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Sample records for non-threshold lnt dose-based

  1. Regulatory implications of a linear non-threshold (LNT) dose-based risks.

    PubMed

    Aleta, C R

    2009-01-01

    Current radiation protection regulatory limits are based on the linear non-threshold (LNT) theory using health data from atomic bombing survivors. Studies in recent years sparked debate on the validity of the theory, especially at low doses. The present LNT overestimates radiation risks since the dosimetry included only acute gammas and neutrons; the role of other bomb-caused factors, e.g. fallout, induced radioactivity, thermal radiation (UVR), electromagnetic pulse (EMP), and blast, were excluded. Studies are proposed to improve the dose-response relationship.

  2. Observations on the Chernobyl Disaster and LNT

    PubMed Central

    Jaworowski, Zbigniew

    2010-01-01

    The Chernobyl accident was probably the worst possible catastrophe of a nuclear power station. It was the only such catastrophe since the advent of nuclear power 55 years ago. It resulted in a total meltdown of the reactor core, a vast emission of radionuclides, and early deaths of only 31 persons. Its enormous political, economic, social and psychological impact was mainly due to deeply rooted fear of radiation induced by the linear non-threshold hypothesis (LNT) assumption. It was a historic event that provided invaluable lessons for nuclear industry and risk philosophy. One of them is demonstration that counted per electricity units produced, early Chernobyl fatalities amounted to 0.86 death/GWe-year), and they were 47 times lower than from hydroelectric stations (∼40 deaths/GWe-year). The accident demonstrated that using the LNT assumption as a basis for protection measures and radiation dose limitations was counterproductive, and lead to sufferings and pauperization of millions of inhabitants of contaminated areas. The projections of thousands of late cancer deaths based on LNT, are in conflict with observations that in comparison with general population of Russia, a 15% to 30% deficit of solid cancer mortality was found among the Russian emergency workers, and a 5% deficit solid cancer incidence among the population of most contaminated areas. PMID:20585443

  3. Observations on the Chernobyl Disaster and LNT.

    PubMed

    Jaworowski, Zbigniew

    2010-01-28

    The Chernobyl accident was probably the worst possible catastrophe of a nuclear power station. It was the only such catastrophe since the advent of nuclear power 55 years ago. It resulted in a total meltdown of the reactor core, a vast emission of radionuclides, and early deaths of only 31 persons. Its enormous political, economic, social and psychological impact was mainly due to deeply rooted fear of radiation induced by the linear non-threshold hypothesis (LNT) assumption. It was a historic event that provided invaluable lessons for nuclear industry and risk philosophy. One of them is demonstration that counted per electricity units produced, early Chernobyl fatalities amounted to 0.86 death/GWe-year), and they were 47 times lower than from hydroelectric stations ( approximately 40 deaths/GWe-year). The accident demonstrated that using the LNT assumption as a basis for protection measures and radiation dose limitations was counterproductive, and lead to sufferings and pauperization of millions of inhabitants of contaminated areas. The projections of thousands of late cancer deaths based on LNT, are in conflict with observations that in comparison with general population of Russia, a 15% to 30% deficit of solid cancer mortality was found among the Russian emergency workers, and a 5% deficit solid cancer incidence among the population of most contaminated areas.

  4. Identification of apolipoprotein N-acyltransferase (Lnt) in mycobacteria.

    PubMed

    Tschumi, Andreas; Nai, Corrado; Auchli, Yolanda; Hunziker, Peter; Gehrig, Peter; Keller, Peter; Grau, Thomas; Sander, Peter

    2009-10-02

    Lipoproteins of Gram-negative and Gram-positive bacteria carry a thioether-bound diacylglycerol but differ by a fatty acid amide bound to the alpha-amino group of the universally conserved cysteine. In Escherichia coli the N-terminal acylation is catalyzed by the N-acyltransferase Lnt. Using E. coli Lnt as a query in a BLASTp search, we identified putative lnt genes also in Gram-positive mycobacteria. The Mycobacterium tuberculosis lipoprotein LppX, heterologously expressed in Mycobacterium smegmatis, was N-acylated at the N-terminal cysteine, whereas LppX expressed in a M. smegmatis lnt::aph knock-out mutant was accessible for N-terminal sequencing. Western blot analyses of a truncated and tagged form of LppX indicated a smaller size of about 0.3 kDa in the lnt::aph mutant compared with the parental strain. Matrix-assisted laser desorption ionization time-of-flight/time-of-flight analyses of a trypsin digest of LppX proved the presence of the diacylglycerol modification in both strains, the parental strain and lnt::aph mutant. N-Acylation was found exclusively in the M. smegmatis parental strain. Complementation of the lnt::aph mutant with M. tuberculosis ppm1 restored N-acylation. The substrate for N-acylation is a C16 fatty acid, whereas the two fatty acids of the diacylglycerol residue were identified as C16 and C19:0 fatty acid, the latter most likely tuberculostearic acid. We demonstrate that mycobacterial lipoproteins are triacylated. For the first time to our knowledge, we identify Lnt activity in Gram-positive bacteria and assigned the responsible genes. In M. smegmatis and M. tuberculosis the open reading frames are annotated as MSMEG_3860 and M. tuberculosis ppm1, respectively.

  5. The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT.

    PubMed

    Calabrese, Edward J

    2017-04-01

    This paper reveals that nearly 25 years after the National Academy of Sciences (NAS), Biological Effects of Ionizing Radiation (BEIR) I Committee (1972) used Russell's dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment, Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it to incorrectly adopt the LNT model, which was a decision that profoundly changed the course of risk assessment for radiation and chemicals to the present.

  6. LNT IS THE BEST WE CAN DO - TO-DAY

    EPA Science Inventory

    Abstract

    The form of the dose-response curve for radiation-induced cancers, particularly at low doses, is the subject of an ongoing and spirited debate. The present review describes the current data base and basis for establishing a low dose, linear no threshold (LNT) mode...

  7. Do non-targeted effects increase or decrease low dose risk in relation to the linear-non-threshold (LNT) model?

    PubMed

    Little, M P

    2010-05-01

    In this paper we review the evidence for departure from linearity for malignant and non-malignant disease and in the light of this assess likely mechanisms, and in particular the potential role for non-targeted effects. Excess cancer risks observed in the Japanese atomic bomb survivors and in many medically and occupationally exposed groups exposed at low or moderate doses are generally statistically compatible. For most cancer sites the dose-response in these groups is compatible with linearity over the range observed. The available data on biological mechanisms do not provide general support for the idea of a low dose threshold or hormesis. This large body of evidence does not suggest, indeed is not statistically compatible with, any very large threshold in dose for cancer, or with possible hormetic effects, and there is little evidence of the sorts of non-linearity in response implied by non-DNA-targeted effects. There are also excess risks of various types of non-malignant disease in the Japanese atomic bomb survivors and in other groups. In particular, elevated risks of cardiovascular disease, respiratory disease and digestive disease are observed in the A-bomb data. In contrast with cancer, there is much less consistency in the patterns of risk between the various exposed groups; for example, radiation-associated respiratory and digestive diseases have not been seen in these other (non-A-bomb) groups. Cardiovascular risks have been seen in many exposed populations, particularly in medically exposed groups, but in contrast with cancer there is much less consistency in risk between studies: risks per unit dose in epidemiological studies vary over at least two orders of magnitude, possibly a result of confounding and effect modification by well known (but unobserved) risk factors. In the absence of a convincing mechanistic explanation of epidemiological evidence that is, at present, less than persuasive, a cause-and-effect interpretation of the reported statistical associations for cardiovascular disease is unreliable but cannot be excluded. Inflammatory processes are the most likely mechanism by which radiation could modify the atherosclerotic disease process. If there is to be modification by low doses of ionizing radiation of cardiovascular disease through this mechanism, a role for non-DNA-targeted effects cannot be excluded.

  8. Ammonia Production and Utilization in a Hybrid LNT+SCR System

    SciTech Connect

    Prikhodko, Vitaly Y; Parks, II, James E

    2009-01-01

    A hybrid LNT+SCR system is used to control NOx from a light-duty diesel engine with in-cylinder regeneration controls. A diesel oxidation catalyst and diesel particulate filter are upstream of the LNT and SCR catalysts. Ultraviolet (UV) adsorption spectroscopy performed directly in the exhaust path downstream of the LNT and SCR catalysts is used to characterize NH3 production and utilization in the system. Extractive exhaust samples are analyzed with FTIR and magnetic sector mass spectrometry (H2) as well. Furthermore, standard gas analyzers are used to complete the characterization of exhaust chemistry. NH3 formation increases strongly with extended regeneration (or over regeneration ) of the LNT, but the amount of NOx reduction occurring over the SCR catalyst is limited by the amount of NH3 produced as well as the amount of NOx available downstream of the LNT. Control of lean-rich cycling parameters enables control of the ratio of NOx reduction between the LNT and SCR catalysts. During lean-rich cycling, fuel penalties are similar for either LNT dominant or LNT with supplemental SCR NOx reduction. However, stored NH3 after multiple lean-rich cycles can enable continued NOx reduction by the SCR after lean-rich cycling stops; thus, requirements for active regeneration of the LNT+SCR system can be modified during transient operation.

  9. The LNT Debate in Radiation Protection: Science vs. Policy

    PubMed Central

    Mossman, Kenneth L.

    2012-01-01

    There is considerable interest in revisiting LNT theory as the basis for the system of radiation protection in the US and worldwide. Arguing the scientific merits of policy options is not likely to be fruitful because the science is not robust enough to support one theory to the exclusion of others. Current science cannot determine the existence of a dose threshold, a key piece to resolving the matter scientifically. The nature of the scientific evidence is such that risk assessment at small effective doses (defined as <100 mSv) is highly uncertain, and several policy alternatives, including threshold and non-linear dose-response functions, are scientifically defensible. This paper argues for an alternative approach by looking at the LNT debate as a policy question and analyzes the problem from a social and economic perspective. In other words, risk assessment and a strictly scientific perspective are insufficiently broad enough to resolve the issue completely. A wider perspective encompassing social and economic impacts in a risk management context is necessary, but moving the debate to the policy and risk management arena necessarily marginalizes the role of scientists. PMID:22740781

  10. Radiation, ecology and the invalid LNT model: the evolutionary imperative.

    PubMed

    Parsons, Peter A

    2006-09-27

    Metabolic and energetic efficiency, and hence fitness of organisms to survive, should be maximal in their habitats. This tenet of evolutionary biology invalidates the linear-no threshold (LNT) model for the risk consequences of environmental agents. Hormesis in response to selection for maximum metabolic and energetic efficiency, or minimum metabolic imbalance, to adapt to a stressed world dominated by oxidative stress should therefore be universal. Radiation hormetic zones extending substantially beyond common background levels, can be explained by metabolic interactions among multiple abiotic stresses. Demographic and experimental data are mainly in accord with this expectation. Therefore, non-linearity becomes the primary model for assessing risks from low-dose ionizing radiation. This is the evolutionary imperative upon which risk assessment for radiation should be based.

  11. Radiation, Ecology and the Invalid LNT Model: The Evolutionary Imperative

    PubMed Central

    Parsons, Peter A.

    2006-01-01

    Metabolic and energetic efficiency, and hence fitness of organisms to survive, should be maximal in their habitats. This tenet of evolutionary biology invalidates the linear-nothreshold (LNT) model for the risk consequences of environmental agents. Hormesis in response to selection for maximum metabolic and energetic efficiency, or minimum metabolic imbalance, to adapt to a stressed world dominated by oxidative stress should therefore be universal. Radiation hormetic zones extending substantially beyond common background levels, can be explained by metabolic interactions among multiple abiotic stresses. Demographic and experimental data are mainly in accord with this expectation. Therefore, non-linearity becomes the primary model for assessing risks from low-dose ionizing radiation. This is the evolutionary imperative upon which risk assessment for radiation should be based. PMID:18648598

  12. Perspective on the use of LNT for radiation protection and risk assessment by the U.S. Environmental Protection Agency.

    PubMed

    Puskin, Jerome S

    2009-08-21

    The U.S. Environmental Protection Agency (EPA) bases its risk assessments, regulatory limits, and nonregulatory guidelines for population exposures to low level ionizing radiation on the linear no-threshold (LNT) hypothesis, which assumes that the risk of cancer due to a low dose exposure is proportional to dose, with no threshold. The use of LNT for radiation protection purposes has been repeatedly endorsed by authoritative scientific advisory bodies, including the National Academy of Sciences' BEIR Committees, whose recommendations form a primary basis of EPA's risk assessment methodology. Although recent radiobiological findings indicate novel damage and repair processes at low doses, LNT is supported by data from both epidemiology and radiobiology. Given the current state of the science, the consensus positions of key scientific and governmental bodies, as well as the conservatism and calculational convenience of the LNT assumption, it is unlikely that EPA will modify this approach in the near future.

  13. Lipoprotein N-acyl transferase (Lnt1) is dispensable for protein O-mannosylation by Streptomyces coelicolor.

    PubMed

    Córdova-Dávalos, Laura Elena; Espitia, Clara; González-Cerón, Gabriela; Arreguín-Espinosa, Roberto; Soberón-Chávez, Gloria; Servín-González, Luis

    2014-01-01

    A protein glycosylation system related to that for protein mannosylation in yeast is present in many actinomycetes. This system involves polyprenyl phosphate mannose synthase (Ppm), protein mannosyl transferase (Pmt), and lipoprotein N-acyl transferase (Lnt). In this study, we obtained a series of mutants in the ppm (sco1423), lnt1 (sco1014), and pmt (sco3154) genes of Streptomyces coelicolor, which encode Ppm, Lnt1, and Pmt, to analyze their requirement for glycosylation of the heterologously expressed Apa glycoprotein of Mycobacterium tuberculosis. The results show that both Ppm and Pmt were required for Apa glycosylation, but that Lnt1 was dispensable for both Apa and the bacteriophage φC31 receptor glycosylation. A bacterial two-hybrid assay revealed that contrary to M. tuberculosis, Lnt1 of S. coelicolor does not interact with Ppm. The D2 catalytic domain of M. tuberculosisPpm was sufficient for complementation of an S. coelicolor double mutant lacking Lnt1 and Ppm, both for Apa glycosylation and for glycosylation of φC31 receptor. On the other hand, M. tuberculosisPmt was not active in S. coelicolor, even when correctly localized to the cytoplasmic membrane, showing fundamental differences in the requirements for Pmt activity in these two species.

  14. Health Effects of High Radon Environments in Central Europe: Another Test for the LNT Hypothesis?

    PubMed Central

    Becker, Klaus

    2003-01-01

    Morbus Bechterew, radon treatments are beneficial, with the positive effect lasting until at least 6 months after the normally 3-week treatment by inhalation or bathes. Studies on the mechanism of these effects are progressing. In other cases of extensive use of radon treatment for a wide spectrum of various diseases, for example, in the former Soviet Union, the positive results are not so well established. However, according to a century of radon treatment experience (after millenniums of unknown radon therapy), in particular in Germany and Austria, the positive medical effects for some diseases far exceed any potential detrimental health effects. The total amount of available data in this field is too large to be covered in a brief review. Therefore, less known — in particular recent — work from Central Europe has been analyzed in an attempt to summarize new developments and trends. This includes cost/benefit aspects of radon reduction programs. As a test case for the LNT (linear non-threshold) hypothesis and possible biopositive effects of low radiation exposures, the data support a nonlinear human response to low and medium-level radon exposures. PMID:19330110

  15. Development of Optimal Catalyst Designs and Operating Strategies for Lean NOx Reduction in Coupled LNT-SCR Systems

    SciTech Connect

    Harold, Michael; Crocker, Mark; Balakotaiah, Vemuri; Luss, Dan; Choi, Jae-Soon; Dearth, Mark; McCabe, Bob; Theis, Joe

    2013-09-30

    Oxides of nitrogen in the form of nitric oxide (NO) and nitrogen dioxide (NO{sub 2}) commonly referred to as NO{sub x}, is one of the two chemical precursors that lead to ground-level ozone, a ubiquitous air pollutant in urban areas. A major source of NO{sub x} is generated by equipment and vehicles powered by diesel engines, which have a combustion exhaust that contains NO{sub x} in the presence of excess O{sub 2}. Catalytic abatement measures that are effective for gasoline-fueled engines such as the precious metal containing three-way catalytic converter (TWC) cannot be used to treat O2-laden exhaust containing NO{sub x}. Two catalytic technologies that have emerged as effective for NO{sub x} abatement are NO{sub x} storage and reduction (NSR) and selective catalytic reduction (SCR). NSR is similar to TWC but requires much larger quantities of expensive precious metals and sophisticated periodic switching operation, while SCR requires an on-board source of ammonia which serves as the chemical reductant of the NO{sub x}. The fact that NSR produces ammonia as a byproduct while SCR requires ammonia to work has led to interest in combining the two together to avoid the need for the cumbersome ammonia generation system. In this project a comprehensive study was carried out of the fundamental aspects and application feasibility of combined NSR/SCR. The project team, which included university, industry, and national lab researchers, investigated the kinetics and mechanistic features of the underlying chemistry in the lean NOx trap (LNT) wherein NSR was carried out, with particular focus on identifying the operating conditions such as temperature and catalytic properties which lead to the production of ammonia in the LNT. The performance features of SCR on both model and commercial catalysts focused on the synergy between the LNT and SCR converters in terms of utilizing the upstream-generated ammonia and alternative reductants such as propylene, representing the

  16. The Genetics Panel of the NAS BEAR I Committee (1956): epistolary evidence suggests self-interest may have prompted an exaggeration of radiation risks that led to the adoption of the LNT cancer risk assessment model.

    PubMed

    Calabrese, Edward J

    2014-09-01

    This paper extends a series of historical papers which demonstrated that the linear-no-threshold (LNT) model for cancer risk assessment was founded on ideological-based scientific deceptions by key radiation genetics leaders. Based on an assessment of recently uncovered personal correspondence, it is shown that some members of the United States (US) National Academy of Sciences (NAS) Biological Effects of Atomic Radiation I (BEAR I) Genetics Panel were motivated by self-interest to exaggerate risks to promote their science and personal/professional agenda. Such activities have profound implications for public policy and may have had a significant impact on the adoption of the LNT model for cancer risk assessment.

  17. Consideration of non-linear, non-threshold and threshold approaches for assessing the carcinogenicity of oral exposure to hexavalent chromium.

    PubMed

    Haney, J

    2015-12-01

    A non-linear approach, consistent with available mode of action (MOA) data, is most scientifically defensible for assessing the carcinogenicity of oral exposure to hexavalent chromium (CrVI). Accordingly, the current paper builds upon previous studies (Haney, 2015a, 2015b) to first develop a non-linear, non-threshold approach as well as a non-linear threshold approach for assessing the oral carcinogenicity of CrVI, and then utilizes available MOA analyses and information for selection of the most scientifically-supported approach. More specifically, a non-linear, non-threshold dose-response function was developed that adequately describes the non-linearity predicted for potential human excess risk versus oral dose due to the sub-linear relationship between oral dose and internal dose (added mg Cr/kg target tissue) across environmentally-relevant doses of regulatory interest. Additionally, benchmark dose modeling was used to derive a reference dose (RfD of 0.003 mg/kg-day) with cytotoxicity-induced regenerative hyperplasia as a key precursor event to carcinogenesis in the mouse small intestine. This RfD value shows remarkable agreement with that published previously (0.006 mg/kg-day) based on a more scientifically-sophisticated, physiologically-based pharmacokinetic modeling approach (Thompson et al., 2013b). The RfD approach is the most scientifically-defensible approach based on the weight-of-evidence of available MOA information and analyses conducted for the most scientifically-supported MOA.

  18. Cancer risk assessment foundation unraveling: new historical evidence reveals that the US National Academy of Sciences (US NAS), Biological Effects of Atomic Radiation (BEAR) Committee Genetics Panel falsified the research record to promote acceptance of the LNT.

    PubMed

    Calabrese, Edward J

    2015-04-01

    The NAS Genetics Panel (1956) recommended a switch from a threshold to a linear dose response for radiation risk assessment. To support this recommendation, geneticists on the panel provided individual estimates of the number of children in subsequent generations (one to ten) that would be adversely affected due to transgenerational reproductive cell mutations. It was hoped that there would be close agreement among the individual risk estimates. However, extremely large ranges of variability and uncertainty characterized the wildly divergent expert estimates. The panel members believed that sharing these estimates with the scientific community and general public would strongly undercut their linearity recommendation, as it would have only highlighted their own substantial uncertainties. Essentially, their technical report in the journal Science omitted and misrepresented key adverse reproductive findings in an effort to ensure support for their linearity recommendation. These omissions and misrepresentations not only belie the notion of an impartial and independent appraisal by the NAS Panel, but also amount to falsification and fabrication of the research record at the highest possible level, leading ultimately to the adoption of LNT by governments worldwide. Based on previously unexamined correspondence among panel members and Genetics Panel meeting transcripts, this paper provides the first documentation of these historical developments.

  19. A bounding estimate of neutron dose based on measured photon dose around single pass reactors at the Hanford site.

    PubMed

    Taulbee, Timothy D; Glover, Samuel E; Macievic, Gregory V; Hunacek, Mickey; Smith, Cheryl; DeBord, Gary W; Morris, Donald; Fix, Jack

    2010-07-01

    Neutron and photon radiation survey records have been used to evaluate and develop a neutron to photon (NP) ratio to reconstruct neutron doses to workers around Hanford's single pass reactors that operated from 1945 to 1972. A total of 5,773 paired neutron and photon measurements extracted from 57 boxes of survey records were used in the development of the NP ratio. The development of the NP ratio enables the use of the recorded dose from an individual's photon dosimeter badge to be used to estimate the unmonitored neutron dose. The Pearson rank correlation between the neutron and photon measurements was 0.71. The NP ratio best fit a lognormal distribution with a geometric mean (GM) of 0.8, a geometric standard deviation (GSD) of 2.95, and the upper 95 th % of this distribution was 4.75. An estimate of the neutron dose based on this NP ratio is considered bounding due to evidence that up to 70% of the total photon exposure received by workers around the single pass reactors occurs during shutdown maintenance and refueling activities when there is no significant neutron exposure. Thus when this NP ratio is applied to the total measured photon dose from an individual film badge dosimeter, the resulting neutron dose is considered bounded.

  20. SU-E-J-181: Effect of Prostate Motion On Combined Brachytherapy and External Beam Dose Based On Daily Motion of the Prostate

    SciTech Connect

    Narayana, V; McLaughlin, P; Ealbaj, J

    2015-06-15

    Purpose: In this study, the adequacy of target expansions on the combined external beam and implant dose was examined based on the measured daily motion of the prostate. Methods: Thirty patients received an I–125 prostate implant prescribed to dose of 90Gy. This was followed by external beam to deliver a dose of 90Gyeq (external beam equivalent) to the prostate over 25 to 30 fractions. An ideal IMRT plan was developed by optimizing the external beam dose based on the delivered implant dose. The implant dose was converted to an equivalent external beam dose using the linear quadratic model. Patients were set up on the treatment table by daily orthogonal imaging and aligning the marker seeds in the prostate. Orthogonal images were obtained at the end of treatment to assess prostate intrafraction motion. Based on the observed motion of the markers between the initial and final images, 5 individual plans showing the actual dose delivered to the patient were calculated. A final true dose distribution was established based on summing the implant dose and the 5 external beam plans. Dose to the prostate, seminal vesicles, lymphnodes and normal tissues, rectal wall, urethra and lower sphincter were calculated and compared to ideal. On 18 patients who were sexually active, dose to the corpus cavernosum and internal pudendal artery was also calculated. Results: The average prostate motion in 3 orthogonal directions was less than 1 mm with a standard deviation of less than +2 mm. Dose and volume parameters showed that there was no decrease in dose to the targets and a marginal decrease in dose to in normal tissues. Conclusion: Dose delivered by seed implant moves with the prostate, decreasing the impact of intrafractions dose movement on actual dose delivered. Combined brachytherapy and external beam dose delivered to the prostate was not sensitive to prostate motion.

  1. Anomalous dielectric nonlinearity and dielectric relaxation in xBST-(1- x) (LMT-LNT) ceramics

    NASA Astrophysics Data System (ADS)

    Liu, Cheng; Liu, Peng

    2011-11-01

    xwt%Ba0.6Sr0.4TiO3-(1- x)wt%[0.4La (Mg0.5Ti0.5)O3-0.6(La0.5Na0.5)TiO3] ( x=0.30, 0.40, 0.50, 0.60, 0.70, 0.80, 0.90, 0.95) ceramics were prepared via a traditional solid-state reaction route. Interesting anomalous dielectric nonlinearity (ADN)—permittivity increased with dc bias electric field ( E-field), and low-temperature dielectric relaxation (LTDR) behaviors—were observed within a x range of 0.30˜0.70 for the first time. Based on our experimental facts, it was suggested that the LTDR was originated from a charge-associated process between electron-oxygen vacancy pairs during a thermal stimulation, while the ADN was related with a metastable state of polarized nano-regions (PNRs).

  2. THE HIGH BACKGROUND RADIATION AREA IN RAMSAR IRAN: GEOLOGY, NORM, BIOLOGY, LNT, AND POSSIBLE REGULATORY FUN

    SciTech Connect

    Karam, P. A.

    2002-02-25

    The city of Ramsar Iran hosts some of the highest natural radiation levels on earth, and over 2000 people are exposed to radiation doses ranging from 1 to 26 rem per year. Curiously, inhabitants of this region seem to have no greater incidence of cancer than those in neighboring areas of normal background radiation levels, and preliminary studies suggest their blood cells experience fewer induced chromosomal abnormalities when exposed to 150 rem ''challenge'' doses of radiation than do the blood cells of their neighbors. This paper will briefly describe the unique geology that gives Ramsar its extraordinarily high background radiation levels. It will then summarize the studies performed to date and will conclude by suggesting ways to incorporate these findings (if they are borne out by further testing) into future radiation protection standards.

  3. Scientific foundation of regulating ionizing radiation: application of metrics for evaluation of regulatory science information.

    PubMed

    Moghissi, A Alan; Gerraa, Vikrham Kumar; McBride, Dennis K; Swetnam, Michael

    2014-11-01

    This paper starts by describing the historical evolution of assessment of biologic effects of ionizing radiation leading to the linear non-threshold (LNT) system currently used to regulate exposure to ionizing radiation. The paper describes briefly the concept of Best Available Science (BAS) and Metrics for Evaluation of Scientific Claims (MESC) derived for BAS. It identifies three phases of regulatory science consisting of the initial phase, when the regulators had to develop regulations without having the needed scientific information; the exploratory phase, when relevant tools were developed; and the standard operating phase, when the tools were applied to regulations. Subsequently, an attempt is made to apply the BAS/MESC system to various stages of LNT. This paper then compares the exposure limits imposed by regulatory agencies and also compares them with naturally occurring radiation at several cities. Controversies about LNT are addressed, including judgments of the U.S. National Academies and their French counterpart. The paper concludes that, based on the BAS/MESC system, there is no disagreement between the two academies on the scientific foundation of LNT; instead, the disagreement is based on their judgment or speculation.

  4. Logic and ethics in radiation protection.

    PubMed

    Lindell, B

    2001-12-01

    The International Commission on Radiological Protection (ICRP) continues to accept the assumption of a linear non-threshold dose-response relationship (LNT) as the most likely one. In that case, basic logic as well as widely accepted ethics require that the full collective dose be used for detriment assessments and in procedures for optimisation of radiation protection. This means that even the smallest doses must be taken into account in the assessment of the global collective dose if they contribute significantly together. However, in calculating collective doses over time, some reasonable restriction of the integration period has to be employed, mainly because of the uncertainties involved in the assessment of future detriment. There are also uncertainties in the LNT assumption, but the precautionary principle would not permit that this is taken as an excuse for neglecting small doses.

  5. Systems Cancer Biology and the Controlling Mechanisms for the J-Shaped Cancer Dose Response: Towards Relaxing the LNT Hypothesis.

    PubMed

    Lou, In Chio; Zhao, Yuchao; Wu, Yingjie; Ricci, Paolo F

    2012-01-01

    The hormesis phenomena or J-shaped dose response have been accepted as a common phenomenon regardless of the involved biological model, endpoint measured and chemical class/physical stressor. This paper first introduced a mathematical dose response model based on systems biology approach. It links molecular-level cell cycle checkpoint control information to clonal growth cancer model to predict the possible shapes of the dose response curves of Ionizing Radiation (IR) induced tumor transformation frequency. J-shaped dose response curves have been captured with consideration of cell cycle checkpoint control mechanisms. The simulation results indicate the shape of the dose response curve relates to the behavior of the saddle-node points of the model in the bifurcation diagram. A simplified version of the model in previous work of the authors was used mathematically to analyze behaviors relating to the saddle-node points for the J-shaped dose response curve. It indicates that low-linear energy transfer (LET) is more likely to have a J-shaped dose response curve. This result emphasizes the significance of systems biology approach, which encourages collaboration of multidiscipline of biologists, toxicologists and mathematicians, to illustrate complex cancer-related events, and confirm the biphasic dose-response at low doses.

  6. LNTgate: How scientific misconduct by the U.S. NAS led to governments adopting LNT for cancer risk assessment.

    PubMed

    Calabrese, Edward J

    2016-07-01

    This paper provides a detailed rebuttal to the letter of Beyea (2016) which offered a series of alternative interpretations to those offered in my article in Environmental Research (Calabrese, 2015a) concerning the role of the U.S. National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Committee Genetics Panel in the adoption of the linear dose response model for cancer risk assessment. Significant newly uncovered evidence is presented which supports and extends the findings of Calabrese (2015a), reaffirming the conclusion that the Genetics Panel should be evaluated for scientific misconduct for deliberate misrepresentation of the research record in order to enhance an ideological agenda. This critique documents numerous factual errors along with extensive and deliberate filtering of information in the Beyea letter (2016) that leads to consistently incorrect conclusions and an invalid general perspective.

  7. Dosimetry in Mammography: Average Glandular Dose Based on Homogeneous Phantom

    NASA Astrophysics Data System (ADS)

    Benevides, Luis A.; Hintenlang, David E.

    2011-05-01

    The objective of this study was to demonstrate that a clinical dosimetry protocol that utilizes a dosimetric breast phantom series based on population anthropometric measurements can reliably predict the average glandular dose (AGD) imparted to the patient during a routine screening mammogram. AGD was calculated using entrance skin exposure and dose conversion factors based on fibroglandular content, compressed breast thickness, mammography unit parameters and modifying parameters for homogeneous phantom (phantom factor), compressed breast lateral dimensions (volume factor) and anatomical features (anatomical factor). The patient fibroglandular content was evaluated using a calibrated modified breast tissue equivalent homogeneous phantom series (BRTES-MOD) designed from anthropomorphic measurements of a screening mammography population and whose elemental composition was referenced to International Commission on Radiation Units and Measurements Report 44 and 46 tissues. The patient fibroglandular content, compressed breast thickness along with unit parameters and spectrum half-value layer were used to derive the currently used dose conversion factor (DgN). The study showed that the use of a homogeneous phantom, patient compressed breast lateral dimensions and patient anatomical features can affect AGD by as much as 12%, 3% and 1%, respectively. The protocol was found to be superior to existing methodologies. The clinical dosimetry protocol developed in this study can reliably predict the AGD imparted to an individual patient during a routine screening mammogram.

  8. Dosimetry in Mammography: Average Glandular Dose Based on Homogeneous Phantom

    SciTech Connect

    Benevides, Luis A.; Hintenlang, David E.

    2011-05-05

    The objective of this study was to demonstrate that a clinical dosimetry protocol that utilizes a dosimetric breast phantom series based on population anthropometric measurements can reliably predict the average glandular dose (AGD) imparted to the patient during a routine screening mammogram. AGD was calculated using entrance skin exposure and dose conversion factors based on fibroglandular content, compressed breast thickness, mammography unit parameters and modifying parameters for homogeneous phantom (phantom factor), compressed breast lateral dimensions (volume factor) and anatomical features (anatomical factor). The patient fibroglandular content was evaluated using a calibrated modified breast tissue equivalent homogeneous phantom series (BRTES-MOD) designed from anthropomorphic measurements of a screening mammography population and whose elemental composition was referenced to International Commission on Radiation Units and Measurements Report 44 and 46 tissues. The patient fibroglandular content, compressed breast thickness along with unit parameters and spectrum half-value layer were used to derive the currently used dose conversion factor (DgN). The study showed that the use of a homogeneous phantom, patient compressed breast lateral dimensions and patient anatomical features can affect AGD by as much as 12%, 3% and 1%, respectively. The protocol was found to be superior to existing methodologies. The clinical dosimetry protocol developed in this study can reliably predict the AGD imparted to an individual patient during a routine screening mammogram.

  9. Simulation of computed tomography dose based on voxel phantom

    NASA Astrophysics Data System (ADS)

    Liu, Chunyu; Lv, Xiangbo; Li, Zhaojun

    2017-01-01

    Computed Tomography (CT) is one of the preferred and the most valuable imaging tool used in diagnostic radiology, which provides a high-quality cross-sectional image of the body. It still causes higher doses of radiation to patients comparing to the other radiological procedures. The Monte-Carlo method is appropriate for estimation of the radiation dose during the CT examinations. The simulation of the Computed Tomography Dose Index (CTDI) phantom was developed in this paper. Under a similar conditions used in physical measurements, dose profiles were calculated and compared against the measured values that were reported. The results demonstrate a good agreement between the calculated and the measured doses. From different CT exam simulations using the voxel phantom, the highest absorbed dose was recorded for the lung, the brain, the bone surface. A comparison between the different scan type shows that the effective dose for a chest scan is the highest one, whereas the effective dose values during abdomen and pelvis scan are very close, respectively. The lowest effective dose resulted from the head scan. Although, the dose in CT is related to various parameters, such as the tube current, exposure time, beam energy, slice thickness and patient size, this study demonstrates that the MC simulation is a useful tool to accurately estimate the dose delivered to any specific organs for patients undergoing the CT exams and can be also a valuable technique for the design and the optimization of the CT x-ray source.

  10. Comparison of radon doses based on different radon monitoring approaches.

    PubMed

    Vaupotič, Janja; Smrekar, Nataša; Žunić, Zora S

    2017-04-01

    In 43 places (23 schools, 3 kindergartens, 16 offices and one dwelling), indoor radon has been monitored as an intercomparison experiment, using α-scintillation cells (SC - Jožef Stefan Institute, Slovenia), various kinds of solid state nuclear track detectors (KfK - Karlsruhe Institute of Technology, Germany; UFO - National Institute of Radiological Sciences, Chiba, Japan; RET - University College Dublin, Ireland) and active electronic devices (EQF, Sarad, Germany). At the same place, the radon levels and, consequently, the effective doses obtained with different radon devices differed substantially (by a factor of 2 or more), and no regularity was observed as regards which detector would show a higher or lower dose.

  11. 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

  12. Modeling Dose-response at Low Dose: A Systems Biology Approach for Ionization Radiation.

    PubMed

    Zhao, Yuchao; Ricci, Paolo F

    2010-03-18

    For ionization radiation (IR) induced cancer, a linear non-threshold (LNT) model at very low doses is the default used by a number of national and international organizations and in regulatory law. This default denies any positive benefit from any level of exposure. However, experimental observations and theoretical biology have found that both linear and J-shaped IR dose-response curves can exist at those very low doses. We develop low dose J-shaped dose-response, based on systems biology, and thus justify its use regarding exposure to IR. This approach incorporates detailed, molecular and cellular descriptions of biological/toxicological mechanisms to develop a dose-response model through a set of nonlinear, differential equations describing the signaling pathways and biochemical mechanisms of cell cycle checkpoint, apoptosis, and tumor incidence due to IR. This approach yields a J-shaped dose response curve while showing where LNT behaviors are likely to occur. The results confirm the hypothesis of the J-shaped dose response curve: the main reason is that, at low-doses of IR, cells stimulate protective systems through a longer cell arrest time per unit of IR dose. We suggest that the policy implications of this approach are an increasingly correct way to deal with precautionary measures in public health.

  13. Setting standards for radiation protection: A time for change

    SciTech Connect

    Patterson, H.W.; Hickman, D.P.

    1996-01-01

    In 1950, the International Commission on Radiation Protection (ICRP) recommended that ``certain radiation effects are irreversible and cumulative.`` Furthermore, the ICRP ``strongly recommended that every effort be made to reduce exposures to all types of ionizing radiations to the lowest possible level.`` Then in 1954, the ICRP published its assumption that human response to ionizing radiation was linear with dose, together with the recommendation that exposures be kept as low as practicable. These concepts are still the foundation of radiation protection policy today, even though, as Evans has stated, ``The linear non-threshold (LNT) model was adopted specifically on a basis of mathematical simplicity, not from radio-biological data.... Groups responsible for setting standards for radiation protection should be abreast of new developments and new data as they are published; however, this does not seem to be the case. For example, there have been many reports in scientific, peer-reviewed, and other publications during the last three decades that have shown the LNT model and the policy of As Low As Reasonably Achievable (ALARA) to be invalid. However, none of these reports has been refuted or even discussed by standard-setting groups. We believe this mandates a change in the standard-setting process.

  14. Regulatory-Science: Biphasic Cancer Models or the LNT—Not Just a Matter of Biology!

    PubMed Central

    Ricci, Paolo F.; Sammis, Ian R.

    2012-01-01

    There is no doubt that prudence and risk aversion must guide public decisions when the associated adverse outcomes are either serious or irreversible. With any carcinogen, the levels of risk and needed protection before and after an event occurs, are determined by dose-response models. Regulatory law should not crowd out the actual beneficial effects from low dose exposures—when demonstrable—that are inevitably lost when it adopts the linear non-threshold (LNT) as its causal model. Because regulating exposures requires planning and developing protective measures for future acute and chronic exposures, public management decisions should be based on minimizing costs and harmful exposures. We address the direct and indirect effects of causation when the danger consists of exposure to very low levels of carcinogens and toxicants. The societal consequences of a policy can be deleterious when that policy is based on a risk assumed by the LNT, in cases where low exposures are actually beneficial. Our work develops the science and the law of causal risk modeling: both are interwoven. We suggest how their relevant characteristics differ, but do not attempt to keep them separated; as we demonstrate, this union, however unsatisfactory, cannot be severed. PMID:22740778

  15. Strategy of the scientific committee on occupational exposure limits (SCOEL) in the derivation of occupational exposure limits for carcinogens and mutagens.

    PubMed

    Bolt, Hermann M; Huici-Montagud, Alicia

    2008-01-01

    Setting standards, such as occupational exposure limits (OELs) for carcinogenic substances must consider modes of action. At the European Union level, the scientific committee on occupational exposure limits (SCOEL) has discussed a number of chemical carcinogens and has issued recommendations. For some carcinogens, health-based OELs were recommended, while quantitative assessments of carcinogenic risks were performed for others. For purposes of setting limits this led to the consideration of the following groups of carcinogens. (A) Non-threshold genotoxic carcinogens; for low-dose assessment of risk, the linear non-threshold (LNT) model appears appropriate. For these chemicals, regulations (risk management) may be based on the ALARA principle ("as low as reasonably achievable"), technical feasibility, and other socio-political considerations. (B) Genotoxic carcinogens, for which the existence of a threshold cannot be sufficiently supported at present. In these cases, the LNT model may be used as a default assumption, based on the scientific uncertainty. (C) Genotoxic carcinogens with a practical threshold, as supported by studies on mechanisms and/or toxicokinetics; health-based exposure limits may be based on an established NOAEL (no observed adverse effect level). (D) Non-genotoxic carcinogens and non-DNA-reactive carcinogens; for these compounds a true ("perfect") threshold is associated with a clearly founded NOAEL. The mechanisms shown by tumour promoters, spindle poisons, topoisomerase II poisons and hormones are typical examples of this category. Health-based OELs are derived for carcinogens of groups C and D, while a risk assessment is carried out for carcinogens of groups A and B. Substantial progress is currently being made in the incorporation of new types of mechanistic data into these regulatory procedures.

  16. The estrogenic effects of benzylparaben at low doses based on uterotrophic assay in immature SD rats.

    PubMed

    Hu, Ying; Zhang, Zhaobin; Sun, Libei; Zhu, Desheng; Liu, Qingchun; Jiao, Jian; Li, Jun; Qi, Mingwen

    2013-03-01

    Benzylparaben (BzP), a type of parabens being used as a preservative agent in cosmetics, food, and pharmaceutical products, may be ingested by humans. In this study, we performed an immature uterotrophic assay using Sprague Dawley (SD) rats by intragastric administration to determine the estrogenic effects of BzP and found significant increases in uterine weight with doses of 0.16 mg/kg body weight and higher (P<0.05). The in vivo estrogenicity of BzP was supported by in vitro results from the human estrogen receptor α (hERα)-coactivator recruiting assay and in silico molecular docking analysis performed in this study. The in vitro estrogenic activity of BzP can be observed at concentrations of 1.0×10(-8) M and higher. Molecular docking analysis showed that BzP fits well into the agonist pocket of hERα. The lowest observed effect dose (LOED) (0.16 mg/kg/day) of BzP is much lower than the documented LOEDs of other parabens. Actual risk may exist for people who consume a diet high in BzP or use BzP-laden cosmetics. In addition, we tested the sensitivity of Wistar rats to 17β-estradiol by immature uterotrophic assay, and no obvious uterotrophic response was observed in the rats given doses up to 100 μg/kg body weight.

  17. Blood alcohol levels in rats: non-uniform yields from intraperitoneal doses based on body weight.

    PubMed Central

    Bloom, F.; Lad, P.; Pittman, Q.; Rogers, J.

    1982-01-01

    1 Sprague-Dawley rats (n = 72) weighing from 125 to 450 g were injected intraperitoneally (i.p.) with 16% (w/v) ethanol to provide 1, 2 or 3 g/kg doses. 2 Resulting blood alcohol levels (BALs) demonstrated a general inadequacy of dose/body weight (g/kg) formulations of ethanol to provide uniform BALs in animals of different weights. 3 BAL differences between heavier and lighter rats were not well accounted for by developmental changes in liver weight or alcohol dehydrogenase activity. 4 From the data, a table was derived of more appropriate ethanol injection volumes to produce 0-300 mg% BALs (20 mg% increments) in rats from 100-500 g (10 g increments). PMID:7074285

  18. SU-E-T-04: 3D Dose Based Patient Compensator QA Procedure for Proton Radiotherapy

    SciTech Connect

    Zou, W; Reyhan, M; Zhang, M; Davis, R; Jabbour, S; Khan, A; Yue, N

    2015-06-15

    Purpose: In proton double-scattering radiotherapy, compensators are the essential patient specific devices to contour the distal dose distribution to the tumor target. Traditional compensator QA is limited to checking the drilled surface profiles against the plan. In our work, a compensator QA process was established that assess the entire compensator including its internal structure for patient 3D dose verification. Methods: The fabricated patient compensators were CT scanned. Through mathematical image processing and geometric transformations, the CT images of the proton compensator were combined with the patient simulation CT images into a new series of CT images, in which the imaged compensator is placed at the planned location along the corresponding beam line. The new CT images were input into the Eclipse treatment planning system. The original plan was calculated to the combined CT image series without the plan compensator. The newly computed patient 3D dose from the combined patientcompensator images was verified against the original plan dose. Test plans include the compensators with defects intentionally created inside the fabricated compensators. Results: The calculated 3D dose with the combined compensator and patient CT images reflects the impact of the fabricated compensator to the patient. For the test cases in which no defects were created, the dose distributions were in agreement between our method and the corresponding original plans. For the compensator with the defects, the purposely changed material and a purposely created internal defect were successfully detected while not possible with just the traditional compensator profiles detection methods. Conclusion: We present here a 3D dose verification process to qualify the fabricated proton double-scattering compensator. Such compensator detection process assesses the patient 3D impact of the fabricated compensator surface profile as well as the compensator internal material and structure changes. This research receives funding support from CURA Medical Technologies.

  19. Estimation of the effects of normal tissue sparing using equivalent uniform dose-based optimization

    PubMed Central

    Senthilkumar, K.; Maria Das, K. J.; Balasubramanian, K.; Deka, A. C.; Patil, B. R.

