demonstrate that radiation protection methods used are compliant with regulatory limits and conform to the philosophy to keep exposures to radiation As Low As is Reasonably Achievable (ALARA). This included a review and evaluation of personnel dosimetry (external and internal) results at Sandia National Laboratories, New Mexico as well as at Sandia National Laboratories, California. Additionally, results of environmental monitoring efforts at Sandia National Laboratories, New Mexico were reviewed. ALARA is a philosophical approach to radiation protection by managing and controlling radiation exposures (individualmore » and collective) to the work force and to the general public to levels that are As Low As is Reasonably Achievable taking social, technical, economic, practical, and public policy considerations into account. ALARA is not a dose limit but a process which has the objective of attaining doses as far below applicable dose limits As Low As is Reasonably Achievable.« less

Radiation exposure to the eye lens of orthopaedic surgeons during various orthopaedic procedures.

PubMed

Romanova, K; Vassileva, J; Alyakov, M

2015-07-01

The aim of the present study was to assess the radiation dose to the eye lens of orthopaedic surgeons during various orthopaedic procedures and to make efforts to ensure that radiation protection is optimised. The study was performed for Fractura femoris and Fractura cruris procedures performed in orthopaedic operating theatres, as well as for fractures of wrist, ankle and hand/shoulder performed in the emergency trauma room. The highest mean value of the eye lens dose of 47.2 μSv and higher mean fluoroscopy time of 3 min, as well as the corresponding highest maximum values of 77.1 μSv and 5.0 min were observed for the Fractura femoris procedure performed with the Biplanar 500e fluoroscopy systems. At a normal workload, the estimated mean annual dose values do not exceed the annual occupational dose limit for the lens of eye, but at a heavy workload in the department, this dose limit could be achieved or exceeded. The use of protective lead glasses is recommended as they could reduce the radiation exposure of the lens of the eye. The phantom measurements demonstrated that the use of half-dose mode could additionally reduce dose to the operator's eye lens. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Peak Dose Assessment for Proposed DOE-PPPO Authorized Limits

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maldonado, Delis

2012-06-01

The Oak Ridge Institute for Science and Education (ORISE), a U.S. Department of Energy (DOE) prime contractor, was contracted by the DOE Portsmouth/Paducah Project Office (DOE-PPPO) to conduct a peak dose assessment in support of the Authorized Limits Request for Solid Waste Disposal at Landfill C-746-U at the Paducah Gaseous Diffusion Plant (DOE-PPPO 2011a). The peak doses were calculated based on the DOE-PPPO Proposed Single Radionuclides Soil Guidelines and the DOE-PPPO Proposed Authorized Limits (AL) Volumetric Concentrations available in DOE-PPPO 2011a. This work is provided as an appendix to the Dose Modeling Evaluations and Technical Support Document for the Authorizedmore » Limits Request for the C-746-U Landfill at the Paducah Gaseous Diffusion Plant, Paducah, Kentucky (ORISE 2012). The receptors evaluated in ORISE 2012 were selected by the DOE-PPPO for the additional peak dose evaluations. These receptors included a Landfill Worker, Trespasser, Resident Farmer (onsite), Resident Gardener, Recreational User, Outdoor Worker and an Offsite Resident Farmer. The RESRAD (Version 6.5) and RESRAD-OFFSITE (Version 2.5) computer codes were used for the peak dose assessments. Deterministic peak dose assessments were performed for all the receptors and a probabilistic dose assessment was performed only for the Offsite Resident Farmer at the request of the DOE-PPPO. In a deterministic analysis, a single input value results in a single output value. In other words, a deterministic analysis uses single parameter values for every variable in the code. By contrast, a probabilistic approach assigns parameter ranges to certain variables, and the code randomly selects the values for each variable from the parameter range each time it calculates the dose (NRC 2006). The receptor scenarios, computer codes and parameter input files were previously used in ORISE 2012. A few modifications were made to the parameter input files as appropriate for this effort. Some of these changes included increasing the time horizon beyond 1,050 years (yr), and using the radionuclide concentrations provided by the DOE-PPPO as inputs into the codes. The deterministic peak doses were evaluated within time horizons of 70 yr (for the Landfill Worker and Trespasser), 1,050 yr, 10,000 yr and 100,000 yr (for the Resident Farmer [onsite], Resident Gardener, Recreational User, Outdoor Worker and Offsite Resident Farmer) at the request of the DOE-PPPO. The time horizons of 10,000 yr and 100,000 yr were used at the request of the DOE-PPPO for informational purposes only. The probabilistic peak of the mean dose assessment was performed for the Offsite Resident Farmer using Technetium-99 (Tc-99) and a time horizon of 1,050 yr. The results of the deterministic analyses indicate that among all receptors and time horizons evaluated, the highest projected dose, 2,700 mrem/yr, occurred for the Resident Farmer (onsite) at 12,773 yr. The exposure pathways contributing to the peak dose are ingestion of plants, external gamma, and ingestion of milk, meat and soil. However, this receptor is considered an implausible receptor. The only receptors considered plausible are the Landfill Worker, Recreational User, Outdoor Worker and the Offsite Resident Farmer. The maximum projected dose among the plausible receptors is 220 mrem/yr for the Outdoor Worker and it occurs at 19,045 yr. The exposure pathways contributing to the dose for this receptor are external gamma and soil ingestion. The results of the probabilistic peak of the mean dose analysis for the Offsite Resident Farmer indicate that the average (arithmetic mean) of the peak of the mean doses for this receptor is 0.98 mrem/yr and it occurs at 1,050 yr. This dose corresponds to Tc-99 within the time horizon of 1,050 yr.« less