    2016-01-01

    In this study, we intend to estimate the effects of normal tissue sparing between intensity modulated radiotherapy (IMRT) treatment plans generated with and without a dose volume (DV)-based physical cost function using equivalent uniform dose (EUD). Twenty prostate cancer patients were retrospectively selected for this study. For each patient, two IMRT plans were generated (i) EUD-based optimization with a DV-based physical cost function to control inhomogeneity (EUDWith DV) and (ii) EUD-based optimization without a DV-based physical cost function to allow inhomogeneity (EUDWithout DV). The generated plans were prescribed a dose of 72 Gy in 36 fractions to planning target volume (PTV). Mean dose, D30%, and D5% were evaluated for all organ at risk (OAR). Normal tissue complication probability was also calculated for all OARs using BioSuite software. The average volume of PTV for all patients was 103.02 ± 27 cm3. The PTV mean dose for EUDWith DV plans was 73.67 ± 1.7 Gy, whereas for EUDWithout DV plans was 80.42 ± 2.7 Gy. It was found that PTV volume receiving dose more than 115% of prescription dose was negligible in EUDWith DV plans, whereas it was 28% in EUDWithout DV plans. In almost all dosimetric parameters evaluated, dose to OARs in EUDWith DV plans was higher than in EUDWithout DV plans. Allowing inhomogeneous dose (EUDWithout DV) inside the target would achieve better normal tissue sparing compared to homogenous dose distribution (EUDWith DV). Hence, this inhomogeneous dose could be intentionally dumped on the high-risk volume to achieve high local control. Therefore, it was concluded that EUD optimized plans offer added advantage of less OAR dose as well as selectively boosting dose to gross tumor volume. PMID:27217624

  20. Proposal of human spinal cord reirradiation dose based on collection of data from 40 patients

    SciTech Connect

    Nieder, Carsten . E-mail: cnied@hotmail.com; Grosu, Anca L.; Andratschke, Nicolaus H.; Molls, Michael

    2005-03-01

    Purpose: Driven by numerous reports on recovery of occult radiation injury, reirradiation of the spinal cord today is considered a realistic option. In rodents, long-term recovery was observed to start at approximately 8 weeks. However, prospective clinical studies are lacking. Therefore, a combined analysis of all published clinical data might provide a valuable basis for future trials. Methods and materials: We collected data from 40 individual patients published in eight different reports after a comprehensive MEDLINE search. These represent all patients with data available for dose per fraction and total dose of each of both treatment courses. We recalculated the biologically effective dose (BED) according to the linear-quadratic model using an {alpha}/{beta} value of 2 Gy for the cervical and thoracic cord and 4 Gy for the lumbar cord. In this model, a dose of 50 Gy given in single daily fractions of 2 Gy is equivalent to a BED of 100 Gy{sub 2} or 75 Gy{sub 4}. For treatment with two daily fractions, a correction term was introduced to take incomplete repair of sublethal damage into account. Results: The cumulative doses ranged from 108 to 205 Gy{sub 2} (median dose, 135 Gy{sub 2}). The median interval between both series was 20 months. Three patients were treated to the lumbar segments only. The median follow-up was 17 months for patients without myelopathy. Eleven patients developed myelopathy after 4-25 months (median, 11 months). Myelopathy was seen only in patients who had received one course to a dose of {>=}102 Gy{sub 2} (n = 9) or were retreated after 2 months (n = 2). In the absence of these two risk factors, no myelopathy developed in 19 patients treated with {<=}135.5 Gy{sub 2} or 7 patients treated with 136-150 Gy{sub 2}. A risk score based on the cumulative BED, the greatest BED for all treatment series in a particular individual, and interval was developed. Low-risk patients remained free of myelopathy and 33% of intermediate-risk patients and 90% of high-risk patients developed myelopathy. Conclusion: On the basis of these literature data (and with due caution), the risk of myelopathy appears small after {<=}135.5 Gy{sub 2} when the interval is not shorter than 6 months and the dose of each course is {<=}98 Gy{sub 2}. We would recommend limiting the dose to this level, whenever technically feasible. However, it appears prudent to propose the collection of prospective data from a greater number of patients receiving doses in the range of 136-150 Gy{sub 2} to assess the safety of higher retreatment doses for those patients in whom limited doses might compromise tumor control.

  1. Implications for human and environmental health of low doses of ionising radiation.

    PubMed

    Mothersill, Carmel; Seymour, Colin

    2014-07-01

    The last 20 years have seen a major paradigm shift in radiation biology. Several discoveries challenge the DNA centric view which holds that DNA damage is the critical effect of radiation irrespective of dose. This theory leads to the assumption that dose and effect are simply linked - the more energy deposition, the more DNA damage and the greater the biological effect. This is embodied in radiation protection (RP) regulations as the linear-non-threshold (LNT) model. However the science underlying the LNT model is being challenged particularly in relation to the environment because it is now clear that at low doses of concern in RP, cells, tissues and organisms respond to radiation by inducing responses which are not readily predictable by dose. These include adaptive responses, bystander effects, genomic instability and low dose hypersensitivity, and are commonly described as stress responses, while recognizing that "stress" can be good as well as bad. The phenomena contribute to observed radiation responses and appear to be influenced by genetic, epigenetic and environmental factors, meaning that dose and response are not simply related. The question is whether our discovery of these phenomena means that we need to re-evaluate RP approaches. The so-called "non-targeted" mechanisms mean that low dose radiobiology is very complex and supra linear or sub-linear (even hormetic) responses are possible but their occurrence is unpredictable for any given system level. Issues which may need consideration are synergistic or antagonistic effects of other pollutants. RP, at present, only looks at radiation dose but the new (NTE) radiobiology means that chemical or physical agents, which interfere with tissue responses to low doses of radiation, could critically modulate the predicted risk. Similarly, the "health" of the organism could determine the effect of a given low dose by enabling or disabling a critical response. These issues will be discussed.

  2. Optimizing CT radiation dose based on patient size and image quality: the size-specific dose estimate method.

    PubMed

    Larson, David B

    2014-10-01

    The principle of ALARA (dose as low as reasonably achievable) calls for dose optimization rather than dose reduction, per se. Optimization of CT radiation dose is accomplished by producing images of acceptable diagnostic image quality using the lowest dose method available. Because it is image quality that constrains the dose, CT dose optimization is primarily a problem of image quality rather than radiation dose. Therefore, the primary focus in CT radiation dose optimization should be on image quality. However, no reliable direct measure of image quality has been developed for routine clinical practice. Until such measures become available, size-specific dose estimates (SSDE) can be used as a reasonable image-quality estimate. The SSDE method of radiation dose optimization for CT abdomen and pelvis consists of plotting SSDE for a sample of examinations as a function of patient size, establishing an SSDE threshold curve based on radiologists' assessment of image quality, and modifying protocols to consistently produce doses that are slightly above the threshold SSDE curve. Challenges in operationalizing CT radiation dose optimization include data gathering and monitoring, managing the complexities of the numerous protocols, scanners and operators, and understanding the relationship of the automated tube current modulation (ATCM) parameters to image quality. Because CT manufacturers currently maintain their ATCM algorithms as secret for proprietary reasons, prospective modeling of SSDE for patient populations is not possible without reverse engineering the ATCM algorithm and, hence, optimization by this method requires a trial-and-error approach.

  3. Predictive Dose-Based Estimation of Systemic Exposure Multiples in Mouse and Monkey Relative to Human for Antisense Oligonucleotides With 2′-O-(2-Methoxyethyl) Modifications

    PubMed Central

    Yu, Rosie Z; Grundy, John S; Henry, Scott P; Kim, Tae-Won; Norris, Daniel A; Burkey, Jennifer; Wang, Yanfeng; Vick, Andrew; Geary, Richard S

    2015-01-01

    Evaluation of species differences and systemic exposure multiples (or ratios) in toxicological animal species versus human is an ongoing exercise during the course of drug development. The systemic exposure ratios are best estimated by directly comparing area under the plasma concentration-time curves (AUCs), and sometimes by comparing the dose administered, with the dose being adjusted either by body surface area (BSA) or body weight (BW). In this study, the association between AUC ratio and the administered dose ratio from animals to human were studied using a retrospective data-driven approach. The dataset included nine antisense oligonucleotides (ASOs) with 2′-O-(2-methoxyethyl) modifications, evaluated in two animal species (mouse and monkey) following single and repeated parenteral administrations. We found that plasma AUCs were similar between ASOs within the same species, and are predictable to human exposure using a single animal species, either mouse or monkey. Between monkey and human, the plasma exposure ratio can be predicted directly based on BW-adjusted dose ratios, whereas between mouse and human, the exposure ratio would be nearly fivefold lower in mouse compared to human based on BW-adjusted dose values. Thus, multiplying a factor of 5 for the mouse BW-adjusted dose would likely provide a reasonable AUC exposure estimate in human at steady-state. PMID:25602582

  4. SU-D-201-02: Prediction of Delivered Dose Based On a Joint Histogram of CT and FDG PET Images

    SciTech Connect

    Park, M; Choi, Y; Cho, A; Hwang, S; Cha, J; Lee, N; Yun, M

    2015-06-15

    Purpose: To investigate whether pre-treatment images can be used in predicting microsphere distribution in tumors. When intra-arterial radioembolization using Y90 microspheres was performed, the microspheres were often delivered non-uniformly within the tumor, which could lead to an inefficient therapy. Therefore, it is important to estimate the distribution of microspheres. Methods: Early arterial phase CT and FDG PET images were acquired for patients with primary liver cancer prior to radioembolization (RE) using Y90 microspheres. Tumor volume was delineated on CT images and fused with FDG PET images. From each voxel (3.9×3.9×3.3 mm3) in the tumor, the Hounsfield unit (HU) from the CT and SUV values from the FDG PET were harvested. We binned both HU and SUV into 11 bins and then calculated a normalized joint-histogram in an 11×11 array.Patients also underwent a post-treatment Y90 PET imaging. Radiation dose for the tumor was estimated using convolution of the Y90 distribution with a dose-point kernel. We also calculated a fraction of the tumor volume that received a radiation dose great than 100Gy. Results: Averaged over 40 patients, 55% of tumor volume received a dose greater than 100Gy (range : 1.1 – 100%). The width of the joint histogram was narrower for patients with a high dose. For patients with a low dose, the width was wider and a larger fraction of tumor volume had low HU. Conclusion: We have shown the pattern of joint histogram of the HU and SUV depends on delivered dose. The patterns can predict the efficacy of uniform intra-arterial delivery of Y90 microspheres.

  5. Clinical Outcomes of Biological Effective Dose-Based Fractionated Stereotactic Radiation Therapy for Metastatic Brain Tumors From Non-Small Cell Lung Cancer

    SciTech Connect

    Matsuyama, Tomohiko; Kogo, Kasei; Oya, Natsuo

    2013-03-15

    Purpose: To evaluate the efficacy and toxicity of fractionated stereotactic radiation therapy (FSRT) based on biological effective dose (BED), a novel approach to deliver a fixed BED irrespective of dose fractionation, for brain metastases from non-small cell lung cancer (NSCLC). Methods and Materials: Between March 2005 and March 2009 we treated 299 patients with 1 to 5 lesions from NSCLC (573 total brain metastases) with FSRT using Novalis. The dose fractionation schedules were individually determined to deliver a peripheral BED10 (α/β ratio = 10) of approximately 80 Gy{sub 10}. The median number of fractions was 3 (range, 2-10), the median peripheral BED10 was 83.2 Gy (range, 19.1-89.6 Gy). Patients were followed up with magnetic resonance imaging (MRI) studies performed at 1- to 2-month intervals. The local tumor control rate and overall local progression-free and intracranial relapse-free survival were calculated by the Kaplan-Meier method. Results: Local control rates for all 573 lesions at 6 and 12 months were 96.3% and 94.5%, respectively. By multivariate analysis the tumor diameter was the only factor predictive of the local control rate (P=.001). The median overall survival, local progression-free survival, and intracranial relapse-free survival were 17.1, 14.9, and 4.4 months, respectively. The overall survival, local progression-free survival, and intracranial relapse-free survival rates at 6 and 12 months were 78.5% and 63.3%, 74.3% and 57.8%, and 41.0% and 21.8%, respectively. Six patients (2%) manifested progressive radiation injury to the brain even during therapy with corticosteroids; they underwent hyperbaric oxygen therapy, and follow-up MRI showed improvement. Conclusions: This study showed that BED-based FSRT for brain metastases from NSCLC is a promising strategy that may yield excellent outcomes with acceptable toxicity. Criteria must be established to determine the optimal dose fractionation for individual patients.

  6. A tissue dose-based comparative exposure assessment of manganese using physiologically based pharmacokinetic modeling-The importance of homeostatic control for an essential metal.

    PubMed

    Gentry, P Robinan; Van Landingham, Cynthia; Fuller, William G; Sulsky, Sandra I; Greene, Tracy B; Clewell, Harvey J; Andersen, Melvin E; Roels, Harry A; Taylor, Michael D; Keene, Athena M

    2017-02-22

    A physiologically-based pharmacokinetic (PBPK) model (Schroeter et al., 2011) was applied to simulate target tissue manganese (Mn) concentrations following occupational and environmental exposures. These estimates of target tissue Mn concentrations were compared to determine margins of safety (MOS) and to evaluate the biological relevance of applying safety factors to derive acceptable Mn air concentrations. Mn blood concentrations measured in occupational studies permitted verification of the human PBPK models, increasing confidence in the resulting estimates. Mn exposure was determined based on measured ambient air Mn concentrations and dietary data in Canada and the United States (US). Incorporating dietary and inhalation exposures into the models indicated that increases in target tissue concentrations above endogenous levels only begin to occur when humans are exposed to levels of Mn in ambient air (i.e. >10μg/m(3)) that are far higher than those currently measured in Canada or the US. A MOS greater than three orders of magnitude was observed, indicating that current Mn air concentrations are far below concentrations that would be required to produce the target tissue Mn concentrations associated with subclinical neurological effects. This application of PBPK modeling for an essential element clearly demonstrates that the conventional application of default factors to "convert" an occupational exposure to an equivalent continuous environmental exposure, followed by the application of safety factors, is not appropriate in the case of Mn. PBPK modeling demonstrates that the relationship between ambient Mn exposures and dose-to-target tissue is not linear due to normal tissue background levels and homeostatic controls.

  7. GLUT1: A novel tool reflecting proliferative activity of lung neuroendocrine tumors?

    PubMed

    Benzerdjeb, Nazim; Berna, Pascal; Sevestre, Henri

    2017-01-01

    Lung neuroendocrine tumors (LNT) represents approximately 20% of all lung cancers. The classification of LNT relies upon morphology. Recently, in the World Health Organization (WHO) classification, Ki-67 rate has been proposed for classification. It is, however, known that Ki-67 count has a poor interlaboratory reproducibly. For that reason, our team has looked for a new biomarker. GLUT1 protein a facilitative glucose transporter protein which has ubiquitous expression in mammalian. GLUT1 is overexpressed in many human cancers. But, no study has evaluated the GLUT1 staining as an aid diagnosis in LNT. Our team have assessed the GLUT1 immunohistochemical staining in 36 LNT and to assess its diagnostic value. GLUT1 staining was higher in neuroendocrine carcinoma than in carcinoid tumor. A positive predictive value in a priori and posteriori testing for diagnosis of LNT is demonstrated. GLUT1 staining could aid in the diagnosis and should be validated in a large prospective cohort.

  8. Lymph Node Transplantation Decreases Swelling and Restores Immune Responses in a Transgenic Model of Lymphedema

    PubMed Central

    Hespe, Geoffrey E.; García Nores, Gabriela D.; Kataru, Raghu P.; Martínez-Corral, Inés; Ortega, Sagrario; Mehrara, Babak J.

    2016-01-01

    Introduction Secondary lymphedema is a common complication of cancer treatment and recent studies have demonstrated that lymph node transplantation (LNT) can decrease swelling, as well as the incidence of infections. However, although these results are exciting, the mechanisms by which LNT improves these pathologic findings of lymphedema remain unknown. Using a transgenic mouse model of lymphedema, this study sought to analyze the effect of LNT on lymphatic regeneration and T cell-mediated immune responses. Methods We used a mouse model in which the expression of the human diphtheria toxin receptor is driven by the FLT4 promoter to enable the local ablation of the lymphatic system through subdermal hindlimb diphtheria toxin injections. Popliteal lymph node dissection was subsequently performed after a two-week recovery period, followed by either orthotopic LNT or sham surgery after an additional two weeks. Hindlimb swelling, lymphatic vessel regeneration, immune cell trafficking, and T cell-mediated immune responses were analyzed 10 weeks later. Results LNT resulted in a marked decrease in hindlimb swelling, fibroadipose tissue deposition, and decreased accumulation of perilymphatic inflammatory cells, as compared to controls. In addition, LNT induced a marked lymphangiogenic response in both capillary and collecting lymphatic vessels. Interestingly, the resultant regenerated lymphatics were abnormal in appearance on lymphangiography, but LNT also led to a notable increase in dendritic cell trafficking from the periphery to the inguinal lymph nodes and improved adaptive immune responses. Conclusions LNT decreases pathological changes of lymphedema and was shown to potently induce lymphangiogenesis. Lymphatic vessels induced by LNT were abnormal in appearance, but were functional and able to transport antigen-presenting cells. Animals treated with LNT have an increased ability to mount T cell-mediated immune responses when sensitized to antigens in the affected

  9. Global and local cancer risks after the Fukushima Nuclear Power Plant accident as seen from Chernobyl: a modeling study for radiocaesium ((134)Cs &(137)Cs).

    PubMed

    Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Møller, Anders Pape

    2014-03-01

    The accident at the Fukushima Daiichi Nuclear Power Plant (NPP) in Japan resulted in the release of a large number of fission products that were transported worldwide. We study the effects of two of the most dangerous radionuclides emitted, (137)Cs (half-life: 30.2years) and (134)Cs (half-life: 2.06years), which were transported across the world constituting the global fallout (together with iodine isotopes and noble gasses) after nuclear releases. The main purpose is to provide preliminary cancer risk estimates after the Fukushima NPP accident, in terms of excess lifetime incident and death risks, prior to epidemiology, and compare them with those occurred after the Chernobyl accident. Moreover, cancer risks are presented for the local population in the form of high-resolution risk maps for 3 population classes and for both sexes. The atmospheric transport model LMDZORINCA was used to simulate the global dispersion of radiocaesium after the accident. Air and ground activity concentrations have been incorporated with monitoring data as input to the LNT-model (Linear Non-Threshold) frequently used in risk assessments of all solid cancers. Cancer risks were estimated to be small for the global population in regions outside Japan. Women are more sensitive to radiation than men, although the largest risks were recorded for infants; the risk is not depended on the sex at the age-at-exposure. Radiation risks from Fukushima were more enhanced near the plant, while the evacuation measures were crucial for its reduction. According to our estimations, 730-1700 excess cancer incidents are expected of which around 65% may be fatal, which are very close to what has been already published (see references therein). Finally, we applied the same calculations using the DDREF (Dose and Dose Rate Effectiveness Factor), which is recommended by the ICRP, UNSCEAR and EPA as an alternative reduction factor instead of using a threshold value (which is still unknown). Excess lifetime cancer

  10. A comparison approach to explain risks related to X-ray imaging for scoliosis, 2012 SOSORT award winner

    PubMed Central

    2013-01-01

    Background X-ray imaging is frequently used as diagnostic approach for scoliosis in children and adolescents. X-ray procedures are considered as justified only when expected benefits exceed related risks. While benefits are well known to physicians, radiological risk awareness can be vague, impeding an optimal communication with patients’ parents and possibly leading to discomfort and anxiety. Objective of the study is the suggestion of a risk comparison approach for better communicating the radiological risks related to X-ray investigation of scoliosis. Methods Starting point of the analysis is the Linear Non-Threshold (LNT) assumption for radiation stochastic effect, which states that for effective doses (E, Sievert – Sv) below 100 mSv, the probability of future stochastic damage is linearly related to E: absorbing two E’s in separate moments results in the addition of the risks related to each E. This allows to add E from different sources to calculate a cumulative risk of health detriment. Medline (Pubmed) was systematically searched in order to determine the average E delivered during X-ray investigation of scoliosis. Subsequently, the major natural sources of radiation were considered. The average yearly E due to natural sources was compared with E due to the imaging of the vertebral column. Results E’s due to X-ray scoliosis examinations show a large variability: under 7 years of age, 0.03-0.54 mSv; 7–12 years, 0.11-0.80 mSv; 13–18 years, 0.17-1.09 mSv. Overall, 65% of the world population is expected to be exposed to an annual E between 1 and 3 mSv. More in detail, worldwide the total annual average E due to natural sources is 2.4 mSv (range 1–10), of which half originates from Radon exposure. Other sources are cosmic rays and ingestion and inhalation of radionuclides. For example, one flight between Europe and America accounts for 0.030-0.045 mSv because of exposure to cosmic rays. Conclusions X-rays are carcinogenic and exposures to them

  11. Prediction of drug terminal half-life and terminal volume of distribution after intravenous dosing based on drug clearance, steady-state volume of distribution, and physiological parameters of the body.

    PubMed

    Berezhkovskiy, Leonid M

    2013-02-01

    The steady state, V(ss), terminal volume of distribution, V(β), and the terminal half-life, t(1/2), are commonly obtained from the drug plasma concentration-time profile, C(p)(t), following intravenous dosing. Unlike V(ss) that can be calculated based on the physicochemical properties of drugs considering the equilibrium partitioning between plasma and organ tissues, t(1/2) and V(β) cannot be calculated that way because they depend on the rates of drug transfer between blood and tissues. Considering the physiological pharmacokinetic model pertinent to the terminal phase of drug elimination, a novel equation that calculates t(1/2) (and consequently V(β)) was derived. It turns out that V(ss), the total body clearance, Cl, equilibrium blood-plasma concentration ratio, r; and the physiological parameters of the body such as cardiac output, and blood and tissue volumes are sufficient for determination of terminal kinetics. Calculation of t(1/2) by the obtained equation appears to be in good agreement with the experimentally observed vales of this parameter in pharmacokinetic studies in rat, monkey, dog, and human. The equation for the determination of the pre-exponent of the terminal phase of C(p)(t) is also found. The obtained equation allows to predict t(1/2) in human assuming that V(ss) and Cl were either obtained by allometric scaling or, respectively, calculated in silico or based on in vitro drug stability measurements. For compounds that have high clearance, the derived equation may be applied to calculate r just using the routine data on Cl, V(ss), and t(1/2), rather than doing the in vitro assay to measure this parameter.

  12. Lipid Nanotube Tailored Fabrication of Uniquely Shaped Polydopamine Nanofibers as Photothermal Converters.

    PubMed

    Ding, Wuxiao; Chechetka, Svetlana A; Masuda, Mitsutoshi; Shimizu, Toshimi; Aoyagi, Masaru; Minamikawa, Hiroyuki; Miyako, Eijiro

    2016-03-18

    Helically coiled and linear polydopamine (PDA) nanofibers were selectively fabricated with two different types of lipid nanotubes (LNTs) that acted as templates. The obtained coiled PDA-LNT hybrid showed morphological advantages such as higher light absorbance and photothermal conversion effect compared to a linear counterpart. Laser irradiation of the coiled PDA-LNT hybrid induced a morphological change and subsequent release of the encapsulated guest molecule. In cellular experiments, the coiled PDA-LNT efficiently eliminated HeLa cells because of its strong affinity with the tumor cells. This work illustrates the first approach to construct characteristic morphologies of PDA nanofibers using LNTs as simple templates, and the coiled PDA-LNT hybrid exhibits attractive photothermal features derived from its unique coiled shape.

  13. Night temperature and source–sink effects on overall growth, cell number and cell size in bell pepper ovaries

    PubMed Central

    Darnell, Rebecca L.; Cruz-Huerta, Nicacio; Williamson, Jeffrey G.

    2012-01-01

    Background and Aims Ovary swelling, and resultant fruit malformation, in bell pepper flowers is favoured by low night temperature or a high source–sink ratio. However, the interaction between night temperature and source–sink ratio on ovary swelling and the contribution of cell size and cell number to ovary swelling are unknown. The present research examined the interactive effects of night temperature and source–sink ratio on ovary size, cell number and cell size at anthesis in bell pepper flowers. Methods Bell pepper plants were grown in growth chambers at night temperatures of either 20 °C (HNT) or 12 °C (LNT). Within each temperature treatment, plants bore either 0 (non-fruiting) or two developing fruits per plant. Ovary fresh weight, cell size and cell number were measured. Key Results Ovary fresh weights in non-fruiting plants grown at LNT were the largest, while fresh weights were smallest in plants grown at HNT with fruits. In general, mesocarp cell size in ovaries was largest in non-fruiting plants grown at either LNT or HNT and smallest in fruiting plants at HNT. Mesocarp cell number was greater in non-fruiting plants under LNT than in the rest of the night temperature/fruiting treatments. These responses were more marked in ovaries sampled after 18 d of treatment compared with those sampled after 40 d of treatment. Conclusions Ovary fresh weight of flowers at anthesis increased 65 % in non-fruiting plants grown under LNT compared with fruiting plants grown under HNT. This increase was due primarily to increases in mesocarp cell number and size. These results indicate that the combined effects of LNT and high source–sink ratio on ovary swelling are additive. Furthermore, the combined effects of LNT and low source–sink ratio or HNT and high source–sink ratio can partially overcome the detrimental effects of LNT and high source–sink ratio. PMID:22933415

  14. Communicating Leave No Trace ethics and practices: Efficacy of two-day trainer courses

    USGS Publications Warehouse

    Daniels, M.L.; Marion, J.L.

    2005-01-01

    Heavy recreational visitation within protected natural areas has resulted in many ecological impacts. Many of these impacts may be avoided or minimized through adoption of low-impact hiking and camping practices. Although ?No Trace? messages have been promoted in public lands since the 1970s, few studies have documented the reception and effectiveness of these messages. The U.S. Leave No Trace Center for Outdoor Ethics develops and promotes two-day Trainer courses that teach Leave No Trace (LNT) skills and ethics to outdoor professionals, groups, and interested individuals. This study examined the change in knowledge, ethics, and behavior of LNT Trainer course participants. The respondents were a convenience sample of participants in Trainer courses offered from April through August 2003. Trainer course instructors administered pre-course and post-course questionnaires to their participants, and we contacted participants individually with a followup questionnaire 4 months after completion of their course. Scores for each of the sections increased immediately following the course, and decreased slightly over the 4 months following the course. Overall, more than half of the knowledge and behavior items, and half of the ethics items, showed significant improvement from pre-course measures to the follow-up. Age, reported LNT experience, and backpacking experience affected the participants? pre-course knowledge and behavior scores. Younger, less experienced respondents also showed a greater improvement in behavior following the course. Trainer course participants also shared their LNT skills and ethics with others both formally and informally. In summary, the LNT Trainer course was successful in increasing participants? knowledge, ethics, and behavior, which they then shared with others. Since many low impact skills taught in the LNT curriculum are supported by scientific research, LNT educational programs have the potential to effectively minimize the environmental

  15. Construction of selenium nanoparticles/β-glucan composites for enhancement of the antitumor activity.

    PubMed

    Jia, Xuewei; Liu, Qingye; Zou, Siwei; Xu, Xiaojuan; Zhang, Lina

    2015-03-06

    We report on a green procedure for the stabilization of selenium nanoparticles (SeNPs) by a naturally occurring β-glucan with triple helical conformation known as Lentinan (t-LNT) in water after denaturing into single chains (s-LNT) at 140 °C. The results demonstrated that the s-LNT can interact with SeNPs through Se-O-H interaction. Transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectra, UV/vis, X-ray diffraction (XRD) and dynamic light scattering (DLS) showed that s-LNT coated SeNPs to form a stable nano-composite Se/s-LNT, leading to good dispersion of SeNPs. Especially, the as-prepared Se/s-LNT composite in the solution could remain homogeneous and translucent for 30 days without any precipitates. Different size distribution of SeNPs was prepared by simply controlling the concentrations of selenite sodium and the corresponding reducing agent ascorbic acid. The size effect of SeNPs on anti-tumor activity was revealed that the SeNPs with more evenly particle size distribution show the higher anticancer activity.

  16. Sulfated lentinan induced mitochondrial dysfunction leads to programmed cell death of tobacco BY-2 cells.

    PubMed

    Wang, Jie; Wang, Yaofeng; Shen, Lili; Qian, Yumei; Yang, Jinguang; Wang, Fenglong

    2017-04-01

    Sulphated lentinan (sLTN) is known to act as a resistance inducer by causing programmed cell death (PCD) in tobacco suspension cells. However, the underlying mechanism of this effect is largely unknown. Using tobacco BY-2 cell model, morphological and biochemical studies revealed that mitochondrial reactive oxygen species (ROS) production and mitochondrial dysfunction contribute to sLNT induced PCD. Cell viability, and HO/PI fluorescence imaging and TUNEL assays confirmed a typical cell death process caused by sLNT. Acetylsalicylic acid (an ROS scavenger), diphenylene iodonium (an inhibitor of NADPH oxidases) and protonophore carbonyl cyanide p-trifluoromethoxyphenyl hydrazone (a protonophore and an uncoupler of mitochondrial oxidative phosphorylation) inhibited sLNT-induced H2O2 generation and cell death, suggesting that ROS generation linked, at least partly, to a mitochondrial dysfunction and caspase-like activation. This conclusion was further confirmed by double-stained cells with the mitochondria-specific marker MitoTracker RedCMXRos and the ROS probe H2DCFDA. Moreover, the sLNT-induced PCD of BY-2 cells required cellular metabolism as up-regulation of the AOX family gene transcripts and induction of the SA biosynthesis, the TCA cycle, and miETC related genes were observed. It is concluded that mitochondria play an essential role in the signaling pathway of sLNT-induced ROS generation, which possibly provided new insight into the sLNT-mediated antiviral response, including PCD.

  17. [Tremendous Human, Social, and Economic Losses Caused by Obstinate Application of the Failed Linear No-threshold Model].

    PubMed

    Sutou, Shizuyo

    2015-01-01

    The linear no-threshold model (LNT) was recommended in 1956, with abandonment of the traditional threshold dose-response for genetic risk assessment. Adoption of LNT by the International Commission on Radiological Protection (ICRP) became the standard for radiation regulation worldwide. The ICRP recommends a dose limit of 1 mSv/year for the public, which is too low and which terrorizes innocent people. Indeed, LNT arose mainly from the lifespan survivor study (LSS) of atomic bomb survivors. The LSS, which asserts linear dose-response and no threshold, is challenged mainly on three points. 1) Radiation doses were underestimated by half because of disregard for major residual radiation, resulting in cancer risk overestimation. 2) The dose and dose-rate effectiveness factor (DDREF) of 2 is used, but the actual DDREF is estimated as 16, resulting in cancer risk overestimation by several times. 3) Adaptive response (hormesis) is observed in leukemia and solid cancer cases, consistently contradicting the linearity of LNT. Drastic reduction of cancer risk moves the dose-response curve close to the control line, allowing the setting of a threshold. Living organisms have been evolving for 3.8 billion years under radiation exposure, naturally acquiring various defense mechanisms such as DNA repair mechanisms, apoptosis, and immune response. The failure of LNT lies in the neglect of carcinogenesis and these biological mechanisms. Obstinate application of LNT continues to cause tremendous human, social, and economic losses. The 60-year-old LNT must be rejected to establish a new scientific knowledge-based system.

  18. Structural and mechanical properties of lanthanide doped La1/3Nb0.8Ta0.2O3 thin films prepared by sol–gel method

    NASA Astrophysics Data System (ADS)

    Brunckova, Helena; Medvecky, Lubomir; Kovalcikova, Alexandra; Fides, Martin; Mudra, Erika; Durisin, Juraj; Skvarla, Jiri; Kanuchova, Maria

    2017-04-01

    Transparent Eu and Nd doped lanthanum niobate tantalate La1/3Nb0.8Ta0.2O3 (LNT) thin films (∼150 nm) were prepared by sol–gel/spin-coating process on Pt/SiO2/Si substrates and annealing at 1100 °C. The x-ray diffraction analysis of films confirmed formation of the perovskite La1/3NbO3 and La1/3TaO3 phases with traces of pyrochlore LaNbO4. Eu and Nd doped LNT films were smoother with roughness 17.1 and 25.4 nm in comparison with LNT (43.3 nm). In all films was observed heterogeneous microstructure with the perovskite spherical and pyrochlore needle-like particles. The mechanical properties of films were characterized for the first time by conventional and continuous stiffness (CSM) nanoindentation. The Eu and Nd doped LNT film modulus (E) and hardness (H) were higher than LNT (∼99.8 and 4.4 GPa) determined by conventional nanoindentation. It was measured the significant effect of substrate on properties of Eu or Nd films (H ∼ 5.9 or 4.9 GPa and E ∼ 107.3 or 104.1 GPa) by CSM nanoindentation.

  19. Survey of cryogenic semiconductor devices

    SciTech Connect

    Talarico, L.J.; McKeever, J.W.

    1996-04-01

    Improved reliability and electronic performance can be achieved in a system operated at cryogenic temperatures because of the reduction in mechanical insult and in disruptive effects of thermal energy on electronic devices. Continuing discoveries of new superconductors with ever increasing values of T{sub c} above that of liquid nitrogen temperature (LNT) have provided incentive for developing semiconductor electronic systems that may also operate in the superconductor`s liquid nitrogen bath. Because of the interest in high-temperature superconductor (HTS) devices, liquid nitrogen is the cryogen of choice and LNT is the temperature on which this review is focused. The purpose of this survey is to locate and assemble published information comparing the room temperature (298 K), performance of commercially available conventional and hybrid semiconductor device with their performance at LNT (77K), to help establish their candidacy as cryogenic electronic devices specifically for use at LNT. The approach to gathering information for this survey included the following activities. Periodicals and proceedings were searched for information on the behavior of semiconductor devices at LNT. Telephone calls were made to representatives of semiconductor industries, to semiconductor subcontractors, to university faculty members prominent for their research in the area of cryogenic semiconductors, and to representatives of the National Aeronautics and Space Administration (NASA) and NASA subcontractors. The sources and contacts are listed with their responses in the introduction, and a list of references appears at the end of the survey.

  20. Regulatory Initiatives for Control and Release of Technologically Enhanced Naturally-Occurring Radioactive Materials

    SciTech Connect

    Egidi, P.V.

    1999-03-02

    Current drafts of proposed standards and suggested State regulations for control and release of technologically-enhanced naturally-occurring radioactive material (TENORM), and standards for release of volumetrically-contaminated material in the US are reviewed. These are compared to the recommendations of the International Atomic Energy Association (IAEA) Safety Series and the European Commission (EC) proposals. Past regulatory efforts with respect to TENORM in the US dealt primarily with oil-field related wastes. Currently, nine states (AK, GA, LA, MS, NM, OH, OR SC, TX) have specific regulations pertaining to TENORM, mostly based on uranium mill tailings cleanup criteria. The new US proposals are dose- or risk-based, as are the IAEA and EC recommendations, and are grounded in the linear no threshold hypothesis (LNT). TENORM wastes involve extremely large volumes, particularly scrap metal and mine wastes. Costs to control and dispose of these wastes can be considerable. The current debate over the validity of LNT at low doses and low dose rates is particularly germane to this discussion. Most standards setting organizations and regulatory agencies base their recommendations on the LNT. The US Environmental Protection Agency has released a draft Federal Guidance Report that recommends calculating health risks from low-level exposure to radionuclides based on the LNT. However, some scientific and professional organizations are openly questioning the validity of LNT and its basis for regulations, practices, and costs to society in general. It is not clear at this time how a non-linear regulatory scheme would be implemented.

  1. Experimental Assessment of NOx Emissions from 73 Euro 6 Diesel Passenger Cars.

    PubMed

    Yang, Liuhanzi; Franco, Vicente; Mock, Peter; Kolke, Reinhard; Zhang, Shaojun; Wu, Ye; German, John

    2015-12-15

    Controlling nitrogen oxides (NOx) emissions from diesel passenger cars during real-world driving is one of the major technical challenges facing diesel auto manufacturers. Three main technologies are available for this purpose: exhaust gas recirculation (EGR), lean-burn NOx traps (LNT), and selective catalytic reduction (SCR). Seventy-three Euro 6 diesel passenger cars (8 EGR only, 40 LNT, and 25 SCR) were tested on a chassis dynamometer over both the European type-approval cycle (NEDC, cold engine start) and the more realistic Worldwide harmonized light-duty test cycle (WLTC version 2.0, hot start) between 2012 and 2015. Most vehicles met the legislative limit of 0.08 g/km of NOx over NEDC (average emission factors by technology: EGR-only 0.07 g/km, LNT 0.04 g/km, and SCR 0.05 g/km), but the average emission factors rose dramatically over WLTC (EGR-only 0.17 g/km, LNT 0.21 g/km, and SCR 0.13 g/km). Five LNT-equipped vehicles exhibited very poor performance over the WLTC, emitting 7-15 times the regulated limit. These results illustrate how diesel NOx emissions are not properly controlled under the current, NEDC-based homologation framework. The upcoming real-driving emissions (RDE) regulation, which mandates an additional on-road emissions test for EU type approvals, could be a step in the right direction to address this problem.

  2. Kinetic and Performance Studies of the Regeneration Phase of Model Pt/Ba/Rh NOx Traps for Design and Optimization

    SciTech Connect

    Michael Harold; Vemuri Balakotaiah

    2010-05-31

    In this project a combined experimental and theoretical approach was taken to advance our understanding of lean NOx trap (LNT) technology. Fundamental kinetics studies were carried out of model LNT catalysts containing variable loadings of precious metals (Pt, Rh), and storage components (BaO, CeO{sub 2}). The Temporal Analysis of Products (TAP) reactor provided transient data under well-characterized conditions for both powder and monolith catalysts, enabling the identification of key reaction pathways and estimation of the corresponding kinetic parameters. The performance of model NOx storage and reduction (NSR) monolith catalysts were evaluated in a bench scale NOx trap using synthetic exhaust, with attention placed on the effect of the pulse timing and composition on the instantaneous and cycle-averaged product distributions. From these experiments we formulated a global model that predicts the main spatio-temporal features of the LNT and a mechanistic-based microkinetic models that incorporates a detailed understanding of the chemistry and predicts more detailed selectivity features of the LNT. The NOx trap models were used to determine its ability to simulate bench-scale data and ultimately to evaluate alternative LNT designs and operating strategies. The four-year project led to the training of several doctoral students and the dissemination of the findings as 47 presentations in conferences, catalysis societies, and academic departments as well 23 manuscripts in peer-reviewed journals. A condensed review of NOx storage and reduction was published in an encyclopedia of technology.

  3. Atomic Bomb Health Benefits

    PubMed Central

    Luckey, T. D.

    2008-01-01

    Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment. PMID:19088902

  4. Atomic bomb health benefits.

    PubMed

    Luckey, T D

    2008-01-01

    Media reports of deaths and devastation produced by atomic bombs convinced people around the world that all ionizing radiation is harmful. This concentrated attention on fear of miniscule doses of radiation. Soon the linear no threshold (LNT) paradigm was converted into laws. Scientifically valid information about the health benefits from low dose irradiation was ignored. Here are studies which show increased health in Japanese survivors of atomic bombs. Parameters include decreased mutation, leukemia and solid tissue cancer mortality rates, and increased average lifespan. Each study exhibits a threshold that repudiates the LNT dogma. The average threshold for acute exposures to atomic bombs is about 100 cSv. Conclusions from these studies of atomic bomb survivors are: One burst of low dose irradiation elicits a lifetime of improved health.Improved health from low dose irradiation negates the LNT paradigm.Effective triage should include radiation hormesis for survivor treatment.

  5. Liquid Nitrogen Temperature Operation of a Switching Power Converter

    NASA Technical Reports Server (NTRS)

    Ray, Biswajit; Gerber, Scott S.; Patterson, Richard L.; Myers, Ira T.

    1995-01-01

    The performance of a 42/28 V, 175 W, 50 kHz pulse-width modulated buck dc/dc switching power converter at liquid nitrogen temperature (LNT) is compared with room temperature operation. The power circuit as well as the control circuit of the converter, designed with commercially available components, were operated at LNT and resulted in a slight improvement in converter efficiency. The improvement in power MOSFET operation was offset by deteriorating performance of the output diode rectifier at LNT. Performance of the converter could be further improved at low temperatures by using only power MOSFET's as switches. The use of a resonant topology will further improve the circuit performance by reducing the switching noise and loss.

  6. CRADA Final Report for CRADA Number ORNL00-0605: Advanced Engine/Aftertreatment System R&D

    SciTech Connect

    Pihl, Josh A; West, Brian H; Toops, Todd J; Adelman, Brad; Derybowski, Edward

    2011-10-01

    Navistar and ORNL established this CRADA to develop diesel engine aftertreatment configurations and control strategies that could meet emissions regulations while maintaining or improving vehicle efficiency. The early years of the project focused on reducing the fuel penalty associated with lean NOx trap (LNT), also known as NOx adsorber catalyst regeneration and desulfation. While Navistar pursued engine-based (in-cylinder) approaches to LNT regeneration, complementary experiments at ORNL focused on in-exhaust fuel injection. ORNL developed a PC-based controller for transient electronic control of EGR valve position, intake throttle position, and actuation of fuel injectors in the exhaust system of a Navistar engine installed at Oak Ridge. Aftertreatment systems consisting of different diesel oxidation catalysts (DOCs) in conjunction with a diesel particle filter and LNT were evaluated under quasi-steady-state conditions. Hydrocarbon (HC) species were measured at multiple locations in the exhaust system with Gas chromatograph mass spectrometry (GC-MS) and Fourier transform infrared (FTIR) spectroscopy. Under full-load, rated speed conditions, injection of fuel upstream of the DOC reduced the fuel penalty for a given level of NOx reduction by 10-20%. GC-MS showed that fuel compounds were 'cracked' into smaller hydrocarbon species over the DOC, particularly light alkenes. GC-MS analysis of HC species entering and exiting the LNT showed high utilization of light alkenes, followed by mono-aromatics; branched alkanes passed through the LNT largely unreacted. Follow-on experiments at a 'road load' condition were conducted, revealing that the NOx reduction was better without the DOC at lower temperatures. The improved performance was attributed to the large swings in the NOx adsorber core temperature. Split-injection experiments were conducted with ultra-low sulfur diesel fuel and three pure HC compounds: 1-pentene, toluene, and iso-octane. The pure compound experiments

  7. TU-C-18A-01: Models of Risk From Low-Dose Radiation Exposures: What Does the Evidence Say?

    SciTech Connect

    Bushberg, J; Boreham, D; Ulsh, B

    2014-06-15

    At dose levels of (approximately) 500 mSv or more, increased cancer incidence and mortality have been clearly demonstrated. However, at the low doses of radiation used in medical imaging, the relationship between dose and cancer risk is not well established. As such, assumptions about the shape of the dose-response curve are made. These assumptions, or risk models, are used to estimate potential long term effects. Common models include 1) the linear non-threshold (LNT) model, 2) threshold models with either a linear or curvilinear dose response above the threshold, and 3) a hormetic model, where the risk is initially decreased below background levels before increasing. The choice of model used when making radiation risk or protection calculations and decisions can have significant implications on public policy and health care decisions. However, the ongoing debate about which risk model best describes the dose-response relationship at low doses of radiation makes informed decision making difficult. This symposium will review the two fundamental approaches to determining the risk associated with low doses of ionizing radiation, namely radiation epidemiology and radiation biology. The strengths and limitations of each approach will be reviewed, the results of recent studies presented, and the appropriateness of different risk models for various real world scenarios discussed. Examples of well-designed and poorly-designed studies will be provided to assist medical physicists in 1) critically evaluating publications in the field and 2) communicating accurate information to medical professionals, patients, and members of the general public. Equipped with the best information that radiation epidemiology and radiation biology can currently provide, and an understanding of the limitations of such information, individuals and organizations will be able to make more informed decisions regarding questions such as 1) how much shielding to install at medical facilities, 2) at

  8. Radiation leukaemogenesis at low doses DE-FG02-05 ER 63947 Final Technical Report 15 May 2005; 14 May 2010

    SciTech Connect

    Bouffler, Simon

    2010-07-28

    This report provides a complete summary of the work undertaken and results obtained under US Department of Energy grant DF-FG02-05 ER 63947, Radiation leukaemogenesis at low doses. There is ample epidemiological evidence indicating that ionizing radiation is carcinogenic in the higher dose range. This evidence, however, weakens and carries increasing uncertainties at doses below 100-200 mSv. At these low dose levels the form of the dose-response curve for radiation-induced cancer cannot be determined reliably or directly from studies of human populations. Therefore animal, cellular and other experimental systems must be employed to provide supporting evidence on which to base judgements of risk at low doses. Currently in radiological protection a linear non-threshold (LNT) extrapolation of risk estimates derived from human epidemiological studies is used to estimate risks in the dose range of interest for protection purposes. Myeloid leukaemias feature prominently among the cancers associated with human exposures to ionising radiation (eg UNSCEAR 2006; IARC 2000). Good animal models of radiation-induced acute myeloid leukaemia (AML) are available including strains such as CBA, RFM and SJL (eg Major and Mole 1978; Ullrich et al 1976; Resnitzky et al 1985). Early mechanistic studies using cytogenetic methods in these mouse models established that the majority of radiation-induced AMLs carried substantial interstitial deletions in one copy of chromosome (chr) 2 (eg Hayata et al 1983; Trakhtenbrot et al 1988; Breckon et al 1991; Rithidech et al 1993; Bouffler et al 1996). Chr2 aberrations are known to occur in bone marrow cells as early as 24 hours after in vivo irradiation (Bouffler et al 1997). Subsequent molecular mapping studies defined a distinct region of chr2 that is commonly lost in AMLs (Clark et al 1996; Silver et al 1999). Further, more detailed, analysis identified point mutations at a specific region of the Sfpi1/PU.1 haemopoietic transcription factor gene

  9. A Kilogauss-scale, High-vacuum Toroidal Electron Plasma Experiment

    SciTech Connect

    Marler, J. P.; Stoneking, M. R.

    2006-10-18

    We describe in detail the newly constructed Lawrence Non-Neutral Torus (LNT) II apparatus. The LNT II features an improved toroidal magnetic field magnitude ({approx} 1 kG) and base vacuum pressure (<10-9 Torr). A segmented Au-plated Al electrode shell contributes to the reduction in field asymmetries and enables enhanced diagnostic capabilities. Additionally, the electron source is located on a retractable bellows for study of confinement dynamics in a complete torus. Conservative estimates suggest confinement times on the order of 1 second are achievable which would represent almost two orders of magnitude improvement over measurements made with the previous apparatus.

  10. Plant Physiological, Morphological and Yield-Related Responses to Night Temperature Changes across Different Species and Plant Functional Types.

    PubMed

    Jing, Panpan; Wang, Dan; Zhu, Chunwu; Chen, Jiquan

    2016-01-01

    Land surface temperature over the past decades has shown a faster warming trend during the night than during the day. Extremely low night temperatures have occurred frequently due to the influence of land-sea thermal difference, topography and climate change. This asymmetric night temperature change is expected to affect plant ecophysiology and growth, as the plant carbon consumption processes could be affected more than the assimilation processes because photosynthesis in most plants occurs during the daytime whereas plant respiration occurs throughout the day. The effects of high night temperature (HNT) and low night temperature (LNT) on plant ecophysiological and growing processes and how the effects vary among different plant functional types (PFTs) have not been analyzed extensively. In this meta-analysis, we examined the effect of HNT and LNT on plant physiology and growth across different PFTs and experimental settings. Plant species were grouped according to their photosynthetic pathways (C3, C4, and CAM), growth forms (herbaceous, woody), and economic purposes (crop, non-crop). We found that HNT and LNT both had a negative effect on plant yield, but the effect of HNT on plant yield was primarily related to a reduction in biomass allocation to reproduction organs and the effect of LNT on plant yield was more related to a negative effect on total biomass. Leaf growth was stimulated at HNT and suppressed at LNT. HNT accelerated plants ecophysiological processes, including photosynthesis and dark respiration, while LNT slowed these processes. Overall, the results showed that the effects of night temperature on plant physiology and growth varied between HNT and LNT, among the response variables and PFTs, and depended on the magnitude of temperature change and experimental design. These findings suggest complexities and challenges in seeking general patterns of terrestrial plant growth in HNT and LNT. The PFT specific responses of plants are critical for

  11. Plant Physiological, Morphological and Yield-Related Responses to Night Temperature Changes across Different Species and Plant Functional Types

    PubMed Central

    Jing, Panpan; Wang, Dan; Zhu, Chunwu; Chen, Jiquan

    2016-01-01

    Land surface temperature over the past decades has shown a faster warming trend during the night than during the day. Extremely low night temperatures have occurred frequently due to the influence of land-sea thermal difference, topography and climate change. This asymmetric night temperature change is expected to affect plant ecophysiology and growth, as the plant carbon consumption processes could be affected more than the assimilation processes because photosynthesis in most plants occurs during the daytime whereas plant respiration occurs throughout the day. The effects of high night temperature (HNT) and low night temperature (LNT) on plant ecophysiological and growing processes and how the effects vary among different plant functional types (PFTs) have not been analyzed extensively. In this meta-analysis, we examined the effect of HNT and LNT on plant physiology and growth across different PFTs and experimental settings. Plant species were grouped according to their photosynthetic pathways (C3, C4, and CAM), growth forms (herbaceous, woody), and economic purposes (crop, non-crop). We found that HNT and LNT both had a negative effect on plant yield, but the effect of HNT on plant yield was primarily related to a reduction in biomass allocation to reproduction organs and the effect of LNT on plant yield was more related to a negative effect on total biomass. Leaf growth was stimulated at HNT and suppressed at LNT. HNT accelerated plants ecophysiological processes, including photosynthesis and dark respiration, while LNT slowed these processes. Overall, the results showed that the effects of night temperature on plant physiology and growth varied between HNT and LNT, among the response variables and PFTs, and depended on the magnitude of temperature change and experimental design. These findings suggest complexities and challenges in seeking general patterns of terrestrial plant growth in HNT and LNT. The PFT specific responses of plants are critical for

  12. Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal?**

    EPA Science Inventory

    Nonmonotonic Dose-Response Curves and Endocrine-Disrupting Chemicals: Fact or Falderal? The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncanc...

  13. Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? ###SETAC

    EPA Science Inventory

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. Recently, claims have arisen tha...

  14. NONMONOTONIC DOSE RESPONSE CURVES (NMDRCS) ARE COMMON AFTER ESTROGEN OR ANDROGEN SIGNALING PATHWAY DISRUPTION. FACT OR FALDERAL?

    EPA Science Inventory

    ABSTRACT BODY: The shape of the dose response curve in the low dose region has been debated since the 1940s, originally focusing on linear no threshold (LNT) versus threshold responses for cancer and noncancer effects. Recently, it has been claimed that endocrine disrupters (EDCs...

  15. Synergies of PCCI-Type Combustion and Lean NOx Trap Catalysis for Diesel Engines

    SciTech Connect

    Parks, II, James E; Prikhodko, Vitaly Y; Kass, Michael D; Huff, Shean P

    2008-01-01

    It is widely recognized that future NOx and PM emission targets for diesel engines cannot be met solely via advanced combustion over the full engine drive cycle. Therefore some combination of advanced combustion methodology with an aftertreatment technology will be required. In this study, NOx reduction, fuel efficiency, and regeneration performance of lean NOx trap (LNT) were evaluated for four operating conditions. The combustion approaches included baseline engine operation with and without EGR, two exhaust enrichment methods (post injection and delayed injection), and one advanced combustion mode to enable high efficiency clean combustion (HECC). A 1.7 liter 4-cylinder diesel engine was operated under five conditions, which represent key interest points for light-duty diesel operation. At the low load setting the exhaust temperature was too low to enable LNT regeneration and oxidation; however, HECC (low NOx) was achievable. HECC was also reached under more moderate loads and the exhaust temperatures were high enough to enable even further NOx reductions by the LNT. At high loads HECC becomes difficult but the LNT performance improves and acceptable regeneration can be met with enrichment methodologies.

  16. Investigation of the Dielectric Strength of Syntactic Foam at 77 K under DC Stress

    NASA Astrophysics Data System (ADS)

    Winkel, D.; Puffer, R.; Schnettler, A.

    2014-05-01

    Liquid nitrogen (LN2) based electrical insulation systems for superconducting equipment of electrical power distribution networks are state of the art. Since LN2 is a cryogenic liquid it has some disadvantages when used as insulation. This paper deals with syntactic foam as an alternative insulation system for superconducting apparatus. Syntactic foam is a composite material consisting of a polymeric matrix and embedded hollow microspheres with diameters of several 10 μp?. As hollow microspheres are gas-filled, using those as filling material features significant reductions of the relative permittivity and of the thermal contraction due to cooling the material to liquid nitrogen temperature (LNT, T = 77 K). In this study both an epoxy resin (ER) and an unsaturated polyester resin (UPR) serve as matrix material. The hollow microspheres used in this investigation are made of untreated and silanized glass. The results of measurements of the dielectric DC strength show, that the dielectric strength of all investigated syntactic foam compositions are significantly higher at LNT compared to ambient temperature (AT). Furthermore, the effect of a higher dielectric strength of syntactic foam with silanized glass spheres at ambient temperature vanishes at LNT. Hence, the dielectric strength at LNT is unaffected by silanization of glass microspheres.

  17. Structure-based rationale for differential recognition of lacto- and neolacto- series glycosphingolipids by the N-terminal domain of human galectin-8

    NASA Astrophysics Data System (ADS)

    Bohari, Mohammad H.; Yu, Xing; Zick, Yehiel; Blanchard, Helen

    2016-12-01

    Glycosphingolipids are ubiquitous cell surface molecules undertaking fundamental cellular processes. Lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are the representative core structures for lacto- and neolacto-series glycosphingolipids. These glycolipids are the carriers to the blood group antigen and human natural killer antigens mainly found on blood cells, and are also principal components in human milk, contributing to infant health. The β-galactoside recognising galectins mediate various cellular functions of these glycosphingolipids. We report crystallographic structures of the galectin-8 N-terminal domain (galectin-8N) in complex with LNT and LNnT. We reveal the first example in which the non-reducing end of LNT binds to the primary binding site of a galectin, and provide a structure-based rationale for the significant ten-fold difference in binding affinities of galectin-8N toward LNT compared to LNnT, such a magnitude of difference not being observed for any other galectin. In addition, the LNnT complex showed that the unique Arg59 has ability to adopt a new orientation, and comparison of glycerol- and lactose-bound galectin-8N structures reveals a minimum atomic framework for ligand recognition. Overall, these results enhance our understanding of glycosphingolipids interactions with galectin-8N, and highlight a structure-based rationale for its significantly different affinity for components of biologically relevant glycosphingolipids.

  18. ENERGY EFFICIENT THERMAL MANAGEMENT FOR NATURAL GAS ENGINE AFTERTREATMENT VIA ACTIVE FLOW CONTROL

    SciTech Connect

    David K. Irick; Ke Nguyen

    2004-04-01

    The project is focused on the development of an energy efficient aftertreatment system capable of reducing NOx and methane by 90% from lean-burn natural gas engines by applying active exhaust flow control. Compared to conventional passive flow-through reactors, the proposed scheme cuts supplemental energy by 50%-70%. The system consists of a Lean NOx Trap (LNT) system and an oxidation catalyst. Through alternating flow control, a major amount of engine exhaust flows through a large portion of the LNT system in the absorption mode, while a small amount of exhaust goes through a small portion of the LNT system in the regeneration or desulfurization mode. By periodically reversing the exhaust gas flow through the oxidation catalyst, a higher temperature profile is maintained in the catalyst bed resulting in greater efficiency of the oxidation catalyst at lower exhaust temperatures. The project involves conceptual design, theoretical analysis, computer simulation, prototype fabrication, and empirical studies. This report details the progress during the first twelve months of the project. The primary activities have been to develop the bench flow reactor system, develop the computer simulation and modeling of the reverse-flow oxidation catalyst, install the engine into the test cell, and begin design of the LNT system.

  19. The debate on the use of linear no threshold for assessing the effects of low doses.

    PubMed

    Tubiana, M; Aurengo, A; Averbeck, D; Masse, R

    2006-09-01

    From December 2004 to July 2005, three reports on the effects of low doses of ionising radiation were released: ICRP (2004), the joint report of the French Academies of Science and Medicine (Tubiana et al 2005), and a report from the American Academy of Sciences (BEIR VII 2005). These reports quote the same recent articles on the biological effects of low doses, yet their conclusions diverge. The French report concludes that recent biological data show that the efficacy of defense mechanisms is modulated by dose and dose rate and that linear no threshold (LNT) is no longer plausible. The ICRP and the BEIR VII reports recognise that there are biologic arguments against LNT but feel that there are not sufficient biological proofs against it to change risk assessment methodology and subsequent regulatory policy based on LNT. They point out the remaining uncertainties and the lack of mechanistic explanations of phenomena such as low dose hyperlethality or the adaptive response. In this context, a critical analysis of the available data is necessary. The epidemiological data and the experimental data challenge the validity of the LNT hypothesis for assessing the carcinogenic effect of low doses, but do not allow its exclusion. Therefore, the main criteria for selecting the most reliable dose-effect relationship from a scientific point of view should be based on biological data. Their analysis should help one to understand the current controversy.

  20. Dose Response Data for Hormonally Active Chemicals ...

    EPA Pesticide Factsheets

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the default assumption is that noncancer effects generally display threshold rather than LNT responses. More recently, claims have arisen that the chemicals, like endocrine disrupters (EDS), which act via high affinity, low capacity nuclear receptors, may display LNT or nonmonotonic low dose responses: responses that could be missed in multigenerational guideline toxicity testing. This presentation will discuss LNT, threshold and nonmonotonic dose response relationships from case studies of chemicals that disrupt reproductive development and function via the ER, AR and AhR pathways and will include in vitro and in vivo multigenerational data. The in vivo studies in this discussion include only robust, well designed, comprehensive studies that administered the chemical via a relevant route(s) of exposure over a broad dose response range, including low dose(s) in the microgram/kg/d range. The chemicals include ethinyl estradiol, estradiol, genistein, bisphenol a, trenbolone, finasteride, flutamide, phthalate esters and 2,3,7,8 TCDD. The objective is to critically evaluate the data from well done studies in this field to address concerns that current multigenerational reproductive test gui

  1. Energy Efficient Thermal Management for Natural Gas Engine Aftertreatment via Active Flow Control

    SciTech Connect

    David K. Irick; Ke Nguyen; Vitacheslav Naoumov; Doug Ferguson

    2006-04-01

    The project is focused on the development of an energy efficient aftertreatment system capable of reducing NOx and methane by 90% from lean-burn natural gas engines by applying active exhaust flow control. Compared to conventional passive flow-through reactors, the proposed scheme cuts supplemental energy by 50%-70%. The system consists of a Lean NOx Trap (LNT) system and an oxidation catalyst. Through alternating flow control, a major amount of engine exhaust flows through a large portion of the LNT system in the absorption mode, while a small amount of exhaust goes through a small portion of the LNT system in the regeneration or desulfurization mode. By periodically reversing the exhaust gas flow through the oxidation catalyst, a higher temperature profile is maintained in the catalyst bed resulting in greater efficiency of the oxidation catalyst at lower exhaust temperatures. The project involves conceptual design, theoretical analysis, computer simulation, prototype fabrication, and empirical studies. This report details the progress during the first twelve months of the project. The primary activities have been to develop the bench flow reactor system, develop the computer simulation and modeling of the reverse-flow oxidation catalyst, install the engine into the test cell, and begin design of the LNT system.

  2. Energy Efficient Thermal Management for Natural Gas Engine Aftertreatment via Active Flow Control

    SciTech Connect

    David K. Irick; Ke Nguyen; Vitacheslav Naoumov; Doug Ferguson

    2005-04-01

    The project is focused on the development of an energy efficient aftertreatment system capable of reducing NOx and methane by 90% from lean-burn natural gas engines by applying active exhaust flow control. Compared to conventional passive flow-through reactors, the proposed scheme cuts supplemental energy by 50%-70%. The system consists of a Lean NOx Trap (LNT) system and an oxidation catalyst. Through alternating flow control, a major amount of engine exhaust flows through a large portion of the LNT system in the absorption mode, while a small amount of exhaust goes through a small portion of the LNT system in the regeneration or desulfurization mode. By periodically reversing the exhaust gas flow through the oxidation catalyst, a higher temperature profile is maintained in the catalyst bed resulting in greater efficiency of the oxidation catalyst at lower exhaust temperatures. The project involves conceptual design, theoretical analysis, computer simulation, prototype fabrication, and empirical studies. This report details the progress during the first twelve months of the project. The primary activities have been to develop the bench flow reactor system, develop the computer simulation and modeling of the reverse-flow oxidation catalyst, install the engine into the test cell, and begin design of the LNT system.

  3. Commentary: ethical issues of current health-protection policies on low-dose ionizing radiation.

    PubMed

    Socol, Yehoshua; Dobrzyński, Ludwik; Doss, Mohan; Feinendegen, Ludwig E; Janiak, Marek K; Miller, Mark L; Sanders, Charles L; Scott, Bobby R; Ulsh, Brant; Vaiserman, Alexander

    2014-05-01

    The linear no-threshold (LNT) model of ionizing-radiation-induced cancer is based on the assumption that every radiation dose increment constitutes increased cancer risk for humans. The risk is hypothesized to increase linearly as the total dose increases. While this model is the basis for radiation safety regulations, its scientific validity has been questioned and debated for many decades. The recent memorandum of the International Commission on Radiological Protection admits that the LNT-model predictions at low doses are "speculative, unproven, undetectable and 'phantom'." Moreover, numerous experimental, ecological, and epidemiological studies show that low doses of sparsely-ionizing or sparsely-ionizing plus highly-ionizing radiation may be beneficial to human health (hormesis/adaptive response). The present LNT-model-based regulations impose excessive costs on the society. For example, the median-cost medical program is 5000 times more cost-efficient in saving lives than controlling radiation emissions. There are also lives lost: e.g., following Fukushima accident, more than 1000 disaster-related yet non-radiogenic premature deaths were officially registered among the population evacuated due to radiation concerns. Additional negative impacts of LNT-model-inspired radiophobia include: refusal of some patients to undergo potentially life-saving medical imaging; discouragement of the study of low-dose radiation therapies; motivation for radiological terrorism and promotion of nuclear proliferation.

  4. Structure-based rationale for differential recognition of lacto- and neolacto- series glycosphingolipids by the N-terminal domain of human galectin-8

    PubMed Central

    Bohari, Mohammad H.; Yu, Xing; Zick, Yehiel; Blanchard, Helen

    2016-01-01

    Glycosphingolipids are ubiquitous cell surface molecules undertaking fundamental cellular processes. Lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are the representative core structures for lacto- and neolacto-series glycosphingolipids. These glycolipids are the carriers to the blood group antigen and human natural killer antigens mainly found on blood cells, and are also principal components in human milk, contributing to infant health. The β-galactoside recognising galectins mediate various cellular functions of these glycosphingolipids. We report crystallographic structures of the galectin-8 N-terminal domain (galectin-8N) in complex with LNT and LNnT. We reveal the first example in which the non-reducing end of LNT binds to the primary binding site of a galectin, and provide a structure-based rationale for the significant ten-fold difference in binding affinities of galectin-8N toward LNT compared to LNnT, such a magnitude of difference not being observed for any other galectin. In addition, the LNnT complex showed that the unique Arg59 has ability to adopt a new orientation, and comparison of glycerol- and lactose-bound galectin-8N structures reveals a minimum atomic framework for ligand recognition. Overall, these results enhance our understanding of glycosphingolipids interactions with galectin-8N, and highlight a structure-based rationale for its significantly different affinity for components of biologically relevant glycosphingolipids. PMID:28000747

  5. Revisiting the gram-negative lipoprotein paradigm

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The processing of lipoproteins (lpps) in Gram-negative bacteria is generally considered to be an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein n-acyltransferase. The mature lipoproteins are then sorted...

  6. A Participative and Individualized Laboratory: A Strategy for Increasing Student Success in College-Level Math Courses

    ERIC Educational Resources Information Center

    Toro Clarke, Jose Antonio

    2016-01-01

    This research was carried out within a qualitative research paradigm. The objective was to observe, analyze and enrich pedagogical practice through the use of pedagogical learning strategies. The learning strategy was a participative and individualized lab carried out during a research project in a non-Traditional Laboratory (LnT). The primary aim…

  7. Dose Response Data for Hormonally Active Chemicals: Estrogens, Antiandrogens and Androgens

    EPA Science Inventory

    The shape of the dose response curve in the low dose region has been debated since the late 1940s. The debate originally focused on linear no threshold (LNT) vs threshold responses in the low dose range for cancer and noncancer related effects. For noncancer effects the defaul...

  8. Practical Approaches for Teaching Leave No Trace.

    ERIC Educational Resources Information Center

    Attarian, Aram

    As participation in outdoor recreation grows, natural resources suffer a variety of environmental and social impacts. A minimum-impact back country educational program first developed during the 1970s, Leave No Trace (LNT), has been revitalized by the National Outdoor Leadership School, six federal agencies, and members of the outdoor products…

  9. Revisiting the Gram-Negative Lipoprotein Paradigm

    PubMed Central

    LoVullo, Eric D.; Wright, Lori F.; Isabella, Vincent; Huntley, Jason F.

    2015-01-01

    ABSTRACT The processing of lipoproteins (Lpps) in Gram-negative bacteria is generally considered an essential pathway. Mature lipoproteins in these bacteria are triacylated, with the final fatty acid addition performed by Lnt, an apolipoprotein N-acyltransferase. The mature lipoproteins are then sorted by the Lol system, with most Lpps inserted into the outer membrane (OM). We demonstrate here that the lnt gene is not essential to the Gram-negative pathogen Francisella tularensis subsp. tularensis strain Schu or to the live vaccine strain LVS. An LVS Δlnt mutant has a small-colony phenotype on sucrose medium and increased susceptibility to globomycin and rifampin. We provide data indicating that the OM lipoprotein Tul4A (LpnA) is diacylated but that it, and its paralog Tul4B (LpnB), still sort to the OM in the Δlnt mutant. We present a model in which the Lol sorting pathway of Francisella has a modified ABC transporter system that is capable of recognizing and sorting both triacylated and diacylated lipoproteins, and we show that this modified system is present in many other Gram-negative bacteria. We examined this model using Neisseria gonorrhoeae, which has the same Lol architecture as that of Francisella, and found that the lnt gene is not essential in this organism. This work suggests that Gram-negative bacteria fall into two groups, one in which full lipoprotein processing is essential and one in which the final acylation step is not essential, potentially due to the ability of the Lol sorting pathway in these bacteria to sort immature apolipoproteins to the OM. IMPORTANCE This paper describes the novel finding that the final stage in lipoprotein processing (normally considered an essential process) is not required by Francisella tularensis or Neisseria gonorrhoeae. The paper provides a potential reason for this and shows that it may be widespread in other Gram-negative bacteria. PMID:25755189

  10. Effects of Rapid High Temperature Cyclic Aging on a Fully-Formulated Lean NOx Trap Catalyst

    SciTech Connect

    Ottinger, Nathan; Nguyen, Ke; Bunting, Bruce G; Toops, Todd J; Howe, Janet E

    2009-01-01

    In this study, high-temperature deactivation of a fully-formulated lean NOx trap (LNT) is investigated with an accelerated aging protocol where accelerated aging is accomplished by rapid temperature cycling and by higher temperatures. Thermal aging is carried out in a bench-flow reactor at nominal temperatures of 700, 800, 900, and 1000 C using an aging cycle consisting of a 130s lean-phase and a 50s rich-phase. After a prescribed number of lean/rich aging cycles, the NOx conversion of the aged LNT is evaluated at 200, 300, and 400 C. The NOx performance is obtained at a GHSV of 30,000 h-1 using an evaluation cycle consisting of a 60s lean-phase and 5s rich-phase. The effects of aging on the LNT washcoat are determined with EPMA, XRD, STEM/EDS, and BET. Aging at 700 and 800 C has a minimal effect on LNT performance and material properties. However, at aging temperatures of 900 and 1000 C reduction in surface area and sintering of PGM particles are observed and result in a drastic reduction in NOx conversion. Additionally, after aging at 900 C and 1000 C the NOx storage medium, BaCO3, is no longer visible in the XRD patterns, even though a Ba-phase identified by EPMA still exists in all aged samples. BaAl2O4 is not identified at any aging temperatures; possibly due to stabilization effects provided by washcoat additives present in this particular LNT.

  11. Emissions from premixed charge compression ignition (PCCI) combustion and affect on emission control devices

    SciTech Connect

    Parks, II, James E; Kass, Michael D; Huff, Shean P; Barone, Teresa L; Lewis Sr, Samuel Arthur; Prikhodko, Vitaly Y; Storey, John Morse

    2010-01-01

    A light-duty diesel engine has been operated in advanced combustion modes known generally as premixed charge compression ignition (PCCI). The emissions have been characterized for several load and speed combinations. Fewer NO{sub x} and particulate matter (PM) emissions are produced by PCCI, but higher CO and hydrocarbon (HC) emissions result. In addition, the nature of the PM differs from conventional combustion; the PM is smaller and has a much higher soluble organic fraction (SOF) content (68% vs. 30% for conventional combustion). Three catalyst technologies were studied to determine the affects of HECC on catalyst performance; the technologies were a lean NO{sub x} trap (LNT), diesel oxidation catalyst (DOC), and diesel particulate filter (DPF). The LNT benefited greatly from the reduced NO{sub x} emissions associated with PCCI. NO{sub x} capacity requirements are reduced as well as overall tailpipe NO{sub x} levels particularly at low load and temperature conditions where regeneration of the LNT is difficult. The DOC performance requirements for PCCI are more stringent due to the higher CO and HC emissions; however, the DOC was effective at controlling the higher CO and HC emissions at conditions above the light-off temperature. Below light-off, CO and HC emissions are problematic. The study of DPF technology focused on the fuel penalties associated with DPF regeneration or 'desoot' due to the different PM loading rates from PCCI vs. conventional combustion. Less frequent desoot events were required from the lower PM from PCCI and, when used in conjunction with an LNT, the lower PM from less frequent LNT regeneration. The lower desoot frequency leads a {approx}3% fuel penalty for a mixture of PCCI and conventional loads vs. {approx}4% for conventional only combustion.

  12. CLEERS Aftertreatment Modeling and Analysis

    SciTech Connect

    Devarakonda, Maruthi N.; Herling, Darrell R.; Kim, Do Heui; Kwak, Ja Hun; Peden, Charles HF; Stewart, Mark L.; Strzelec, Andrea; Szanyi, Janos; Tran, Diana N.; Lee, Jong H.

    2012-02-08

    DOE FY 2011 Advanced Combustion Technologies Annual Report. CLEERS is a research and development focus project of the Diesel Cross-Cut Team. The overall objective is to promote the development of improved computational tools for simulating realistic full-system performance of lean-burn engines and the associated emissions control systems. Three fundamental research projects are sponsored at PNNL through CLEERS: DPF, SCR, and LNT. Resources are shared between the three efforts in order to actively respond to current industrial needs. In FY 2011, more emphasis was placed on the SCR and LNT activities because of urgent application issues associated with these technologies. Objectives of this project are to lead and contribute to the Cross-Cut Lean Exhaust Emissions Reduction Simulations (CLEERS) activities - (a) Provide project updates to the industry sub-team, solicit feedback, and adjust work scope accordingly; and (b) Lead technical discussions, invite distinguished speakers, and maintain an open dialogue on selective catalytic reduction (SCR), lean-NOx trap (LNT), and diesel particulate filter (DPF) modeling issues. Fiscal Year (FY) 2011 Objectives are to: (1) Develop improved modeling capabilities for SCR and DPFs through fundamental experiments; and (2) Develop a fundamental understanding of SCR and LNT catalysts with primary focus on reaction mechanisms and material characterization. Some accomplishments are: (1) Participated in monthly CLEERS teleconferences and coordinated the calls focused on SCR, LNT and DPF technologies; (2) Updated PNNL's SCR model for the state-of-the-art commercial Cu-zeolite SCR catalyst to extract kinetic parameters and to quantitatively describe the effects of hydrothermal aging; (3) Examined the effects of hydrothermal aging on the physicochemical properties and SCR reactions using the commercial Cu catalyst in collaboration with Oak Ridge National Laboratory (ORNL); (4) Investigated the nature of Cu species and obtained kinetic

  13. Forward sum rule for the 2 γ -exchange correction to the charge-radius extraction from elastic electron scattering

    NASA Astrophysics Data System (ADS)

    Gorchtein, Mikhail

    2014-11-01

    Two-photon-exchange (TPE) contributions to elastic electron-proton scattering in the forward regime in leading logarithmic ˜t ln|t | approximation in the momentum transfer t are considered. The imaginary part of the TPE amplitude in the forward kinematics is related to the total photoabsorption cross section. The real part of the TPE amplitude is obtained from an unsubtracted fixed-t dispersion relation. This allows a clean prediction of the real part of the TPE amplitude at forward angles with the leading term ˜t ln|t | . Numerical estimates are comparable with or exceed the experimental precision in extracting the charge radius from the experimental data.

  14. Bifidobacterium breve UCC2003 metabolises the human milk oligosaccharides lacto-N-tetraose and lacto-N-neo-tetraose through overlapping, yet distinct pathways

    PubMed Central

    James, Kieran; Motherway, Mary O’Connell; Bottacini, Francesca; van Sinderen, Douwe

    2016-01-01

    In this study, we demonstrate that the prototype B. breve strain UCC2003 possesses specific metabolic pathways for the utilisation of lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT), which represent the central moieties of Type I and Type II human milk oligosaccharides (HMOs), respectively. Using a combination of experimental approaches, the enzymatic machinery involved in the metabolism of LNT and LNnT was identified and characterised. Homologs of the key genetic loci involved in the utilisation of these HMO substrates were identified in B. breve, B. bifidum, B. longum subsp. infantis and B. longum subsp. longum using bioinformatic analyses, and were shown to be variably present among other members of the Bifidobacterium genus, with a distinct pattern of conservation among human-associated bifidobacterial species. PMID:27929046

  15. Using numerical simulations to extract parameters of toroidal electron plasmas from experimental data

    SciTech Connect

    Ha, B. N.; Stoneking, M. R.; Marler, J. P.

    2009-03-15

    Measurements of the image charge induced on electrodes provide the primary means of diagnosing plasmas in the Lawrence Non-neutral Torus II (LNT II) [Phys. Rev. Lett. 100, 155001 (2008)]. Therefore, it is necessary to develop techniques that determine characteristics of the electron plasma from features of the induced image charge signal. This paper presents a numerical study which finds that the frequency of the image charge signal due to the toroidal version of the m=1 diocotron mode is proportional to the total trapped charge and inversely proportional to magnetic field strength, as in the cylindrical case. In the toroidal case, additional information about the m=1 motion of the plasma can be obtained by analysis of the image charge signal amplitude and shape. Finally, results from the numerical simulations are compared to experimental data from the LNT II and plasma characteristics are reported.

  16. Low Noise Performance Perspectives Of Wideband Aperture Phased Arrays

    NASA Astrophysics Data System (ADS)

    Woestenburg, E. E. M.; Kuenen, J. C.

    2004-06-01

    A general analysis of phased array noise properties and measurements, applied to one square meter tiles of the Thousand Element Array (THEA), has resulted in a procedure to define the noise budget for a THEA-tile (Woestenburg and Dijkstra, 2003). The THEA system temperature includes LNA and receiver noise, antenna connecting loss, noise coupling between antenna elements and other possible contributions. This paper discusses the various noise contributions to the THEA system temperature and identifies the areas where improvement can be realized. We will present better understanding of the individual noise contributions using measurements and analysis of single antenna/receiver elements. An improved design for a 1-m2 Low Noise Tile (LNT) will be discussed and optimized low noise performance for the LNT is presented. We will also give future perspectives of the noise performance for such tiles, in relation to the requirements for SKA in the 1 GHz frequency range.

  17. Lean Gasoline Engine Reductant Chemistry During Lean NOx Trap Regeneration

    SciTech Connect

    Choi, Jae-Soon; Prikhodko, Vitaly Y; Partridge Jr, William P; Parks, II, James E; Norman, Kevin M; Huff, Shean P; Chambon, Paul H; Thomas, John F

    2010-01-01

    Lean NOx Trap (LNT) catalysts can effectively reduce NOx from lean engine exhaust. Significant research for LNTs in diesel engine applications has been performed and has led to commercialization of the technology. For lean gasoline engine applications, advanced direct injection engines have led to a renewed interest in the potential for lean gasoline vehicles and, thereby, a renewed demand for lean NOx control. To understand the gasoline-based reductant chemistry during regeneration, a BMW lean gasoline vehicle has been studied on a chassis dynamometer. Exhaust samples were collected and analyzed for key reductant species such as H2, CO, NH3, and hydrocarbons during transient drive cycles. The relation of the reductant species to LNT performance will be discussed. Furthermore, the challenges of NOx storage in the lean gasoline application are reviewed.

  18. CLEERS Aftertreatment Modeling and Analysis

    SciTech Connect

    Devarakonda, Maruthi N.; Kim, Do Heui; Kwak, Ja Hun; Lee, Jong H.; Peden, Charles HF; Stewart, Mark L.; Szanyi, Janos; Tonkyn, Russell G.; Tran, Diana N.; Zelenyuk, Alla; Herling, Darrell R.

    2009-12-01

    Cross-Cut Lean Exhaust Emissions Reduction Simulations (CLEERS) is a R&D focus project of the Diesel Cross-Cut Team. The overall objective is to promote the development of improved computational tools for simulating realistic full-system performance of lean-burn engines and the associated emissions control systems. Three fundamental research projects are sponsored at Pacific Northwest National Laboratory through CLEERS, focusing on the three most prominent technologies for diesel exhaust after-treatment: • Diesel Particulate Filters (DPF) • Selective Catalytic Reduction (SCR) • Lean NOX Traps (LNT) Resources are shared between the three efforts in order to actively respond to current industrial needs. In FY09, more emphasis was placed on the SCR and LNT activities because of urgent application issues associated with these technologies.

  19. A Certified Health Physicist’s Reflections on a 40-Year Career in Radiation Protection

    PubMed Central

    2016-01-01

    This is a reflection from a certified health physicist regarding his becoming aware, during his 40-year career, that the linear no-threshold (LNT) model and the associated As Low As Reasonably Achievable concept have no scientific basis and make no positive contribution to radiation safety. They should be replaced by an alternative, scientifically based model that includes a threshold, below which there is no harm, and recognition of hormesis and the adaptive response, which reflect the benefits of low-dose and low-dose-rate radiation exposure. Continued use of the unscientific LNT model is not conservative, as most regulators complacently claim but actually harmful. Examples of these harmful impacts in the areas of nuclear power, nuclear medicine, and environmental management are included. PMID:27867322

  20. Effect of sulfur loading on the desulfation chemistry of a commercial lean NOx trap catalyst

    SciTech Connect

    Kim, Do Heui; Yezerets, Aleksey; Li, Junhui; Currier, Neal; Chen, Haiying; Hess, Howard ..; Engelhard, Mark H.; Muntean, George G.; Peden, Charles HF

    2012-12-15

    We investigate the effects of initial sulfur loadings on the desulfation chemistry and the subsequent final activity of a commercial LNT catalyst. Identical total amounts of SO2 are applied to the samples, albeit with the frequency of desulfation varied. The results indicate that performance is better with less frequent desulfations. The greater the amount of sulfur deposited before desulfation, the more amount of SO2 evolution before H2S is observed during desulfation, which can be explained by two sequential reactions; initial conversion of sulfate to SO2, followed by the reduction of SO2 to H2S. After completing all sulfation/desulfation steps, the sample with only a single desulfation results in a fairly uniform sulfur distribution along the z-axis inside of the monolith. We expect that the results obtained in this study will provide useful information for optimizing regeneration strategies in vehicles that utilize the LNT technology.

  1. The Healthy Worker Effect and Nuclear Industry Workers

    PubMed Central

    Fornalski, Krzysztof W.; Dobrzyński, Ludwik

    2010-01-01

    The linear no-threshold (LNT) dose-effect relationship has been consistently used by most radiation epidemiologists to estimate cancer mortality risk. The large scattering of data by International Agency for Research on Cancer, IARC (Vrijheid et al. 2007; Therry-Chef et al. 2007; Cardis et al. 2007), interpreted in accordance with LNT, has been previously demonstrated (Fornalski and Dobrzyński 2009). Using conventional and Bayesian methods the present paper demonstrates that the standard mortality ratios (SMRs), lower in the IARC cohort of exposed nuclear workers than in the non exposed group, should be considered as a hormetic effect, rather than a healthy worker effect (HWE) as claimed by the IARC group. PMID:20585442

  2. Cathodoluminescence microscopy and spectroscopy of micro- and nanodiamonds: an implication for laboratory astrophysics.

    PubMed

    Gucsik, Arnold; Nishido, Hirotsugu; Ninagawa, Kiyotaka; Ott, Ulrich; Tsuchiyama, Akira; Kayama, Masahiro; Simonia, Irakli; Boudou, Jean-Paul

    2012-12-01

    Color centers in selected micro- and nanodiamond samples were investigated by cathodoluminescence (CL) microscopy and spectroscopy at 298 K [room temperature (RT)] and 77 K [liquid-nitrogen temperature (LNT)] to assess the value of the technique for astrophysics. Nanodiamonds from meteorites were compared with synthetic diamonds made with different processes involving distinct synthesis mechanisms (chemical vapor deposition, static high pressure high temperature, detonation). A CL emission peak centered at around 540 nm at 77 K was observed in almost all of the selected diamond samples and is assigned to the dislocation defect with nitrogen atoms. Additional peaks were identified at 387 and 452 nm, which are related to the vacancy defect. In general, peak intensity at LNT at the samples was increased in comparison to RT. The results indicate a clear temperature-dependence of the spectroscopic properties of diamond. This suggests the method is a useful tool in laboratory astrophysics.

  3. Spin fluctuations and superconductivity in UPt3

    NASA Astrophysics Data System (ADS)

    Fay, D.; Appel, J.

    1985-11-01

    We attempt to assess the importance of spin fluctuations in the heavy-fermion system UPt3, the most unambiguous evidence for which is the T3 lnT term in the specific heat. We investigate whether other contributions, such as that from a peak in the electronic density of states or from the electron-phonon interaction, could account for the experimental data. We conclude that they cannot although the data are consistent with the presence of both a T3 lnT term and a density-of-states peak of width greater than about 60 K. We determine the input parameters for the paramagnon theory with a self-consistent method developed by Boring, Albers, Stewart, and Koelling for UAl2 and we calculate the s- and p-wave pairing interactions. A one-band model favors p-wave pairing, while a two-band model leads to conventional s-wave superconductivity.

  4. Radiation Hormesis: The Good, the Bad, and the Ugly

    PubMed Central

    Luckey, T.D.

    2006-01-01

    Three aspects of hormesis with low doses of ionizing radiation are presented: the good, the bad, and the ugly. The good is acceptance by France, Japan, and China of the thousands of studies showing stimulation and/or benefit, with no harm, from low dose irradiation. This includes thousands of people who live in good health with high background radiation. The bad is the nonacceptance of radiation hormesis by the U. S. and most other governments; their linear no threshold (LNT) concept promulgates fear of all radiation and produces laws which have no basis in mammalian physiology. The LNT concept leads to poor health, unreasonable medicine and oppressed industries. The ugly is decades of deception by medical and radiation committees which refuse to consider valid evidence of radiation hormesis in cancer, other diseases, and health. Specific examples are provided for the good, the bad, and the ugly in radiation hormesis. PMID:18648595

  5. Industrial Protection Manual.

    DTIC Science & Technology

    1981-06-01

    packaged and cushioned equipment with cable, rope , chain link fencing and/or burying it; disassembly of vulnerable structures, etc. Returning the...lashing down packaged and cushioned equipment with cable, rope , chain link fencing; disassembly of vulnerable structures, etc. Returning the facility...Boilers 2- Package unit ..... 3- Bus Bars .. .. ...... ........ ....... ...... 3B-3) 2 LQU1I’LNT I DEX M AIN DIVISION 0v o I I ION CAI LYORY Cableways

  6. Comment on ``Critical behavior of the zero-temperature conductivity in compensated silicon, Si:(P,B)''

    NASA Astrophysics Data System (ADS)

    Möbius, A.

    1989-08-01

    In a recently published conductivity study of Si:(P,B) very close to the metal-insulator transition, Hirsch and co-workers performed the zero-temperature extrapolation by using the relation σ(T)=σ(0)+mT1/2+BT3/4, based on modern localization theory. This extrapolation is critically reconsidered studying the temperature dependence of the logarithmic derivative, dlnσ/d lnT. .AE

  7. The Effects of Temperature and Electron Radiation on the Electrical Properties of AlGaN/GaN Heterostructure Field Effect Transistors

    DTIC Science & Technology

    2009-03-01

    electron irradiation and temperature on drain current, gate leakage current, threshold voltage shifts, and gate- channel capacitance . Measurements...were taken of transistor current and gate-channel capacitance at LNT and room temperature (RT) and gate leakage current vs. gate bias at 4 K...irradiation values after RT anneal periods. Gate-channel capacitance levels showed little post-irradiation change and negligible temperature

  8. A randomized control study of treating secondary stage II breast cancer-related lymphoedema with free lymph node transfer.

    PubMed

    Dionyssiou, Dimitrios; Demiri, Efterpi; Tsimponis, Antonis; Sarafis, Alexandros; Mpalaris, Vasillios; Tatsidou, Georgia; Arsos, Georgios

    2016-02-01

    Microsurgical techniques are increasingly used for treating severe lymphoedema cases. The purpose of this study was to evaluate the effectiveness of free vascularized lymph node transfer (LNT) in stage II breast cancer-related lymphoedema patients in comparison with non-surgical management. During the last 3 years, 83 female patients were examined at our lymphoedema clinic. Finally, 36 cases were included in this study and randomly divided in two groups: group A patients (n = 18, mean age 47 years) underwent microsurgical LNT; followed by 6 months of physiotherapy and compression, while group B patients (n = 18, mean age 49 years) were managed by physiotherapy and compression alone for 6 months. Patients of both groups removed their elastic garments after 6 months and were re-examined 1 year later. All the 36 patients had detailed evaluation of the affected extremity including limb volume measurement, infection episodes and scale scoring of pain, feeling of heaviness and functional status both at baseline and 18 month. Limb volume reduction was observed in both groups; mean reduction was greater in group A (57 %) than in group B (18 %). Infection episodes in group A were significantly reduced compared to those in group B patients. All group A patients reported painless and feeling of heaviness-free extremities with overall functional improvement, while the corresponding changes in group B patients were no more than marginal. Moreover, the LNT procedure was estimated as cost effective compared to conservative treatment alone. LNT represents an effective therapeutic approach for stage II lymphoedema patients; it significantly reduces limb volume, decreases recurrent infections and improves the overall function.

  9. Enhanced Preliminary Assessment. Task Order 2. Nike Battery Kansas City 30, Pleasant Hill, Missouri

    DTIC Science & Technology

    1989-12-01

    a/ Geneva Van Cami Doty _ :.’ .S .. ,, I:.~ io ~ b~.±2, bar ~.2 c.ir~w~j €" -- .’ ’ .:u :.x\\ ’Z :,. (a.’,:, Lh....... . .. .b"n, J.Ŕ" A -7: .: : I...thence:in anortheastcrlydirection blong :thd. coextar of said ditch, nprorximatoly 125" fdot.torthe poLnt of Latersaction*with I-[n- the abova-d

  10. Characterization of the Human Proteomic Response to Hydrocodone: A Preliminary Study

    DTIC Science & Technology

    2013-03-01

    hippocampus and striatum after exposure to morphine , lnt J Mol Med 18 (2006) 775-784. [50] Z.H. Wen, G.J. Wu, L.C. Hsu, W.F. Chen, J.Y. Chen, H.A...McMillin, F.M. Urry, Simultaneous determination of codeine, morphine , hydrocodone, hydromorphone, oxycodone, and 6-acetylmorphine in urine, serum...Simultaneous assay of morphine , morphine -3-glucuronide and morphine -6-glucuronide in human plasma using normal-phase liquid chromatography-tandem

  11. Development of the United States Leave No Trace programme: A historical perspective

    USGS Publications Warehouse

    Marion, J.L.; Reid, S.; Usher, M.B.

    2001-01-01

    This paper describes the historical development of the U.S. Leave No Trace (LNT) educational program. It begins with a review of the need for the program and traces it?s conception and early development in the 1970`s, revitalization in 1991, creation of Leave No Trace, Inc., and the current status. The paper concludes with a discussion of the program?s elements that have made it successful and recommendations for the development of similar educational programs.

  12. Correlation function for generalized Pólya urns: Finite-size scaling analysis

    NASA Astrophysics Data System (ADS)

    Mori, Shintaro; Hisakado, Masato

    2015-11-01

    We describe a universality class for the transitions of a generalized Pólya urn by studying the asymptotic behavior of the normalized correlation function C (t ) using finite-size scaling analysis. X (1 ),X (2 ),... are the successive additions of a red (blue) ball [X (t )=1 (0 )] at stage t and C (t )≡Cov[X (1 ),X (t +1 )]/Var[X (1 )] . Furthermore, z (t ) =∑s=1tX (s ) /t represents the successive proportions of red balls in an urn to which, at the (t +1 )th stage, a red ball is added [X (t +1 )=1 ] with probability q [z (t )]=(tanh{J [2 z (t )-1 ]+h }+1 )/2 ,J ≥0 , and a blue ball is added [X (t +1 )=0 ] with probability 1 -q [z (t )] . A boundary [Jc(h ) ,h ] exists in the (J ,h ) plane between a region with one stable fixed point and another region with two stable fixed points for q (z ) . C (t ) ˜c +c'.tl -1 with c =0 (>0 ) for J Jc) , and l is the (larger) value of the slope(s) of q (z ) at the stable fixed point(s). On the boundary J =Jc(h ) ,C (t ) ≃c +c'.(lnt) -α' and c =0 (c >0 ) ,α'=1 /2 (1 ) for h =0 (h ≠0 ) . The system shows a continuous phase transition for h =0 and C (t ) behaves as C (t ) ≃(lnt) -α'g [(1 -l ) lnt ] with a universal function g (x ) and a length scale 1 /(1 -l ) with respect to lnt . β =ν||.α' holds with β =1 /2 and ν||=1 .