Dose-response relationships for carcinogens: a review.

PubMed Central

Zeise, L; Wilson, R; Crouch, E A

1987-01-01

We review the experimental evidence for various shapes of dose-response relationships for carcinogens and summarize those experiments that give the most information on relatively low doses. A brief review of some models is given to illustrate the shapes of dose-response curve expected from them. Our major interest is in the use of dose-response relationships to estimate risks to humans at low doses, and so we pay special attention to experimentally observed and theoretically expected nonlinearities. There are few experimental examples of nonlinear dose-response relations in humans, but this may simply be due to the limitations in the data. The several examples in rodents, even though for high dose data, suggest that nonlinearity is common. In some cases such nonlinearities may be rationalized on the basis of the pharmacokinetics of the test compound or its metabolites. PMID:3311725

[Brachytherapy for head and neck cancers].

PubMed

Peiffert, D; Coche-Dequéant, B; Lapeyre, M; Renard, S

2018-05-29

The main indications of the brachytherapy of head and neck cancers are the limited tumours of the lip, the nose, the oral cavity and the oropharynx. Nasopharynx tumours are nowadays treated by intensity-modulated radiotherapy. This technique can be exclusive, associated with external radiotherapy or postoperative. It can also be a salvage treatment for the second primaries in previously irradiated areas. If the low dose rate brachytherapy rules remain the reference, the pulse dose rate technique allows the prescription of the dose rate and the optimisation of the dose distribution. Results of high dose rate brachytherapy are now published. This paper reports the recommendations of the Gec-ESTRO, published in 2017, and takes into account the data of the historical low dose rate series, and is upgraded with the pulsed-dose rate and high dose rate series. Copyright © 2018. Published by Elsevier SAS.

Survey of Occupational Noise Exposure in CF Personnel in Selected High-Risk Trades

DTIC Science & Technology

2003-11-01

peak, maximum level , minimum level , average sound level , time weighted average, dose, projected 8-hour dose, and upper limit time were measured for...10 4.4.2 Maximum Sound Level ...11 4.4.3 Minimum Sound Level

Immuno-oncology Clinical Trial Design: Limitations, Challenges, and Opportunities

PubMed Central

Baik, Christina S.; Rubin, Eric H.; Forde, Patrick M.; Mehnert, Janice M.; Collyar, Deborah; Butler, Marcus O.; Dixon, Erica L.; Chow, Laura Q.M.

2017-01-01

Recent advances in immuno-oncology and regulatory approvals have been rapid and paradigm shifting in many difficult-to-treat malignancies. Despite immune checkpoint inhibitor therapy becoming the standard of care across multiple tumor types, there are many unanswered questions that need to be addressed before this therapeutic modality can be fully harnessed. Areas of limitations include treatment of patients not sufficiently represented in clinical trials, uncertainty of the optimal treatment dosing and duration, and lack of understanding regarding long-term immune related toxicities and atypical tumor responses. Patients such as those with autoimmune disease, chronic viral infections, limited performance status, and brain metastases were often excluded from initial trials due to concerns of safety. However, limited data suggest that some of these patients can benefit from therapy with manageable toxicities; thus, future studies should incorporate these patients to clearly define safety and efficacy. There are still controversies regarding the optimal dosing strategy that can vary from weight-based to flat dosing, with undefined treatment duration. Further elucidation of the optimal dosing approach and evaluation of predictive biomarkers should be incorporated in the design of future trials. Finally, there are long-term immune-mediated toxicities, atypical tumor responses such as pseudoprogression and endpoints unique to immuno-oncology that are not adequately captured by traditional trial designs; thus, novel study designs are needed. In this article, we discuss in detail the above challenges and propose needed areas of research for exploration and incorporation in the next generation of immuno-oncology clinical trials. PMID:28864727

Dosimetric evaluation of the staff working in a PET/CT department

NASA Astrophysics Data System (ADS)

Dalianis, K.; Malamitsi, J.; Gogou, L.; Pagou, M.; Efthimiadou, R.; Andreou, J.; Louizï, A.; Georgiou, E.

2006-12-01

The dosimetric literature data concerning the medical personnel working in positron emission tomography/computed tomography (PET/CT) departments are limited. Therefore, we measured the radiation dose of the staff working in the first PET/CT department in Greece at the Diagnostic and Therapeutic Center of Athens HYGEIA—Harvard Medical International. As, for the time being, only 2-deoxy-2-[ 18F]fluoro-d-glucose (FDG) PET studies are performed, radiation dose measurements concern those derived from dispensing of the radiopharmaceutical as well as from the patients undergoing FDG-PET imaging. Our aim is to develop more effective protective measures against radionuclide exposure. To estimate the effective dose from external exposure, all seven members of the staff (two nurses, two medical physicists, two technologists, one secretary) had TLD badges worn at the upper pocket of their overall, TLD rings on the right hand and digital dosimeters at their upper side pocket. In addition, isodose curves were measured with thermoluminescence detectors for distances of 20, 50, 70 and 100 cm away from patients who had been injected with 18F-FDG. Dose values of the PET/CT staff were measured with digital detectors, TLD badges and TLD rings over the first 8 months for a total of 160 working days of the department's operation, consisting of a workload of about 10-15 patients/week who received 250-420 MBq of 18F-FDG each. Whole - body collective doses and hand doses for the staff were the following: Nurse #1 received 1.6 mSv as a whole body dose and 2,1 as a hand dose, Nurse #2 received 1.9 and 2.4 mSv respectively. For medical physicist #1 the dose values were 1.45 mSv whole body and 1.7 mSv hand dose, for medical physicist #2 1.67 mSv wholebody dose and 1.55 mSv hand dose and for technologists #1 & #2 the whole body doses were 0.7 and 0.64 mSv respectively. Lastly, the secretary received 0.1 mSv whole body dose. These preliminary data have shown that the dose levels of our PET/CT staff are within acceptable limits.

Risk of eye lens radiation exposure for members of the public.

PubMed

Chevallier, M-A; Rannou, A; Villagrasa, C; Clairand, I

2016-01-01

In 2011, the International Commission on Radiological Protection (ICRP) reviewed its recommendation concerning the equivalent dose limit for the eye lens, lowering it to 20 mSv in a year, for occupational exposure in planned exposure situations. The ICRP's statement does not contain any explicit recommendations regarding the organ dose limit for the eye lens for public exposure. For the moment, no change is proposed. But, to be coherent in the overall approach, the current equivalent limit for the public might be lowered. A similar yardstick than in the former recommendation may be used, that is to say a reduction of 10 times lower than that for occupational exposure. In this context, additional data on potential scenarios for public exposure of the eye lens are necessary. This paper, mainly based on a literature study, aims to provide, as far as possible, an exhaustive list of the situations in which members of the public can be exposed at the level of the eye lens. Once these situations have been defined, some calculations, made to assess the associated doses to the eye lens, are presented. This literature study did not reveal any current situations where members of the public would receive significant radiation doses to the eye lens. Indeed, the situations in which the dose to the eye lens might reach around 1 mSv per year for the public are extremely rare. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetité, Bahia, Brazil

NASA Astrophysics Data System (ADS)

Pereira, Wagner de S.; Kelecom, Alphonse; Py Júnior, Delcy de Azevedo

2008-08-01

The uranium mining at Caetité (Uranium Concentrate Unit—URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210). As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5×103 μGy y-1 has been used. The derived absorbed dose rate calculated for Tilapia was 2.51×100 μGy y-1, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.