  13. An Automated Hollow Fiber System for the Deglycerolization of Thawed Frozen Human Blood. Phase 1.

    DTIC Science & Technology

    1994-09-13

    EDTA, Vol. 17, 1980, pp. 353-356. 22. Tova A. Stepner and Edward F. Leonard, "Evaluation of Plasmapheresis Membranes, Journal of Membrane Science...Research Laboratory, Boston, MA, December 20, 1993. 31. C.R. Valeri, et al, "The Safety and Therapeutic Effectiveness of Human Red Cells Stored at - 80 0C...Membrane Plasmapheresis ," Proc. lnt Symposium on Artificial Organs, Biomedical Engineering and Transplantation, Salt Lake City, Utah, January 20-23

  14. An Analysis of the Impact of Job Search Behaviors on Air Force Company Grade Officer Turnover

    DTIC Science & Technology

    2012-03-01

    life while deployed? a Books •• b OVOs.. C05, video &- c. Mag;;u!Oe$ and --d Accep to lnt.cmet and ~ mal ••. e •Rud to the Kid $" PfOQfilr’n...Contuct: Mi700A.,4001 The’!k you for yourplr’Sopation. You have bttn sdected to lakes survey on yautattitudes and percepuoos of ptt’sonnd policies

  15. A More Flexible Lipoprotein Sorting Pathway

    PubMed Central

    Chahales, Peter

    2015-01-01

    Lipoprotein biogenesis in Gram-negative bacteria occurs by a conserved pathway, each step of which is considered essential. In contrast to this model, LoVullo and colleagues demonstrate that the N-acyl transferase Lnt is not required in Francisella tularensis or Neisseria gonorrhoeae. This suggests the existence of a more flexible lipoprotein pathway, likely due to a modified Lol transporter complex, and raises the possibility that pathogens may regulate lipoprotein processing to modulate interactions with the host. PMID:25755190

  16. Travel time statistics under radially converging flow in single fractures

    NASA Astrophysics Data System (ADS)

    Gotovac, Hrvoje; Srzic, Veljko; Cvetkovic, Vladimir; Kekez, Toni; Malenica, Luka

    2015-04-01

    A stochastic methodology based on Adaptive Fup Monte Carlo Method is used to investigate transport of a conservative solute by steady flow to a single pumping well in two-dimensional randomly heterogeneous single fractures. The spatially variable hydraulic transmissivity is modeled as a stationary random function for three different correlation structures (multi-Gaussian, connected and disconnected fields with correlated mean, high and low lnT values, respectively, according to the Zinn and Harvey, 2003) and heterogeneity levels (lnT variance is 1 and 8). Initially, solute particles are injected at outer circle located at 32 correlation lengths from well according to the in flux and resident injection mode. Therefore, breakthrough curve (BTC) statistics in single well due to different spatial structures, heterogeneity levels, injection modes and dispersion influence is considered. For small heterogeneity, all considered effects have small influences on BTC and related moments. As expected in single fractures, high lnT variance is more usual case which considerably changes flow patterns including channelling effect and fact that only few narrow channels carry out most pumping flow rate. Channelling implies significant differences between different injection modes. Resident mode uniformly injects particles implying that most particles pass through "slower" zones that especially increase late arrivals and contribute to the non-Fickian behaviour of transport. Contrary, "in flux" mode drastically reduces first arrivals and mean values, especially for connected correlation fields. The results from two injection modes lie on different sides of homogeneous mean travel time solution and give complementary information for complete representation of conservative transport. For advection transport, correlation structure and especially lnT variance seems to have major influence on BTC characteristics. On the other side, influence of longitudinal and lateral local scale

  17. The 10th anniversary of the publication of genes and environment: memoir of establishing the Japanese environmental mutagen society and a proposal for a new collaborative study on mutagenic hormesis.

    PubMed

    Sutou, Shizuyo

    2017-01-01

    The Japanese Environmental Mutagen Society (JEMS) was established in 1972 by 147 members, 11 of whom are still on the active list as of May 1, 2016. As one of them, I introduce some historic topics here. These include 1) establishment of JEMS, 2) the issue of 2-(2-furyl)-3-(3-nitro-2-furyl)acrylamide (AF-2), 3) the Mammalian Mutagenicity Study Group (MMS) and its achievements, and 4) the Collaborative Study Group of the Micronucleus Test (CSGMT) and its achievements. In addition to these historic matters, some of which are still ongoing, a new collaborative study is proposed on adaptive response or hormesis by mutagens. There is a close relationship between mutagens and carcinogens, the dose-response relationship of which has been thought to follow the linear no-threshold model (LNT). LNT was fabricated on the basis of Drosophila sperm experiments using high dose radiation delivered in a short period. The fallacious 60 years-old LNT is applied to cancer induction by radiation without solid data and then to cancer induction by carcinogens also without solid data. Therefore, even the smallest amount of carcinogens is postulated to be carcinogenic without thresholds now. Radiation hormesis is observed in a large variety of living organisms; radiation is beneficial at low doses, but hazardous at high doses. There is a threshold at the boundary between benefit and hazard. Hormesis denies LNT. Not a few papers report existence of chemical hormesis. If mutagens and carcinogens show hormesis, the linear dose-response relationship in mutagenesis and carcinogenesis is denied and thresholds can be introduced.

  18. Lean NOx Trap Modeling in Vehicle Systems Simulations

    SciTech Connect

    Gao, Zhiming; Chakravarthy, Veerathu K; Daw, C Stuart; Conklin, Jim

    2010-09-01

    A one-dimensional model for simulating lean NOx trap (LNT) performance is developed and validated using both steady state cycling data and transient data from FTP testing cycles. The model consists of the conservation equations for chemical species and energy in the bulk flow, energy of the solid walls, O2 storage and NOx storage (in the form of nitrites and nitrates). Nitrites and nitrates are formed by diffusion of NO and NO2, respectively, into sorbent particles (assumed to be hemi-spherical in shape) along with O2 and their formation rates are controlled by chemical kinetics as well as solid-phase diffusion rates of NOx species. The model also accounts for thermal aging and sulfation of LNTs. Empirical correlations are developed on the basis of published experimental data to capture these effects. These empirical correlations depend on total mileage for which the LNT has been in use, the mileage accumulated since the last desulfation event in addition to the freshly degreened catalyst characteristics. The model has been used in studies of vehicle systems (integration, performance etc.) including hybrid powertrain configurations. Since the engines in hybrid vehicles turn on and off multiple number of times during single drive cycles, the exhaust systems may encounter multiple cold start transients. Accurate modeling of catalyst warm-up and cooling is, therefore, very important to simulate LNT performance in such vehicles. For this purpose, the convective heat loss from the LNT to the ambient is modeled using a Nusselt number correlation that includes effects of both forced convection and natural convection (with later being important when vehicle is stationary). Using the model, the fuel penalty associated with operating LNTs on small diesel engine powered car during FTP drive cycles is estimated.

  19. Micro Computer Feedback Report for the Strategic Leader Development Inventory; Source Code

    DTIC Science & Technology

    1994-03-01

    dir INC DI ;ptr to next byte LOOP COP3 ;loop until CX m 0 -------.find next match NOV AX,4F00h ;fine next file function lNT 21h ;do next search aNC COP0...continue if J > 0. COP3 : POP DX ;restore registers POP CX POP AX RUT ;return to ShellSort ENDP COI1ARX SWAP IMP SHILLSORT ;------- oSend a 16 byte

  20. Mitigating Stress, Workload, and Fatigue on the Electronic Battlefield

    DTIC Science & Technology

    2007-03-28

    340 ~ E ~ • Emergency 1.0 ------~----~------1 0 Non-emergency 2 miles 4 miles or more 0.5 mile 1 mile Estimated frequency of SB use during Mid...3118 • Fax: +81 3 ~08 3553 E -mail: tokyo.ofcCcomputer.org EXECUTIVE STAFF Executive Director: DAVID W. HENNAGE Publ"her: ANGELA BURGESS ~k,t.lnt...Transaction Publishers. Durkheim , E . (1895). Rules of sociological method. New York: Free Press. Edmondson, A. (1999). Psychological safety and learning

  1. Honoring Identity Through Mealtimes in Chinese Canadian Immigrants.

    PubMed

    Lam, Ivy T Y; Keller, Heather H

    2015-11-01

    Mealtimes are opportunities for social interactions and expressions of individual and family identity, and serve as a microcosm of the broader lives of families living with dementia. The Eating Together study and its resulting Life Nourishment Theory (LNT) explicated the importance of mealtimes for honouring individual and family identities in the context of dementia. This sub-study examined a specific ethnocultural group with cultural food-ways and caring expectations, to determine if the concept of honouring identity needed to be modified or extended. Using active interview techniques, two Cantonese speaking researchers completed dyad/triad family and individual interviews with six Chinese Canadian immigrant families, recruited from two service providers in a large, urban, multicultural city. This sub-study provided insight into the challenges and rewards of mealtimes for Chinese immigrant families with dementia in the community and specifically provided further insights into the honouring identity concept. Although LNT and specifically the honouring identity concept was generally confirmed in this group, some culturally-specific themes were also identified. This work serves as a basis for future studies examining the meaning and experience of mealtimes in specific cultural groups living with dementia. Such work would confirm if the LNT can be applied to specific ethnocultural groups as well as the general population living with dementia.

  2. Qualitative Assessment of Speech Perception Performance of Early and Late Cochlear Implantees.

    PubMed

    Kant, Anjali R; Pathak, Sonal

    2015-09-01

    The present study aims to provide a qualitative description and comparison of speech perception performance using model based tests like multisyllabic lexical neighborhood test (MLNT) and lexical neighborhood test (LNT), in early and late implanted (prelingual) hearing impaired children using cochlear implants. The subjects comprised of cochlear implantees; Group I (early implantees)-n = 15, 3-6 years of age; mean age at implantation-3½ years. Group II (late implantees)-n = 15, 7-13 years of age; mean age at implantation-5 years. The tests were presented in a sound treated room at 70 dBSPL. The children were instructed to repeat the words on hearing them. Responses were scored as percentage of words correctly repeated. Their means were computed. The late implantees achieved higher scores for words on MLNT than those on LNT. This may imply that late implantees are making use of length cues in order to aid them in speech perception. The major phonological process used by early implantees was deletion and by the late implantees was substitution. One needs to wait until the child achieves a score of 20 % on LNT before assessing other aspects of his/her speech perception abilities. There appears to be a need to use speech perception tests which are based on theoretical empirical models, in order to enable us to give a descriptive analysis of post implant speech perception performance.

  3. Advanced Engine/Aftertreatment System R&D

    SciTech Connect

    Pihl, J.; West, B.; Toops, T.; Adelman, B.; Derybowski, E.

    2011-09-30

    Navistar and ORNL established this CRADA to develop diesel engine aftertreatment configurations and control strategies that could meet emissions regulations while maintaining or improving vehicle efficiency. The early years of the project focused on reducing the fuel penalty associated with lean NOx trap (LNT, also known as NOx adsorber catalyst) regeneration and desulfation. While Navistar pursued engine-based (in-cylinder) approaches to LNT regeneration, complementary experiments at ORNL focused on in-exhaust fuel injection. ORNL developed a PC-based controller for transient electronic control of EGR valve position, intake throttle position, and actuation of fuel injectors in the exhaust system of a Navistar engine installed at Oak Ridge. Aftertreatment systems consisting of different diesel oxidation catalysts (DOCs) in conjunction with a diesel particle filter and LNT were evaluated under quasi-steady-state conditions. Hydrocarbon (HC) species were measured at multiple locations in the exhaust system with Gas chromatograph mass spectrometry (GC-MS) and Fourier transform infrared (FTIR) spectroscopy.

  4. Effect of Grain Refinement on the Mechanical Behaviour of an Al6061 Alloy at Cryogenic Temperatures

    SciTech Connect

    Moreno-Valle, E.; Sabirov, I.; Murashkin, M. Yu.; Valiev, R. Z.; Bobruk, E. V.; Perez-Prado, M. T.

    2011-05-04

    A solution treated coarse grained (CG) Al6061 was subjected to high pressure torsion (HPT) at room temperature resulting in the formation of a homogeneous ultra-fine grained (UFG) microstructure with an average grain size of 170 nm. Tensile tests were performed at room temperature (RT) and liquid nitrogen temperature (LNT). The as-HPT UFG Al6061 alloy shows an increased strength at both RT and LNT. The decrease of testing temperature results in increased flow stress and in enhanced elongation to failure in both CG and UFG samples. The ratio {sigma}{sub y}{sup LNT}/{sigma}{sub y}{sup RT} was found to be larger for the CG Al6061 than for the UFG Al6061. Both surface relief and fracture surface observations were performed. The effect of the grain size and of the testing temperature on the mechanical behaviour of the Al6061 alloy is analyzed in detail. It is suggested that the solute atoms play an important role in the plastic deformation of the UFG Al6061 alloy.

  5. Investigation of Mixed Oxide Catalysts for NO Oxidation

    SciTech Connect

    Szanyi, Janos; Karim, Ayman M.; Pederson, Larry R.; Kwak, Ja Hun; Mei, Donghai; Tran, Diana N.; Herling, Darrell R.; Muntean, George G.; Peden, Charles HF; Howden, Ken; Qi, Gongshin; Li, Wei

    2014-12-09

    The oxidation of engine-generated NO to NO2 is an important step in the reduction of NOx in lean engine exhaust because NO2 is required for the performance of the LNT technology [2], and it enhances the activities of ammonia selective catalytic reduction (SCR) catalysts [1]. In particular, for SCR catalysts an NO:NO2 ratio of 1:1 is most effective for NOx reduction, whereas for LNT catalysts, NO must be oxidized to NO2 before adsorption on the storage components. However, NO2 typically constitutes less than 10% of NOx in lean exhaust, so catalytic oxidation of NO is essential. Platinum has been found to be especially active for NO oxidation, and is widely used in DOC and LNT catalysts. However, because of the high cost and poor thermal durability of Pt-based catalysts, there is substantial interest in the development of alternatives. The objective of this project, in collaboration with partner General Motors, is to develop mixed metal oxide catalysts for NO oxidation, enabling lower precious metal usage in emission control systems. [1] M. Koebel, G. Madia, and M. Elsener, Catalysis Today 73, 239 (2002). [2] C. H. Kim, G. S. Qi, K. Dahlberg, and W. Li, Science 327, 1624 (2010).

  6. Probabilistic Interpolation of Wind Hazard Maps

    NASA Astrophysics Data System (ADS)

    Xu, L.

    2012-12-01

    Wind hazard maps are widely used to compute design loads and to evaluate insurance risks. While building codes often provide these maps for only a few return periods, wind hazard maps for other return periods are often needed for risk assessments. In this study, we evaluate a probabilistic interpolation approach for deriving wind hazard maps for return periods other than those available. The probabilistic interpolation approach assumes that probabilities of wind values in a wind hazard map follow Gumbel distribution. Although most studies have been performed on data from individual weather stations, it remains to be seen how well the Gumbel distribution-based interpolation performs for wind hazard maps. The Gumbel distribution F(V) =exp{-exp[-α(V - u)]} is assumed for wind speed at a wind map location, where α and u are parameters that vary with location. VT = u + α-1lnT is the wind speed of return period T when T is large. If T0 and T1 are two given return periods and T1 is greater, then VT = (1-θ)VT0 + θVT1 where θ = (lnT - lnT0)/(lnT1 - lnT0). Therefore, VT is a weighted average between VT0 and VT1. Here we select the US and Mexican hazard maps to evaluate the probabilistic interpolation method. In ASCE 7-10 wind maps, the basic wind speed has a single value for most inland areas, which is 54, 51, and 47 m/s for 1700-year, 700-year, and 300-year return periods, respectively. We use the 1700-year and 300-year values to obtain the 700-year value using the Gumbel distribution-based interpolation. The computed 700-year value is 50.4 m/s compared to 51 m/s provided in the code, about 1% difference. For coastal regions subjected to hurricane winds, the relative error between the interpolated 700-year values and the original 700-year values are within 2% for most areas except for areas where hurricane zones transition to inland non-hurricane zones; there the relative errors can increase to 4%. The Mexican wind code includes wind maps of three return periods: 10

  7. A Longitudinal Study of Speech Perception Skills and Device Characteristics of Adolescent Cochlear Implant Users

    PubMed Central

    Robinson, Elizabeth J.; Davidson, Lisa S.; Uchanski, Rosalie M.; Brenner, Christine M.; Geers, Ann E.

    2012-01-01

    Background For pediatric cochlear implant (CI) users, CI processor technology, map characteristics and fitting strategies are known to have a substantial impact on speech perception scores at young ages. It is unknown whether these benefits continue over time as these children reach adolescence. Purpose To document changes in CI technology, map characteristics, and speech perception scores in children between elementary grades and high school, and to describe relations between map characteristics and speech perception scores over time. Research Design A longitudinal design with participants 8–9 years old at session 1 and 15–18 years old at session 2. Study Sample Participants were 82 adolescents with unilateral CIs, who are a subset of a larger longitudinal study. Mean age at implantation was 3.4 years (range: 1.7 – 5.4), and mean duration of device use was 5.5 years (range: 3.8–7.5) at session 1 and 13.3 years (range: 10.9–15) at session 2. Data Collection and Analysis Speech perception tests at sessions 1 and 2 were the Lexical Neighborhood word Test (LNT-70) and Bamford-Kowal-Bench sentences in quiet (BKB-Q), presented at 70 dB SPL. At session 2, the LNT was also administered at 50 dB SPL (LNT-50) and BKB sentences were administered in noise with a +10 dB SNR (BKB-N). CI processor technology type and CI map characteristics (coding strategy, number of electrodes, map threshold levels [T levels], and map comfort levels [C levels]) were obtained at both sessions. Electrical dynamic range [EDR] was computed [C level – T level], and descriptive statistics, correlations, and repeated-measures ANOVAs were employed. Results Participants achieved significantly higher LNT and BKB scores, at 70 dB SPL, at ages 15-18 than at ages 8-9 years. Forty-two participants had 1-3 electrodes either activated or deactivated in their map between test sessions, and 40 had no change in number of active electrodes (mean change: -0.5; range: -3 to +2). After conversion from

  8. Dose-responses from multi-model inference for the non-cancer disease mortality of atomic bomb survivors.

    PubMed

    Schöllnberger, H; Kaiser, J C; Jacob, P; Walsh, L

    2012-05-01

    The non-cancer mortality data for cerebrovascular disease (CVD) and cardiovascular diseases from Report 13 on the atomic bomb survivors published by the Radiation Effects Research Foundation were analysed to investigate the dose-response for the influence of radiation on these detrimental health effects. Various parametric and categorical models (such as linear-no-threshold (LNT) and a number of threshold and step models) were analysed with a statistical selection protocol that rated the model description of the data. Instead of applying the usual approach of identifying one preferred model for each data set, a set of plausible models was applied, and a sub-set of non-nested models was identified that all fitted the data about equally well. Subsequently, this sub-set of non-nested models was used to perform multi-model inference (MMI), an innovative method of mathematically combining different models to allow risk estimates to be based on several plausible dose-response models rather than just relying on a single model of choice. This procedure thereby produces more reliable risk estimates based on a more comprehensive appraisal of model uncertainties. For CVD, MMI yielded a weak dose-response (with a risk estimate of about one-third of the LNT model) below a step at 0.6 Gy and a stronger dose-response at higher doses. The calculated risk estimates are consistent with zero risk below this threshold-dose. For mortalities related to cardiovascular diseases, an LNT-type dose-response was found with risk estimates consistent with zero risk below 2.2 Gy based on 90% confidence intervals. The MMI approach described here resolves a dilemma in practical radiation protection when one is forced to select between models with profoundly different dose-responses for risk estimates.

  9. Implications of the temperature dependence of Nd:YAG spectroscopic values for low temperature laser operation at 946 nm

    NASA Astrophysics Data System (ADS)

    Yoon, S. J.; Mackenzie, J. I.

    2014-05-01

    We present our measurements of the key spectroscopic properties over the temperature range of 77 K to 450 K for Nd3+ ions doped in Y3Al5O12 (YAG). From room to liquid nitrogen temperature (LNT), the peak absorption cross section around 808 nm increased by almost 3 times, in conjunction the bandwidth of this absorption line reduced by the same factor. At LNT the peak of the absorption line was blue shifted by 0.25 nm with respect to that at 300 K. The fluorescence spectrum between 850 nm - 1450 nm was measured, from which the emission cross sections for the three main transitions were calculated. One note of particular interest for the dominant emission wavelengths around 1064nm and 1061nm (4F3/2 --> 4I11/2) was the switch in their relative strength below 170K, and at LNT the 1061 nm line has almost twice the cross section as at 1064nm.. The fluorescence and lifetime of the upper laser level (4F3/2) was measured and the effective emission cross section determined by the Fuchtbauer-Ladenburg (F-L) method. The effective emission cross section for 946 nm (R1 --> Z5) increased by more than two times over the 300 K to 77 K range. A numerical fit for the temperature dependent emission cross section at 946 nm and 1064 nm and also calculated absorption coefficient at 808 nm pump diode laser have also obtained from the measured spectroscopic data.

  10. Investigation of the Effects of Biodiesel-based Na on Emissions Control Components

    SciTech Connect

    Brookshear, D. William; Nguyen, Ke; Toops, Todd J; Bunting, Bruce G; Howe, Janet E

    2012-01-01

    A single-cylinder diesel engine was used to investigate the impact of biodiesel-based Na on emissions control components using specially blended 20% biodiesel fuel (B20). The emissions control components investigated were a diesel oxidation catalyst (DOC), a Cu-zeolite-based NH{sub 3}-SCR (selective catalytic reduction) catalyst, and a diesel particulate filter (DPF). Both light-duty vehicle, DOC-SCR-DPF, and heavy-duty vehicle, DOC-DPF-SCR, emissions control configurations were employed. The accelerated Na aging is achieved by introducing elevated Na levels in the fuel, to represent full useful life exposure, and periodically increasing the exhaust temperature to replicate DPF regeneration. To assess the validity of the implemented accelerated Na aging protocol, engine-aged lean NO{sub x} traps (LNTs), DOCs and DPFs are also evaluated. To fully characterize the impact on the catalytic activity the LNT, DOC and SCR catalysts were evaluated using a bench flow reactor. The evaluation of the aged DOC samples and LNT show little to no deactivation as a result of Na contamination. However, the SCR in the light-duty configuration (DOC-SCR-DPF) was severely affected by Na contamination, especially when NO was the only fed NO{sub x} source. In the heavy-duty configuration (DOC-DPF-SCR), no impact is observed in the SCR NO{sub x} reduction activity. Electron probe micro-analysis (EPMA) reveals that Na contamination on the LNT, DOC, and SCR samples is present throughout the length of the catalysts with a higher concentration on the washcoat surface. In both the long-term engine-aged DPF and the accelerated Na-aged DPFs, there is significant Na ash present in the upstream channels; however, in the engine-aged sample lube oil-based ash is the predominant constituent.

  11. Infrared and Raman spectra of magnesium ammonium phosphate hexahydrate ( struvite) and its isomorphous analogues. VII: Spectra of protiated and partially deuterated hexagonal magnesium caesium phosphate hexahydrate

    NASA Astrophysics Data System (ADS)

    Stefov, V.; Cahil, A.; Šoptrajanov, B.; Najdoski, M.; Spirovski, F.; Engelen, B.; Lutz, H. D.; Koleva, V.

    2009-04-01

    The Fourier transform infrared and Raman spectra of the struvite analogue, hexagonal magnesium caesium phosphate hexahydrate, MgCsPO 4·6H 2O ( hP50) and of its partially deuterated analogues were recorded from room temperature (RT) down to the boiling temperature of liquid nitrogen (LNT). The existence of strong hydrogen bonds between water molecules and PO 43- ions is supported by the appearance of a broad band from 3600 to 2200 cm -1 in the O-H stretching region of the vibrational spectra. In the region of the OD stretching vibrations of isotopically isolated HDO molecules of the analogue with a small deuterium content (≈5% D), at least two bands (from the expected three) are observed in the difference LNT infrared spectrum. In the region of ν3(PO 4) modes of the infrared spectra, a broad and asymmetric band (at around 1000 cm -1) is found, while in the region of the ν4(PO 4) bending vibration and of the external modes of the water molecules, several bands can be seen. The intense band at 945 cm -1 in the Raman spectra can with certainty be attributed to the ν1(PO 4) mode. On the basis of a careful analysis of the RT and LNT spectra of the protiated compound, as well as those of its partially deuterated analogues, the asymmetric band at around 550 cm -1 could be assigned to the components of the ν4(PO 4) mode, the bands between 470 and 430 cm -1 to the ν2(PO 4) vibrations and the remaining ones as due to pure or coupled librational and translational modes of the water molecules. The external modes of the phosphate ions and those of the water molecules are mixed.

  12. Lessons to be learned from a contentious challenge to mainstream radiobiological science (the linear no-threshold theory of genetic mutations).

    PubMed

    Beyea, Jan

    2017-04-01

    There are both statistically valid and invalid reasons why scientists with differing default hypotheses can disagree in high-profile situations. Examples can be found in recent correspondence in this journal, which may offer lessons for resolving challenges to mainstream science, particularly when adherents of a minority view attempt to elevate the status of outlier studies and/or claim that self-interest explains the acceptance of the dominant theory. Edward J. Calabrese and I have been debating the historical origins of the linear no-threshold theory (LNT) of carcinogenesis and its use in the regulation of ionizing radiation. Professor Calabrese, a supporter of hormesis, has charged a committee of scientists with misconduct in their preparation of a 1956 report on the genetic effects of atomic radiation. Specifically he argues that the report mischaracterized the LNT research record and suppressed calculations of some committee members. After reviewing the available scientific literature, I found that the contemporaneous evidence overwhelmingly favored a (genetics) LNT and that no calculations were suppressed. Calabrese's claims about the scientific record do not hold up primarily because of lack of attention to statistical analysis. Ironically, outlier studies were more likely to favor supra-linearity, not sub-linearity. Finally, the claim of investigator bias, which underlies Calabrese's accusations about key studies, is based on misreading of text. Attention to ethics charges, early on, may help seed a counter narrative explaining the community's adoption of a default hypothesis and may help focus attention on valid evidence and any real weaknesses in the dominant paradigm.

  13. Controlled synthesis and photocatalytic investigation of different-shaped one-dimensional titanic acid nanomaterials

    NASA Astrophysics Data System (ADS)

    Li, Qiuye; Lu, Gongxuan

    Different-shaped one-dimensional (1D) titanic acid nanomaterials (TANs) were prepared by hydrothermal synthesis. By changing the reaction temperature (120, 170 and 200 °C), three kinds of 1D TAN, short-nanotubes (SNT), long-nanotubes (LNT), and nanorods (NR), were obtained. The obtained TANs were characterized by transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), powder X-ray diffraction (XRD), and solid-stated diffuse reflectance UV-vis spectra (UV-vis DRS) techniques. Based on these 1D TAN, Eosin Y-sensitized Pt-loaded TAN were prepared by the in situ impregnation and photo-reduction method. Their photocatalytic activity for hydrogen generation was evaluated in triethanolamine (TEOA) aqueous solution under visible light irradiation (λ ≥ 420 nm). The results indicated that the morphology difference led to a significant variation of photocatalytic performance for hydrogen generation, with the activity order as follows: Eosin Y-sensitized Pt-loaded LNT > Eosin Y-sensitized Pt-loaded NR > Eosin Y-sensitized Pt-loaded SNT. The experimental conditions for photocatalytic hydrogen generation such as Pt loading content, the mass ratio of Eosin Y to TAN, and so on, were optimized. As a result, the highest apparent quantum yields of hydrogen generation for Eosin Y-sensitized Pt-loaded SNT, LNT, and NR were 6.65, 17.36, and 15.04%, respectively. The stability of these photocatalysts and the reaction mechanism of the photocatalytic hydrogen generation are also discussed in detail.

  14. Phase separation of polymer thin films and some applications

    NASA Astrophysics Data System (ADS)

    Zhu, Shaoming

    Phase separation of polymer thin film is a common issue in polymer thin film application. The existence of surface and surfactant are understood to play an important role in thin film final topography. In chapter two, the configuration of polymer blend thin film phase separation on cobalt substrate with PMMA phase forming column structure, and PS phase encapsulating the PMMA phase was used as resist mask to transfer the topographical feature to cobalt thin film. Isolated near spherical single and multi domain magnetic islands were obtained. The island made using this method had a broad single domain range from below 1000 to 5000A. In chapter three, when the polymer blend thin film was in bilayer configuration and diblock copolymer was added on the top layer, we found the confinement can increase the mixing of two homopolymers in highly incompatible polymer blends. By affecting the formation of micelles, the copolymers are forced to the interface between the two homopolymer phases where they reduce the interfacial tension to zero and form a microemulsion. Our findings have two important implications: first, they elucidate the role entropy plays in determining the phase behaviour of confined polymer blends and second, they offer a simple pathway to create thin film coatings with precisely controlled properties and surfaces. In chapter four, the kinetics process of microemulsion formation in confinement configuration has been analyzed. The microemulsion formation proceeded at initial stage by capillary wave, then it followed the growth regime t1/3 and lnt, then followed a more slow growth regime (lnt).56 or (lnt).60 till finally reached equilibrium, when the structure was frozen. In chapter five, we study the evolution of the morphologies of polymer blend thin films on silicon, cobalt, and gold substrates. In asymmetrical system, the substrate surface energy determined the wetting degree of the substrate preferring phases. In chapter six, we present a novel method for

  15. Commentary on Inhaled 239PuO2 in Dogs — A Prophylaxis against Lung Cancer?

    DOE PAGES

    Cuttler, Jerry M.; Feinendegen, Ludwig E.

    2015-01-01

    Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.

  16. CLEERS Aftertreatment Modeling and Analysis

    SciTech Connect

    Muntean, George G.; Devarakonda, Maruthi N.; Gao, Feng; Kwak, Ja Hun; Luo, Jin-Yong; Peden, Charles HF; Stewart, Mark L.; Szanyi, Janos; Tran, Diana N.; Howden, Ken

    2012-12-31

    CLEERS is a research and development focus project of the Diesel Cross-Cut Team. The overall objective is to promote the development of improved computational tools for simulating realistic full-system performance of lean-burn engines and the associated emissions control systems. Three fundamental research projects are sponsored at PNNL through CLEERS: DPF, SCR, and LNT. Resources are shared between the three efforts in order to actively respond to current industrial needs. In FY 2012, primary emphasis continued to be placed on the SCR activities because of urgent application issues associated with these technologies.

  17. Multidimensional Many-Body Theory.

    DTIC Science & Technology

    1982-03-31

    which is for U n thro h the resolvent operator a unit matrix in the van Vleck case). The correspond- R 0) = Q )i (24) ing eigenfunctions k, of H are...Bent, G. D. Purvis, and R . J. Bartlett. J. Chem. Phys. 71, 3697 (1979). tions, beginning with Eq. (68) and using Eqs. (58) and 18j. A . Pople, J. S...expressed in any of the " R . Krishnan and J. A . Pople, Lnt. J. Quantum Chem. 14, 91 forms (1978). iot 20S. Wilson and D. M. Silver, J. Chem. Phvs. 66

  18. Detailed Analysis Plan for Validation of Close Air Support (CAS). Phase 2 Results

    DTIC Science & Technology

    1974-06-01

    CONMTL DATA PORN QUESTIONS LftIM/AIR b 1M MDRQUVEST PrASE RD, DIV OR CORPS (ALLOCATED RESOURCE ABORTS, ONLY) 1. Unit 1D No: 2. Location of TACP in UTM...Terminal Area Control (FAC(r) , PiC (A) , or ASRT) Type Control Call Sign Delay Abort CNX N/A Reason Codes Ist Znd 01 Cons Security 07 lnt’rm’t Com 14...NETWORK FOR ATTACK HELICOPTER CAB - DATA PORN QUESTIONS TO ANNEX C[ DATA COLLECTION CIoS CABA D AND CONTROL DATA FOlRM QUESTIONS No. 1-2-3-4-S.-6* ARMY

  19. CLEERS Aftertreatment Modeling and Analysis

    SciTech Connect

    Stewart, Mark L.; Zelenyuk, Alla; Gao, Feng; Muntean, George G.; Peden, Charles HF; Rappe, Kenneth G.; Szanyi, Janos; Howden, Ken

    2014-12-09

    CLEERS is an R&D focus project of the Diesel Cross-Cut Team. The overall objective is to promote the development of improved computational tools for simulating realistic full-system performance of lean-burn engines and the associated emissions control systems. Three fundamental research projects are sponsored at PNNL through CLEERS: DPF, SCR, and LNT. Resources are shared between the three efforts in order to actively respond to current industrial needs. This report documents recent results obtained during FY14.

  20. DYNLET1: Dynamic Implicit Numerical Model of One-Dimensional Tidal Flow through Inlets

    DTIC Science & Technology

    1991-09-01

    tor)’ ), tdoiemrer il -0 Budogel Papie- -rrt Rfdro0 crn P-rJ,. C𔃾 ’~ ihn r r > 1. AGENCY USE ONLY (Leave blank) 2. REPORT DATE 3. REPORT TYPE AND...MONITORING US Army Cors of r , Leers AGENCY REPORT NUMBER ",-ashi n4ton, 1)C :1314-1Ouo 11. SUPPLEMENTARY NOTES Avai[able from Natir.,nai Technicai...i rctan ce-’rve. quantitative studies o inlets rare pre orLnt.,. , :Au .c. 4I,, Ii ror its nL- lmenlsional mode lin1g of the ol’,’li’. I t ilt 5. r

  1. Maildriver: A Distributed Campus-Wide Mail System.

    DTIC Science & Technology

    1986-01-01

    Machine List (DM1). Then it creates a list for that machine, called the Dead Machine Catchup List (I)MCI), which will contain all actions which the dead...DoYouHavelt; /* list of files we couldn’t find a/ Queue *DMCL; /* array of Dead Machine Catchup Lists 5/ extern void EmergencyBailout0; nt FinishUpAndDie = 0... Catchup LI3t */ void MessageHandler(sig, fd) lnt sg, fd; { whatever message = read message from fd; switch(message) { "sending letter": "deleting letter

  2. Restructuring NATO Forces--Northern Tier

    DTIC Science & Technology

    1975-06-06

    attac. tbera „Ui, "uided weapons bevond thp r-in™ ^^ eyona the ran-e of weapon release for free fall ^ or direet fire ^ and roo.eta...Scjot,. „nlv iM free rort ln ^^ ^^ ^^^ to th« ocnann 1, at -,lrraanSk. u „an boen Cn^op«, lnt,0 an enormou£ "n-Uan.v bann...rather Orpheus , orGani?,atlo„s. hATO has not yet reached the ataße of Interdependence where national ^^li.ation Is a possibility

  3. High-Redundancy Draft Sequencing of 15 Clinical and Environmental Burkholderia Strains

    DTIC Science & Technology

    2010-12-01

    after a near-drowning incident (5). B. ubonensis strain Bu was isolated from a rhizosphere sam- ple from a mine site in northern Australia ( 12...species formerly known as the Oklahoma s1rain of Pseudomonas pseudoma- llei. lnt. J. Syst. Evol. Microhiol. 56:217l-217!i. 8. Howard. K .. and T. J. Inglis... Pseudomonas pseudoma- llei-lik.: organism isolated from the soil: case report and epidemiol(lgJc study J. Infect. Dis. l.lS:l03-l07. 15. Nussbaum, J. J

  4. Commentary on Inhaled 239PUO2 in Dogs — A Prophylaxis Against Lung Cancer?

    PubMed Central

    Feinendegen, Ludwig E.

    2015-01-01

    Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer. PMID:26675366

  5. Computer Aided Engineering of Semiconductor Integrated Circuits

    DTIC Science & Technology

    1976-04-01

    transistor opera tion; (4) theoretical invest! jations of carrifr mobli *!;y *"« inversion layer of an MOSFET; (5) mathematical investigations for high...satisfactory greLnt «Lh experiment. In time, the rapid groWth of se.r- oonduotor integrated circuit (IC, technology created ^ ^ °n" £or which this theory was...and Technology of Semiconductor Devices, John Wiley and Sons, Inc., N.Y. (1967). [2] S. K. Ghandi, The Theory and Practice of

  6. Commentary on Inhaled 239PuO2 in Dogs — A Prophylaxis against Lung Cancer?

    SciTech Connect

    Cuttler, Jerry M.; Feinendegen, Ludwig E.

    2015-01-01

    Several studies on the effect of inhaled plutonium-dioxide particulates and the incidence of lung tumors in dogs reveal beneficial effects when the cumulative alpha-radiation dose is low. There is a threshold at an exposure level of about 100 cGy for excess tumor incidence and reduced lifespan. The observations conform to the expectations of the radiation hormesis dose-response model and contradict the predictions of the LNT hypothesis. These studies suggest investigating the possibility of employing low-dose alpha-radiation, such as from 239PuO2 inhalation, as a prophylaxis against lung cancer.

  7. 76 FR 19701 - Glyphosate (N-

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-08

    ... part 2 may be disclosed publicly by EPA without prior notice. Submit a copy of your non-CBI objection... = chronic) or a reference dose (RfD)--and a safe margin of exposure (MOE). For non-threshold risks, the... incidental oral exposure may occur to young children (swimmer and turf non-dietary ingestion) and...

  8. Experimental realization of nearly steady-state toroidal electron plasmas

    SciTech Connect

    Stoneking, M. R.; Ha, B. N.; Smoniewski, J.; Marler, J. P.

    2009-05-15

    Electron plasmas with densities of 5x10{sup 6} cm{sup -3} are trapped in the Lawrence Non-neutral Torus II (LNT II) for times exceeding 1 s. LNT II is a high aspect ratio (R{sub 0}/a > or approx.10) partially toroidal trap (270 deg. arc, B{sub 0}=670 G). The m=1 diocotron mode is launched and detected using isolated segments of a fully sectored conducting boundary and its frequency is used to determine the total trapped charge as a function of time. The observed confinement time ({approx_equal}3 s) approaches the theoretical limit ({approx_equal}6 s) set by the magnetic pumping transport mechanism of Crooks and O'Neil [Phys. Plasmas 3, 2533 (1996)]. We also present equilibrium modeling and numerical simulations of the toroidal m=1 mode constrained by experimental data. Future work includes the identification of the dominant transport mechanisms via confinement scaling experiments and measurement of the m=2 mode frequency and development of a strategy for making a transition to fully toroidal confinement.

  9. Evidence supporting radiation hormesis in atomic bomb survivor cancer mortality data.

    PubMed

    Doss, Mohan

    2012-12-01

    A recent update on the atomic bomb survivor cancer mortality data has concluded that excess relative risk (ERR) for solid cancers increases linearly with dose and that zero dose is the best estimate for the threshold, apparently validating the present use of the linear no threshold (LNT) model for estimating the cancer risk from low dose radiation. A major flaw in the standard ERR formalism for estimating cancer risk from radiation (and other carcinogens) is that it ignores the potential for a large systematic bias in the measured baseline cancer mortality rate, which can have a major effect on the ERR values. Cancer rates are highly variable from year to year and between adjacent regions and so the likelihood of such a bias is high. Calculations show that a correction for such a bias can lower the ERRs in the atomic bomb survivor data to negative values for intermediate doses. This is consistent with the phenomenon of radiation hormesis, providing a rational explanation for the decreased risk of cancer observed at intermediate doses for which there is no explanation based on the LNT model. The recent atomic bomb survivor data provides additional evidence for radiation hormesis in humans.

  10. Simulating the Impact of Premixed Charge Compression Ignition on Light-Duty Diesel Fuel Economy and Emissions of Particulates and NOx

    SciTech Connect

    Gao, Zhiming; Daw, C Stuart; Wagner, Robert M; Edwards, Kevin Dean; Smith, David E

    2013-01-01

    We utilize the Powertrain Systems Analysis Toolkit (PSAT) combined with transient engine and aftertreatment component models implemented in Matlab/Simulink to simulate the effect of premixed charge compression ignition (PCCI) on the fuel economy and emissions of light-duty diesel-powered conventional and hybrid electric vehicles (HEVs). Our simulated engine is capable of both conventional diesel combustion (CDC) and premixed charge compression ignition (PCCI) over real transient driving cycles. Our simulated aftertreatment train consists of a diesel oxidation catalyst (DOC), lean NOx trap (LNT), and catalyzed diesel particulate filter (DPF). The results demonstrate that, in the simulated conventional vehicle, PCCI can significantly reduce fuel consumption and emissions by reducing the need for LNT and DPF regeneration. However, the opportunity for PCCI operation in the simulated HEV is limited because the engine typically experiences higher loads and multiple stop-start transients that are outside the allowable PCCI operating range. Thus developing ways of extending the PCCI operating range combined with improved control strategies for engine and emissions control management will be especially important for realizing the potential benefits of PCCI in HEVs.

  11. Could time itself be logarithmic?

    NASA Astrophysics Data System (ADS)

    George, William

    2016-11-01

    This presentation hypothesizes that increments of time may be logarithmic and measured from an initial instant - the log of absolute time if you will. In this alternative view all equations involving time must be written with lnt /to where t is measured in linear increments from the beginning of the universe and to is the universal time scale. All equations involving time derivatives must be written not as d / dt but d / dlnt / to = td / dt . An immediate consequence, for example, is that our definition of mass in Newton's Law must change as well: from mdv / dt = F to m* dv / dlnt / to =m* tdv / dt = F where F is force applied and v is velocity (however defined). m* = m / t is the 'true' or absolute mass. Since we have been measuring for only about 500 years and the universe is estimated to be about 18 billion years (millions of billions of seconds) old, the differences are impossible to measure; i.e., ln (t + δt) - lnt δt / t . It is only when we look backwards towards the beginning of the universe that we notice the difference - mass, m =m* t , appears to be missing. So we need "dark matter" to make our equations balance - when in fact it might be our "linear-time" equations and definitions that are wrong.

  12. Effect of reductive treatments on Pt behavior and NOx storage in lean NOx trap catalysts

    SciTech Connect

    Wang, Xianqin; Kim, Do Heui; Kwak, Ja Hun; Wang, Chong M.; Szanyi, Janos; Peden, Charles HF

    2011-10-01

    Lean NOx trap (LNT) catalysts represent a promising approach to meet increasingly stringent NOx emission regulations on diesel and other lean-burn engines. Pt material properties, including dispersion and particle size, are known to be important factors in determining NOx uptake performance, since Pt provides active sites for NO oxidation to NO2 necessary for storing NOx as nitrates, and for the reduction of nitrates to N2. In this work, the physicochemical properties of Pt in Pt-BaO/Al2O3 LNT catalysts, such as the Pt accessible surface area and particle size, were investigated by using various tools, such as irreversible volumetric H2 chemisorption, high resolution transmission electron microscopy (HRTEM), and X-ray diffraction (XRD), following successive reductive treatments at elevated temperatures. NOx uptake activities were also measured to establish a relationship between the properties of Pt and NOx storage following identical high-temperature reductive treatments. We find that the reductive treatments of Pt-BaO/Al2O3 lean NOx trap catalysts at temperatures up to 500 ºC promote a significant increase in NOx uptake explained, in part, by an induced close interaction between Pt and BaO phases in the catalyst, thus enabling facilitation of the NOx storage process.

  13. Oscillatory characteristics of metallic nanoparticles inside lipid nanotubes

    NASA Astrophysics Data System (ADS)

    Sadeghi, Fatemeh; Ansari, Reza; Darvizeh, Mansour

    2015-12-01

    This study is concerned with the oscillatory behavior of metallic nanoparticles, and in particular silver and gold nanoparticles, inside lipid nanotubes (LNTs) using the continuum approximation along with the 6-12 Lennard-Jones (LJ) potential function. The nanoparticle is modeled as a dense sphere and the LNT is assumed to be comprised of six layers including two head groups, two intermediate layers and two tail groups. To evaluate van der Waals (vdW) interactions, analytical expressions are first derived through undertaking surface and volume integrals which are then validated by a fully numerical scheme based on the differential quadrature (DQ) technique. Using the actual force distribution between the two interacting molecules, the equation of motion is directly solved utilizing the Runge-Kutta numerical integration scheme to arrive at the time history of displacement and velocity of the inner core. Also, a semi-analytical expression incorporating both geometrical parameters and initial conditions is introduced for the precise evaluation of oscillation frequency. A comprehensive study is conducted to gain an insight into the influences of nanoparticle radius, LNT length, head and tail group thicknesses and initial conditions on the oscillatory behavior of the metallic nanoparticles inside LNTs. It is found that the escape velocity and oscillation frequency of silver nanoparticles are higher than those of gold ones. It is further shown that the oscillation frequency is less affected by the tail group thickness when compared to the head group thickness.

  14. The Effect of Short-Term Auditory Training on Speech in Noise Perception and Cortical Auditory Evoked Potentials in Adults with Cochlear Implants

    PubMed Central

    Barlow, Nathan; Purdy, Suzanne C.; Sharma, Mridula; Giles, Ellen; Narne, Vijay

    2016-01-01

    This study investigated whether a short intensive psychophysical auditory training program is associated with speech perception benefits and changes in cortical auditory evoked potentials (CAEPs) in adult cochlear implant (CI) users. Ten adult implant recipients trained approximately 7 hours on psychophysical tasks (Gap-in-Noise Detection, Frequency Discrimination, Spectral Rippled Noise [SRN], Iterated Rippled Noise, Temporal Modulation). Speech performance was assessed before and after training using Lexical Neighborhood Test (LNT) words in quiet and in eight-speaker babble. CAEPs evoked by a natural speech stimulus /baba/ with varying syllable stress were assessed pre- and post-training, in quiet and in noise. SRN psychophysical thresholds showed a significant improvement (78% on average) over the training period, but performance on other psychophysical tasks did not change. LNT scores in noise improved significantly post-training by 11% on average compared with three pretraining baseline measures. N1P2 amplitude changed post-training for /baba/ in quiet (p = 0.005, visit 3 pretraining versus visit 4 post-training). CAEP changes did not correlate with behavioral measures. CI recipients' clinical records indicated a plateau in speech perception performance prior to participation in the study. A short period of intensive psychophysical training produced small but significant gains in speech perception in noise and spectral discrimination ability. There remain questions about the most appropriate type of training and the duration or dosage of training that provides the most robust outcomes for adults with CIs. PMID:27587925

  15. Simulating Study of Premixed Charge Compression Ignition on Light-Duty Diesel Fuel Economy and Emissions Control

    SciTech Connect

    Gao, Zhiming; Daw, C Stuart; Wagner, Robert M

    2012-01-01

    We utilize the Powertrain Systems Analysis Toolkit (PSAT) combined with transient engine and aftertreatment component models to simulate the impact of premixed charge compression ignition (PCCI) on the fuel economy and emissions of light-duty (LD) diesel-powered conventional and hybrid electric vehicles (HEVs). Our simulated aftertreatment train consists of a diesel oxidation catalyst (DOC), lean NOx trap (LNT), and catalyzed diesel particulate filter (DPF). The results indicate that utilizing PCCI combustion significantly reduces fuel consumption and tailpipe emissions for the conventional diesel-powered vehicle with NOx and particulate emissions controls. These benefits result from a favorable engine speed-load distribution over the cycle combined with a corresponding reduction in the need to regenerate the LNT and DPF. However, the current PCCI technology appears to offer less potential benefit for diesel HEVs equipped with similar emissions controls. This is because PCCI can only be activated over a relatively small part of the drive cycle. Thus we conclude that future utilization of PCCI in diesel HEVs will require significant extension of the available speed-load range for PCCI and revision of current HEV engine management strategies before significant benefits can be realized.