Absorbed Dose Rate Due to Intake of Natural Radionuclides by Tilapia Fish (Tilapia nilotica,Linnaeus, 1758) Estimated Near Uranium Mining at Caetite, Bahia, Brazil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pereira, Wagner de S; Universidade Federal Fluminense, Programa de Pos-graduacao em Biologia Marinha; Kelecom, Alphonse

2008-08-07

The uranium mining at Caetite (Uranium Concentrate Unit--URA) is in its operational phase. Aiming to estimate the radiological environmental impact of the URA, a monitoring program is underway. In order to preserve the biota of the deleterious effects from radiation and to act in a pro-active way as expected from a licensing body, the present work aims to use an environmental protection methodology based on the calculation of absorbed dose rate in biota. Thus, selected target organism was the Tilapia fish (Tilapia nilotica, Linnaeus, 1758) and the radionuclides were: uranium (U-238), thorium (Th-232), radium (Ra-226 and Ra-228) and lead (Pb-210).more » As, in Brazil there are no radiation exposure limits adopted for biota the value proposed by the Department of Energy (DOE) of the United States of 3.5x10{sup 3} {mu}Gy y{sup -1} has been used. The derived absorbed dose rate calculated for Tilapia was 2.51x10{sup 0} {mu}Gy y{sup -1}, that is less than 0.1% of the dose limit established by DOE. The critical radionuclide was Ra-226, with 56% of the absorbed dose rate, followed by U-238 with 34% and Th-232 with 9%. This value of 0.1% of the limit allows to state that, in the operational conditions analyzed, natural radionuclides do not represent a radiological problem to biota.« less

Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

PubMed

Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

2015-05-01

This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

Phase I study of the c-raf-1 antisense oligonucleotide ISIS 5132 in combination with carboplatin and paclitaxel in patients with previously untreated, advanced non-small cell lung cancer.

PubMed

Fidias, Panos; Pennell, Nathan A; Boral, Anthony L; Shapiro, Geoffrey I; Skarin, Arthur T; Eder, Joseph P; Kwoh, T Jesse; Geary, Richard S; Johnson, Bruce E; Lynch, Thomas J; Supko, Jeffrey G

2009-09-01

A phase I trial was performed to evaluate the administration of carboplatin/paclitaxel in combination with ISIS-5132, a phosphorothioate antisense oligodeoxynucleotide inhibitor of c-raf-1 kinase expression, in patients with advanced non-small cell lung cancer (NSCLC). Previously untreated patients with stage IIIB/IV NSCLC received ISIS 5132 by continuous intravenous infusion at 2.0 mg/kg/d for 14 days. Starting doses were paclitaxel 175 mg/m(2) and carboplatin targeting an area under the free platinum plasma concentration-time curve (AUC(fp)) of 5 mg . min/ml (dose level 1). The carboplatin dose was then increased to AUC(fp) 6 mg . min/ml (dose level 2) after which the paclitaxel dose was increased to 200 mg/m(2) (dose level 3). The maximum tolerated dose was established by toxicity during the first two 21-day cycles of therapy. The pharmacokinetics of all three agents was determined before and during the ISIS 5132 infusion. Thirteen patients were treated with the carboplatin/paclitaxel/ISIS 5132 combination. Dose-limiting neutropenia occurred in two patients at dose level 3. Grade 3 and 4 nonhematologic toxicities were infrequent and limited to nausea and constipation. The maximum tolerated doses were carboplatin AUC(fp) 6 mg . min/ml, paclitaxel 175 mg/m(2), and ISIS 5132 2.0 mg/kg/d for 14 days. There were no objective responses and the concurrent infusion of ISIS 5132 did not alter the plasma pharmacokinetics of paclitaxel or total platinum. ISIS 5132 can be safely combined with standard doses of carboplatin and paclitaxel. Combining cytotoxic chemotherapeutic agents with inhibitors of aberrant signal transduction mediated by Raf proteins produced no objective responses in the dose and schedule administered in this study.

Phase 1 dose-escalation study of mirvetuximab soravtansine (IMGN853), a folate receptor α-targeting antibody-drug conjugate, in patients with solid tumors.

PubMed

Moore, Kathleen N; Borghaei, Hossein; O'Malley, David M; Jeong, Woondong; Seward, Shelly M; Bauer, Todd M; Perez, Raymond P; Matulonis, Ursula A; Running, Kelli L; Zhang, Xiaoyan; Ponte, Jose F; Ruiz-Soto, Rodrigo; Birrer, Michael J