  16. Radon Treatment Controversy

    PubMed Central

    Zdrojewicz, Zygmunt; Strzelczyk, Jadwiga (Jodi)

    2006-01-01

    In spite of long traditions, treatments utilizing radon-rich air or water have not been unequivocally embraced by modern medicine. The objective of this work is to examine factors that contribute to this continuing controversy. While the exact mechanism of radon's effect on human body is not completely understood, recent advances in radiobiology offer new insights into biochemical processes occurring at low-level exposures to ionizing radiation. Medical evidence and patients' testimonials regarding effectiveness of radon spa treatments of various ailments, most notably rheumatoid arthritis are accumulating worldwide. They challenge the premise of the Linear-No-Threshold (LNT) theory that the dose-effect response is the same per unit dose regardless of the total dose. Historically, such inference overshadowed scientific inquiries into the low-dose region and lead to a popular belief that no amount of radiation can be good. Fortunately, the LNT theory, which lacks any scientific basis, did not remain unchallenged. As the reviewed literature suggests, a paradigm shift, reflected in the consideration of hormetic effects at low-doses, is gaining momentum in the scientific community worldwide. The impetus comes from significant evidence of adaptive and stimulatory effects of low-levels of radiation on human immune system. PMID:18648641

  17. Infrared and Raman spectra of magnesium ammonium phosphate hexahydrate (struvite) and its isomorphous analogues. Part VI: FT-IR spectra of isomorphously isolated species. NH4+ ions isolated in MKPO 4·6H 2O (M = Mg; Ni) and PO43- ions isolated in MgNH 4AsO 4·6H 2O

    NASA Astrophysics Data System (ADS)

    Cahil, A.; Šoptrajanov, B.; Najdoski, M.; Lutz, H. D.; Engelen, B.; Stefov, V.

    2008-03-01

    Examination of mixed crystals, especially those with isomorphously isolated ions, has proved very useful in spectra-structure correlation studies. Room (RT) and low temperature (LNT) FT-IR spectra of ammonium doped in MgKPO 4·6H 2O and NiKPO 4·6H 2O and phosphate doped in MgNH 4AsO 4·6H 2O in different degrees were recorded. All three compounds are isostructural with struvite, MgNH 4PO 4·6H 2O, space group Pmn2 1, forming substitutional mixed crystals with Cs symmetry of the anions. Analysis of the region of ν 4(NH 4), ν 3(PO 4) and ν 4(PO 4) modes of LNT FT-IR difference spectra of analogues with a small content of NH4+ and PO43- revealed the expected decrease of Td symmetry of free NH4+ and PO43- ions to Cs site symmetry. Due to the Cs site symmetry of the anions, the degeneration of the ν 4(NH 4), ν 3PO 4) and ν 4PO 4) modes is raised and, hence, three components are observed in the difference FT-IR spectra. This conclusion can not be derived only from studies of no-doped polycrystalline samples of struvite type compounds.

  18. Infrared and Raman spectra of magnesium ammonium phosphate hexahydrate ( struvite) and its isomorphous analogues. IV. FTIR spectra of protiated and partially deuterated nickel ammonium phosphate hexahydrate and nickel potassium phosphate hexahydrate

    NASA Astrophysics Data System (ADS)

    Cahil, A.; Najdoski, M.; Stefov, V.

    2007-05-01

    The Fourier transform infrared spectra recorded from room temperature down to the boiling temperature of liquid nitrogen of two struvite analogues, nickel ammonium phosphate hexahydrate (NiNH 4PO 4·6H 2O) and nickel potassium phosphate hexahydrate (NiKPO 4·6H 2O) and their partially deuterated analogues were analyzed and compared to the previously studied spectra of struvite and its potassium analogue. In the stretching mode region of the water molecules and ammonium ions, a broad asymmetric and deuteration sensitive band appears, which is an indication for strong hydrogen bonds in the structure of NiNP. In the LNT difference spectra of samples with low deuterium content (≈2-3% D), several bands appear between 2520 and 2080 cm -1 due to vibrations of isotopically isolated HDO molecules and NH 3D + ions. The most significant difference between the two studied spectra is between 2350 and 2250 cm -1 where additional bands from ND stretching modes of isotopically isolated NH 3D + ions are expected in the spectrum of NiNP. In the region of ν3(PO 4) modes one strong, slightly asymmetric, temperature-sensitive band appears above 1000 cm -1 in both spectra. The analysis of the RT and LNT spectra of the protiated and partially deuterated compounds, the band at around 575 cm -1 is assigned to the ν4(PO 4) modes and the remaining ones as due to librational and translational modes of the water molecules.

  19. Changing the Risk Paradigms Can be Good for Our Health: J-Shaped, Linear and Threshold Dose-Response Models.

    PubMed

    Ricci, P F; Straja, S R; Cox, A L

    2012-01-01

    Both the linear (at low doses)-no-threshold (LNT) and the threshold models (S-shapes) dose-response lead to no benefit from low exposure. We propose three new models that allow and include, but do not require - unlike LNT and S-shaped models - this strong assumption. We also provide the means to calculate benefits associated with bi-phasic biological behaviors, when they occur and propose:THREE HORMETIC (PHASIC) MODELS: the J-shaped, inverse J-shaped, the min-max, andMethod for calculating the direct benefits associated with the J and inverse J-shaped models.The J-shaped and min-max models for mutagens and carcinogenic agents include an experimentally justified repair stage for toxic and carcinogenic damage. We link these to stochastic transition models for cancer and show how abrupt transitions in cancer hazard rates, as functions of exposure concentrations and durations, can emerge naturally in large cell populations even when the rates of cell-level events increase smoothly (e.g., proportionally) with concentration. In this very general family of models, J-shaped dose-response curves emerge. These results are universal, i.e., independent of specific biological details represented by the stochastic transition networks. Thus, using them suggests a more complete and realistic way to assess risks at low doses or dose-rates.

  20. Crystal Structure and Anisotropic c--f Hybridization in CeT2Al10 (T=Ru, Fe)

    NASA Astrophysics Data System (ADS)

    Sera, Masafumi; Tanaka, Daiki; Tanida, Hiroshi; Moriyoshi, Chikako; Ogawa, Mayuko; Kuroiwa, Yoshihiro; Nishioka, Takashi; Matsumura, Masahiro; Kim, Jungeun; Tsuji, Naruki; Takata, Masaki

    2013-02-01

    We have performed the investigation of the charge density distribution of CeT2Al10 (T=Ru, Fe) and the crystal structure parameters of LnT2Al10. The lattice parameters of a-, b-, and c-axes exhibit the anisotropic contraction when Ru is replaced by Fe in LnT2Al10, different from the isotropic contraction simply expected from the smaller ionic radius of Fe than Ru. The contraction is larger in the a- and c-axes than in the b-axis. This anisotropic contraction of the YbFe2Al10-type crystal structure originates from the zigzag degree of the zigzag chain formed by T and Al bond along the a- and c-axes are larger than that along the b-axis. The lattice parameters of CeT2Al10 (T=Ru, Fe) exhibit the anisotropic deviation from the lanthanide contraction. The deviation is largest in the a-axis and is very small in the b-axis. Both the characteristic YbFe2Al10-type crystal structure and the anisotropic deviation towards the intermediate valence indicate that the largest c--f hybridization along the a-axis plays the important role and is associated with the unusual antiferromagnetic order in CeT2Al10 (T=Ru, Os).

  1. Enzyme catalysed production of sialylated human milk oligosaccharides and galactooligosaccharides by Trypanosoma cruzi trans-sialidase.

    PubMed

    Holck, Jesper; Larsen, Dorte M; Michalak, Malwina; Li, Haiying; Kjærulff, Louise; Kirpekar, Finn; Gotfredsen, Charlotte H; Forssten, Sofia; Ouwehand, Arthur C; Mikkelsen, Jørn D; Meyer, Anne S

    2014-03-25

    A Trypanosoma cruzi trans-sialidase (E.C. 3.2.1.18) was cloned into Pichia pastoris and expressed. The pH and temperature optimum of the enzyme was determined as pH 5.7 and 30°C. Using casein glycomacropeptide (CGMP) and lactose as sialyl-donor and acceptor respectively, the optimal donor/acceptor ratio for the trans-sialidase catalysed 3'-sialyllactose production was found to be 1:4. Quantitative amounts of 3'-sialyllactose were produced from CGMP and lactose at a yield of 40mg/g CGMP. The 3'-sialyllactose obtained exerted a stimulatory effect on selected probiotic strains, including different Bifidobacterium strains in single culture fermentations. The trans-sialidase also catalysed the transfer of sialic acid from CGMP to galacto-oligosaccharides (GOS) and to the human milk oligosaccharide (HMO) backbone lacto-N-tetraose (LNT) to produce 3'-sialyl-GOS, including doubly sialylated GOS products, and 3'-sialyl-LNT, respectively. This work thus provides proof of the concept of producing 3'-sialyllactose and potentially other sialylated HMOs as well as sialylated GOS enzymatically by trans-sialidase activity, while at the same time providing valorisation of CGMP, a co-processing product from cheese manufacture.

  2. Aminoacylation of the N-terminal cysteine is essential for Lol-dependent release of lipoproteins from membranes but does not depend on lipoprotein sorting signals.

    PubMed

    Fukuda, Ayumu; Matsuyama, Shin-Ichi; Hara, Takashi; Nakayama, Jiro; Nagasawa, Hiromichi; Tokuda, Hajime

    2002-11-08

    Lipoproteins are present in a wide variety of bacteria and are anchored to membranes through lipids attached to the N-terminal cysteine. The Lol system of Escherichia coli mediates the membrane-specific localization of lipoproteins. Aspartate at position 2 functions as a Lol avoidance signal and causes the retention of lipoproteins in the inner membrane, whereas lipoproteins having residues other than aspartate at position 2 are released from the inner membrane and localized to the outer membrane by the Lol system. Phospholipid:apolipoprotein transacylase, Lnt, catalyzes the last step of lipoprotein modification, converting apolipoprotein into mature lipoprotein. To reveal the importance of this aminoacylation for the Lol-dependent membrane localization, apolipoproteins were prepared by inhibiting lipoprotein maturation. Lnt was also purified and used to convert apolipoprotein into mature lipoprotein in vitro. The release of these lipoproteins was examined in proteoliposomes. We show here that the aminoacylation is essential for the Lol-dependent release of lipoproteins from membranes. Furthermore, lipoproteins with aspartate at position 2 were found to be aminoacylated both in vivo and in vitro, indicating that the lipoprotein-sorting signal does not affect lipid modification.

  3. Ion-beam synthesis of zinc-based nanoparticles in SiO2

    NASA Astrophysics Data System (ADS)

    Czarnacka, Karolina; Makhavikou, Maksim A.; Komarov, Fadei F.

    2016-12-01

    In this paper production process of Zn nanocrystals in SiO2 by using an implantation of high dose zinc ions with energy of 130 keV and annealing process in 700°C were described. Using electron microscopy was established that annealing causes extension of admixtures distribution on depth and zinc nanoparticles size increasing from approx. 1 - 6 nm to 12 - 18 nm. For prepared material AC conductivity measurements were made in temperatures range from liquid nitride temperature (LNT) to 373 K and at frequencies range from 50 Hz to 5 MHz. Strong frequency dependence on conductivity proves that in this nanocomposite Zn-SiO2 conduction takes place by electron hopping exchange (tunneling) between metallic phase nanoparticles. It was established that three activation energies of conductivity occurs in temperatures range of LNT - 373 K - in low temperatures ΔE1≍0.001 eV, in medium temperatures ΔE2≍0.025 eV and in higher temperatures area ΔE3≍0.096 eV. This is due to the presence of at least two types of nanoparticles. First there are zinc nanoparticles with zinc oxide coating, second there are nanoparticles without the coating. The highest activation energy occurs during electrons tunneling between nanoparticles with zinc oxide coating. Intermediate activation energy corresponds to tunneling from nanoparticle with coating to nanoparticle without coating or conversely. The lowest activation energy corresponds to electrons hopping between nanoparticles without coatings.

  4. Implications of Low Particulate Matter Emissions on System Fuel Efficiency for High Efficiency Clean Combustion

    SciTech Connect

    Parks, II, James E; Prikhodko, Vitaly Y

    2009-01-01

    Advanced diesel combustion regimes such as High Efficiency Clean Combustion (HECC) offer the benefits of reduced engine out NOX and particulate matter (PM) emissions. Lower PM emissions during advanced combustion reduce the demand on diesel particulate filters (DPFs) and can, thereby, reduce the fuel penalty associated with DPF regeneration. In this study, a SiC DPF was loaded and regenerated on a 1.7-liter 4-cylinder diesel engine operated in conventional and advanced combustion modes at different speed and load conditions. A diesel oxidation catalyst (DOC) and a lean NOX trap (LNT) were also installed in the exhaust stream. Five steady-state speed and load conditions were weighted to estimate Federal Test Procedure (FTP) fuel efficiency. The DPF was loaded using lean-rich cycling with frequencies that resulted in similar levels of NOX emissions downstream of the LNT. The pressure drop across the DPF was measured at a standard point (1500 rpm, 5.0 bar) before and after loading, and a P rise rate was determined for comparison between conventional and advanced combustion modes. Higher PM emissions in conventional combustion resulted in a higher rate of backpressure rise across the DPF at all of the load points leading to more frequent DPF regenerations and higher fuel penalty. The fuel penalty during conventional combustion was 4.2% compared with 3.1% for a mixture of conventional and advanced modes.

  5. Simulation of lean NOx trap performance with microkinetic chemistry and without mass transfer.

    SciTech Connect

    Larson, Rich; Daw, C. Stuart; Pihl, Josh A.; Chakravarthy, V. Kalyana

    2011-08-01

    A microkinetic chemical reaction mechanism capable of describing both the storage and regeneration processes in a fully formulated lean NO{sub x} trap (LNT) is presented. The mechanism includes steps occurring on the precious metal, barium oxide (NO{sub x} storage), and cerium oxide (oxygen storage) sites of the catalyst. The complete reaction set is used in conjunction with a transient plug flow reactor code to simulate not only conventional storage/regeneration cycles with a CO/H{sub 2} reductant, but also steady flow temperature sweep experiments that were previously analyzed with just a precious metal mechanism and a steady state code. The results show that NO{sub x} storage is not negligible during some of the temperature ramps, necessitating a re-evaluation of the precious metal kinetic parameters. The parameters for the entire mechanism are inferred by finding the best overall fit to the complete set of experiments. Rigorous thermodynamic consistency is enforced for parallel reaction pathways and with respect to known data for all of the gas phase species involved. It is found that, with a few minor exceptions, all of the basic experimental observations can be reproduced with these purely kinetic simulations, i.e., without including mass-transfer limitations. In addition to accounting for normal cycling behavior, the final mechanism should provide a starting point for the description of further LNT phenomena such as desulfation and the role of alternative reductants.

  6. Longitudinal change of selected human milk oligosaccharides and association to infants’ growth, an observatory, single center, longitudinal cohort study

    PubMed Central

    Lee, Le Ye; De Castro, Carlos Antonio; Steenhout, Philippe; Thakkar, Sagar K.

    2017-01-01

    Background Human milk is the recommended and sole nutrient source for newborns. One of the largest components of human milk is oligosaccharides (HMOs) with major constituents determined by the mother genotype for the fucosyltransferase 2 (FUT2, secretor) gene. HMO variation has been related with infant microbiota establishment, diarrhea incidence, morbidity and mortality, IgE associated eczema and body composition. Objectives We investigated the (i) dependence of several major representative HMOs on the FUT2 status assessed through breast milk 2’Fucosyllactose (2’FL) and (ii) the relation of the 2’FL status with infant growth up to 4 months of life. Design From an open observatory, single center, longitudinal cohort study with quantitative human milk collection at 30, 60, and 120 days postpartum from 50 mothers, who gave birth to 25 female and 25 male singleton infants, we collected a representative sample of human milk. We quantified the following 5 representative HMOs: 2’FL, Lacto-N-tetraose (LNT), Lacto-N-neotetraose (LNnT), 3’Sialyllactose (3’SL) and 6’Sialyllactose (6’SL). We grouped the milk samples and corresponding infants according to the measured milk 2’FL concentrations at 30 days of lactation, which clustered around low concentrations (95% CI of mean 12–42 mg/L) and high concentrations (95% CI of mean 1880–2460 mg/L) with the former likely representing Secretor negative mothers. Infant anthropometric measures were recorded at birth, 1, 2 and 4 months of age. Relations among the quantified HMOs and the relation of the high and low 2’FL HMOs groups with infant growth parameters were investigated via linear mixed models. Results The milk samples with low 2’FL concentration had higher LNT and lower LNnT concentrations compared to the samples with high 2’FL. The milk 3’- and 6’SL concentrations were independent of 2’FL. Over lactation time we observed a drop in the concentration of 2’FL, LNT, LNnT and 6’SL, especially

  7. Application of Low Dose Radiation Adaptive Response to Control Aging-Related Disease

    SciTech Connect

    Doss, Mohan

    2013-11-01

    Oxidative damage has been implicated in the pathogenesis of most aging-related diseases including neurodegenerative diseases. Antioxidant supplementation has been found to be ineffective in reducing such diseases, but increased endogenous production of antioxidants from the adaptive response due to physical and cognitive exercises (which increase oxidative metabolism and oxidative stress) has been effective in reducing some of the diseases. Low dose radiation (LDR), which increases oxidative stress and results in adaptive response of increased antioxidants, may provide an alternative method of controlling the aging-related diseases. We have studied the effect of LDR on the induction of adaptive response in rat brains and the effectiveness of the LDR in reducing the oxidative damage caused by subsequent high dose radiation. We have also investigated the effect of LDR on apomorphine-induced rotations in the 6-hydroxydopamine (6-OHDA) unilaterally-lesioned rat model of Parkinson?s disease (PD). LDR was observed to initiate an adaptive response in the brain, and reduce the oxidative damage from subsequent high dose radiation exposure, confirming the effectiveness of LDR adaptive response in reducing the oxidative damage from the free radicals due to high dose radiation. LDR resulted in a slight improvement in Tyrosine hydroxylase expression on the lesioned side of substantia nigra (indicative of its protective effect on the dopaminergic neurons), and reduced the behavioral symptoms in the 6-OHDA rat model of PD. Translation of this concept to humans, if found to be applicable, may be a possible approach for controlling the progression of PD and other neurodegenerative diseases. Since any translation of the concept to humans would be hindered by the currently prevalent carcinogenic concerns regarding LDR based on the linear no-threshold (LNT) model, we have also studied the justifications for the use of the LNT model. One of the shortcomings of the LNT model is that it

  8. Nonlinear threshold effect in the Z-scan method of characterizing limiters for high-intensity laser light

    NASA Astrophysics Data System (ADS)

    Tereshchenko, S. A.; Savelyev, M. S.; Podgaetsky, V. M.; Gerasimenko, A. Yu.; Selishchev, S. V.

    2016-09-01

    A threshold model is described which permits one to determine the properties of limiters for high-powered laser light. It takes into account the threshold characteristics of the nonlinear optical interaction between the laser beam and the limiter working material. The traditional non-threshold model is a particular case of the threshold model when the limiting threshold is zero. The nonlinear characteristics of carbon nanotubes in liquid and solid media are obtained from experimental Z-scan data. Specifically, the nonlinear threshold effect was observed for aqueous dispersions of nanotubes, but not for nanotubes in solid polymethylmethacrylate. The threshold model fits the experimental Z-scan data better than the non-threshold model. Output characteristics were obtained that integrally describe the nonlinear properties of the optical limiters.

  9. Magnetic excitations and c-f hybridization effect in PrTi2Al20 and PrV2Al20

    NASA Astrophysics Data System (ADS)

    Tokunaga, Yo; Sakai, Hironori; Kambe, Shinsaku; Sakai, Akito; Nakatsuji, Satoru; Harima, Hisatomo

    2013-08-01

    By means of 27Al NMR studies, we have investigated magnetic excitations and the hybridization effect between Pr 4f and conduction electrons in a pair of cubic compounds PrTr2Al20 (Tr=Ti, V). From Knight shift measurements we have evaluated comparative strengths for the c-f hybridization effect in these compounds and confirm a definite increase of hybridization on replacing Ti with V. Analysis of the spin-lattice relaxation rate 1/T1 reveals that the spectral width of magnetic fluctuations in crystalline electric field excited states is strongly temperature dependent. This result indicates that magnetic fluctuations are dominated by strong c-f exchange coupling at high temperatures and thus is nicely consistent with the Kondo picture that features lnT dependence of resistivity over the same temperature region.

  10. Low doses of ionizing radiation to mammalian cells may rather control than cause DNA damage

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced metabolic changes that induce mechanisms of DNA damage mitigation, which do not operate at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. This paper aims at demonstrating tissue effects as an expression of cellular responses, both damaging and defensive, in relation to the energy deposited in cell mass, by use of microdosimetric concepts.

  11. Protecting effects specifically from low doses of ionizing radiation to mammalian cells challenge the concept of linearity

    SciTech Connect

    Feinendegen, L.E.; Bond, V.P.; Sondhaus, C.A.; Altman, K.I.

    1998-12-31

    This report examines the origin of tissue effects that may follow from different cellular responses to low-dose irradiation, using published data. Two principal categories of cellular responses are considered. One response category relates to the probability of radiation-induced DNA damage. The other category consists of low-dose induced changes in intracellular signaling that induce mechanisms of DNA damage control different from those operating at high levels of exposure. Modeled in this way, tissue is treated as a complex adaptive system. The interaction of the various cellular responses results in a net tissue dose-effect relation that is likely to deviate from linearity in the low-dose region. This suggests that the LNT hypothesis should be reexamined. The aim of this paper is to demonstrate that by use of microdosimetric concepts, the energy deposited in cell mass can be related to the occurrence of cellular responses, both damaging and defensive.

  12. In defence of collective dose.

    PubMed

    Fairlie, I; Sumner, D

    2000-03-01

    Recent proposals for a new scheme of radiation protection leave little room for collective dose estimations. This article discusses the history and present use of collective doses for occupational, ALARA, EIS and other purposes with reference to practical industry papers and government reports. The linear no-threshold (LNT) hypothesis suggests that collective doses which consist of very small doses added together should be used. Moral and ethical questions are discussed, particularly the emphasis on individual doses to the exclusion of societal risks, uncertainty over effects into the distant future and hesitation over calculating collective detriments. It is concluded that for moral, practical and legal reasons, collective dose is a valid parameter which should continue to be used.

  13. Effect of long-range hopping and interactions on entanglement dynamics and many-body localization

    NASA Astrophysics Data System (ADS)

    Singh, Rajeev; Moessner, Roderich; Roy, Dibyendu

    2017-03-01

    We numerically investigate the dynamics of entanglement in a chain of spinless fermions with nonrandom but long-range hopping and interactions, and with random on-site energies. For moderate disorder in the absence of interactions, the chain hosts delocalized states at the top of the band which undergo a delocalization-localization transition with increasing disorder. We find an interesting regime in this noninteracting disordered chain where the long-time entanglement entropy scales as S (t )˜lnt and the saturated entanglement entropy scales with system size L as S (L ,t →∞ )˜lnL . We further study the interplay of long-range hopping and interactions on the growth of entanglement and the many-body localization (MBL) transition in this system. We develop an analogy to higher-dimensional short-range systems to compare and contrast such behavior with the physics of MBL in a higher dimension.

  14. Quantum statistical vibrational entropy and enthalpy of formation of helium-vacancy complex in BCC W

    NASA Astrophysics Data System (ADS)

    Wen, Haohua; Woo, C. H.

    2016-12-01

    High-temperature advance-reactor design and operation require knowledge of in-reactor materials properties far from the thermal ground state. Temperature-dependence due to the effects of lattice vibrations is important to the understanding and formulation of atomic processes involved in irradiation-damage accumulation. In this paper, we concentrate on the formation of He-V complex. The free-energy change in this regard is derived via thermodynamic integration from the phase-space trajectories generated from MD simulations based on the quantum fluctuation-dissipation relation. The change of frequency distribution of vibration modes during the complex formation is properly accounted for, and the corresponding entropy change avoids the classical ln(T) divergence that violates the third law. The vibrational enthalpy and entropy of formation calculated this way have significant effects on the He kinetics during irradiation.

  15. Effects of Phase Noise and Thermal Noise upon Coherent PSK Demodulation and Their Impact on Phase Noise Specifications for Terminals of the Phase II DSCS.

    DTIC Science & Technology

    1974-08-01

    TDMA With PLL Noise Bandwidth of 100 Hz. Operation With Possible Phase 11 DS (S Noise Contributors and With Soft Decision (3-biti, Rate 1 2, Constraint...vith a fixed s )lh, lQ :t 11’ , it is tossilil t () ’ause the cairrier referen ce total phase error \\:i’lnt(c it) int’.cr S , ds e crease, or renain...Mod.F17 JF Lof-E(701) LOSF(’TH) LOSS(TOr) LOS1THi T/f CFF ) crp) (DB) (DB 71377k>6 >6 15rI . 7f-3 A.877PP >6 >6 300 P. 9A704 S. f7 ORd >6 >6 S,),3. 791

  16. KWIK Smoke Obscuration Model: User’s Guide.

    DTIC Science & Technology

    1982-09-01

    t ’ustr ( td I IK,j) 384: prt 3o :: pr t 6 k AC 1-4G" 36~b : pr t " ~ L 3b7: if j~i;prt &t(t1,] 3 8 8: it J=2;pr. "&str(Zjl,1,KI) 3 0 9: j~r t "I 39u...t.2~t71. * j3 3 2u: w r t 7uX ,"i(Lz~j i21iJ "c3wt70, )i: lnt 4 5X, "irI I U uIL - = 01 17.2;wrt 701,kq3 j~b: Lirt. 45x,"a..~c4 uAT - LiLY = g,t4.2

  17. Threshold for Radon-Induced Lung Cancer From Inhaled Plutonium Data.

    PubMed

    Cuttler, Jerry M; Sanders, Charles L

    2015-01-01

    Cohen's lung cancer mortality data, from his test of the LNT theory, do not extend to the no observed adverse effects level (NOAEL) above which inhaled radon decay products begin to induce excess lung cancer mortality. Since there is concern about the level of radon in homes, it is important to set the radon limit near the NOAEL to avoid the risk of losing a health benefit. Assuming that dogs model humans, data from a study on inhaled plutonium dioxide particulates in dogs were assessed, and the NOAEL for radon-induced lung tumors was estimated to be about 2100 Bq/m(3). The US Environmental Protection Agency should consider raising its radon action level from 150 to at least 1000 Bq/m(3).

  18. Nanofoams Response to Radiation Damage

    SciTech Connect

    Fu, Engang; Serrano De Caro, Magdalena; Wang, Yongqiang; Nastasi, Michael; Zepeda-Ruiz, Luis; Bringa, Eduardo M.; Baldwin, Jon K.; Caro, Jose A.

    2012-07-30

    Conclusions of this presentation are: (1) np-Au foams were successfully synthesized by de-alloying process; (2) np-Au foams remain porous structure after Ne ion irradiation to 1 dpa; (3) SFTs were observed in irradiated np-Au foams with highest and intermediate flux, while no SFTs were observed with lowest flux; (4) SFTs were observed in irradiated np-Au foams at RT, whereas no SFTs were observed at LNT irradiation; (5) The diffusivity of vacancies in Au at RT is high enough so that the vacancies have enough time to agglomerate and thus collapse. As a result, SFTs were formed; (6) The high flux created much more damage/time, vacancies don't have enough time to diffuse or recombine. As a result, SFTs were formed.

  19. Compliance of Royal Naval ships with nitrogen oxide emissions legislation.

    PubMed

    Blatcher, D J; Eames, I

    2013-09-15

    Nitrogen oxide (NOx) emissions from marine diesel engines pose a hazard to human health and the environment. From 2021, demanding emissions limits are expected to be applied to sea areas that the Royal Navy (RN) accesses. We analyze how these future constraints affect the choice of NOx abatement systems for RN ships, which are subject to more design constraints than civilian ships. A weighted matrix approach is used to facilitate a quantitative assessment. For most warships to be built soon after 2021 Lean Nitrogen Traps (LNT) in conjunction with Exhaust Gas Recirculation (EGR) represents a relatively achievable option with fewer drawbacks than other system types. Urea-selective catalytic reduction is likely to be most appropriate for ships that are built to civilian standards. The future technologies that are at an early stage of development are discussed.

  20. Inkjet printing technology and conductive inks synthesis for microfabrication techniques

    NASA Astrophysics Data System (ADS)

    Chien Dang, Mau; Dung Dang, Thi My; Fribourg-Blanc, Eric

    2013-03-01

    Inkjet printing is an advanced technique which reliably reproduces text, images and photos on paper and some other substrates by desktop printers and is now used in the field of materials deposition. This interest in maskless materials deposition is coupled with the development of microfabrication techniques for the realization of circuits or patterns on flexible substrates for which printing techniques are of primary interest. This paper is a review of some results obtained in inkjet printing technology to develop microfabrication techniques at Laboratory for Nanotechnology (LNT). Ink development, in particular conductive ink, study of printed patterns, as well as application of these to the realization of radio-frequency identification (RFID) tags on flexible substrates, are presented. Invited talk at the 6th International Workshop on Advanced Materials Science and Nanotechnology, 30 October-2 November 2012, Ha Long, Vietnam.

  1. A Perspective on the Scientific, Philosophical, and Policy Dimensions of Hormesis

    PubMed Central

    Hoffmann, George R.

    2009-01-01

    The hormesis concept has broad implications for biology and the biomedical sciences. This perspective on hormesis concentrates on toxicology and toxicological risk assessment and secondarily explores observations from other fields. It considers the varied manifestations of hormesis in the context of a broad family of biological stress responses. Evidence for hormesis is reviewed, and the hormesis model is contrasted with more widely accepted dose-response models in toxicology: a linear nonthreshold (LNT) model for mutagenesis and carcinogenesis, and a threshold model for most other toxicologic effects. Scientific, philosophical, and political objections to the hormesis concept are explored, and complications in the hormesis concept are analyzed. The review concludes with a perspective on the current state of hormesis and challenges that the hormesis model poses for risk assessment. PMID:19343115

  2. Effect of Ceria on the Sulfation and Desulfation Characteristics of a Model Lean NOx Trap Catalyst

    SciTech Connect

    Ji, Yaying; Toops, Todd J; Crocker, Mark

    2009-01-01

    The effect of ceria addition on the sulfation and desulfation characteristics of a model Ba-based lean NO{sub x} trap (LNT) catalyst was studied. According to DRIFTS and NO{sub x} storage capacity measurements, ceria is able to store sulfur during catalyst exposure to SO{sub 2}, thereby helping to limit sulfation of the main (Ba) NO{sub x} storage phase and maintain NO{sub x} storage capacity. Temperature programmed desulfation experiments revealed that desulfation of a model ceria-containing catalyst occurred in two stages, corresponding to sulfur elimination from the ceria phase at {approx}450 C, followed by sulfur loss from the Ba phase at {approx}650 C. Significantly, the ceria-containing catalyst displayed relatively lower sulfur evolution from the Ba phase than its non-ceria analog, confirming that the presence of ceria lessened the degree of sulfur accumulation on the Ba phase.

  3. Observation of suppressed Auger mechanism in type-I quantum well structures with delocalized electron-hole wavefunctions

    SciTech Connect

    Hassani Nia, Iman; Fathipour, Vala; Mohseni, Hooman

    2015-08-15

    We report the first observation of non-threshold Auger mechanism for a quantum well structure with Type-I band alignment. Excitation-dependent photoluminescence measurements were used to extract the Auger recombination coefficients from 77 K up to room temperature. The results verify the role of interface mediated momentum exchange as well as suppression of Auger recombination for delocalized electron-hole wavefunctions.

  4. NOx Storage and Reduction Properties of Model Ceria-based Lean NOx Trap Catalysts

    SciTech Connect

    Shi, Chuan; Ji, Yaying; Graham, Uschi; Jacobs, Gary; Crocker, Mark; Zhang, Zhaoshun; Wang, Yu; Toops, Todd J

    2012-01-01

    Three kinds of model ceria-containing LNT catalysts, corresponding to Pt/Ba/CeO{sub 2}, Pt/CeO{sub 2}/Al{sub 2}O{sub 3} and Pt/BaO/CeO{sub 2}/Al{sub 2}O{sub 3}, were prepared for comparison with a standard LNT catalyst of the Pt/BaO/Al{sub 2}O{sub 3} type. In these catalysts ceria functioned as a No{sub x} storage component and/or a support material. The influence of ceria on the microstructure of the catalysts was investigated, in addition to the effect on No{sub x} storage capacity, regeneration behavior and catalyst performance during lean/rich cycling. The Pt/Ba/CeO{sub 2} and Pt/BaO/CeO{sub 2}/Al{sub 2}O{sub 3} catalysts exhibited higher No{sub x} storage capacity at 200 and 300 C relative to the Pt/BaO/Al{sub 2}O{sub 3} catalyst, although the latter displayed better storage capacity at 400 C. Catalyst regeneration behavior at low temperature was also improved by the presence of ceria, as reflected by TPR measurements. These factors contributed to the superior No{sub x} storage-reduction performance exhibited by the Pt/Ba/CeO{sub 2} and Pt/BaO/CeO{sub 2}/Al{sub 2}O{sub 3} catalysts under cycling conditions in the temperature range 200-300 C. Overall, Pt/BaO/CeO{sub 2}/Al{sub 2}O{sub 3} (which displayed well balanced No{sub x} storage and regeneration behavior), showed the best performance, affording consistently high No{sub x} conversion levels in the temperature range 200-400 C under lean-rich cycling conditions.

  5. Cytogenetic Low-Dose Hyperradiosensitivity Is Observed in Human Peripheral Blood Lymphocytes

    SciTech Connect

    Seth, Isheeta; Joiner, Michael C.; Tucker, James D.

    2015-01-01

    Purpose: The shape of the ionizing radiation response curve at very low doses has been the subject of considerable debate. Linear-no-threshold (LNT) models are widely used to estimate risks associated with low-dose exposures. However, the low-dose hyperradiosensitivity (HRS) phenomenon, in which cells are especially sensitive at low doses but then show increased radioresistance at higher doses, provides evidence of nonlinearity in the low-dose region. HRS is more prominent in the G2 phase of the cell cycle than in the G0/G1 or S phases. Here we provide the first cytogenetic mechanistic evidence of low-dose HRS in human peripheral blood lymphocytes using structural chromosomal aberrations. Methods and Materials: Human peripheral blood lymphocytes from 2 normal healthy female donors were acutely exposed to cobalt 60 γ rays in either G0 or G2 using closely spaced doses ranging from 0 to 1.5 Gy. Structural chromosomal aberrations were enumerated, and the slopes of the regression lines at low doses (0-0.4 Gy) were compared with doses of 0.5 Gy and above. Results: HRS was clearly evident in both donors for cells irradiated in G2. No HRS was observed in cells irradiated in G0. The radiation effect per unit dose was 2.5- to 3.5-fold higher for doses ≤0.4 Gy than for doses >0.5 Gy. Conclusions: These data provide the first cytogenetic evidence for the existence of HRS in human cells irradiated in G2 and suggest that LNT models may not always be optimal for making radiation risk assessments at low doses.

  6. Infrared and Raman spectra of magnesium ammonium phosphate hexahydrate (struvite) and its isomorphous analogues. III. Spectra of protiated and partially deuterated magnesium ammonium phosphate hexahydrate

    NASA Astrophysics Data System (ADS)

    Stefov, V.; Šoptrajanov, B.; Kuzmanovski, I.; Lutz, H. D.; Engelen, B.

    2005-10-01

    Magnesium ammonium phosphate hexahydrate, MgNH 4PO 4·6H 2O (synthetic struvite) is a well-known biomineral, its major biological importance being related to its presence in human urinary sediments and vesical and renal calculi. The Fourier transform infrared and Raman spectra of magnesium ammonium phosphate hexahydrate were recorded and analyzed from room temperature (RT) down to the boiling temperature of liquid nitrogen (LNT). Also recorded and analyzed were the spectra of its partially deuterated analogues. The recorded spectra were compared with the corresponding ones of the previously studied potassium analogue. On the basis of such a comparison it was concluded that the main contribution to the intensity of the broad and structured feature in the O-H/N-H stretching region comes from the bands originating from the H-O-H stretches. The location of at least some of the stretching vibrations of the ammonium ions (albeit one of its deuterated forms) is possible in the spectrum of the sample containing ≈2% deuterium. The bands at 2326 and 2277 cm -1 (and probably, at least partially, that at 2393 cm -1) can be assigned with certainty to N-D stretching vibrations of isotopically isolated NH 3D + ions. The LNT Raman bands at 1702 and 1685 cm -1 are attributed to the ν2NH4+ mode and those at 1477 and 1442 cm -1 are observed are attributed to the ν4 mode. The relatively high frequencies (1302 and 1295 cm -1) of some of the bands due to the ND bending vibrations of isotopically isolated NH 3D + ions are in line with the existence of quite strong hydrogen bonds formed by ammonium ions. The librations of the deuterated forms of water molecules may be coupled with the components of the phosphate ν4 vibration.

  7. Characteristics of Pt-K/MgAl2O4 lean NOx trap catalysts

    SciTech Connect

    Kim, Do Heui; Mudiyanselage, Kumudu K.; Szanyi, Janos; Zhu, Haiyang; Kwak, Ja Hun; Peden, Charles HF

    2012-04-30

    We report the various characteristics of Pt-K/MgAl{sub 2}O{sub 4} lean NOx trap (LNT) catalysts including the effect of K loading on nitrate formation/decomposition, NOx storage activity and durability. Upon the adsorption of NO{sub 2} on K/MgAl{sub 2}O{sub 4} samples, potassium nitrates formed on Mg-related sites in MgAl{sub 2}O{sub 4} support are observed, in addition to the typical two potassium nitrates (ionic and bidentate) formed also on Al{sub 2}O{sub 3} supported sample. Based on NO{sub 2} TPD and FTIR results, the Mg-bound KNO{sub 3} thermally decompose at higher temperature than Al-bound KNO{sub 3}, implying its superior thermal stability. At a potassium loading of 5wt%, the temperature of maximum NOx uptake (T{sub max}) is 300 C. Increasing the potassium loading from 5wt% to 10 wt%, the T{sub max} gradually shifted from 300 C to 450 C, indicating the dependence of T{sub max} on the potassium loading. However, increase in potassium loading above 10 wt% only gives rise to the reduction in the overall NOx storage capacity. This work also underlines the obstacles these materials have prior to their practical application (e.g., durability and sulfur poisoning/ removal). This work provides fundamental understanding of Pt-K/MgAl{sub 2}O{sub 4}-based lean NOx trap catalysts, which could be good candidates for high temperature LNT applications.

  8. Interpretation of the source-specific substantive control measures of the Minamata Convention on Mercury.

    PubMed

    You, Mingqing

    2015-02-01

    Being persistent, toxic, and bio-accumulative, Mercury (Hg) seriously affects the environment and human health. Due to Hg's attribute of long-range environmental transport across national borders, especially through atmospheric transport, no country can fully protect its environment and human health with its own efforts, without global cooperation. The Minamata Convention on Mercury, which was formally adopted and opened for signature in October 2013, is the only global environmental regime on the control of Hg pollution. Its main substantive control measures are source-specific: its phasing-out, phasing-down, and other main substantive requirements all direct to specific categories of pollution sources through the regulation of specific sectors of the economy and social life. This Convention does not take a national quota approach to quantify the Parties' nationwide total allowable consumption or discharge of Hg or Hg compounds, nor does it quantify their nationwide total reduction requirements. This paper attempts to find the underlying reasons for this source-specific approach and offers two interpretations. One possible interpretation is that Hg might be a non-threshold pollutant, i.e., a pollutant without a risk-free value of concentration. The existence of a reference dose (RfD), reference concentration (RfC), provisional tolerable weekly intake (PTWI), minimal risk level (MRL) or other similar reference values of Hg does not necessarily mean that Hg cannot be regarded as non-threshold because such reference values have scientific uncertainties and may also involve policy considerations. Another interpretation is that Hg lacks a feasibly determinable total allowable quantity. There is evidence that negotiators might have treated Hg as non-threshold, or at least accepted that Hg lacks a feasibly determinable total allowable quantity: (1) The negotiators were informed about the serious situations of the current emissions, releases, and legacy deposition; (2

  9. CRADA Final Report: Mechanisms of Sulfur Poisoning of NOx Adsorber Materials

    SciTech Connect

    Kim, Do Heui; Muntean, George G.; Peden, Charles H. F.; Howden, Ken; Stafford, Randy; Stang, John; Yezerets, Aleksey; Currier, Neal; Chen, H. -Y.; Hess, H.

    2009-03-01

    The control of NOx (NO and NO2) emissions from so-called ‘lean-burn’ vehicle engines remains a challenge. The now commercial NOx adsorber (also known as lean-NOx trap (LNT) and NOx storage reduction (NSR) catalyst) technology is based upon the concept of storing NOx as nitrates over storage components, typically alkali or alkaline-earth species such as barium, during a lean-burn operation cycle and then reducing the stored nitrates to N2 during fuel-rich conditions over a precious metal catalyst. In part via this successful five-year CRADA project between PNNL and Cummins Inc. (CRADA PNNL/213), Cummins and the Johnson/Matthey Company commercialized this technology on the 2007 Dodge Ram pickup truck. In particular, this CRADA has focused on problems arising from either or both thermal and SO2 deactivation which were impeding the ability of the technology to meet durability standards. The results obtained in this CRADA have provided an essential understanding of these deactivation processes thereby leading to materials and process improvements that enabled the commercialization effort. The objective of this project has been to identify a clear pathway to robust NOx after-treatment solutions for light-duty diesel engines. The project focussed on understanding and characterizing the NOx storage, release and conversion of existing NOx adsorber materials. The impact of sulfur on these processes was studied, with special attention given to methods of regenerating the catalyst in the presence of sulfur and the effects of these regeneration treatments on long-term catalyst durability. Model catalysts and more fully formulated catalysts were both studied. The goal of this project has been to identify and understand the deactivation mechanisms of LNT materials in order to provide more robust systems for diesel after-treatment systems that will meet the key emission standards for NOx. Furthermore, the project aimed to provide information critical to

  10. Risk evaluation - conventional and low level effects of radiation

    SciTech Connect

    Bond, V.P.; Varma, M.N.

    1984-04-01

    Any discussion of the risk of exposure to potentially-hazardous agents in the environment inevitably involves the question of whether the dose effect curve is of the threshold or linear, non-threshold type. A principal objective of this presentation is to show that the function is actually two separate relationships, each representing distinctly different functions with differing variables on the axes, and each characteristic of quite different functions with differing variables on the axes, and each characteristic of quite different disciplines (i.e., the threshold function, of Pharmacology, Toxicology and Medicine (PTM); the linear, non-threshold function, of Public Health including safety and accident statistics (PHS)). It is shown that low-level exposure (LLE) to radiation falls clearly in the PHS category. A function for cell dose vs. the fraction of single cell quantal responses is characterized, which reflects the absolute and relative sensitivities of cells. Acceptance of this function would obviate any requirement for the use in Radiation Protection of the concepts of a standard radiation, Q, dose equivalent and rem. 9 references, 4 figures.

  11. Spectroscopy of the Schwarzschild black hole at arbitrary frequencies.

    PubMed

    Casals, Marc; Ottewill, Adrian

    2012-09-14

    Linear field perturbations of a black hole are described by the Green function of the wave equation that they obey. After Fourier decomposing the Green function, its two natural contributions are given by poles (quasinormal modes) and a largely unexplored branch cut in the complex frequency plane. We present new analytic methods for calculating the branch cut on a Schwarzschild black hole for arbitrary values of the frequency. The branch cut yields a power-law tail decay for late times in the response of a black hole to an initial perturbation. We determine explicitly the first three orders in the power-law and show that the branch cut also yields a new logarithmic behavior T(-2ℓ-5)lnT for late times. Before the tail sets in, the quasinormal modes dominate the black hole response. For electromagnetic perturbations, the quasinormal mode frequencies approach the branch cut at large overtone index n. We determine these frequencies up to n(-5/2) and, formally, to arbitrary order. Highly damped quasinormal modes are of particular interest in that they have been linked to quantum properties of black holes.