2017-08-15

Mirvetuximab soravtansine (IMGN853) is an antibody-drug conjugate that selectively targets folate receptor α (FRα). In this phase 1 dose-escalation study, the authors investigated IMGN853 in patients with FRα-positive solid tumors. Patients received IMGN853 on day 1 of a 21-day cycle (once every 3 weeks dosing), with cycles repeated until patients experienced dose-limiting toxicity or progression. Dose escalation commenced in single-patient cohorts for the first 4 planned dose levels and then followed a standard 3 + 3 scheme. The primary objectives were to determine the maximum tolerated dose and the recommended phase 2 dose. Secondary objectives were to determine safety and tolerability, to characterize the pharmacokinetic profile, and to describe preliminary clinical activity. In total, 44 patients received treatment at doses escalating from 0.15 to 7.0 mg/kg. No meaningful drug accumulation was observed with the dosing regimen of once every 3 weeks. The most common treatment-related adverse events were fatigue, blurred vision, and diarrhea, the majority of which were grade 1 or 2. The dose-limiting toxicities observed were grade 3 hypophosphatemia (5.0 mg/kg) and grade 3 punctate keratitis (7.0 mg/kg). Two patients, both of whom were individuals with epithelial ovarian cancer, achieved confirmed tumor responses according to Response Evaluation Criteria in Solid Tumors 1.1, and each was a partial response. IMGN853 demonstrated a manageable safety profile and encouraging preliminary clinical activity, particularly in patients with ovarian cancer. The results establish a recommended phase 2 dosing of 6.0 mg/kg (based on adjusted ideal body weight) once every 3 weeks. Cancer 2017. © 2017 American Cancer Society. Cancer 2017;123:3080-7. © 2017 American Cancer Society. © 2017 American Cancer Society.

Test of ring, eye lens and whole body dosemeters for the dose quantity Hp(3) to be used in interventional radiology

NASA Astrophysics Data System (ADS)

Szumska, A.; Budzanowski, M.; Kopeć, R.

2017-11-01

In its statement on tissue reactions approved on 21st April 2011, the International Commission on Radiological Protection (ICRP, 2012) reviewed its recommendation concerning the equivalent dose limit for the eye lens and reduced the dose limits for occupationally exposed persons to 20 mSv in a year, averaged over defined periods of 5 years, with no single year exceeding 50 mSv. This limit was approved and written down in the new EURATOM (European Atomic Energy Community) directive 2013/59 and in the IAEA (International Atomic Energy Agency) BSS (Basic Safety Standard) of July 2014. For that reason, the necessity to monitor the eye lens may become more important than it was before. However, specially dedicated dosemeters for the dose quantity Hp(3) are using very rarely. Commonly use are only whole body personal dosemeters for the personal dose equivalent quantities Hp(10) worn on the trunk and ring dosemeters worn on finger to measure the quantity Hp(0.07). Therefore, in this work it was investigated whether dosemeters from routine use calibrated in terms of Hp(10) and Hp(0.07) and worn on thyroid collar and protective apron could deliver similar results like dedicated eye lens dosemeter worn close to the eyes. The results show that the best method if dedicated eye lens dosimeters is not used is to measure doses in terms of Hp(0.07) on the thyroid collar (Pearson product, r=0.85). Obtained results shows also importance of proper localization of eye lens dosimeter (close to the eye, from side of the X-ray source).

Subcutaneous Administration of Otelixizumab is Limited by Injection Site Reactions: Results of an Exploratory Study in Type 1 Diabetes Mellitus Patients.

PubMed

MacDonald, A; Ambery, P; Donaldson, J; Hicks, K; Keymeulen, B; Parkin, J

2016-05-01

Targeting CD3 antigens on human T lymphocytes with monoclonal antibodies has been shown to reduce the rate of decline of C-peptides in recent-onset type 1 diabetes mellitus patients. However, effective doses are associated with infusion reactions typical of "cytokine release syndrome" and appear to be dose-limiting when administered as short-duration infusions. A possible alternative approach, which may reduce the rate of T cell activation and consequent systemic cytokine release, is to inject subcutaneously. We investigated single- and repeat-dose subcutaneous administration of the anti-CD3 monoclonal antibody otelixizumab in small cohorts of patients with type 1 diabetes. Transient reductions in free or unbound CD3 antigen on CD4+ and CD8+ cells and absolute lymphocyte count were observed in the blood of these patients during treatment, consistent with the known mechanism of action of otelixizumab and other anti-CD3 monoclonal antibodies. This was despite the very low systemic exposure of antibodies measured during the same time period. With the exception of sporadic headaches, other symptoms associated with cytokine release syndrome, such as fever, nausea, vomiting, myalgia, and arthralgia, were absent in treated patients. However, treatment-related injection site reactions were consistently observed. The reactions were erythematous and their sizes were dose-dependent; in some cases, reactions persisted for up to 2 weeks following the start of treatment. While patients responded well to topical corticosteroid treatment and prophylaxis reduced the intensity of injection site reactions, the reactions were considered dose-limiting and higher doses were not investigated. © Georg Thieme Verlag KG Stuttgart · New York.

SUDOQU, a new dose-assessment methodology for radiological surface contamination.

PubMed

van Dillen, Teun; van Dijk, Arjan

2018-06-12

A new methodology has been developed for the assessment of the annual effective dose resulting from removable and fixed radiological surface contamination. It is entitled SUDOQU (SUrface DOse QUantification) and it can for instance be used to derive criteria for surface contamination related to the import of non-food consumer goods, containers and conveyances, e.g., limiting values and operational screening levels. SUDOQU imposes mass (activity)-balance equations based on radioactive decay, removal and deposition processes in indoor and outdoor environments. This leads to time-dependent contamination levels that may be of particular importance in exposure scenarios dealing with one or a few contaminated items only (usually public exposure scenarios, therefore referred to as the 'consumer' model). Exposure scenarios with a continuous flow of freshly contaminated goods also fall within the scope of the methodology (typically occupational exposure scenarios, thus referred to as the 'worker model'). In this paper we describe SUDOQU, its applications, and its current limitations. First, we delineate the contamination issue, present the assumptions and explain the concepts. We describe the relevant removal, transfer, and deposition processes, and derive equations for the time evolution of the radiological surface-, air- and skin-contamination levels. These are then input for the subsequent evaluation of the annual effective dose with possible contributions from external gamma radiation, inhalation, secondary ingestion (indirect, from hand to mouth), skin contamination, direct ingestion and skin-contact exposure. The limiting effective surface dose is introduced for issues involving the conservatism of dose calculations. SUDOQU can be used by radiation-protection scientists/experts and policy makers in the field of e.g. emergency preparedness, trade and transport, exemption and clearance, waste management, and nuclear facilities. Several practical examples are worked out demonstrating the potential applications of the methodology. . Creative Commons Attribution license.

A reaction limited in vivo dissolution model for the study of drug absorption: Towards a new paradigm for the biopharmaceutic classification of drugs.

PubMed

Macheras, Panos; Iliadis, Athanassios; Melagraki, Georgia

2018-05-30

The aim of this work is to develop a gastrointestinal (GI) drug absorption model based on a reaction limited model of dissolution and consider its impact on the biopharmaceutic classification of drugs. Estimates for the fraction of dose absorbed as a function of dose, solubility, reaction/dissolution rate constant and the stoichiometry of drug-GI fluids reaction/dissolution were derived by numerical solution of the model equations. The undissolved drug dose and the reaction/dissolution rate constant drive the dissolution rate and determine the extent of absorption when high-constant drug permeability throughout the gastrointestinal tract is assumed. Dose is an important element of drug-GI fluids reaction/dissolution while solubility exclusively acts as an upper limit for drug concentrations in the lumen. The 3D plots of fraction of dose absorbed as a function of dose and reaction/dissolution rate constant for highly soluble and low soluble drugs for different "stoichiometries" (0.7, 1.0, 2.0) of the drug-reaction/dissolution with the GI fluids revealed that high extent of absorption was found assuming high drug- reaction/dissolution rate constant and high drug solubility. The model equations were used to simulate in vivo supersaturation and precipitation phenomena. The model developed provides the theoretical basis for the interpretation of the extent of drug's absorption on the basis of the parameters associated with the drug-GI fluids reaction/dissolution. A new paradigm emerges for the biopharmaceutic classification of drugs, namely, a model independent biopharmaceutic classification scheme of four drug categories based on either the fulfillment or not of the current dissolution criteria and the high or low % drug metabolism. Copyright © 2018. Published by Elsevier B.V.

Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls.

PubMed

Mendenhall, William M; Amdur, Robert J; Palta, Jatinder R

2006-06-10

The purpose of this article is to review the role of intensity-modulated radiotherapy (IMRT) in the standard management of patients with head and neck cancer through a critical review of the pertinent literature. IMRT may result in a dose distribution that is more conformal than that achieved with three-dimensional conformal radiotherapy (3D CRT), allowing dose reduction to normal structures and thus decreasing toxicity and possibly enhancing locoregional control through dose escalation. Disadvantages associated with IMRT include increased risk of a marginal miss, decreased dose homogeneity, increased total body dose, and increased labor and expense. Outcomes data after IMRT are limited, and follow-up is relatively short. Locoregional control rates appear to be comparable to those achieved with 3D CRT and, depending on the location and extent of the tumor, late toxicity may be lower. Despite limited data on clinical outcomes, IMRT has been widely adopted as a standard technique in routine practice and clinical trials. The use of IMRT involves a learning curve for the practitioner and will continue to evolve, requiring continuing education and monitoring of outcomes from routine practice. Additional standards pertaining to a variety of issues, including target definitions and dose specification, need to be developed. Phase III trials will better define the role of IMRT in coming years.