  12. Altered native stability is the dominant basis for susceptibility of α1-antitrypsin mutants to polymerization.

    PubMed

    Irving, James A; Haq, Imran; Dickens, Jennifer A; Faull, Sarah V; Lomas, David A

    2014-05-15

    Serpins are protease inhibitors whose most stable state is achieved upon transition of a central 5-stranded β-sheet to a 6-stranded form. Mutations, low pH, denaturants and elevated temperatures promote this transition, which can result in a growing polymer chain of inactive molecules. Different types of polymer are possible, but, experimentally only heat has been shown to generate polymers in vitro consistent with ex vivo pathological specimens. Many mutations that alter the rate of heat-induced polymerization have been described, but interpretation is problematic because discrimination is lacking between the effect of global changes in native stability and specific effects on structural mechanism. We show that the temperature midpoint (Tm) of thermal denaturation reflects the transition of α1-antitrypsin to the polymerization intermediate, and determine the relationship with fixed-temperature polymerization half-times (t0.5) in the presence of stabilizing additives [TMAO (trimethylamine N-oxide), sucrose and sodium sulfate], point mutations and disulfide bonds. Combined with a retrospective analysis of 31 mutants characterized in the literature, the results of the present study show that global changes to native state stability are the predominant basis for the effects of mutations and osmolytes on heat-induced polymerization, summarized by the equation: ln(t0.5,mutant/t0.5,wild-type)=0.34×ΔTm. It is deviations from this relationship that hold key information about the polymerization process.

  13. Phase Evolution upon Aging of Air-Plasma Sprayed t'-Zirconia Coatings: I-Synchrotron X-Ray Diffraction

    SciTech Connect

    Lipkin, Don M; Krogstad, Jessica A; Gao, Yan; Johnson, Curtis A; Nelson, Warren A; Levi, Carlos G

    2012-10-08

    Phase evolution accompanying the isothermal aging of free-standing air-plasma sprayed (APS) 7–8 wt% yttria-stabilized zirconia (8YSZ) thermal barrier coatings (TBCs) is described. Aging was carried out at temperatures ranging from 982°C to 1482°C in air. The high-temperature kinetics of the phase evolution from the metastable t' phase into a mixture of transformable Y-rich (cubic) and Y-lean (tetragonal) phases are documented through ambient temperature X-ray diffraction (XRD) characterization. A Hollomon–Jaffe parameter (HJP), T[27 + ln(t)], was used to satisfactorily normalize the extent of phase decomposition over the full range of times and temperatures. Comparison to vapor deposited TBCs reveal potential differences in the destabilization mechanism in APS coatings. Furthermore, the lattice parameters extracted from Rietveld refinement of the XRD patterns were used to deduce the stabilizer concentrations of the respective phases, which suggest a retrograde tetragonal solvus over the temperature range studied. In concert with a complementary microstructural study presented in Part II, this effort offers new insights into the mechanisms governing the phase evolution and raises implications for the high-temperature use of 8YSZ ceramics.

  14. Magnetotransport study of Kondo compound Ce(Ni0.7Cu0.3)2Al3

    NASA Astrophysics Data System (ADS)

    Yadam, Sankararao; Singh, Durgesh; Venkateshwarlu, D.; Gangrade, Mohan Kumar; Samatham, S. Shanmukharao; Ganesan, V.

    2015-06-01

    CeNi2Al3 system has evolved in to a known thermoelectric material with a usable figure of merit at low temperatures. Kondo effect plays a crucial role in the enhancement of TEP in this system especially when the Ni site is substituted with non-magnetic elements like Cu. Effect of high magnetic fields on various properties of this system is yet to be explored. Ce(Ni0.7Cu0.3)2Al3 is a representative sample that has a significant enhancement of TEP whose reasons are being explored recently. Here we report the magnetoresistivity measurements on this sample down to 2K and fields upto 14T. The famous negative ln(T) rise with a minimum at 14.5 K is getting suppressed by the magnetic fields. Magnetic correlations are observed with increasing magnetic field strength in the form of a hump like behavior due to competition between Kondo and RKKY interactions. This hump is shifted to higher temperatures with increase in the field strength which indicates probable onset of ferromagnetic correlations that is being corroborated by the observed negative magnetoresistance at low temperatures.

  15. Synthesis, crystal structure and spectroscopic and electrochemical properties of bridged trisbenzoato copper-zinc heterobinuclear complex of 2,2‧-bipyridine

    NASA Astrophysics Data System (ADS)

    Koch, Angira; Kumar, Arvind; Singh, Suryabhan; Borthakur, Rosmita; Basumatary, Debajani; Lal, Ram A.; Shangpung, Sankey

    2015-03-01

    The synthesis of the heterobinuclear copper-zinc complex [CuZn(bz)3(bpy)2]ClO4 (bz = benzoate) from benzoic acid and bipyridine is described. Single crystal X-ray diffraction studies of the heterobinuclear complex reveals the geometry of the benzoato bridged Cu(II)-Zn(II) centre. The copper or zinc atom is pentacoordinate, with two oxygen atoms from bridging benzoato groups and two nitrogen atoms from one bipyridine forming an approximate plane and a bridging oxygen atom from a monodentate benzoate group. The Cu-Zn distance is 3.345 Å. The complex is normal paramagnetic having μeff value equal to 1.75 BM, ruling out the possibility of Cu-Cu interaction in the structural unit. The ESR spectrum of the complex in CH3CN at RT exhibit an isotropic four line spectrum centred at g = 2.142 and hyperfine coupling constants Aav = 63 × 10-4 cm-1, characteristic of a mononuclear square-pyramidal copper(II) complexes. At LNT, the complex shows an isotropic spectrum with g|| = 2.254 and g⊥ = 2.071 and A|| = 160 × 10-4 cm-1. The Hamiltonian parameters are characteristic of distorted square pyramidal geometry. Cyclic voltammetric studies of the complex have indicated quasi-reversible behaviour in acetonitrile solution.

  16. Reaction rate theory of radiation exposure:Effects of dose rate on mutation frequency

    NASA Astrophysics Data System (ADS)

    Bando, Masako; Nakamura, Issei; Manabe, Yuichiro

    2014-03-01

    We revisit the linear no threshold (LNT) hypothesis deduced from the prominent works done by H. J. Muller for the DNA mutation induced by the artificial radiation and by W. L. Russell and E. M. Kelly for that of mega-mouse experiments, developing a new kinetic reaction theory. While the existing theoretical models primarily rely on the dependence of the total dose D on the mutation frequency, the key ingredient in our theory is the dose rate d(t) that accounts for decrease in the mutation rate during the time course of the cellular reactions. The general form for the mutation frequency with the constant dose rate d is simply expressed as, dFm(t)/dt = A - BFm(t) , with A =a0 +a1(d +deff) and B =b0 +b1(d +deff) . We discuss the solution for a most likely case with B > 0 ; Fm(t) = [A/B -Fm(0) ] (1 -e-Bt) +Fm(0) with the control value Fm(0) . We show that all the data of mega-mouse experiments by Russel with different dose rates fall on the universal scaling function Φ(τ) ≡ [Fm(τ) -Fm(0) ]/[ A / B -Fm(0) ] = 1 - exp(- τ) with scaled time τ = Bt . The concept of such a scaling rule provides us with a strong tool to study different species in a unified manner.

  17. Catalytic activity of acid and base with different concentration on sol-gel kinetics of silica by ultrasonic method.

    PubMed

    Das, R K; Das, M

    2015-09-01

    The effects of both acid (acetic acid) and base (ammonia) catalysts in varying on the sol-gel synthesis of SiO2 nanoparticles using tetra ethyl ortho silicate (TEOS) as a precursor was determined by ultrasonic method. The ultrasonic velocity was received by pulsar receiver. The ultrasonic velocity in the sol and the parameter ΔT (time difference between the original pulse and first back wall echo of the sol) was varied with time of gelation. The graphs of ln[ln1/ΔT] vs ln(t), indicate two region - nonlinear region and a linear region. The time corresponds to the point at which the non-linear region change to linear region is considered as gel time for the respective solutions. Gelation time is found to be dependent on the concentration and types of catalyst and is found from the graphs based on Avrami equation. The rate of condensation is found to be faster for base catalyst. The gelation process was also characterized by viscosity measurement. Normal sol-gel process was also carried out along with the ultrasonic one to compare the effectiveness of ultrasonic. The silica gel was calcined and the powdered sample was characterized with scanning electron microscopy, energy dispersive spectra, X-ray diffractogram, and FTIR spectroscopy.

  18. Irradiation response and stability of nanoporous materials

    SciTech Connect

    Fu, Engang; Wang, Yongqiang; Serrano De Caro, Magdalena; Caro, Jose A.; Zepeda-Ruiz, L; Bringa, E.; Nastasi, Mike; Baldwin, Jon K.

    2012-08-28

    Nanoporous materials consist of a regular organic or inorganic framework supporting a regular, porous structure. Pores are by definition roughly in the nanometre range, that is between 0.2 nm and 100 nm. Nanoporous materials can be subdivided into 3 categories (IUPAC): (1) Microporous materials - 0.2-2 nm; (2) Mesoporous materials - 2-50 nm; and (3) Macroporous materials - 50-1000 nm. np-Au foams were successfully synthesized by de-alloying process. np-Au foams remain porous structure after Ne ion irradiation to 1 dpa. Stacking Fault Tetrahedra (SFTs) were observed in RT irradiated np-Au foams under the highest and intermediate fluxes, but not under the lowest flux. SFTs were not observed in LNT irradiated np-Au foams under all fluxes. The vacancy diffusivity in Au at RT is high enough so that the vacancies have enough time to agglomerate and then collapse to form SFTs. The high ion flux creates more damage per unit time; vacancies don't have enough time to diffuse or recombine. As a result, SFTs were formed at high ion fluxes.

  19. The New Radiobiology: Returning to Our Roots

    PubMed Central

    Ulsh, Brant A.

    2012-01-01

    In 2005, two expert advisory bodies examined the evidence on the effects of low doses of ionizing radiation. The U.S. National Research Council concluded that current scientific evidence is consistent with the linear no-threshold dose-response relationship (NRCNA 2005) while the French National Academies of Science and Medicine concluded the opposite (Aurengo et al. 2005). These contradictory conclusions may stem in part from an emphasis on epidemiological data (a “top down” approach) versus an emphasis on biological mechanisms (a “bottom up” approach). In this paper, the strengths and limitations of the top down and bottom up approaches are discussed, and proposals for strengthening and reconciling them are suggested. The past seven years since these two reports were published have yielded increasing evidence of nonlinear responses of biological systems to low radiation doses delivered at low dose-rates. This growing body of evidence is casting ever more doubt on the extrapolation of risks observed at high doses and dose-rates to estimate risks associated with typical environmental and occupational exposures. This paper compares current evidence on low dose, low dose-rate effects against objective criteria of causation. Finally, some questions for a post-LNT world are posed. PMID:23304107

  20. Organization of growing random networks

    SciTech Connect

    Krapivsky, P. L.; Redner, S.

    2001-06-01

    The organizational development of growing random networks is investigated. These growing networks are built by adding nodes successively, and linking each to an earlier node of degree k with an attachment probability A{sub k}. When A{sub k} grows more slowly than linearly with k, the number of nodes with k links, N{sub k}(t), decays faster than a power law in k, while for A{sub k} growing faster than linearly in k, a single node emerges which connects to nearly all other nodes. When A{sub k} is asymptotically linear, N{sub k}(t){similar_to}tk{sup {minus}{nu}}, with {nu} dependent on details of the attachment probability, but in the range 2{lt}{nu}{lt}{infinity}. The combined age and degree distribution of nodes shows that old nodes typically have a large degree. There is also a significant correlation in the degrees of neighboring nodes, so that nodes of similar degree are more likely to be connected. The size distributions of the in and out components of the network with respect to a given node{emdash}namely, its {open_quotes}descendants{close_quotes} and {open_quotes}ancestors{close_quotes}{emdash}are also determined. The in component exhibits a robust s{sup {minus}2} power-law tail, where s is the component size. The out component has a typical size of order lnt, and it provides basic insights into the genealogy of the network.

  1. Dosimeter-Type NOx Sensing Properties of KMnO4 and Its Electrical Conductivity during Temperature Programmed Desorption

    PubMed Central

    Groβ, Andrea; Kremling, Michael; Marr, Isabella; Kubinski, David J.; Visser, Jacobus H.; Tuller, Harry L.; Moos, Ralf

    2013-01-01

    An impedimetric NOx dosimeter based on the NOx sorption material KMnO4 is proposed. In addition to its application as a low level NOx dosimeter, KMnO4 shows potential as a precious metal free lean NOx trap material (LNT) for NOx storage catalysts (NSC) enabling electrical in-situ diagnostics. With this dosimeter, low levels of NO and NO2 exposure can be detected electrically as instantaneous values at 380 °C by progressive NOx accumulation in the KMnO4 based sensitive layer. The linear NOx sensing characteristics are recovered periodically by heating to 650 °C or switching to rich atmospheres. Further insight into the NOx sorption-dependent conductivity of the KMnO4-based material is obtained by the novel eTPD method that combines electrical characterization with classical temperature programmed desorption (TPD). The NOx loading amount increases proportionally to the NOx exposure time at sorption temperature. The cumulated NOx exposure, as well as the corresponding NOx loading state, can be detected linearly by electrical means in two modes: (1) time-continuously during the sorption interval including NOx concentration information from the signal derivative or (2) during the short-term thermal NOx release. PMID:23549366

  2. Thermal conductivity measurement in clay dominant consolidated material by Transient Hot-Wire method.

    NASA Astrophysics Data System (ADS)

    Garnier, J. P.; Gallier, J.; Mercx, B.; Dudoignon, P.; Milcent, D.

    2010-06-01

    The transient hot-wire (THW) technique is widely used for measurements of the thermal-conductivity of most fluids and some attempts have also been carried out for simultaneous measurements of the thermal-diffusivity with the same hot wire. This technique was also tried to determine thermal properties of soils by the mean of probes which can be considered as wire with some assumptions. The purpose of this paper is to validate the thermal conductivity measurement by the THW technique in geomaterials, composed of compacted sand + clay mineral that can be used for earth construction (Compacted Earth Brick). The thermal transfer behaviors are mainly governed by the texture and moisture of the geomaterials. Thus the investigations were performed (1) in media made of glass beads of different diameters in dry and saturated state in order to observe the role of grain sizes and saturation state on the wire temperature (Δt) measurements and (2) in the compacted clay-geomaterial at different moisture states. The Δt / ln(t) diagrams allow the calculation of two thermal conductivities. The first one, measured in the short time acquisition (< 1s), characterizes the microtexture of the material and its hydrated state. The second one, measured for longer time acquisitions, characterizes the mean thermal conductivity of the material.

  3. Axial length effects on lean NOx trap performance

    SciTech Connect

    Prikhodko, Vitaly Y; Nguyen, Ke; Choi, Jae-Soon; Daw, C Stuart

    2009-01-01

    The effect of axial length on the NO{sub x} reduction performance of two different commercial Lean NO{sub x} Trap (LNT) monolithic catalysts was experimentally investigated in a bench flow reactor. The washcoat composition of one of the catalysts consisted of Pt and K on {gamma}-Al{sub 2}O{sub 3}; whereas the other catalyst contained a complex mixture of Pt, Pd, Rh, Ba, Ce, Zr, Mg, Al and others. The NO{sub x} removal characteristics of cylindrical monolith segments of constant diameter (2.22 cm) and axial lengths of 2.54, 5.08 and 7.62 cm were evaluated using a simulated lean engine exhaust containing water and carbon dioxide at a constant space velocity of 30,000 h{sup -1}. No significant effects of length were observed when the catalysts were fully reduced with hydrogen between NO{sub x} capture phases. However when the catalysts were only partially regenerated NO{sub x} reduction efficiency increased with monolith length. Intra-catalyst H{sub 2} measurements at different axial locations indicated that at least some of the efficiency loss during partial regeneration occurred when back-mixed H{sub 2} was directly oxidized and became unavailable for nitrate reduction.

  4. Localized electrons on a lattice with incommensurate magnetic flux

    NASA Astrophysics Data System (ADS)

    Fishman, Shmuel; Shapir, Yonathan; Wang, Xiang-Rong

    1992-11-01

    The magnetic-field effects on lattice wave functions of Hofstadter electrons strongly localized at boundaries are studied analytically and numerically. The exponential decay of the wave function is modulated by a field-dependent amplitude J(t)=tprodt-1r=02 cos(παr), where α is the magnetic flux per plaquette (in units of a flux quantum) and t is the distance from the boundary (in units of the lattice spacing). The behavior of ||J(t)|| is found to depend sensitively on the value of α. While for rational values α=p/q the envelope of J(t) increases as 2t/q, the behavior for α irrational (q-->∞) is erratic with an aperiodic structure which drastically changes with α. For algebraic α it is found that J(t) increases as a power law tβ(α) while it grows faster (presumably as tβ(α)lnt) for transcendental α. This is very different from the growth rate J(t)~e√t that is typical for cosines with random phases. The theoretical analysis is extended to products of the type Jν(t)=tprodt-1r=02 cos(παrν) with ν>0. Different behavior of Jν(t) is found in various regimes of ν. It changes from periodic for small ν to randomlike for large ν.

  5. Synthesis, spectral and electrochemical studies of binuclear Ru(III) complexes containing dithiosemicarbazone ligand.

    PubMed

    Kanchana Devi, A; Ramesh, R

    2014-01-03

    Synthesis of several new octahedral binuclear ruthenium(III) complexes of the general composition [(EPh3)2(X)Ru-L-Ru(X)(EPh3)2] containing benzene dithiosemicarbazone ligands (where E=P or As; X=Cl or Br; L=binucleating ligands) is presented. All the complexes have been fully characterized by elemental analysis, FT-IR, UV-vis and EPR spectroscopy together with magnetic susceptibility measurements. IR study shows that the dithiosemicarbazone ligands behave as dianionic tridentate ligands coordinating through the oxygen atom of the deprotonated phenolic group, nitrogen atom of the azomethine group and thiolate sulphur. In DMF solution, all the complexes exhibit intense d-d transition and ligand-to-metal charge transfer (LMCT) transition in the visible region. The magnetic moment values of the complexes are in the range 1.78-1.82 BM, which reveals the presence of one unpaired electron on each metal ion. The EPR spectra of the liquid samples at LNT show the presence of three different 'g' values (gx≠gy≠gz) indicate a rhombic distortion around the ruthenium ion. All the complexes exhibit two quasi-reversible one electron oxidation responses (Ru(III)-Ru(III)/Ru(III)-Ru(IV); Ru(III)-Ru(IV)/Ru(IV)-Ru(IV)) within the E1/2 range of 0.61-0.74 V and 0.93-0.98 V respectively, versus Ag/AgCl.

  6. Reduction in mutation frequency by very low-dose gamma irradiation of Drosophila melanogaster germ cells.

    PubMed

    Ogura, Keiji; Magae, Junji; Kawakami, Yasushi; Koana, Takao

    2009-01-01

    To determine whether the linear no-threshold (LNT) model for stochastic effects of ionizing radiation is applicable to very low-dose radiation at a low dose rate, we irradiated immature male germ cells of the fruit fly, Drosophila melanogaster, with several doses of (60)Co gamma rays at a dose rate of 22.4 mGy/h. Thereafter, we performed the sex-linked recessive lethal mutation assay by mating the irradiated males with nonirradiated females. The mutation frequency in the group irradiated with 500 microGy was found to be significantly lower than that in the control group (P < 0.01), whereas in the group subjected to 10 Gy irradiation, the mutation frequency was significantly higher than that in the control group (P < 0.03). A J-shaped dose-response relationship was evident. Molecular experiments using DNA microarray and quantitative reverse transcription PCR indicated that several genes known to be expressed in response to heat or chemical stress and grim, a positive regulator of apoptosis, were up-regulated immediately after irradiation with 500 microGy. The involvement of an apoptosis function in the non-linear dose-response relationship was suggested.

  7. Effective field theory and dispersion law of the phonons of a nonrelativistic superfluid

    SciTech Connect

    Escobedo, Miguel Angel; Manuel, Cristina

    2010-08-15

    We study the recently proposed effective-field theory for the phonon of an arbitrary nonrelativistic superfluid. After computing the one-loop phonon self-energy, we obtain the low-temperature T contributions to the phonon dispersion law at low momentum and see that the real part of those can be parametrized as a thermal correction to the phonon velocity. Because the phonons are the quanta of the sound waves, at low momentum their velocity should agree with the speed of sound. We find that our results match at order T{sup 4}lnT with those predicted by Andreev and Khalatnikov for the speed of sound, derived from the superfluid hydrodynamical equations and the phonon kinetic theory. We get also higher-order corrections of order T{sup 4}, which are not reproduced pushing naively the kinetic theory computation. Finally, as an application, we consider the cold Fermi gas in the unitarity limit and find a universal expression for the low-T relative correction to the speed of sound for these systems.

  8. Response properties in the adsorption-desorption model on a triangular lattice

    NASA Astrophysics Data System (ADS)

    Šćepanović, J. R.; Stojiljković, D.; Jakšić, Z. M.; Budinski-Petković, Lj.; Vrhovac, S. B.

    2016-06-01

    The out-of-equilibrium dynamical processes during the reversible random sequential adsorption (RSA) of objects of various shapes on a two-dimensional triangular lattice are studied numerically by means of Monte Carlo simulations. We focused on the influence of the order of symmetry axis of the shape on the response of the reversible RSA model to sudden perturbations of the desorption probability Pd. We provide a detailed discussion of the significance of collective events for governing the time coverage behavior of shapes with different rotational symmetries. We calculate the two-time density-density correlation function C(t ,tw) for various waiting times tw and show that longer memory of the initial state persists for the more symmetrical shapes. Our model displays nonequilibrium dynamical effects such as aging. We find that the correlation function C(t ,tw) for all objects scales as a function of single variable ln(tw) / ln(t) . We also study the short-term memory effects in two-component mixtures of extended objects and give a detailed analysis of the contribution to the densification kinetics coming from each mixture component. We observe the weakening of correlation features for the deposition processes in multicomponent systems.

  9. Long-range epidemic spreading in a random environment

    NASA Astrophysics Data System (ADS)

    Juhász, Róbert; Kovács, István A.; Iglói, Ferenc

    2015-03-01

    Modeling long-range epidemic spreading in a random environment, we consider a quenched, disordered, d -dimensional contact process with infection rates decaying with distance as 1 /rd +σ . We study the dynamical behavior of the model at and below the epidemic threshold by a variant of the strong-disorder renormalization-group method and by Monte Carlo simulations in one and two spatial dimensions. Starting from a single infected site, the average survival probability is found to decay as P (t ) ˜t-d /z up to multiplicative logarithmic corrections. Below the epidemic threshold, a Griffiths phase emerges, where the dynamical exponent z varies continuously with the control parameter and tends to zc=d +σ as the threshold is approached. At the threshold, the spatial extension of the infected cluster (in surviving trials) is found to grow as R (t ) ˜t1 /zc with a multiplicative logarithmic correction and the average number of infected sites in surviving trials is found to increase as Ns(t ) ˜(lnt) χ with χ =2 in one dimension.

  10. Long-range epidemic spreading in a random environment.

    PubMed

    Juhász, Róbert; Kovács, István A; Iglói, Ferenc

    2015-03-01

    Modeling long-range epidemic spreading in a random environment, we consider a quenched, disordered, d-dimensional contact process with infection rates decaying with distance as 1/rd+σ. We study the dynamical behavior of the model at and below the epidemic threshold by a variant of the strong-disorder renormalization-group method and by Monte Carlo simulations in one and two spatial dimensions. Starting from a single infected site, the average survival probability is found to decay as P(t)∼t-d/z up to multiplicative logarithmic corrections. Below the epidemic threshold, a Griffiths phase emerges, where the dynamical exponent z varies continuously with the control parameter and tends to zc=d+σ as the threshold is approached. At the threshold, the spatial extension of the infected cluster (in surviving trials) is found to grow as R(t)∼t1/zc with a multiplicative logarithmic correction and the average number of infected sites in surviving trials is found to increase as Ns(t)∼(lnt)χ with χ=2 in one dimension.

  11. Toxicological awakenings: the rebirth of hormesis as a central pillar of toxicology

    SciTech Connect

    Calabrese, Edward J. . E-mail: edwardc@schoolph.umass.edu

    2005-04-01

    This paper assesses historical reasons that may account for the marginalization of hormesis as a dose-response model in the biomedical sciences in general and toxicology in particular. The most significant and enduring explanatory factors are the early and close association of the concept of hormesis with the highly controversial medical practice of homeopathy and the difficulty in assessing hormesis with high-dose testing protocols which have dominated the discipline of toxicology, especially regulatory toxicology. The long-standing and intensely acrimonious conflict between homeopathy and 'traditional' medicine (allopathy) lead to the exclusion of the hormesis concept from a vast array of medical- and public health-related activities including research, teaching, grant funding, publishing, professional societal meetings, and regulatory initiatives of governmental agencies and their advisory bodies. Recent publications indicate that the hormetic dose-response is far more common and fundamental than the dose-response models [threshold/linear no threshold (LNT)] used in toxicology and risk assessment, and by governmental regulatory agencies in the establishment of exposure standards for workers and the general public. Acceptance of the possibility of hormesis has the potential to profoundly affect the practice of toxicology and risk assessment, especially with respect to carcinogen assessment.

  12. Nernst effect in the electron-doped cuprate superconductor Pr2-xCexCuO4: Superconducting fluctuations, upper critical field Hc2, and the origin of the Tc dome

    NASA Astrophysics Data System (ADS)

    Tafti, F. F.; Laliberté, F.; Dion, M.; Gaudet, J.; Fournier, P.; Taillefer, Louis

    2014-07-01

    The Nernst effect was measured in the electron-doped cuprate superconductor Pr2-xCexCuO4 (PCCO) at four concentrations, from underdoped (x =0.13) to overdoped (x=0.17), for a wide range of temperatures above the critical temperature Tc. A magnetic field H up to 15 T was used to reliably access the normal-state quasiparticle contribution to the Nernst signal Nqp, which is subtracted from the total signal N, to obtain the superconducting contribution Nsc. As a function of H, Nsc peaks at a field H whose temperature dependence obeys Hc2ln(T /Tc), as it does in a conventional superconductor such as NbxSi1-x. The doping dependence of the characteristic field scale Hc2, shown to be closely related to the upper critical field Hc2, tracks the domelike dependence of Tc, showing that superconductivity is weakened below the quantum critical point where the Fermi surface is reconstructed, presumably by the onset of antiferromagnetic order. Our data at all dopings are quantitatively consistent with the theory of Gaussian superconducting fluctuations, eliminating the need to invoke unusual vortexlike excitations above Tc, and ruling out phase fluctuations as the mechanism for the fall of Tc with underdoping. We compare the properties of PCCO with those of hole-doped cuprates and conclude that the domes of Tc and Hc2 versus doping in the latter materials are also controlled predominantly by phase competition rather than phase fluctuations.

  13. Improved Radiation Dosimetry/Risk Estimates to Facilitate Environmental Management of Plutonium Contaminated Sites

    SciTech Connect

    Scott, Bobby R.; Cheng, Yung-Sung; Zhou, Yue; Tokarskaya, Zoya B.; Zhuntova, Galina V.

    2003-06-11

    Our Phase II research evaluated health risks associated with inhaled plutonium. Our research objectives were to: (1) extend our stochastic model for deposition of plutonium in the respiratory tract to include additional key variability and uncertainty; (2) generate and analyze risk distributions for deterministic effects in the lung from inhaled plutonium that reflect risk model uncertainty; (3) acquire an improved understanding of key physiological effects of inhaled plutonium, based on evaluations of clinical data (e.g., hematological, respiratory function, chromosomal aberrations in lymphocytes) for Mayak workers in Russia who inhaled plutonium-239; (4) develop biological dosimetry for plutonium-239 that was inhaled by some Mayak workers (with unknown intake) based on clinical data for other workers with known plutonium-239 intake; (5) critically evaluate the validity of the linear no-threshold (LNT) risk model as it relates to cancer risks from inhaled plutonium-239 (base d on Mayak worker data); and (6) evaluate respirator filter penetration frequencies for airborne plutonium aerosols using surrogate high-density metals.

  14. The Adaptive Response, Genetic Haplo-Insufficiency and Genomic Instability

    SciTech Connect

    Geard, Charles R.

    2014-12-12

    The linear no-threshold (LNT) hypothesis is the driving force in the establishment of radiation protection standards. However, the scientific basis for linearity has been brought into question, particularly due to the concerns about induced radiation resistance as it pertains to oxidative stress. Specifically, we investigated the observation that tumor hypoxia is associated with malignant progression, increased metastases, chemo- and radioresistance and poor prognosis. Experiments were conducted with non-malignant 3T3/NIH cells and normal human lung fibroblasts (NHLF) that were subjected to γ-irradiation under the levels of oxygen resembling those in growing tumors, and related our data to the concentrations of dissolved oxygen (DO), which is a better indicator of the amounts of residual oxygen inside the cells cultured in the hypoxic or anoxic atmosphere. We found that at DO levels about 0.5 mg/L cells subjected to both short-term (17 hours) and prolonged (48-72 hours) hypoxia continued to proliferate, and that apoptotic events were decreased at the early hours of hypoxic treatment. We showed that the short-term hypoxia up-regulated p53-binding protein 1 (53BP1) and resulted in facilitated 53BP1 nuclear foci formation and disappearance, thus indicating the higher efficiency of DNA double strand breaks repair processes. The latter was confirmed by the lower micronuclei incidence in irradiated hypoxic cells.

  15. Advanced Computational Approaches for Characterizing Stochastic Cellular Responses to Low Dose, Low Dose Rate Exposures

    SciTech Connect

    Scott, Bobby, R., Ph.D.

    2003-06-27

    OAK - B135 This project final report summarizes modeling research conducted in the U.S. Department of Energy (DOE), Low Dose Radiation Research Program at the Lovelace Respiratory Research Institute from October 1998 through June 2003. The modeling research described involves critically evaluating the validity of the linear nonthreshold (LNT) risk model as it relates to stochastic effects induced in cells by low doses of ionizing radiation and genotoxic chemicals. The LNT model plays a central role in low-dose risk assessment for humans. With the LNT model, any radiation (or genotoxic chemical) exposure is assumed to increase one¡¯s risk of cancer. Based on the LNT model, others have predicted tens of thousands of cancer deaths related to environmental exposure to radioactive material from nuclear accidents (e.g., Chernobyl) and fallout from nuclear weapons testing. Our research has focused on developing biologically based models that explain the shape of dose-response curves for low-dose radiation and genotoxic chemical-induced stochastic effects in cells. Understanding the shape of the dose-response curve for radiation and genotoxic chemical-induced stochastic effects in cells helps to better understand the shape of the dose-response curve for cancer induction in humans. We have used a modeling approach that facilitated model revisions over time, allowing for timely incorporation of new knowledge gained related to the biological basis for low-dose-induced stochastic effects in cells. Both deleterious (e.g., genomic instability, mutations, and neoplastic transformation) and protective (e.g., DNA repair and apoptosis) effects have been included in our modeling. Our most advanced model, NEOTRANS2, involves differing levels of genomic instability. Persistent genomic instability is presumed to be associated with nonspecific, nonlethal mutations and to increase both the risk for neoplastic transformation and for cancer occurrence. Our research results, based on

  16. Geographic List of Prime Contract Awards. Oct 1992-Sep 1993. FY 1993. (Alachua, Florida-DeKalb, Georgia). Part 4

    DTIC Science & Technology

    1994-03-01

    3V 10 100 Nf I (000 N - Sig t o( a0) a) -N -- 4N4) cN -0)0 r, P,( 6N -to) z N 1 (00 N c 1L.nt S-N ItnfV)go S-c S-4 n a)) S-t G -ON SU -- -o S-to Y wN I...Q m m) mo 04I)45 , 1)~vL 0(i) mooc )- A M311)o1Coo)I C04~) 0 IS 1 CIO 00 Go L-W000.4(0 L.Nr L. W IN-W44N(0wmow0( CN L. M0 (n L. 4*N L. CDV(0ILn IS OC...4(W X( n Xw fw V ; a4 D( D(0C D( 4c0 ID v a. N 4c1o 0 m -v 1`4 a)(7)a) x a) x 00 00() MOOc U 7) 0 rn0) ( ) a)a) 0) 00) LU0) 00y) Z U Ic (0 0- 11100

  17. Inferring spatial distribution of the radially integrated transmissivity from pumping tests in heterogeneous confined aquifers

    NASA Astrophysics Data System (ADS)

    Copty, Nadim K.; Trinchero, Paolo; Sanchez-Vila, Xavier

    2011-05-01

    Hydrologists routinely analyze pumping test data using conventional interpretation methods that are based on the assumption of homogeneity and that, consequently, yield single estimates of representative flow parameters. However, natural subsurface formations are intrinsically heterogeneous, and hence, the flow parameters influencing the drawdown vary as the cone of depression expands in time. In this paper a novel procedure for the analysis of pumping tests in heterogeneous confined aquifers is developed. We assume that a given heterogeneous aquifer can be represented by a homogeneous system whose flow parameters evolve in time as the pumping test progresses. At any point in time, the interpreted flow parameters are estimated using the ratio of the drawdown and its derivative observed at that particular time. The procedure is repeated for all times, yielding time-dependent estimates of transmissivity Ti(t) and storativity, Si(t). Based on the analysis of the sensitivity of drawdown to inhomogeneities in the T field, the time-dependent interpreted transmissivity values are found to be a good estimate of Tg(r), the geometric mean of the transmissivity values encompassed within a progressively increasing radius r from the well. The procedure is illustrated for Gaussian heterogeneous fields with ln(T) variances up to a value of 2. The impact of the separation distance between the pumping well and observation point on data interpretation is discussed. The results show that information about the spatial variability of the transmissivity field can be inferred from time-drawdown data collected at a single observation point.

  18. Conformal invariance beyond the leading order in the supersymmetric nonlinear σ model with dilaton

    NASA Astrophysics Data System (ADS)

    Diamandis, G. A.; Georgalas, B. C.; Lahanas, A. B.

    1990-12-01

    We calculate the O(α'3) contributions to the renormalization-group β functions in the N=1 supersymmetric σ model with a dilaton. At this order both metric and dilaton β functions are found to depend nontrivially on the dilaton field and vanish if the dilaton satisfies ∇μ∇νφ=0. By employing the Curci-Paffuti relation it is shown that such dilaton backgrounds in Ricci-flat spaces Rμν=0 satisfy the conformal invariance conditions up to this order. The particular class of Ricci-flat, compact, and orientable manifolds naturally emerge as appropriate internal-space configurations consistent with local scale invariance. We further explore the cosmological consequences of these dilaton configurations. In a Robertson-Walker four-dimensional background we find all dilatons satisfying ∇μ∇νφ=0. Except for the constant and the time-dependent dilaton φ(t)=-2 lnt+λ whose cosmological implications have been already discussed in the literature, additional solutions are found. These may be of relevance beyond leading order and for nonvanishing background values for the antisymmetric tensor Bμν. For these solutions, also the cosmic scale factor is at most linear in time therefore giving rise to either a static or a linearly expanding (contracting) universe.

  19. Time evolution of distributive entropy in rectangular microchannel mixers

    NASA Astrophysics Data System (ADS)

    Kaufman, Miron; Fodor, Petru

    2009-03-01

    Patterning ridges on the surface of microchannels has been found to be a viable strategy to induce mixing in straight channels, despite the characteristically small Reynolds numbers. In this work we evaluate the time evolution of the R'enyi entropy associated with the spatial distribution of tracers advected by an incompressible fluid moving in several straight rectangular channels: staggered herring bone [1], fractal surface patterning [2]. The steady state flow fields are obtained by solving the Navier -- Stokes and continuity equations using a finite element analysis package. The R'enyi entropy is then evaluated at different times using the spatial distribution of the tracers. The entropy increases with time as lnt with a slope approximately equal to unity. The slope quantifies the rate of distributive mixing. The rate of increase in the entropy is found to be independent of the Renyi beta parameter. This is qualitatively different than the distributive mixing in channels with moving walls [3] where the rate of distributive mixing changes with the beta parameter. We also study the dependence of the distributive entropy on the Reynolds number. [1] A.D. Stroock et al., Science 295, 647 (2002); [2] M. Camesasca, M. Kaufman, I. Manas-Zloczower, J. Micromech. Microeng. 16, 2298 (2006); [3] W. Wang, I. Manas-Zloczower, M. Kaufman, Chemical Engineering Communications, 192(4), 405-423 (2005).

  20. Spectroscopic study of copper(II) complexes with carboxymethyl dextran and dextran sulfate

    NASA Astrophysics Data System (ADS)

    Glišić, S.; Nikolić, G.; Cakić, M.; Trutić, N.

    2015-07-01

    The copper(II) ion complexes with carboxymethyl dextran (CMD) and dextran sulfate (DS) were studied by different methods. Content of copper was determined by atomic absorption spectroscopy. It was found that copper : ligand mole ratio (Cu : CMD) is 1 : 2, and Cu : DS is 1 : 1 by mole ratio method. Spectrophotometric parameters of synthesized compounds are characteristic for Cu(II) ion in octahedral ( O h ) coordination. Analyzing of FTIR spectra in ν(C=O) vibration region has showed that -COOH group acts as bidentate ligand, while the compounds of Cu(II) with DS copper ions are in the region of four oxygen atoms of two adjacent sulfo groups. The presence of crystalline water was determined by isotopic substitution of H2O molecules with D2O molecules. Comparison of spectra recorded at room (RT) and liquid nitrogen temperature (LNT) has enabled detection bands of water molecules libration indicating that they are coordinated complementing coordination sphere of Cu(II) ions to six. The complexes are of Cu(II) · (CMD)2 · (H2O)2 or Cu(II) · DS · (H2O)2 type. The similarities of the γ(C-H) range in a part of FTIR spectra indicate that there is no difference in the conformation of the 4 C 1 glucopyranose (Glc) unit CMD and DS synthesized Cu(II) complexes.

  1. Alpha List of Prime Contract Awards. Oct 91 - Sep 92. FY 92 (Branscome Julius Inc - Chriscott Supply)

    DTIC Science & Technology

    1993-01-01

    LL M Mn AULA oLALALALAWW0WfL A LAWII* n~LntLAWOLAUmLAiflLALA LAWWLA WIALAWLALA it I (0-4ŕ ifI -4-1-4 _q4 -1 -f -4 -1- -4 -4 -4 .- f ’ -4 ’ -4 -.4. -4...cc M tic o 0 C113 ɛ -4 11 Z)0000anionoon => u C) 0 U u (-) C) 0 :D (-) D C) D C) (.) = 0 D a : uj I m C, -- 4 It m 0 o v Cp 0 o 0 Cý 0 C> o 00 cr) 0...Z -4O0 C -- 0 MC C O C 4 0 C 00 OC- ccN wm0’)- a0CC- C0 2 2 C- "c) CD(I.- 2 O) CC 0) C 030N 14zCC .20 <>Z 0z 02 tic CX 0.1 z 2 2 00 0 Wcoc CC E C

  2. A Portable Emissions Measurement System (PEMS) study of NOx and primary NO2 emissions from Euro 6 diesel passenger cars and comparison with COPERT emission factors

    NASA Astrophysics Data System (ADS)

    O'Driscoll, Rosalind; ApSimon, Helen M.; Oxley, Tim; Molden, Nick; Stettler, Marc E. J.; Thiyagarajah, Aravinth

    2016-11-01

    Real world emissions of oxides of nitrogen (NOx) often greatly exceed those achieved in the laboratory based type approval process. In this paper the real world emissions from a substantial sample of the latest Euro 6 diesel passenger cars are presented with a focus on NOx and primary NO2. Portable Emissions Measurement System (PEMS) data is analysed from 39 Euro 6 diesel passenger cars over a test route comprised of urban and motorway sections. The sample includes vehicles installed with exhaust gas recirculation (EGR), lean NOx traps (LNT), or selective catalytic reduction (SCR). The results show wide variability in NOx emissions from 1 to 22 times the type approval limit. The average NOx emission, 0.36 (sd. 0.36) g km-1, is 4.5 times the Euro 6 limit. The average fraction primary NO2 (fNO2) is 44 (sd. 20) %. Higher emissions during the urban section of the route are attributed to an increased number of acceleration events. Comparisons between PEMS measurements and COPERT speed dependent emissions factors show PEMS measurements to be on average 1.6 times higher than COPERT estimates for NOx and 2.5 times for NO2. However, by removing the 5 most polluting vehicles average emissions were reduced considerably.

  3. Fractionated elution using the TEKCIS technetium-99m generator.

    PubMed

    Vigne, Jonathan; De Mil, Rémy; Peyronnet, Damien; Hecquard, Claudine; Agostini, Denis; Lemonnier, Françoise

    2016-06-01

    The TEKCIS technetium-99m (Tc) generator was designed to allow dry column shipment and automatized conception. A high Tc radioactive concentration is required in a subset of radiopharmacy procedures. Fractionated elution can be a useful tool to meet this requirement, especially when current elution is close to the generator expiration date. The aim of our study was to assess TEKCIS generator elution kinetics and to determine the optimal fractionated elution time to fit with procedures requiring the highest Tc radioactive concentration in clinical use. After duplicate elution at several predetermined elution times, the volume and activity of each eluate were measured. Two optimal time points were selected to perform fractionated elution and repeatability (n=34 and 33) assessed on TEKCIS generators calibrated at 6 or 8 GBq. The complete eluate volume (5 ml) was collected after 60 s of elution. A logarithmic equation was established between eluate volume (v, ml) from elapsed elution time (t, s): v=1.8335ln(t)-2.5965. Using the reciprocal equation, elution times required to obtain some commonly eluted volumes were calculated. Fractionated elutions during 15 and 20 s were selected and an average elution volume from 2.74 to 3.27 ml was collected, with an average elution yield of approximately 90 and 100%, respectively. Our work provides a simple and reliable methodology for the use of fractionated elution with the new TEKCIS generator.

  4. Successive superconducting transitions in Ta2S2C studied by electrical resistivity and nonlinear ac magnetic susceptibility

    NASA Astrophysics Data System (ADS)

    Suzuki, Masatsugu; Suzuki, Itsuko S.; Noji, Takashi; Koike, Yoji; Walter, Jürgen

    2007-05-01

    Ta2S2C compound undergoes superconducting transitions at Tcl=3.60±0.02K and Tcu=9.0±0.2K . The nature of successive superconducting transitions has been studied from electrical resistivity and linear and nonlinear ac magnetic susceptibilities. The resistivity ρ at H=0 shows a local maximum near Tcu , a kinklike behavior around Tcl , and reduces to zero at below T0=2.1K . The lnT dependence of ρ is observed at H=50kOe at low temperatures, which is due to a two-dimensional weak-localization effect. Below Tcu , a two-dimensional superconducting phase occurs in each TaC layer. The linear and nonlinear susceptibilities χ1″ , χ3' , χ5' , and χ7' as well as the difference δχ (=χFC-χZFC) between the field-cooled (FC) and zero-field-cooled (ZFC) susceptibilities start to appear below 6.0K , the onset temperature of irreversibility. A drastic growth of the in-plane superconducting coherence length below 6.0K gives rise to a three-dimensional superconducting phase below Tcl through interplanar Josephson couplings between adjacent TaC layers. The oscillatory behavior of χ3″ , χ5″ , and χ7″ below Tcl is related to the nonlinear behavior arising from the thermally activated flux flow.

  5. Using the Concept of "Population Dose" in Planning and Evaluating Community-Level Obesity Prevention Initiatives

    ERIC Educational Resources Information Center

    Cheadle, Allen; Schwartz, Pamela M.; Rauzon, Suzanne; Bourcier, Emily; Senter, Sandra; Spring, Rebecca; Beery, William L.

    2013-01-01

    When planning and evaluating community-level initiatives focused on policy and environment change, it is useful to have estimates of the impact on behavioral outcomes of particular strategies (e.g., building a new walking trail to promote physical activity). We have created a measure of estimated strategy-level impact--"population dose"--based on…

  6. The effect of luteinizing hormone releasing hormone analog regime and stage of oocyte maturity for induced ovulation of channel catfish Ictalurus punctatus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The effective LHRHa (luteinizing hormone releasing hormone analog) dose based on the gonadal maturity of channel catfish, Ictalurus punctatus to optimize channel x blue hybrid catfish production was evaluated in 4 trials (twice in early part of the season and twice in the peak spawning season) in a ...

  7. Radioimmunotherapy treatment planning based on radiation absorbed dose or patient size

    SciTech Connect

    Eary, J.F.; Krohn, K.A.; Press, O.W. |

    1996-05-01

    Several approaches have been used to plan treatment doses for patients undergoing radioimmunotherapy. Investigators often use fixed doses, or doses based on patient size (mCi/kg or mCi/m{sup 2}). Our treatment protocols for lymphoma and leukemia involved calculation of tissue radiation absorbed dose based on images from a trace labeled infusion of antibody prior to treatment. In a recent analysis of patients treated in the Phase I and II dose escalation trial for treatment of non-Hodgkin`s lymphoma with I-131 anti-CD20 antibody (B1), we investigated the relationship between our dosimetry based treatment and dose based on patient size. Tissue radiation dose for several normal organs and for tumors were plotted versus the mCi administered per kg or m{sup 2} of the patient to evaluate the relationship between the two treatment approaches. These graphs showed correlation coefficients ranging from 0.021 to 0.684, demonstrating the variability in antibody catabolism between patients. This means that fixed doses or administrations based on patient size do not deliver consistent radiation doses to normal organs or tumors. This finding was extrapolated to show that toxicity from doses based on patient size di not correlate with treatment dose; those based on calculated rad/organ did. Phase I clinical trials using treatment doses based on patient size where there are likely to be variations in patient antibody catabolism will result in confounding toxicities at apparently similar mCi dose levels. Use of pre-treatment scans for treatment dose planning are worth the additional effort by normalizing the normal tissue toxicity.