Radionuclides and radiation doses in heavy mineral sands and other mining operations in Mozambique.

PubMed

Carvalho, Fernando P; Matine, Obete F; Taímo, Suzete; Oliveira, João M; Silva, Lídia; Malta, Margarida

2014-01-01

Sites at the littoral of Mozambique with heavy mineral sands exploited for ilmenite, rutile and zircon and inland mineral deposits exploited for tantalite, uranium and bauxite were surveyed for ambient radiation doses, and samples were collected for the determination of radionuclide concentrations. In heavy mineral sands, (238)U and (232)Th concentrations were 70±2 and 308±9 Bq kg(-1) dry weight (dw), respectively, whereas after separation of minerals, the concentrations in the ilmenite fraction were 2240±64 and 6125±485 Bq kg(-1) (dw), respectively. Tantalite displayed the highest concentrations with 44 738±2474 Bq kg(-1) of (238)U. Radiation exposure of workers in mining facilities is likely to occur at levels above the dose limit for members of the public (1 mSv y(-1)) and therefore radiation doses should be assessed as occupational exposures. Local populations living in these regions in general are not exposed to segregated minerals with high radionuclide concentrations. However, there is intensive artisanal mining and a large number of artisanal miners and their families may be exposed to radiation doses exceeding the dose limit. A radiation protection programme is therefore needed to ensure radiation protection of the public and workers of developing mining projects.

Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

NASA Astrophysics Data System (ADS)

Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

2018-01-01

Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

Dose Volume Histogram (DVH) Analysis in Intensity Modulation Radiation Therapy (IMRT) Treatments for Prostate Cancers

NASA Astrophysics Data System (ADS)

Pyakuryal, Anil

2009-05-01

Studies have shown that as many as 8 out of 10 men had prostate cancer by age 80.Prostate cancer begins with small changes (prostatic intraepithelial neoplasia(PIN)) in size and shape of prostate gland cells,known as prostate adenocarcinoma.With advent in technology, prostate cancer has been the most widely used application of IMRT with the longest follow-up periods.Prostate cancer fits the ideal target criteria for IMRT of adjacent sensitive dose-limiting tissue (rectal, bladder).A retrospective study was performed on 10 prostate cancer patients treated with radiation to a limited pelvic field with a standard 4 field arrangements at dose 45 Gy, and an IMRT boost field to a total isocenter dose of 75 Gy.Plans were simulated for 4 field and the supplementary IMRT treatments with proposed dose delivery at 1.5 Gy/fraction in BID basis.An automated DVH analysis software, HART (S. Jang et al., 2008,Med Phys 35,p.2812)was used to perform DVH assessments in IMRT plans.A statistical analysis of dose coverage at targets in prostate gland and neighboring critical organs,and the plan indices(homogeneity, conformality etc) evaluations were also performed using HART extracted DVH statistics.Analyzed results showed a better correlation with the proposed outcomes (TCP, NTCP) of the treatments.

Current status of radiological protection at nuclear power stations in Japan.

PubMed

Suzuki, Akira; Hori, Shunsuke

2011-07-01

The radiation dose to workers at nuclear power stations (NPSs) in Japan was drastically reduced between the late-1970s and the early-1990s by continuous dose-reduction programmes. The total collective dose of radiation workers in FY 2008 was 84.04 person Sv, while the average collective dose was 1.5 person Sv per reactor. The average annual individual dose was 1.1 mSv and the maximum annual individual dose was 19.5 mSv. These values are sufficiently lower than the regulatory dose limits. Radioactive effluent released from NPSs is already so trivial that additional protective measures will not be necessary. Experience in radiation protection at NPSs has been accumulated over 40 y and will be very useful in establishing a rational radiation control system in the future.

RADIATION DOSE DUE TO RADON AND HEAVY METAL ANALYSIS IN DRINKING WATER SAMPLES OF JAMMU DISTRICT, JAMMU & KASHMIR, INDIA.

PubMed

Kumar, A; Kaur, M; Sharma, S; Mehra, R; Sharma, D K; Mishra, R

2016-10-01

In the present investigation, radon concentration and heavy metal analysis were carried out in drinking water samples in Jammu district, Jammu & Kashmir, India. The radon concentration was measured by using RAD-7, portable alpha particle detector. The values of radon concentration in drinking water samples were also compared within the safe limit recommended by different health agencies. The total annual effective dose ranged from 53.04 to 197.29 µSv y -1 The annual effective dose from few locations from the studied area was found to be greater than the safe limit (100 µSv y -1 ) suggested by World Health Organisation (WHO) and EU Council. Heavy metal concentration was determined by atomic absorption spectrophotometer. A total of eight elements were analysed, viz. arsenic, mercury, zinc, iron, copper, chromium, manganese and cadmium. Heavy metals are considered to be the major pollutants of water sources. The results were compared with the limits of WHO, EU and Indian organisations. The trace metal analysis is not on the exceeding side of the permissible limit in all the samples. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Report of IRPA task group on the impact of the eye lens dose limits.

PubMed

Cantone, Marie Claire; Ginjaume, Merce; Miljanic, Saveta; Martin, Colin J; Akahane, Keiichi; Mpete, Louisa; Michelin, Severino C; Flannery, Cynthia M; Dauer, Lawrence T; Balter, Stephen

2017-06-26

In 2012 IRPA established a task group (TG) to identify key issues in the implementation of the revised eye lens dose limit. The TG reported its conclusions in 2013. In January 2015, IRPA asked the TG to review progress with the implementation of the recommendations from the early report and to collate current practitioner experience. This report presents the results of a survey on the view of the IRPA professionals on the new limit to the lens of the eye and on the wider issue of tissue reactions. Recommendations derived from the survey are presented. This report was approved by IRPA Executive Council on 31 January 2017.

Implications of the implementation of the revised dose limit to the lens of the eye: the view of IRPA professionals.

PubMed

Broughton, J; Cantone, M C; Ginjaume, M; Shah, B; Czarwinski, R

2015-06-01

In April 2011, the International Commission on Radiological Protection issued a statement on reduction of the equivalent dose limits for the lens of the eye, and strongly recommended its consideration in the revision of the International Atomic Energy Agency's International Basic Safety Standards on Radiation Protection. The reduced dose limit was incorporated in the final version of the Basic Safety Standards. As significant concern was expressed by radiation protection professionals worldwide, the International Radiation Protection Association (IRPA) established a task group to assess the impact of implementation of the revised dose limit for the lens of the eye for occupational exposure. IRPA Associate Societies (ASs) were asked for their views using a questionnaire addressing three topics: implications for dosimetry, implications for methods of protection, and wider implications. The responses received indicate various methods of approach and express different points of view, reflecting nuances of particular ASs or specific professional groups. Topic experts nominated by ASs were selected to assist with collation of responses, and a report was produced by the task group. Conclusions were drawn on the three issues, including potential cost implications. A number of recommendations were drawn from the responses received including: the request for more understanding about the relationship between exposure of the lens of the eye and cataract formation, and further guidance to assist implementation; the importance of economic and social considerations when introducing the limits into national regulations; the need to propose or define procedures related to employment of people with existing or pre-cataract conditions; and the practical aspects relating to dosimetry and protective equipment. © The International Society for Prosthetics and Orthotics Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holmes, W.G.

2001-08-16

The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

Reprint of: Chromogranin A: a new proposal for trafficking, processing and induction of granule biogenesis.

PubMed

Koshimizu, Hisatsugu; Kim, Taeyoon; Cawley, Niamh X; Loh, Y Peng

2010-11-30

Chromogranin A (CgA), a member of the granin family serves several important cell biological roles in (neuro)endocrine cells which are summarized in this review. CgA is a "prohormone" that is synthesized at the rough endoplasmic reticulum and transported into the cisternae of this organelle via its signal peptide. It is then trafficked to the Golgi complex and then to the trans-Golgi network (TGN) where CgA aggregates at low pH in the presence of calcium. The CgA aggregates provide the physical driving force to induce budding of the TGN membrane resulting in dense core granule (DCG) formation. Within the granule, a small amount of the CgA is processed to bioactive peptides, including a predicted C-terminal peptide, serpinin. Upon stimulation, DCGs undergo exocytosis and CgA and its derived peptides are released. Serpinin, acting extracellularly is able to signal the increase in transcription of a serine protease inhibitor, protease nexin-1 (PN-1) that protects DCG proteins against degradation in the Golgi complex, which then enhances DCG biogenesis to replenish those that were released. Thus CgA and its derived peptide, serpinin, plays a significant role in granule formation and regulation of granule biogenesis, respectively, in (neuro) endocrine cells. Copyright © 2010. Published by Elsevier B.V.