  8. Threshold effect under nonlinear limitation of the intensity of high-power light

    SciTech Connect

    Tereshchenko, S A; Podgaetskii, V M; Gerasimenko, A Yu; Savel'ev, M S

    2015-04-30

    A model is proposed to describe the properties of limiters of high-power laser radiation, which takes into account the threshold character of nonlinear interaction of radiation with the working medium of the limiter. The generally accepted non-threshold model is a particular case of the threshold model if the threshold radiation intensity is zero. Experimental z-scan data are used to determine the nonlinear optical characteristics of media with carbon nanotubes, polymethine and pyran dyes, zinc selenide, porphyrin-graphene and fullerene-graphene. A threshold effect of nonlinear interaction between laser radiation and some of investigated working media of limiters is revealed. It is shown that the threshold model more adequately describes experimental z-scan data. (nonlinear optical phenomena)

  9. [About Dose-Effect Relationship in the Environment Radiation Protection].

    PubMed

    Udalova, A A

    2015-01-01

    One of the most important stages in the development of a methodology for the environment radiation protection is the assessment and justification of critical radiation exposure levels for ecosystem components. In this study application of the approach for critical dose level estimation is demonstrated on the example of the data about ionizing radiation effect on reproduction and survival of agricultural plants after acute and chronic exposures. Influence of the type of dose-effect relationship on the estimated values of the critical doses and dose rates is studied using three models (linear, logarithmic and logistic). The findings obtained do not provide any robust recommendations in favor of one of the three tested functions. The models of dose-effect relationship (threshold or non-threshold) and types of radiation-induced effects (stochastic and deterministic) are discussed from the viewpoint of developing a system for radiation protection of human and non-human biota.

  10. Radiation cancer analysis and low dose risk estimation: new developments and perspectives - conference to be held Feb 2002. Final technical report for period November 1, 2001--October 31, 2002

    SciTech Connect

    Brugmans, M.J.P.; Leenhouts, H.P.

    2002-10-01

    The Proceedings of the 20th LH Gray Conference on Radiation Cancer Analysis and Low Dose Risk Estimation: New Developments and Perspectives (17-21 February 2002, Ede, the Netherlands) comprises 32 peer-reviewed papers on invited and proffered contributions to the conference with a preface by the guest editors. The on-going discussion of low dose radiation risk; the issue of the linear, non-threshold extrapolation; and the anticipated new recommendations, e.g. from BEIR and ICRP, provided the back-drop for the conference. The meeting dealt with topics such as basic mechanisms and bystander effects, cancer modeling, cancer genetics, radon exposure and lung cancer risk, cancer after medical exposure, cancer risk estimation, dose-effect relationships, and application to radiation protection.

  11. Inorganic arsenic in rice-based products for infants and young children.

    PubMed

    Signes-Pastor, Antonio J; Carey, Manus; Meharg, Andrew A

    2016-01-15

    Inorganic arsenic (Asi) is a chronic, non-threshold carcinogen. Rice and rice-based products can be the major source of Asi for many subpopulations. Baby rice, rice cereals and rice crackers are widely used to feed infants and young children. The Asi concentration in rice-based products may pose a health risk for infants and young children. Asi concentration was determined in rice-based products produced in the European Union and risk assessment associated with the consumption of these products by infants and young children, and compared to an identical US FDA survey. There are currently no European Union or United States of America regulations applicable to Asi in food. However, this study suggests that the samples evaluated may introduce significant concentration of Asi into infants' and young children's diets. Thus, there is an urgent need for regulatory limits on Asi in food, especially for baby rice-based products.

  12. Biological-Based Modeling of Low Dose Radiation Risks

    SciTech Connect

    Scott, Bobby R., Ph.D.

    2006-11-08

    The objective of this project was to refine a biological-based model (called NEOTRANS2) for low-dose, radiation-induced stochastic effects taking into consideration newly available data, including data on bystander effects (deleterious and protective). The initial refinement led to our NEOTRANS3 model which has undergone further refinement (e.g., to allow for differential DNA repair/apoptosis over different dose regions). The model has been successfully used to explain nonlinear dose-response curves for low-linear-energy-transfer (LET) radiation-induced mutations (in vivo) and neoplastic transformation (in vitro). Relative risk dose-response functions developed for neoplastic transformation have been adapted for application to cancer relative risk evaluation for irradiated humans. Our low-dose research along with that conducted by others collectively demonstrate the following regarding induced protection associated with exposure to low doses of low-LET radiation: (1) protects against cell killing by high-LET alpha particles; (2) protects against spontaneous chromosomal damage; (3) protects against spontaneous mutations and neoplastic transformations; (4) suppresses mutations induced by a large radiation dose even when the low dose is given after the large dose; (5) suppresses spontaneous and alpha-radiation-induced cancers; (6) suppresses metastasis of existing cancer; (7) extends tumor latent period; (8) protects against diseases other than cancer; and (9) extends life expectancy. These forms of radiation-induced protection are called adapted protection as they relate to induced adaptive response. Thus, low doses and dose rates of low-LET radiation generally protect rather than harm us. These findings invalidate the linear not threshold (LNT) hypothesis which is based on the premise that any amount of radiation is harmful irrespective of its type. The hypothesis also implicates a linear dose-response curve for cancer induction that has a positive slope and no

  13. Investigation of Aging Mechanisms in Lean NOx Traps

    SciTech Connect

    Mark Crocker

    2010-03-31

    Lean NO{sub x} traps (LNTs) represent a promising technology for the abatement of NO{sub x} under lean conditions. Although LNTs are starting to find commercial application, the issue of catalyst durability remains problematic. LNT susceptibility to sulfur poisoning is the single most important factor determining effective catalyst lifetime. The NO{sub x} storage element of the catalyst has a greater affinity for SO{sub 3} than it does for NO{sub 2}, and the resulting sulfate is more stable than the stored nitrate. Although this sulfate can be removed from the catalyst by means of high temperature treatment under rich conditions, the required conditions give rise to deactivation mechanisms such as precious metal sintering, total surface area loss, and solid state reactions between the various oxides present. The principle objective of this project was to improve understanding of the mechanisms of lean NO{sub x} trap aging, and to understand the effect of washcoat composition on catalyst aging characteristics. The approach utilized involved detailed characterization of model catalysts prior to and after aging, in tandem with measurement of catalyst performance in NO{sub x} storage and reduction. In this manner, NO{sub x} storage and reduction characteristics were correlated with the evolution of catalyst physico-chemical properties upon aging. Rather than using poorly characterized proprietary catalysts, or simple model catalysts of the Pt/BaO/Al{sub 2}O{sub 3} type (representing the first generation of LNTs), Pt/Rh/BaO/Al{sub 2}O{sub 3} catalysts were employed which also incorporated CeO{sub 2} or CeO{sub 2}-ZrO{sub 2}, representing a model system which more accurately reflects current LNT formulations. Catalysts were prepared in which the concentration of each of the main components was systematically varied: Pt (50, 75 or 100 g/ft{sup 3}), Rh (10 or 20 g/ft{sup 3}), BaO (15, 30 or 45 g/L), and either CeO{sub 2} (0, 50 or 100 g/L) or CeO{sub 2}-ZrO{sub 2} (0, 50

  14. ICRP Publication 131: Stem Cell Biology with Respect to Carcinogenesis Aspects of Radiological Protection.

    PubMed

    Niwa, O; Barcellos-Hoff, M H; Globus, R K; Harrison, J D; Hendry, J H; Jacob, P; Martin, M T; Seed, T M; Shay, J W; Story, M D; Suzuki, K; Yamashita, S

    2015-12-01

    This report provides a review of stem cells/progenitor cells and their responses to ionising radiation in relation to issues relevant to stochastic effects of radiation that form a major part of the International Commission on Radiological Protection's system of radiological protection. Current information on stem cell characteristics, maintenance and renewal, evolution with age, location in stem cell 'niches', and radiosensitivity to acute and protracted exposures is presented in a series of substantial reviews as annexes concerning haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. This foundation of knowledge of stem cells is used in the main text of the report to provide a biological insight into issues such as the linear-no-threshold (LNT) model, cancer risk among tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. Knowledge of the biology and associated radiation biology of stem cells and progenitor cells is more developed in tissues that renew fairly rapidly, such as haematopoietic tissue, intestinal mucosa, and epidermis, although all the tissues considered here possess stem cell populations. Important features of stem cell maintenance, renewal, and response are the microenvironmental signals operating in the niche residence, for which a well-defined spatial location has been identified in some tissues. The identity of the target cell for carcinogenesis continues to point to the more primitive stem cell population that is mostly quiescent, and hence able to accumulate the protracted sequence of mutations necessary to result in malignancy. In addition, there is some potential for daughter progenitor cells to be target cells in particular cases, such as in haematopoietic tissue and in skin. Several biological processes could contribute to protecting stem cells from mutation accumulation: (a) accurate DNA repair; (b) rapidly induced death of injured stem cells

  15. Legitimating a nuclear critic: John Gofman, radiation safety, and cancer risks.

    PubMed

    Semendeferi, Ioanna

    2008-01-01

    Whether low-level ionizing radiation has an effect on humans has been a polarizing issue for the last fifty years. The epicenter of this controversy has been the validity of the linear non-threshold dose-response model, according to which any amount of radiation, however small, causes damage to human genes and health. In the late 1960s and early 1970s, the nuclear scientist and medical researcher John Gofman (1918-2007) played a pivotal role in the debate. Historical accounts have treated Gofman as a radical antinuclear scientist whose unscientific arguments put enormous political pressure on the nuclear power industry and regulatory agencies. Gofman's bitter struggle with the Atomic Energy Commission, which funded his research at Lawrence Livermore National Laboratory, partly accounts for this view. However, my analysis of Gofman's involvement in the low-level radiation debate shows how he also helped shift the focus in radiation safety from the risks of genetic damage or leukemia to somatic or cancer risks. His arguments led to the introduction of the linear non-threshold radiation model as a means of numerically estimating cancer risks. This was a watershed event in radiation-safety science and politics. Gofman's case sheds light on the process by which a scientist could secure legitimation even when his technical arguments threatened the government's interests. I conclude that it also points to an open issue in the history of antinuclear scientists, or of other politically active scientists or technology critics: treating them as critics should not preclude historians from treating them as scientists.

  16. Detailed investigation of thermal and electron transport properties in strongly correlated compound Ce6Pd12In5 and its nonmagnetic analog La6Pd12In5

    NASA Astrophysics Data System (ADS)

    Falkowski, M.; Krychowski, D.; Strydom, A. M.

    2016-11-01

    An in-depth study of thermal and electron transport properties including thermal conductivity κ(T), thermoelectric power S(T), and electrical resistivity ρ(T) of the heavy fermion Kondo lattice Ce6Pd12In5 and its nonmagnetic reference compound La6Pd12In5 is presented. The absolute κ(T) value of Ce6Pd12In5 is smaller that than of La6Pd12In5, which indicates that conduction electron-4f electron scattering has a large impact on the reduction of thermal conductivity. The isolated 4f electron contributions to the electrical resistivity ρ 4 f (T), electronic thermal resistivity displayed in the form W e l , 4 f (T) .T, and thermoelectric power S 4 f (T) reveal a low- and high-temperature -lnT behaviour characteristic of Kondo systems with strong crystal-electric field (CEF) interactions. The analysis of phonon scattering processes of lattice thermal conductivity κph(T) in (Ce, La)6Pd12In5 was performed over the whole accessible temperature range according to the Callaway model. In the scope of a theoretical approach based on the perturbation type calculation, we were able to describe our experimental data of ρ 4 f (T) and W e l , 4 f (T) .T by using the model incorporating simultaneously the Kondo effect in the presence of the CEF splitting, as it is foreseen in the framework of the Cornut-Coqblin and Bhattacharjee-Coqblin theory. Considering the fact that there are not many cases of similar studies at all, we also show the numerical calculations of temperature-dependent behaviour of spin-disorder resistivity ρs(T), magnetic resistivity ρ 4 f (T), and occupation number ⟨ N i ⟩ due to the various types of degeneracy of the ground state multiplet of Ce 3 + (J = 5/2).

  17. Control of glioma cell migration and invasiveness by GDF-15.

    PubMed

    Codó, Paula; Weller, Michael; Kaulich, Kerstin; Schraivogel, Daniel; Silginer, Manuela; Reifenberger, Guido; Meister, Gunter; Roth, Patrick

    2016-02-16

    Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-β and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy.

  18. Control of glioma cell migration and invasiveness by GDF-15

    PubMed Central

    Codó, Paula; Weller, Michael; Kaulich, Kerstin; Schraivogel, Daniel; Silginer, Manuela; Reifenberger, Guido; Meister, Gunter; Roth, Patrick

    2016-01-01

    Growth and differentiation factor (GDF)-15 is a member of the transforming growth factor (TGF)-β family of proteins. GDF-15 levels are increased in the blood and cerebrospinal fluid of glioblastoma patients. Using a TCGA database interrogation, we demonstrate that high GDF-15 expression levels are associated with poor survival of glioblastoma patients. To elucidate the role of GDF-15 in glioblastoma in detail, we confirmed that glioma cells express GDF-15 mRNA and protein in vitro. To allow for a detailed functional characterization, GDF-15 expression was silenced using RNA interference in LNT-229 and LN-308 glioma cells. Depletion of GDF-15 had no effect on cell viability. In contrast, GDF-15-deficient cells displayed reduced migration and invasion, in the absence of changes in Smad2 or Smad1/5/8 phosphorylation. Conversely, exogenous GDF-15 stimulated migration and invasiveness. Large-scale expression profiling revealed that GDF-15 gene silencing resulted in minor changes in the miRNA profile whereas several genes, including members of the plasminogen activator/inhibitor complex, were deregulated at the mRNA level. One of the newly identified genes induced by GDF-15 gene silencing was the serpin peptidase inhibitor, clade E nexin group 1 (serpine1) which is induced by TGF-β and known to inhibit migration and invasiveness. However, serpine1 down-regulation alone did not mediate GDF-15-induced promotion of migration and invasiveness. Our findings highlight the complex contributions of GDF-15 to the invasive phenotype of glioma cells and suggest anti-GDF-15 approaches as a promising therapeutic strategy. PMID:26741507

  19. Radiation dose response estimation with emphasis on low dose range using restricted cubic splines: application to all solid cancer mortality data, 1950-2003, in atomic bomb survivors.

    PubMed

    Nakashima, Eiji

    2015-07-01

    Using the all solid cancer mortality data set of the Life Span Study (LSS) cohort from 1950 to 2003 (LSS Report 14) data among atomic bomb survivors, excess relative risk (ERR) statistical analyses were performed using the second degree polynomial and the threshold and restricted cubic spline (RCS) dose response models. For the RCS models with 3 to 7 knots of equally spaced percentiles with margins in the dose range greater than 50 mGy, the dose response was assumed to be linear at less than 70 to 90 mGy. Due to the skewed dose distribution of atomic bomb survivors, the current knot system for the RCS analysis results in a detailed depiction of the dose response as less than approximately 0.5 Gy. The 6 knot RCS models for the all-solid cancer mortality dose response of the whole dose or less than 2 Gy were selected with the AIC model selection criterion and fit significantly better (p < 0.05) than the linear (L) model. The usual RCS includes the L-global model but not the quadratic (Q) nor linear-quadratic (LQ) global models. The authors extended the RCS to include L or LQ global models by putting L or LQ constraints on the cubic spline in the lower and upper tails, and the best RCS model selected with AIC criterion was the usual RCS with L-constraints in both the lower and upper tails. The selected RCS had a linear dose-response model in the lower dose range (i.e., < 0.2-0.3 Gy) and was compatible with the linear no-threshold (LNT) model in this dose range. The proposed method is also useful in describing the dose response of a specific cancer or non-cancer disease incidence/mortality.

  20. Detection of milk oligosaccharides in plasma of infants

    PubMed Central

    Ruhaak, L. Renee; Stroble, Carol; Underwood, Mark A.; Lebrilla, Carlito B.

    2014-01-01

    Human Milk Oligosaccharides (HMO) are one of the major components of human milk. HMO are non-digestible by the human gut, where they are known to play important functions as prebiotics and decoys for binding pathogens. Moreover, it has been proposed that HMO may provide sialic acids to the infant that are important in brain development, however this would require absorption of HMO into the bloodstream. HMO have consistently been found in the urine of humans and other mammals, suggesting systemic absorption. Here we present a procedure for the profiling of milk oligosaccharides (MO) in plasma samples obtained from 13 term infants hospitalized for surgery for congenital heart disease. The method comprises protein denaturation, oligosaccharide reduction and porous graphitized carbon solid phase extraction for purification followed by analysis using nHPLC-PGC-chip-TOF-MS. Approximately 15 free MO were typically observed in the plasma of human infants, including LNT, LDFP, LNFT, 3’SL, 6’SL, 3’SLN and 6’SLN, of which the presence was confirmed using fragmentation studies. A novel third isomer of SLN, not found in human or bovine milk was also consistently detected. Differences in the free MO profiles were observed between infants that were totally formula-fed and infants that received at least some part breast milk. Our results indicate that free MO similar in structure to those found in human milk and urine are present in the blood of infants. The method and results presented here will facilitate further research toward the possible roles of free MO in the development of the infant. PMID:25059723

  1. Effects of Potassium loading and thermal aging on K/Pt/Al2O3 high-temperature lean NOx trap catalysts

    SciTech Connect

    Luo, Jinyong; Gao, Feng; Kim, Do Heui; Peden, Charles HF

    2014-03-31

    The effects of K loading and thermal aging on the structural properties and high temperature performance of Pt/K/Al2O3 lean NOx trap (LNT) catalysts were investigated using in situ X-ray diffraction (XRD), temperature-programmed decomposition/desorption of NOx (NOx-TPD), transmission electron microscopy (TEM), NO oxidation and NOx storage tests. In situ XRD results demonstrate that KNO3 becomes extremely mobile on the Al2O3 surface, and experiences complex transformations between orthorhombic and rhombohedral structures, accompanied by sintering, melting and thermal decomposition upon heating. NOx storage results show an optimum K loading around 10% for the best performance at high temperatures. At lower K loadings where the majority of KNO3 stays as a surface layer, the strong interaction between KNO3 and Al2O3 promotes KNO3 decomposition and deteriorates high-temperature performance. At K loadings higher than 10%, the performance drop is not caused by NOx diffusion limitations as for the case of barium-based LNTs, but rather from the blocking of Pt sites by K species, which adversely affects NO oxidation. Thermal aging at 800 ºC severely deactivates the Pt/K/Al2O3 catalysts due to Pt sintering. However, in the presence of potassium, some Pt remains in a dispersed and oxidized form. These Pt species interact strongly with K and, therefore, do not sinter. After a reduction treatment, these Pt species remain finely dispersed, contributing to a partial recovery of NOx storage performance.

  2. Quark gluon bags as reggeons

    SciTech Connect

    Bugaev, K. A.; Petrov, V. K.; Zinovjev, G. M.

    2009-05-15

    The influence of the medium-dependent finite width of quark gluon plasma (QGP) bags on their equation of state is analyzed within an exactly solvable model. It is argued that the large width of the QGP bags not only explains the observed deficit in the number of hadronic resonances but also clarifies the reason why the heavy QGP bags cannot be directly observed as metastable states in a hadronic phase. The model allows us to estimate the minimal value of the width of QGP bags being heavier than 2 GeV from a variety of the lattice QCD data and get that the minimal resonance width at zero temperature is about 600 MeV, whereas the minimal resonance width at the Hagedorn temperature is about 2000 MeV. As shown, these estimates are almost insensitive to the number of the elementary degrees of freedom. The recent lattice QCD data are analyzed and it is found that in addition to the {sigma}T{sup 4} term the lattice QCD pressure contains T-linear and T{sup 4}lnT terms in the range of temperatures between 240 and 420 MeV. The presence of the last term in the pressure bears almost no effect on the width estimates. Our analysis shows that at high temperatures the average mass and width of the QGP bags behave in accordance with the upper bound of the Regge trajectory asymptotics (the linear asymptotics), whereas at low temperatures they obey the lower bound of the Regge trajectory asymptotics (the square root one). Since the model explicitly contains the Hagedorn mass spectrum, it allows us to remove an existing contradiction between the finite number of hadronic Regge families and the Hagedorn idea of the exponentially growing mass spectrum of hadronic bags.

  3. Combination of photocatalysis and HC/SCR for improved activity and durability of DeNOx catalysts.

    PubMed

    Heo, Iljeong; Kim, Mun Kyu; Sung, Samkyung; Nam, In-Sik; Cho, Byong K; Olson, Keith L; Li, Wei

    2013-04-16

    A photocatalytic HC/SCR system has been developed and its high deNOx performance (54.0-98.6% NOx conversion) at low temperatures (150-250 °C) demonstrated by using a representative diesel fuel hydrocarbon (dodecane) as the reductant over a hybrid SCR system of a photocatalytic reactor (PCR) and a dual-bed HC/SCR reactor. The PCR generates highly active oxidants such as O3 and NO2 from O2 and NO in the feed stream, followed by the subsequent formation of highly efficient reductants such as oxygenated hydrocarbon (OHC), NH3, and organo-nitrogen compounds. These reductants are the key components for enhancing the low temperature deNOx performance of the dual-bed HC/SCR system containing Ag/Al2O3 and CuCoY in the front and rear bed of the reactor, respectively. The OHCs are particularly effective for both NOx reduction and NH3 formation over the Ag/Al2O3 catalyst, while NH3 and organo-nitrogen compounds are effective for NOx reduction over the CuCoY catalyst. The hybrid HC/SCR system assisted by photocatalysis has shown an overall deNOx performance comparable to that of the NH3/SCR, demonstrating its potential as a promising alternative to the current urea/SCR and LNT technologies. Superior durability of HC/SCR catalysts against coking by HCs has also been demonstrated by a PCR-assisted regeneration scheme for deactivating catalysts.

  4. Infrared and Raman spectra of magnesium ammonium phosphate hexahydrate (struvite) and its isomorphous analogues. V. Spectra of protiated and partially deuterated magnesium ammonium arsenate hexahydrate (arsenstruvite)

    NASA Astrophysics Data System (ADS)

    Stefov, V.; Šoptrajanov, B.; Najdoski, M.; Engelen, B.; Lutz, H. D.

    2008-01-01

    The Fourier transform infrared and Raman spectra of magnesium ammonium arsenate hexahydrate, MgNH 4AsO 4 · 6H 2O (arsenstruvite) and of its deuterated analogues were recorded at room temperature (RT) and the boiling temperature of liquid nitrogen (LNT). Not surprisingly, the spectra show pronounced similarities with the corresponding spectra of the previously studied magnesium potassium phosphate hexahydrate and magnesium ammonium phosphate hexahydrate with the expected differences in the regions of the arsenate vibrations. The main contribution to the intensity of the complex feature in the X-H stretching region (X being O or N) comes from the stretching vibrations of the water molecules, whereas the vibrations of the ammonium ions are less important as long as the intensity is concerned. This is due not only to the fact that four crystallographically different water molecules of crystallization exist in the structure (as compared with a single type of ammonium ions) but also because the hydrogen bonds formed by the water molecules are much stronger than those in which the ammonium ions take part. Difference infrared spectra were obtained by subtracting the properly normalized spectrum of the protiated compound from the spectrum of a deuterated analogue with low deuterium content. As evidenced by the spectra of the partially deuterated analogues and by the difference spectra, vibrational interactions are present in the crystal. Probably the most dramatic is the result of such an interaction producing a deep Evans-type hole in the stretching region of the difference spectrum but additional cases of vibrational mixing are found in the low-frequency region.

  5. Photoconductivity, low-temperature conductivity, and magnetoresistance studies on the layered semiconductor GaTe

    SciTech Connect

    Bose, D. N.; Pal, Sarbari

    2001-06-15

    Single crystals of p-GaTe were grown by the Bridgman technique and characterized through x-ray diffraction, energy-dispersive x-ray analysis, x-ray photoemission spectroscopy, and transmission electron microscopy studies. The photoconductivity spectral response for in-plane conduction showed a peak at 747 nm (1.66 eV). Photoconductivity gain was determined in two orthogonal directions from which the majority carrier (hole) lifetimes were found to be 3.43{times}10{sup {minus}7} and 2.03{times}10{sup {minus}6}s, respectively, parallel and perpendicular to the layer planes. Studies of the temperature dependence of conductivity in the directions along and perpendicular to the layer planes were carried out between 10 and 80 K. Along the layer planes the conductance G{sub {parallel}} varied as lnT between 12 and 20 K, characteristic of weak localization, while between 20 and 50 K the conductivity {sigma}{sub {parallel}} varied as T{sup 1/2}. In the perpendicular direction the conductance G{sub {perpendicular}} varied as exp(T/T{sub 0}){sup 1/3} between 9 and 20 K and the conductivity {sigma}{sub {perpendicular}} varied as exp(T/T{sub 0}){sup 1/4} between 20 and 50 K, characteristic of hopping conduction in two and three dimensions, respectively. Negative transverse magnetoresistance was observed at 10 K for conduction in both directions for magnetic fields H{lt}0.4T, the increase in conductance being found to be proportional to H{sup 2}. Band conduction with positive magnetoresistance was observed for both current directions at T{gt}70K. The I-V characteristics at 10 K showed quantized behavior due to electron tunneling across potential barriers caused by stacking faults between layer planes.

  6. Experimental Realization of Nearly Steady-State Toroidal Electron Plasmas

    NASA Astrophysics Data System (ADS)

    Stoneking, M. R.

    2008-11-01

    Non-neutral plasmas are routinely confined in the uniform magnetic field of a Penning-Malmberg trap for arbitrarily long times and approach thermal equilibrium. Theory predicts that dynamically stable and therefore long-lived equilibria exist for non-neutral plasmas confined in the curved, non-uniform field of a toroidal trap, but that ultimately thermal equilibrium states do not exist. On long timescales, the poloidal ExB rotation through the non-uniform toroidal magnetic field leads to magnetic pumping transport. A new experiment has, for the first time, demonstrated the existence of a stable, long-lived (i.e. nearly steady-state) toroidal equilibrium for pure electron plasmas and is poised to observe the magnetic pumping transport mechanism. Electron plasmas with densities of order 10^6 cm-3 are trapped in the Lawrence Non-neutral Torus II for several seconds. LNT II is a high aspect ratio (Ro/a 10), partially toroidal trap (a 270^o arc with Bo=670 G). The m=1 diocotron mode is launched and detected using isolated segments of a fully-sectored conducting boundary and its frequency is used to determine the total trapped charge as a function of time. The observed confinement time ( 3 s) approaches the theoretical limit ( 6 s) set by the magnetic pumping transport mechanism of Crooks and O'Neil. We also present equilibrium modeling and numerical simulation of the toroidal m=1 mode constrained by experimental data. Future work includes the identification of the dominant transport mechanisms via confinement scaling experiments and measurement of the m=2 mode frequency, and development of a strategy for making a transition to fully toroidal confinement. J.P. Marler and M.R. Stoneking, Phys. Rev. Lett. 100, 155001 (2008). S.M. Crooks and T.M. O'Neil, Phys Plamas 3, 2533 (1996).

  7. Biogenesis and Membrane Targeting of Lipoproteins.

    PubMed

    Narita, Shin-Ichiro; Tokuda, Hajime

    2010-09-01

    Bacterial lipoproteins represent a unique class of membrane proteins, which are anchored to membranes through triacyl chains attached to the amino-terminal cysteine. They are involved in various functions localized in cell envelope. Escherichia coli possesses more than 90 species of lipoproteins, most of which are localized in the outer membrane, with others being in the inner membrane. All lipoproteins are synthesized in the cytoplasm with an N-terminal signal peptide, translocated across the inner membrane by the Sec translocon to the periplasmic surface of the inner membrane, and converted to mature lipoproteins through sequential reactions catalyzed by three lipoprotein-processing enzymes: Lgt, LspA, and Lnt. The sorting of lipoproteins to the outer membrane requires a system comprising five Lol proteins. An ATP-binding cassette transporter, LolCDE, initiates the sorting by mediating the detachment of lipoproteins from the inner membrane. Formation of the LolA-lipoprotein complex is coupled to this LolCDE-dependent release reaction. LolA accommodates the amino-terminal acyl chain of lipoproteins in its hydrophobic cavity, thereby generating a hydrophilic complex that can traverse the periplasmic space by diffusion. Lipoproteins are then transferred to LolB on the outer membrane and anchored to the inner leaflet of the outer membrane by the action of LolB. In contrast, since LolCDE does not recognize lipoproteins possessing Asp at position +2, these lipoproteins remain anchored to the inner membrane. Genes for Lol proteins are widely conserved among gram-negative bacteria, and Lol-mediated outer membrane targeting of lipoproteins is considered to be the general lipoprotein localization mechanism.

  8. FTIR spectroscopic characterization of Cu(II) coordination compounds with exopolysaccharide pullulan and its derivatives

    NASA Astrophysics Data System (ADS)

    Mitić, Ž.; Nikolić, G. S.; Cakić, M.; Premović, P.; Ilić, Lj.

    2009-04-01

    Pullulan is a water-soluble, extracellular neutral polysaccharide with a linear flexible chain of α-(1 → 6)-linked maltotriose units, the structure of which is intermediate between pullulan and amylose structures because of the co-existence of both α-(1 → 6) and α-(1 → 4)-glycosidic linkages in single compounds. In alkali solutions Cu(II) ion forms complexes with reduced low-molar pullulan (RLMP). The metal content and the solution composition depends on pH. The complexing process begins in a weak alkali solution (pH > 7), and involves OH groups in C(2) and C(3) or C(6) pullulan monomer units (α- D-glucopyranose). Complexes of Cu(II) ion with reduced low-molar pullulan were synthesized in the water solutions, at the boiling temperature and at different pH values (7.512). Fourier-Transform Infrared (FTIR) spectroscopic data of synthesized complexes are rare in literature. FTIR spectroscopic characterization (FTIR, LNT-FTIR, ATR-FTIR, and FTIR microspectroscopy) of Cu(II) ion complexes with RLMP ( M w 6000 g mol -1) was carried out in this work. The similarities of the γ(C sbnd H) range in a part of FTIR spectra indicate that there is no difference in the conformation of the C 1 glucopyranose (Glc) unit in the RLMP and synthesized Cu(II) complexes. The complexing Cu(II) ion with RLMP in the dependence from the pH form different types of complex (pH 7-8: Cu(II)(Glc) 2(H 2O) 2, pH 8-10: Cu(II)(Glc) 2(H 2O)(OH), pH 10-12: Cu(II)(Glc) 2(OH) 2).

  9. Backbone structures in human milk oligosaccharides: trans-glycosylation by metagenomic β-N-acetylhexosaminidases.

    PubMed

    Nyffenegger, Christian; Nordvang, Rune Thorbjørn; Zeuner, Birgitte; Łężyk, Mateusz; Difilippo, Elisabetta; Logtenberg, Madelon J; Schols, Henk A; Meyer, Anne S; Mikkelsen, Jørn Dalgaard

    2015-10-01

    This paper describes the discovery and characterization of two novel β-N-acetylhexosaminidases HEX1 and HEX2, capable of catalyzing the synthesis of human milk oligosaccharides (HMO) backbone structures with fair yields using chitin oligomers as β-N-acetylglucosamine (GlcNAc) donor. The enzyme-encoding genes were identified by functional screening of a soil-derived metagenomic library. The β-N-acetylhexosaminidases were expressed in Escherichia coli with an N-terminal His6-tag and were purified by nickel affinity chromatography. The sequence similarities of the enzymes with their respective closest homologues are 59 % for HEX1 and 51 % for HEX2 on the protein level. Both β-N-acetylhexosaminidases are classified into glycosyl hydrolase family 20 (GH 20) are able to hydrolyze para-nitrophenyl-β-N-acetylglucosamine (pNP-GlcNAc) as well as para-nitrophenyl-β-N-acetylgalactosamine (pNP-GalNAc) and exhibit pH optima of 8 and 6 for HEX1 and HEX2, respectively. The enzymes are able to hydrolyze N-acetylchitooligosaccharides with a degree of polymerization of two, three, and four. The major findings were, that HEX1 and HEX2 catalyze trans-glycosylation reactions with lactose as acceptor, giving rise to the human milk oligosaccharide precursor lacto-N-triose II (LNT2) with yields of 2 and 8 % based on the donor substrate. In total, trans-glycosylation reactions were tested with the disaccharide acceptors β-lactose, sucrose, and maltose, as well as with the monosaccharides galactose and glucose resulting in the successful attachment of GlcNAc to the acceptor in all cases.

  10. 21 CFR 520.538 - Deracoxib.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... chewable tablet contains 25, 50, 75, or 100 milligrams (mg) deracoxib. (b) Sponsor. See No. 058198 in § 510... a single daily dose based on body weight. (i) 1 to 2 mg/kilograms (kg) (0.45 to 0.91 mg/pound (lb), for use as in paragraph (d)(2)(i) of this section. (ii) 3 to 4 mg/kg (1.4 to 1.8 mg/lb) for up to...

  11. 21 CFR 520.538 - Deracoxib.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... chewable tablet contains 25, 50, 75, or 100 milligrams (mg) deracoxib. (b) Sponsor. See No. 058198 in § 510... a single daily dose based on body weight. (i) 1 to 2 mg/kilograms (kg) (0.45 to 0.91 mg/pound (lb), for use as in paragraph (d)(2)(i) of this section. (ii) 3 to 4 mg/kg (1.4 to 1.8 mg/lb) for up to...

  12. Radiochromic film based transit dosimetry for verification of dose delivery with intensity modulated radiotherapy

    SciTech Connect

    Chung, Kwangzoo; Lee, Kiho; Shin, Dongho; Kyung Lim, Young; Byeong Lee, Se; Yoon, Myonggeun; Son, Jaeman; Yong Park, Sung

    2013-02-15

    Purpose: To evaluate the transit dose based patient specific quality assurance (QA) of intensity modulated radiation therapy (IMRT) for verification of the accuracy of dose delivered to the patient. Methods: Five IMRT plans were selected and utilized to irradiate a homogeneous plastic water phantom and an inhomogeneous anthropomorphic phantom. The transit dose distribution was measured with radiochromic film and was compared with the computed dose map on the same plane using a gamma index with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit. Results: While the average gamma index for comparisons of dose distributions was less than one for 98.9% of all pixels from the transit dose with the homogeneous phantom, the passing rate was reduced to 95.0% for the transit dose with the inhomogeneous phantom. Transit doses due to a 5 mm setup error may cause up to a 50% failure rate of the gamma index. Conclusions: Transit dose based IMRT QA may be superior to the traditional QA method since the former can show whether the inhomogeneity correction algorithm from TPS is accurate. In addition, transit dose based IMRT QA can be used to verify the accuracy of the dose delivered to the patient during treatment by revealing significant increases in the failure rate of the gamma index resulting from errors in patient positioning during treatment.

  13. Kinetic and spectroscopic study of catalysts for water-gas shift and nitrogen oxide removal

    NASA Astrophysics Data System (ADS)

    Kispersky, Vincent Frederick

    Nitrogen oxides (NOx) are formed in high temperature combustion processes such as in power generation and motor vehicles. Increasingly stringent regulation of these harmful emissions continues to drive interest in developing, understanding and studying new catalytic formulations for exhaust aftertreatment. For mobile sources, predominantly heavy duty diesel engines, selective catalytic reduction (SCR) with NH3 has become the principal means of NO x abatement. An alternative technology developed, but now surpassed by SCR, is NOx Storage Reduction (NSR) catalysis. Both technologies have been studied in our laboratory and are the basis for this dissertation. We studied seven different lean NOx trap (LNT) monolith formulations for NSR ranging from 0.6 to 6.2 wt.% Pt and 4 to 20 wt.% Ba loadings on γ-Al 2O3. The noble metal component of a LNT oxidizes NO to NO 2 aiding in the storage of NO2 on the alkaline earth component. Before the storage component saturates, a reductant such as H2 is introduced into the vehicular exhaust and the stored NOx is released and reduced to N2. Once the storage component is free of NOx, reductant flow is ceased and storage is begun anew. Our research focused on understanding the effects that CO2 and H2O have on the storage capacity of the LNT over short as well as extended periods of time. We found that for high Ba loadings, CO 2 had a consistently detrimental effect on the fast NOx storage capacity (NSC), defined as the amount of NOx the catalyst can store before 1% of the inlet NOx is measured in the reactor outlet. Over long NOx storage periods, CO2 continued to inhibit storage compared to the same catalyst in CO2 free conditions. On low loadings of Ba, however, the inhibition of CO2 was significantly reduced. We found that the loading dependent characteristics of the Ba phase affected the way in which CO2 adsorbed on the storage component, which greatly affected the stability of the species on lower Ba loadings. The less stable

  14. Evaluation of potential human health effects associated with the agricultural uses of 1,3-D: Spatial and temporal stochastic risk analysis.

    PubMed

    Driver, Jeffrey H; Price, Paul S; Van Wesenbeeck, Ian; Ross, John H; Gehen, Sean; Holden, Larry R; Landenberger, Bryce; Hastings, Kerry; Yan, Zhongyu June; Rasoulpour, Reza

    2016-11-15

    Dow AgroSciences (DAS) markets and sells 1,3-Dichloropropene (1,3-D), the active ingredient in Telone®, which is used as a pre-plant soil fumigant nematicide in economically important crops in California. 1,3-D has been regulated as a "probable human carcinogen" and the California Department of Pesticide Regulation limits use of 1,3-D based on human health risk assessments for bystanders. This paper presents a risk characterization for bystanders based on advances in the assessment of both exposure and hazard. The revised bystander risk assessment incorporates significant advances: 1) new data on residency duration and mobility in communities where 1,3-D is in high demand; 2) new information on spatial and temporal concentrations of 1,3-D in air based on multi-year modeling using a validated model; and 3) a new stochastic spatial and temporal model of long-term exposures. Predicted distributions of long-term, chronic exposures indicate that current, and anticipated uses of 1,3-D would result in lifetime average daily doses lower than 0.002mg/kg/d, a dose associated with theoretical lifetime excess cancer risk of <10(-5) to >95% of the local population based on a non-threshold risk assessment approach. Additionally, examination of 1,3-D toxicity studies including new chronic toxicity data and mechanism of action supports the use of a non-linear, threshold based risk assessment approach. The estimated maximum annual average daily dose of <0.0016mg/kg/d derived from the updated exposure assessment was then compared with a threshold point of departure. The calculated margin of exposure is >1000-fold, a clear indication of acceptable risk for human health. In summary, the best available science supports 1,3-D's threshold nature of hazard and the revised exposure assessment supports that current agricultural uses of 1,3-D are associated with reasonable certainty of no harm, i.e., estimated long-term exposures pose insignificant health risks to bystanders even when the

  15. SIMPOL.1: A simple group contribution method for predicting vapor pressures and enthalpies of vaporization of multifunctional organic compounds

    NASA Astrophysics Data System (ADS)

    Pankow, J. F.; Asher, W. E.

    2007-08-01

    The SIMPOL.1 group contribution method is developed for predicting the liquid vapor pressure pLo (atm) and enthalpy of vaporization ΔHvap (kJ mol-1) of organic compounds as functions of temperature (T). For each compound i, the method assumes log10pL,io(T)=Σkνk,ibk(T) where νk,i is the number of groups of type k, and bk(T) is the contribution to log10 pL,io(T) by each group of type k. A zeroeth group is included that uses b0(T) with ν0,i=1 for all i. A total of 30 structural groups are considered: molecular carbon, alkyl hydroxyl, aromatic hydroxyl, alkyl ether, alkyl ring ether, aromatic ether, aldehyde, ketone, carboxylic acid, ester, nitrate, nitro, alkyl amine (primary, secondary, and tertiary), aromatic amine, amide (primary, secondary, and tertiary), peroxide, hydroperoxide, peroxy acid, C=C, carbonylperoxynitrate, nitro-phenol, nitro-ester, aromatic rings, non-aromatic rings, C=C-C=O in a non-aromatic ring, and carbon on the acid-side of an amide. The T dependence in each of the bk(T) is assumed to follow b(T)=B1/T+B2+B3T+B4lnT. Values of the B coefficients are fit using an initial basis set of 272 compounds for which experimentally based functions pL,io=fi(T) are available. The range of vapor pressure considered spans fourteen orders of magnitude. The ability of the initially fitted B coefficients to predict pLo values is examined using a test set of 161 compounds and a T range that is as wide as 273.15 to 393.15 K for some compounds. σFIT is defined as the average over all points of the absolute value of the difference between experimental and predicted values of log10pL,io(T). After consideration of σFIT for the test set, the initial basis set and test set compounds are combined, and the B coefficients re-optimized. For all compounds and temperatures, σFIT=0.34: on average, pL,io(T) values are predicted to within a factor of 2. Because d(log10pL,io(T))/d(1/T) is related to the enthalpy of vaporization ΔHvap,i, the fitted B provide predictions of

  16. Final Report [The c-Abl signaling network in the radioadaptive response

    SciTech Connect

    Chi-Min, Yuan

    2014-01-28

    The radioadaptive response, or radiation hormesis, i.e. a low dose of radiation can protect cells and organisms from the effects of a subsequent higher dose, is a widely recognized phenomenon. Mechanisms underlying such radiation hormesis, however, remain largely unclear. Preliminary studies indicate an important role of c-Abl signaling in mediating the radioadaptive response. We propose to investigate how c-Abl regulates the crosstalk between p53 and NFκB in response to low doses irradiation. We found in our recent study that low dose IR induces a reciprocal p53 suppression and NFκB activation, which induces HIF-a and subsequently a metabolic reprogramming resulting in a transition from oxidative phosphorylation to glycolysis. Of importance is that this glycolytic switch is essential for the radioadaptive response. This low-dose radiationinduced HIF1α activation was in sharp contrast with the high-dose IR-induced p53 activation and HIF1α inhibition. HIF1α and p53 seem to play distinct roles in mediating the radiation dose-dependent metabolic response. The induction of HIF1α-mediated glycolysis is restricted to a low dose range of radiation, which may have important implications in assessing the level of radiation exposure and its potential health risk. Our results support a dose-dependent metabolic response to IR. When IR doses are below the threshold of causing detectable DNA damage (<0.2Gy) and thus little p53 activation, HIF1α is induced resulting in induction of glycolysis and increased radiation resistance. When the radiation dose reaches levels eliciting DNA damage, p53 is activated and diminishes the activity of HIF1α and glycolysis, leading to the induction of cell death. Our work challenges the LNT model of radiation exposure risk and provides a metabolic mechanism of radioadaptive response. The study supports a need for determining the p53 and HIF1α activity as a potential reliable biological readout of radiation exposure in humans. The

  17. Combinatorial DNA damage pairing model based on X-ray-induced foci predicts the dose and LET dependence of cell death in human breast cells.

    PubMed

    Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter; Deschamps, Thomas; Heuskin, Anne-Catherine; Tang, Jonathan; Costes, Sylvain V

    2014-09-01

    model are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches that provides a testable biological mechanism (i.e., RIF). In addition, we propose that DSB pairing will help develop more accurate alternatives to the linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.

  18. Suppression of alkylating agent induced cell transformation and gastric ulceration by low-dose alkylating agent pretreatment

    SciTech Connect

    Onodera, Akira; Kawai, Yuichi; Kashimura, Asako; Ogita, Fumiya; Tsutsumi, Yasuo; Itoh, Norio

    2013-06-14

    Highlights: •Low-dose MNNG pretreatment suppresses high-dose MNNG induced in vitro transformation. •Gastric ulcers induced by high-dose MNNG decreased after low-dose MNNG pretreatment. •Efficacy of low-dose MNNG related to resistance of mutation and oxidative stress. -- Abstract: Exposure to mild stress by chemicals and radiation causes DNA damage and leads to acquired stress resistance. Although the linear no-threshold (LNT) model of safety assessment assumes risk from any dose, evidence from radiological research demonstrates a conflicting hormetic phenomenon known as the hormesis effect. However, the mechanisms underlying radiation hormesis have not yet been clarified, and little is known about the effects of low doses of chemical carcinogens. We analyzed the efficacy of pretreatment with low doses of the alkylating agent N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) on the subsequent induction of cell transformation and gastric ulceration by high-dose MNNG. We used an in vitro Balb/3T3 A31-1-1 cell transformation test and monitored the formation of gastric ulcers in 5-week-old male ICR mice that were administered MNNG in drinking water. The treatment concentrations of MNNG were determined by the cell survival rate and past reports. For low-dose in vitro and in vivo experiments, MNNG was used at 0.028 μM, and 2.8 μg/mL, respectively. The frequency of cell transformation induced by 10 μm MNNG was decreased by low-dose MNNG pretreatment to levels similar to that of spontaneous transformation. In addition, reactive oxygen species (ROS) and mutation frequencies induced by 10 μm MNNG were decreased by low-dose MNNG pretreatment. Importantly, low-dose MNNG pretreatment had no effect on cell proliferation. In vivo studies showed that the number of gastric ulcers induced by 1 mg/mL MNNG decreased after low-dose MNNG pretreatment. These data indicate that low-dose pretreatment with carcinogens may play a beneficial role in the prevention of chemical toxicity

  19. Transport in thin polarized Fermi-liquid films

    NASA Astrophysics Data System (ADS)

    Li, David Z.; Anderson, R. H.; Miller, M. D.

    2015-10-01

    We calculate expressions for the state-dependent quasiparticle lifetime τσ, the thermal conductivity κ , the shear viscosity η , and discuss the spin diffusion coefficient D for Fermi-liquid films in two dimensions. The expressions are valid for low temperatures and arbitrary polarization. In two dimensions, as in three dimensions, the integrals over the transition rates factor into energy and angular parts. However, the angular integrations contain a weak divergence. This problem is addressed using the method of K. Miyake and W. J. Mullin [Phys. Rev. Lett. 50, 197 (1983), 10.1103/PhysRevLett.50.197; J. Low Temp. Phys. 56, 499 (1984), 10.1007/BF00681808]. The low-temperature expressions for the transport coefficients are essentially exact. We find that κ-1˜T lnT , and η-1˜T2 for arbitrary polarizations 0 ≤P ≤1 . These results are in agreement with earlier zero-polarization results of H. H. Fu and C. Ebner [Phys. Rev. A 10, 338 (1974)., 10.1103/PhysRevA.10.338], but differ from the temperature dependence of the shear viscosity found by D. S. Novikov (arXiv:cond-mat/0603184). They also differ from the discontinuous change of temperature dependence in D from zero to nonzero polarization that was discovered by Miyake and Mullin. We note that in two dimensions the shear viscosity requires a unique analysis. We obtain predictions for the density, temperature, and polarization dependence of κ ,η , and D for second-layer 3He films on graphite, and thin 3He-4He superfluid mixtures. For 3He on graphite, we find roughly an order of magnitude increase in magnitude for κ and η as the polarization is increased from 0 to 1. For D a similar large increase is predicted from zero polarization to the polarization where D is a maximum (˜0.74 ). We discuss the applicability of 3He thin films to

  20. Wildfires in Chernobyl-contaminated forests and risks to the population and the environment: a new nuclear disaster about to happen?

    PubMed

    Evangeliou, Nikolaos; Balkanski, Yves; Cozic, Anne; Hao, Wei Min; Møller, Anders Pape

    2014-12-01

    Radioactive contamination in Ukraine, Belarus and Russia after the Chernobyl accident left large rural and forest areas to their own fate. Forest succession in conjunction with lack of forest management started gradually transforming the landscape. During the last 28 years dead wood and litter have dramatically accumulated in these areas, whereas climate change has increased temperature and favored drought. The present situation in these forests suggests an increased risk of wildfires, especially after the pronounced forest fires of 2010, which remobilized Chernobyl-deposited radioactive materials transporting them thousand kilometers far. For the aforementioned reasons, we study the consequences of different forest fires on the redistribution of (137)Cs. Using the time frequency of the fires that occurred in the area during 2010, we study three scenarios assuming that 10%, 50% and 100% of the area are burnt. We aim to sensitize the scientific community and the European authorities for the foreseen risks from radioactivity redistribution over Europe. The global model LMDZORINCA that reads deposition density of radionuclides and burnt area from satellites was used, whereas risks for the human and animal population were calculated using the Linear No-Threshold (LNT) model and the computerized software ERICA Tool, respectively. Depending on the scenario, whereas between 20 and 240 humans may suffer from solid cancers, of which 10-170 may be fatal. ERICA predicts insignificant changes in animal populations from the fires, whereas the already extreme radioactivity background plays a major role in their living quality. The resulting releases of (137)Cs after hypothetical wildfires in Chernobyl's forests are classified as high in the International Nuclear Events Scale (INES). The estimated cancer incidents and fatalities are expected to be comparable to those predicted for Fukushima. This is attributed to the fact that the distribution of radioactive fallout after the

  1. Swift heavy ion irradiation of InP: Thermal spike modeling of track formation

    SciTech Connect

    Kamarou, A.; Wesch, W.; Wendler, E.; Undisz, A.; Rettenmayr, M.

    2006-05-01

    Irradiation of single-crystalline InP with swift heavy ions (SHI's) causes the formation of ion tracks for certain irradiation temperatures if the electronic energy deposition exceeds a threshold value. With increasing SHI fluence, more and more ion tracks are formed, until a continuous amorphous layer is produced due to the multiple overlapping of the tracks at high ion fluences. Single-crystalline InP samples were irradiated either at liquid nitrogen temperature (LNT) or at room temperature (RT) with Kr, Xe, or Au ions with specific energies ranging from ca. 0.3 to 3.0 MeV/u. Afterwards, the samples were investigated by means of Rutherford backscattering spectrometry and transmission electron microscopy in the plan-view and cross-section geometry. We show that the experimental data obtained can be qualitatively and quantitatively described on the basis of the inelastic thermal spike (TS) model, which was originally used only for metallic targets. The presented extension of the TS model on semiconductors covers mainly the very first stage of the energy transfer from SHI's (so-called 'ionization spikes'). Our results show that the extended TS model offers a self-consistent way to explain the influence of various irradiation conditions (ion mass, ion energy, irradiation temperature, etc.) on the ion track formation and damage accumulation in InP and, therefore, can make a contribution to a better understanding of the underlying mechanisms. Further, our results prejudice the amenity of a single value of the threshold electronic energy loss as a fundamental quantity that is commonly used for the description of track formation in solids irradiated with different ion species. There is no universal RT threshold for track formation in InP, but it is noticeably higher for lighter ions (12.0 and 14.8 keV/nm for RT irradiations with Au and Xe, respectively). Our experimental and simulation results support the idea that the formation of visible tracks requires a predamaging

  2. Swift heavy ion irradiation of InP: Thermal spike modeling of track formation

    NASA Astrophysics Data System (ADS)

    Kamarou, A.; Wesch, W.; Wendler, E.; Undisz, A.; Rettenmayr, M.

    2006-05-01

    Irradiation of single-crystalline InP with swift heavy ions (SHI’s) causes the formation of ion tracks for certain irradiation temperatures if the electronic energy deposition exceeds a threshold value. With increasing SHI fluence, more and more ion tracks are formed, until a continuous amorphous layer is produced due to the multiple overlapping of the tracks at high ion fluences. Single-crystalline InP samples were irradiated either at liquid nitrogen temperature (LNT) or at room temperature (RT) with Kr, Xe, or Au ions with specific energies ranging from ca. 0.3to3.0MeV/u . Afterwards, the samples were investigated by means of Rutherford backscattering spectrometry and transmission electron microscopy in the plan-view and cross-section geometry. We show that the experimental data obtained can be qualitatively and quantitatively described on the basis of the inelastic thermal spike (TS) model, which was originally used only for metallic targets. The presented extension of the TS model on semiconductors covers mainly the very first stage of the energy transfer from SHI’s (so-called “ionization spikes”). Our results show that the extended TS model offers a self-consistent way to explain the influence of various irradiation conditions (ion mass, ion energy, irradiation temperature, etc.) on the ion track formation and damage accumulation in InP and, therefore, can make a contribution to a better understanding of the underlying mechanisms. Further, our results prejudice the amenity of a single value of the threshold electronic energy loss as a fundamental quantity that is commonly used for the description of track formation in solids irradiated with different ion species. There is no universal RT threshold for track formation in InP, but it is noticeably higher for lighter ions (12.0 and 14.8keV/nm for RT irradiations with Au and Xe, respectively). Our experimental and simulation results support the idea that the formation of visible tracks requires a

  3. Tuning magnetism by Kondo effect and frustration

    NASA Astrophysics Data System (ADS)

    Löhneysen, Hilbert V.

    2014-03-01

    Heavy-fermion systems are an ideal playground for studying the quantum phase transition (QPT) between paramagnetic and magnetically ordered ground states arising from the competition between Kondo and RKKY interactions. Two different routes have been identified by various experiments, i. e., the more traditional spin-density-wave (SDW) and the Kondo-breakdown approaches. However, up to now an a-priori assignment of a given system to these different routes has not been possible. Yet another route to quantum criticality not included in the above approaches might be geometric frustration of magnetic moments, a route well known for insulating magnets with competing interactions. First experiments on metallic systems have recently been conducted. In the canonical partially frustrated antiferromagnetic system CePd1-xNixAl, the Néel temperature TN(x) decreases, with TN --> 0 at the critical concentration xc ~ 0.144. The low-temperature specific heat C(T) evolves toward C/ Tα ln(T0/ T) for x -->xc. The unusual T dependence of C/ T is compatible with the Hertz-Millis-Moriya (HMM) scenario of quantum criticality if the quantum-critical fluctuations are two-dimensional in nature. Here two-dimensionality might arise from antiferromagnetic planes that are effectively decoupled by the frustrated Ce atoms in between. An exciting possibility is that the planes of frustrated Ce moments form a two-dimensional spin liquid. In the prototypical heavy-fermion system CeCu6-xAux the experiments by Schröder et al. provided the initial evidence of local quantum criticality. While concentration and pressure tuning of the quantum phase transition (QPT) are described by this scenario, magnetic-field tuning the QPT is in line with the SDW scenario. Elastic neutron scattering experiments on CeCu5.5Au0.5 under hydrostatic pressure p show that at p = 8 kbar, TN and the magnetic propagation vector attain almost the values of CeCu5.7Au0.3. This x - p analogy away from the QPT is highly remarkable

  4. Combinatorial DNA Damage Pairing Model Based on X-Ray-Induced Foci Predicts the Dose and LET Dependence of Cell Death in Human Breast Cells

    SciTech Connect

    Vadhavkar, Nikhil; Pham, Christopher; Georgescu, Walter; Deschamps, Thomas; Heuskin, Anne-Catherine; Tang, Jonathan; Costes, Sylvain V.

    2014-09-01

    are based on experimental RIF and are three times larger than the hypothetical LEM voxel used to fit survival curves. Our model is therefore an alternative to previous approaches that provides a testable biological mechanism (i.e., RIF). In addition, we propose that DSB pairing will help develop more accurate alternatives to the linear cancer risk model (LNT) currently used for regulating exposure to very low levels of ionizing radiation.

  5. Mammography-oncogenecity at low doses.

    PubMed

    Heyes, G J; Mill, A J; Charles, M W

    2009-06-01

    dose exposure, it is not a low dose rate examination, and protraction of dose should not be confused with fractionation. Although there is potential for a suppressive effect at low doses, recent epidemiological data, and several international radiation risk assessments, continue to promote the linear no-threshold (LNT) model. Finally, recent studies have shown that magnetic resonance imaging (MRI) is more sensitive than mammography in detecting invasive breast cancer in women with a genetic sensitivity. Since an increase in the risk associated with mammographic screening would blur the justification of exposure for this high risk subgroup, the use of other (non-ionising) screening modalities is preferable.

  6. Advantages of MgAlOx over gamma-Al2O3 as a support material for potassium-based high temperature lean NOx traps

    SciTech Connect

    Luo, Jinyong; Gao, Feng; Karim, Ayman M.; Xu, Pinghong; Browning, Nigel D.; Peden, Charles HF

    2015-08-07

    MgAlOx mixed oxides were employed as supports for potassium-based lean NOx traps (LNTs) targeted for high temperature applications. Effects of support compositions, K/Pt loadings, thermal aging and catalyst regeneration on NOx storage capacity were systematically investigated. The catalysts were characterized by XRD, NOx-TPD, TEM, STEM-HAADF and in-situ XAFS. The results indicate that MgAlOx mixed oxides have significant advantages over conventional gamma-Al2O3-supports for LNT catalysts, in terms of high temperature NOx trapping capacity and thermal stability. First, as a basic support, MgAlOx stabilizes stored nitrates (in the form of KNO3) to much higher temperatures than mildly acidic gamma-Al2O3. Second, MgAlOx minimizes Pt sintering during thermal aging, which is not possible for gamma-Al2O3 supports. Notably, combined XRD, in-situ XAFS and STEM-HAADF results indicate that Pt species in the thermally aged Pt/MgAlOx samples are finely dispersed in the oxide matrix as isolated atoms. This strong metal-support interaction stabilizes Pt and minimizes the extent of sintering. However, such strong interactions result in Pt oxidation via coordination with the support so that NO oxidation activity can be adversely affected after aging which, in turn, decreases NOx trapping ability for these catalysts. Interestingly, a high-temperature reduction treatment regenerates essentially full NOx trapping performance. In fact, regenerated Pt/K/MgAlOx catalyst exhibits much better NOx trapping performance than fresh Pt/K/Al2O3 LNTs over the entire temperature range investigated here. In addition to thermal aging, Pt/K loading effects were systemically studied over the fresh samples. The results indicate that NOx trapping is kinetically limited at low temperatures, while thermodynamically limited at high temperatures. A simple conceptual model was developed to explain the Pt and K loading effects on NOx storage. An optimized K loading, which allows balancing between the

  7. Raman, dielectric and variable range hopping nature of Gd2O3-doped K0.5N0.5NbO3 piezoelectric ceramics

    NASA Astrophysics Data System (ADS)

    Peddigari, Mahesh; Dobbidi, Pamu

    2015-10-01

    (K0.5Na0.5)NbO3 (KNN) + x wt% Gd2O3 (x = 0 -1.5) ceramics have been prepared by conventional solid state reaction method. The effect of Gd2O3 on the structural, microstructural and dielectric properties of KNN ceramics were studied systematically. The effect of Gd2O3 on phase transformation from orthorhombic to psuedocubic structure is explained interms of changes in the internal vibration modes of NbO6 octahedra. The Raman intensity of the stretching mode v1 enhanced and shifted toward higher wavenumber with Gd2O3 concentration, which is attributed to the increase in polarizability and change in the O-Nb-O bond angles. Microstructural analysis revealed that the grain size of the KNN ceramics decreases from 2.26 ± 1.07 μm to 0.35 ± 0.13 μm and becomes homogenous with an increase in Gd2O3 concentration. The frequency dependent dielectric spectra are analyzed by using Havriliak-Negami function. The fitted symmetry parameter and relaxation time (τ) are found to be 0.914 and 8.78 × 10-10 ± 5.5 × 10-11 s, respectively for the sample doped with x = 1.0. The addition of Gd2O3 to the KNN shifted the polymorphic phase transition orthorhombic to tetragonal transition temperature (TO-T) from 199oC to 85oC with enhanced dielectric permittivity (ɛ' = 1139 at 1 MHz). The sample with x = 1.0, shown a high dielectric permittivity (ɛ' = 879) and low dielectric loss (<5%) in the broad temperature range (-140oC - 150oC) with the Curie temperature 307 oC can have the potential for high temperature piezoelectric and tunable RF circuit applications. The temperature dependent AC-conductivity follows the variable range hopping conduction mechanism by obtaining the slope -0.25 from the ln[ln(ρac)] versus ln(T) graph in the temperature range of 133 K-308 K. The effect of Gd2O3 on the Mott's parameters such as density of states (N(EF)), hopping length (RH), and hopping energy (WH) have been discussed.

  8. Genotypic and phenotypic analyses of hepatitis C virus variants observed in clinical studies of VX-222, a nonnucleoside NS5B polymerase inhibitor.

    PubMed

    Jiang, Min; Zhang, Eileen Z; Ardzinski, Andrzej; Tigges, Ann; Davis, Andrew; Sullivan, James C; Nelson, Michelle; Spanks, Joan; Dorrian, Jennifer; Nicolas, Olivier; Bartels, Doug J; Rao, B Govinda; Rijnbrand, Rene; Kieffer, Tara L

    2014-09-01

    VX-222, a thiophene-2-carboxylic acid derivative, is a selective nonnucleoside inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase. In phase 1 and 2 clinical studies, VX-222 demonstrated effective antiviral efficacy, with substantial reductions in plasma HCV RNA in patients chronically infected with genotype 1 HCV. To characterize the potential for selection of VX-222-resistant variants in HCV-infected patients, the HCV NS5B gene was sequenced at baseline and during and after 3 days of VX-222 dosing (monotherapy) in a phase 1 study. Variants with the substitutions L419C/I/M/P/S/V, R422K, M423I/T/V, I482L/N/T, A486S/T/V, and V494A were selected during VX-222 dosing, and their levels declined over time after the end of dosing. Phenotypic analysis of these variants was conducted using HCV replicons carrying site-directed mutations. Of the 17 variants, 14 showed reduced susceptibility to VX-222 compared with the wild type, with the L419C/S and R422K variants having higher levels of resistance (>200-fold) than the rest of the variants (6.8- to 76-fold). The M423I and A486S variants remained susceptible to VX-222. The 50% effective concentration (EC50) for the L419P variant could not be obtained due to the poor replication of this replicon. The majority of the variants (15/17) were less fit than the wild type. A subset of the variants, predominately the L419S and R422K variants, were observed when the efficacy and safety of VX-222- and telaprevir-based regimens given for 12 weeks were investigated in genotype 1 HCV-infected patients in a phase 2 study. The NS3 and NS5B variants selected during the dual combination therapy showed reduced susceptibility to both telaprevir and VX-222 and had a lower replication capacity than the wild type. The phase 1b study has the ClinicalTrials.gov identifier NCT00911963, and the phase 2a study has ClinicalTrials.gov identifier NCT01080222.

  9. Health risk assessment linked to filling coastal quarries with treated dredged seaport sediments.

    PubMed

    Perrodin, Yves; Donguy, Gilles; Emmanuel, Evens; Winiarski, Thierry

    2014-07-01

    Dredged seaport sediments raise complex management problems since it is no longer possible to discharge them into the sea. Traditional waste treatments are poorly adapted for these materials in terms of absorbable volumes and cost. In this context, filling quarries with treated sediments appears interesting but its safety regarding human health must be demonstrated. To achieve this, a specific methodology for assessing health risks has been developed and tested on three seaport sediments. This methodology includes the development of a conceptual model of the global scenario studied and the definition of specific protocols for each of its major steps. The approach proposed includes in particular the use of metrological and experimental tools that are new in this context: (i) an experimental lysimeter for characterizing the deposit emissions, and (ii) a geological radar for identifying potential preferential pathways between the sediment deposit and the groundwater. The application of this approach on the three sediments tested for the scenario studied showed the absence of health risk associated with the consumption of groundwater for substances having a "threshold effect" (risk quotient <1), and an acceptable risk for substances having a "non-threshold effect", with the notable exception of arsenic (individual risk equal to 3.10(-6)).

  10. When is a dose not a dose

    SciTech Connect

    Bond, V.P.

    1991-01-01

    Although an enormous amount of progress has been made in the fields of radiation protection and risk assessment, a number of significant problems remain. The one problem which transcends all the rest, and which has been subject to considerable misunderstanding, involves what has come to be known as the 'linear non-threshold hypothesis', or 'linear hypothesis'. Particularly troublesome has been the interpretation that any amount of radiation can cause an increase in the excess incidence of cancer. The linear hypothesis has dominated radiation protection philosophy for more than three decades, with enormous financial, societal and political impacts and has engendered an almost morbid fear of low-level exposure to ionizing radiation in large segments of the population. This document presents a different interpretation of the linear hypothesis. The basis for this view lies in the evolution of dose-response functions, particularly with respect to their use initially in the context of early acute effects, and then for the late effects, carcinogenesis and mutagenesis. 11 refs., 4 figs. (MHB)

  11. Extreme Sensitivity and the Practical Implications of Risk Assessment Thresholds

    PubMed Central

    Bukowski, John; Nicolich, Mark; Lewis, R. Jeffrey

    2013-01-01

    Traditional risk-assessment theory assumes the existence of a threshold for non-cancer health effects. However, a recent trend in environmental regulation rejects this assumption in favor of non-threshold linearity for these endpoints. This trend is driven largely by two related concepts: (1) a theoretical assumption of wide-ranging human sensitivity, and (2) inability to detect thresholds in epidemiologic models. Wide-ranging sensitivity assumes a subpopulation with extreme background vulnerability, so that even trivial environmental exposures are hazardous to someone somewhere. We use examples from the real world of clinical medicine to show that this theoretical assumption is inconsistent with the biology of mammalian systems and the realities of patient care. Using examples from particulate-matter air-pollution research, we further show that failure to reject linearity is usually driven by statistical rather than biological considerations, and that nonlinear/threshold models often have a similar or better fit than their linear counterparts. This evidence suggests the existence of practical, real-world thresholds for most chemical exposures. PMID:23930098

  12. An estimation error bound for pixelated sensing

    NASA Astrophysics Data System (ADS)

    Kreucher, Chris; Bell, Kristine

    2016-05-01

    This paper considers the ubiquitous problem of estimating the state (e.g., position) of an object based on a series of noisy measurements. The standard approach is to formulate this problem as one of measuring the state (or a function of the state) corrupted by additive Gaussian noise. This model assumes both (i) the sensor provides a measurement of the true target (or, alternatively, a separate signal processing step has eliminated false alarms), and (ii) The error source in the measurement is accurately described by a Gaussian model. In reality, however, sensor measurement are often formed on a grid of pixels - e.g., Ground Moving Target Indication (GMTI) measurements are formed for a discrete set of (angle, range, velocity) voxels, and EO imagery is made on (x, y) grids. When a target is present in a pixel, therefore, uncertainty is not Gaussian (instead it is a boxcar function) and unbiased estimation is not generally possible as the location of the target within the pixel defines the bias of the estimator. It turns out that this small modification to the measurement model makes traditional bounding approaches not applicable. This paper discusses pixelated sensing in more detail and derives the minimum mean squared error (MMSE) bound for estimation in the pixelated scenario. We then use this error calculation to investigate the utility of using non-thresholded measurements.

  13. Activation of the Fanconi anemia/BRCA pathway at low doses of ionization radiation.

    PubMed

    Bosch, Pau Castillo; Bogliolo, Massimo; Surrallés, Jordi

    2015-11-01

    Fanconi anemia (FA) is a rare, clinically heterogeneous autosomal recessive or X-linked genetic disease characterized by chromosome fragility, congenital malformations and cancer susceptibility. FA patients are usually radiosensitive when exposed to radiotherapy but the role of the FA in response to ionizing radiation (IR) is controversial. Here we have investigated IR-induced activation of the FA pathway by systematically analyzing monoubiquitination of the central protein FANCD2 and subsequent recruitment to stalled replication forks in primary fibroblasts. We developed an immunolabelling method to simultaneously visualize IR-induced FANCD2 and γH2AX foci in S-phase. We observed FANCD2 foci formation in a subset of IR-induced γH2AX foci in S-phase cells. This was observed at doses of IR ranging from 0.1 to 5.0Gy in a dose dependent non-threshold fashion. Our results indicate that minimum doses of IR can produce replication fork stalling and FA pathway activation during S-phase in primary cells.

  14. Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer.

    PubMed

    Rechner, Laura A; Howell, Rebecca M; Zhang, Rui; Etzel, Carol; Lee, Andrew K; Newhauser, Wayne D

    2012-11-07

    Prostate cancer patients who undergo radiotherapy are at an increased risk to develop a radiogenic second cancer. Proton therapy has been shown to reduce the predicted risk of second cancer when compared to intensity modulated radiotherapy. However, it is unknown if this is also true for the rotational therapies proton arc therapy and volumetric modulated arc therapy (VMAT). The objective of this study was to compare the predicted risk of cancer following proton arc therapy and VMAT for prostate cancer. Proton arc therapy and VMAT plans were created for three patients. Various risk models were combined with the dosimetric data (therapeutic and stray dose) to predict the excess relative risk (ERR) of cancer in the bladder and rectum. Ratios of ERR values (RRR) from proton arc therapy and VMAT were calculated. RRR values ranged from 0.74 to 0.99, and all RRR values were shown to be statistically less than 1, except for the value calculated with the linear-non-threshold risk model. We conclude that the predicted risk of cancer in the bladder or rectum following proton arc therapy for prostate cancer is either less than or approximately equal to the risk following VMAT, depending on which risk model is applied.

  15. Risk of radiogenic second cancers following volumetric modulated arc therapy and proton arc therapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Rechner, Laura A.; Howell, Rebecca M.; Zhang, Rui; Etzel, Carol; Lee, Andrew K.; Newhauser, Wayne D.

    2012-11-01

    Prostate cancer patients who undergo radiotherapy are at an increased risk to develop a radiogenic second cancer. Proton therapy has been shown to reduce the predicted risk of second cancer when compared to intensity modulated radiotherapy. However, it is unknown if this is also true for the rotational therapies proton arc therapy and volumetric modulated arc therapy (VMAT). The objective of this study was to compare the predicted risk of cancer following proton arc therapy and VMAT for prostate cancer. Proton arc therapy and VMAT plans were created for three patients. Various risk models were combined with the dosimetric data (therapeutic and stray dose) to predict the excess relative risk (ERR) of cancer in the bladder and rectum. Ratios of ERR values (RRR) from proton arc therapy and VMAT were calculated. RRR values ranged from 0.74 to 0.99, and all RRR values were shown to be statistically less than 1, except for the value calculated with the linear-non-threshold risk model. We conclude that the predicted risk of cancer in the bladder or rectum following proton arc therapy for prostate cancer is either less than or approximately equal to the risk following VMAT, depending on which risk model is applied.

  16. Linear Versus Non-Linear Dose-Response Relationship Between Prenatal Alcohol Exposure and Meconium Concentration of Nine Different Fatty Acid Ethyl Esters

    PubMed Central

    Yang, J.Y.; Kwak, H.S.; Choi, J.S.; Ahn, H.K.; Oh, Y.J.; Velázquez-Armenta, E.Y.; Nava-Ocampo, A.A.

    2015-01-01

    Presence of individual fatty acid ethyl esters (FAEEs) in meconium is considered to be a reliable biomarker of prenatal alcohol exposure, and their concentration has been found to be linearly associated with poor postnatal development, supporting the widely extended idea that ethanol is a non-threshold teratogen. However, a growing number of epidemiological studies have consistently found a lack of adverse short- and long-term fetal outcomes at low exposure levels. We therefore aimed to investigate the relationship between the concentration of individual FAEEs and prenatal alcohol exposure in meconium samples collected within the first 6 to 12?h after birth from 182 babies born to abstainer mothers and from 54 babies born to women who self-reported either light or moderate alcohol ingestion in the second or third trimester of pregnancy. In most cases, the individual FAEE concentrations were negligible and not significantly different (P >0.05) between exposed and control babies. The concentrations appeared to increase linearly with the dose only in the few babies born to mothers who reported >3 drinks/week. These results provide evidence that the correlation between prenatal alcohol exposure and individual FAEE concentrations in meconium is non-linear shape, with a threshold probably at 3 drinks/week. PMID:26691866

  17. Health risk estimates for groundwater and soil contamination in the Slovak Republic: a convenient tool for identification and mapping of risk areas.

    PubMed

    Fajčíková, K; Cvečková, V; Stewart, A; Rapant, S

    2014-10-01

    We undertook a quantitative estimation of health risks to residents living in the Slovak Republic and exposed to contaminated groundwater (ingestion by adult population) and/or soils (ingestion by adult and child population). Potential risk areas were mapped to give a visual presentation at basic administrative units of the country (municipalities, districts, regions) for easy discussion with policy and decision-makers. The health risk estimates were calculated by US EPA methods, applying threshold values for chronic risk and non-threshold values for cancer risk. The potential health risk was evaluated for As, Ba, Cd, Cu, F, Hg, Mn, NO3 (-), Pb, Sb, Se and Zn for groundwater and As, B, Ba, Be, Cd, Cu, F, Hg, Mn, Mo, Ni, Pb, Sb, Se and Zn for soils. An increased health risk was identified mainly in historical mining areas highly contaminated by geogenic-anthropogenic sources (ore deposit occurrence, mining, metallurgy). Arsenic and antimony were the most significant elements in relation to health risks from groundwater and soil contamination in the Slovak Republic contributing a significant part of total chronic risk levels. Health risk estimation for soil contamination has highlighted the significance of exposure through soil ingestion in children. Increased cancer risks from groundwater and soil contamination by arsenic were noted in several municipalities and districts throughout the country in areas with significantly high arsenic levels in the environment. This approach to health risk estimations and visualization represents a fast, clear and convenient tool for delineation of risk areas at national and local levels.

  18. Extreme sensitivity and the practical implications of risk assessment thresholds.

    PubMed

    Bukowski, John; Nicolich, Mark; Lewis, R Jeffrey

    2013-01-01

    Traditional risk-assessment theory assumes the existence of a threshold for non-cancer health effects. However, a recent trend in environmental regulation rejects this assumption in favor of non-threshold linearity for these endpoints. This trend is driven largely by two related concepts: (1) a theoretical assumption of wide-ranging human sensitivity, and (2) inability to detect thresholds in epidemiologic models. Wide-ranging sensitivity assumes a subpopulation with extreme background vulnerability, so that even trivial environmental exposures are hazardous to someone somewhere. We use examples from the real world of clinical medicine to show that this theoretical assumption is inconsistent with the biology of mammalian systems and the realities of patient care. Using examples from particulate-matter air-pollution research, we further show that failure to reject linearity is usually driven by statistical rather than biological considerations, and that nonlinear/threshold models often have a similar or better fit than their linear counterparts. This evidence suggests the existence of practical, real-world thresholds for most chemical exposures.

  19. Genotoxicity--threshold or not? Introduction of cases of industrial chemicals.

    PubMed

    Bolt, Hermann M

    2003-04-11

    Many industrially and environmentally important industrial carcinogens display effects that lead them to be viewed and regulated as 'genotoxic compounds'. Some of these chemicals cause experimental tumours only at high or toxic doses. The current view is that non-threshold principles should be applied for risk assessments and to define permissible exposure values. The toxicological impact of underlying mechanisms is frequently not well investigated and understood. The classification of carcinogens is now in a state of discussion. In Germany, the 'MAK-Commission' has issued new recommendations to distinguish between 5 groups of proven and suspected carcinogens. This proposal includes a category of 'substances with carcinogenic potential for which genotoxicity plays no or at most a minor role'. Another category comprises 'substances with carcinogenic and genotoxic potential, the potency of which is considered so low that, provided that the MAK-value is observed, no significant contribution to human cancer risk is to be expected'. There is also a number of apparently genotoxic carcinogens where the existence of 'practical thresholds' is at least debated. One outstanding example is vinyl acetate, which must be viewed against the background of discussions on other industrial high-volume chemicals like formaldehyde, acrylonitrile, acrylamide and trichloroethylene. Main arguments in favour or against thresholds of carcinogenicity of these individual compounds are summarised. Current instruments of regulation should be adjusted to allow adequate consideration of carcinogenic effects of chemicals that are practically relevant at high doses only. Also, research into this field is encouraged.

  20. Iron plaque formed under aerobic conditions efficiently immobilizes arsenic in Lupinus albus L roots.

    PubMed

    Fresno, Teresa; Peñalosa, Jesús M; Santner, Jakob; Puschenreiter, Markus; Prohaska, Thomas; Moreno-Jiménez, Eduardo

    2016-09-01

    Arsenic is a non-threshold carcinogenic metalloid. Thus, human exposure should be minimised, e.g. by chemically stabilizing As in soil. Since iron is a potential As immobiliser, it was investigated whether root iron plaque, formed under aerobic conditions, affects As uptake, metabolism and distribution in Lupinus albus plants. White lupin plants were cultivated in a continuously aerated hydroponic culture containing Fe/EDDHA or FeSO4 and exposed to arsenate (5 or 20 μM). Only FeSO4 induced surficial iron plaque in roots. LA-ICP-MS analysis accomplished on root sections corroborated the association of As to this surficial Fe. Additionally, As(V) was the predominant species in FeSO4-treated roots, suggesting less efficient As uptake in the presence of iron plaque. Fe/EDDHA-exposed roots neither showed such surficial FeAs co-localisation nor As(V) accumulation; in contrast As(III) was the predominant species in root tissue. Furthermore, FeSO4-treated plants showed reduced shoot-to-root As ratios, which were >10-fold lower compared to Fe/EDDHA treatment. Our results highlight the role of an iron plaque formed in roots of white lupin under aerobic conditions on As immobilisation. These findings, to our knowledge, have not been addressed before for this plant and have potential implications on soil remediation (phytostabilisation) and food security (minimising As in crops).

  1. Human health risk assessment of nitrosamines and nitramines for potential application in CO2 capture.

    PubMed

    Ravnum, S; Rundén-Pran, E; Fjellsbø, L M; Dusinska, M

    2014-07-01

    Emission and accumulation of carbon dioxide (CO2) in the atmosphere exert an environmental and climate change challenge. An attempt to deal with this challenge is made at Mongstad by application of amines for CO2 capture and storage (CO2 capture Mongstad (CCM) project). As part of the CO2 capture process, nitrosamines and nitramines may be emitted. Toxicological testing of nitrosamines and nitramines indicate a genotoxic potential of these substances. Here we present a risk characterization and assessment for five nitrosamines (N-Nitrosodi-methylamine (NDMA) N-Nitrosodi-ethylamine (NDEA), N-Nitroso-morpholine (NNM), N-Nitroso-piperidine (NPIP), and Dinitroso-piperazine (DNP)) and two nitramines (N-Methyl-nitramine (NTMA), Dimethyl-nitramine (NDTMA)), which are potentially emitted from the CO2 capture plant (CCP). Human health risk assessment of genotoxic non-threshold substances is a heavily debated topic, and no consensus methodology exists internationally. Extrapolation modeling from high-dose animal exposures to low-dose human exposures can be crucial for the final risk calculation. In the work presented here, different extrapolation models are discussed, and suggestions on applications are given. Then, preferred methods for calculating derived minimal effect level (DMEL) are presented with the selected nitrosamines and nitramines.

  2. Genetic Control of the Trigger for the G2/M Checkpoint

    SciTech Connect

    Hall, Eric J.; Smilenov, Lubomir B.; Young, Erik F.

    2013-10-01

    The work undertaken in this project addressed two seminal areas of low dose radiation biology that are poorly understood and controversial. These areas are the challenge to the linear-no-threshold (LNT) paradigm at low doses of radiation and, the fundamental elements of radiation bystander effect biology Genetic contributions to low dose checkpoint engagement: The LNT paradigm is an extrapolation of known, measured cancer induction endpoints. Importantly, data for lower doses is often not available. Debatably, radiation protection standards have been introduced which are prudently contingent on the adherence of cancer risk to the established trend seen at higher doses. Intriguing findings from other labs have hinted at separate DNA damage response programs that engage at low or high levels of radiation. Individual radiation sensitivity commensurate with hemizygosity for a radiation sensitivity gene has been estimated at 1-2% in the U.S.. Careful interrogation of the DNA damage response at low doses of radiation became important and served as the basis for this grant. Several genes were tested in combinations to determine if combined haploinsufficiency for multiple radiosensitizing genes could render a cell more sensitive to lower levels of acute radiation exposure. We measured a classical radiation response endpoint, cell cycle arrest prior to mitosis. Mouse embryo fibroblasts were used and provided a uniform, rapidly dividing and genetically manipulable population of study. Our system did not report checkpoint engagement at acute doses of gamma rays below 100 mGy. The system did report checkpoint engagement reproducibly at 500 mGy establishing a threshold for activation between 100 and 500 mGy. Engagement of the checkpoint was ablated in cells nullizygous for ATM but was otherwise unperturbed in cells combinatorially haploinsufficient for ATM and Rad9, ATM and PTEN or PTEN and Rad9. Taken together, these experiments tell us that, in a sensitive fibroblast culture

  3. Matlab Tools: An Alternative to Planning Systems in Brachytherapy Treatments

    SciTech Connect

    Herrera, Higmar

    2006-09-08

    This work proposes the use of the Matlab environment to obtain the treatment dose based on the reported data by Krishnaswamy and Liu et al. The comparison with reported measurements is showed for the Amersham source model. For the 3M source model, measurements with TLDs and a Monte Carlo simulation are compared to the data obtained by Matlab. The difference for the Amersham model is well under the 15% recommended by the IAEA and for the 3M model, although the difference is greater, the results are consistent. The good agreement to the reported data allows the Matlab calculations to be used in daily brachytherapy treatments.

  4. Development and evaluation of a technique for in vivo monitoring of 60Co in human lungs

    NASA Astrophysics Data System (ADS)

    de Mello, J. Q.; Lucena, E. A.; Dantas, A. L. A.; Dantas, B. M.

    2016-07-01

    60Co is a fission product of 235U and represents a risk of internal exposure of workers in nuclear power plants, especially those involved in the maintenance of potentially contaminated parts and equipment. The control of 60Co intake by inhalation can be performed through in vivo monitoring. This work describes the evaluation of a technique through the minimum detectable activity and the corresponding minimum detectable effective doses, based on biokinetic and dosimetric models of 60Co in the human body. The results allow to state that the technique is suitable either for monitoring of occupational exposures or evaluation of accidental intake.

  5. Comparison of UV-B measurements performed with a Brewer spectrophotometer and a new UVB-1 broad band detector

    NASA Technical Reports Server (NTRS)

    Bais, Alkiviadis F.; Zerefos, Christos S.; Meleti, Charicleia; Ziomas, Ioannis C.

    1994-01-01

    Measurements of the UV-B erythemal dose, based on solar spectra acquired with a Brewer spectrophotometer at Thessaloniki, Greece, are compared to measurements performed with the recently introduced, by the Yankee Environmental Systems, (Robertson type) broad band solar UV-B detector. The spectral response function of this detector, when applied to the Brewer spectral UV-B measurements, results in remarkably comparable estimates of the erythemal UV-B dose. The two instruments provide similar information on the UV-B dose when they are cross-examined under a variety of meteorological and atmospheric conditions and over the a large range of solar zenith angles and total ozone.

  6. Risk assessment for neurobehavioral toxicity: SGOMSEC joint report.

    PubMed Central

    Hattis, D; Glowa, J; Tilson, H; Ulbrich, B

    1996-01-01

    Behavioral end points for neurotoxicity risk assessment have been developed and examined over the past three decades. They are now ready to move from simple qualitative guidelines, such as exemplified by reference doses, to more quantitative models, such as benchmark doses, based on dose-response information. Risk assessors, confronted by a wider array of methodologies and data than in the past, should be offered guidance in interpretation because now they have to deal with unaccustomed questions and problems. These include reversibility, susceptible populations, multiple end points, and the details of dose-response and dose-effect distributions. PMID:8860324

  7. Radiation biodosimetry: Applications for spaceflight

    NASA Astrophysics Data System (ADS)

    Blakely, W. F.; Miller, A. C.; Grace, M. B.; McLeland, C. B.; Luo, L.; Muderhwa, J. M.; Miner, V. L.; Prasanna, P. G. S.

    The multiparametric dosimetry system that we are developing for medical radiological defense applications could be adapted for spaceflight environments. The system complements the internationally accepted personnel dosimeters and cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a portable hematology analyzer, molecular biodosimetry using nucleic acid and antigen-based diagnostic equipment, and a dose assessment management software application. A dry-capillary tube reagent-based centrifuge blood cell counter (QBC Autoread Plus, Beckon Dickinson Bioscience) measures peripheral blood lymphocytes and monocytes, which could determine radiation dose based on the kinetics of blood cell depletion. Molecular biomarkers for ionizing radiation exposure (gene expression changes, blood proteins) can be measured in real time using such diagnostic detection technologies as miniaturized nucleic acid sequences and antigen-based biosensors, but they require validation of dose-dependent targets and development of optimized protocols and analysis systems. The Biodosimetry Assessment Tool, a software application, calculates radiation dose based on a patient's physical signs and symptoms and blood cell count analysis. It also annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. These radiation assessment diagnostic technologies can have dual-use applications supporting general medical-related care.

  8. Final Report of a CRADA Between Pacific Northwest National Laboratory and Cummins, Incorporated (CRADA No.PNNL/283): “Enhanced High and Low Temperature Performance of NOx Reduction Catalyst Materials”

    SciTech Connect

    Gao, Feng; Szanyi, Janos; Wang, Yilin; Wang, Yong; Peden, Charles HF; Howden, Ken; Currier, Neal; Kamasamudram, Krishna; Kumar, Ashok; Li, J.; Stafford, R. J.; Yezerets, Aleksey; Luo, J.; Chen, H. Y.

    2016-09-01

    The NOx Storage-Reduction (NSR, also known as lean-NOx trap – LNT), is based upon the concept of storing NOx as nitrates over storage components, typically barium species, during a lean-burn operation cycle and then reducing the stored nitrates to N2 during fuel-rich conditions over a precious metal catalyst [1]. NOx Selective Catalytic Reduction (SCR), on the other hand, is accomplished by deliberately introducing reductant urea into the engine exhaust to reduce NOx with the aid of a Cu(Fe)/zeolite catalyst [2]. These two technologies have been recognized as the most promising approaches for meeting stringent NOx emission standards for diesel vehicles within the Environmental Protection Agency’s (EPA’s) 2007/2010 mandated limits. For NSR, problems arising from either or both thermal and SO2 deactivation must be addressed to meet durability standards. For SCR, SO2 deactivation is less of an issue, but hydrothermal deactivation of the zeolite catalysts must be addressed. With continuing R&D efforts in advanced powertrains, highly novel operating modes for internal combustion engines (ICEs) are being researched in order to meet the very stringent new demands for fuel efficiency (e.g., U.S. ‘‘CAFE’’ standards for average miles/gallon are scheduled to increase dramatically over the next 10–15 years). These new ICE engine operation modes, while highly fuel-efficient, result in much lower exhaust temperatures than current engines; temperatures so low that it is hard to imagine how the current catalytic emission control technologies will be able to function. For example, while steady-state operation of the NOx reduction technology at 150 °C may be required, current ‘‘light-off’’ temperatures for CHA-based zeolite catalysts are closer to 200 °C. Therefore, understanding low-temperature limitations in NOx reduction has become one

  9. Benzene and its methyl-derivatives: derivation of maximum exposure levels in automobiles.

    PubMed

    Schupp, Thomas; Bolt, Hermann M; Jaeckh, Rudolf; Hengstler, Jan G

    2006-01-05

    Automobile drivers are exposed to several organic hydrocarbons. Concentrations measured in passenger compartments have been reported to range between 13 and 560 microg/m(3) for benzene, 33-258 microg/m(3) for toluene, 20-250 microg/m(3) for xylene (mixed isomers) and 3-23 microg/m(3) for trimethylbenzene (mixed isomers). These aromatic hydrocarbons are emitted from gasoline and from materials inside a car. In the present study we evaluated, whether these exposures pose a potential risk to the health of drivers. Therefore, we derived maximum exposure levels inside cars for chronic (ELIA(chronic)) and short-term (STELIA) exposure. The lowest ELIA's(chronic) for benzene, toluene, xylene and trimethylbenzene were 0.083, 1.2, 8.8 and 0.31 mg/m(3), respectively. The respective STELIA's were 16, 30, 29 and 25 mg/m(3). Obviously concentrations of toluene, xylene and trimethylbenzene inside cars do not exceed their individual STELIA's. In contrast, benzene seems to be problematic, since concentrations inside cars amount up to 0.56 mg/m(3), which exceeds the ELIA(chronic) derived for benzene. This should not be underestimated, since benzene is a genotoxic carcinogen that probably acts by non-threshold mechanisms. In conclusion, concentrations of toluene, xylene and trimethylbenzene usually observed inside cars are unlikely to pose a risk to the health of drivers. A systematic toxicological evaluation of the risk associated with benzene exposure in cars seems to be necessary.

  10. Potential health impacts of residential exposures to extremely low frequency magnetic fields in Europe.

    PubMed

    Grellier, James; Ravazzani, Paolo; Cardis, Elisabeth

    2014-01-01

    Over the last two decades residential exposure to extremely low frequency magnetic fields (ELF MF) has been associated with childhood leukaemia relatively consistently in epidemiological studies, though causality is still under investigation. We aimed to estimate the cases of childhood leukaemia that might be attributable to exposure to ELF MF in the European Union (EU27), if the associations seen in epidemiological studies were causal. We estimated distributions of ELF MF exposure using studies identified in the existing literature. Individual distributions of exposure were integrated using a probabilistic mixture distribution approach. Exposure-response functions were estimated from the most recently published pooled analysis of epidemiological data. Probabilistic simulation was used to estimate population attributable fractions (AFP) and attributable cases of childhood leukaemia in the EU27. By assigning the literature review-based exposure distribution to all EU27 countries, we estimated the total annual number of cases of leukaemia attributable to ELF MF at between ~50 (95% CIs: -14, 132) and ~60 (95% CIs: -9, 610), depending on whether exposure-response was modelled categorically or continuously, respectively, for a non-threshold effect. This corresponds to between ~1.5% and ~2.0% of all incident cases of childhood leukaemia occurring annually in the EU27. Considerable uncertainties are due to scarce data on exposure and the choice of exposure-response model, demonstrating the importance of further research into better understanding mechanisms of the potential association between ELF MF exposure and childhood leukaemia and the need for improved monitoring of residential exposures to ELF MF in Europe.

  11. Community health risk assessment after a fire with asbestos containing fallout

    PubMed Central

    Bridgman, S

    2001-01-01

    BACKGROUND—A factory fire in Tranmere, Merseyside, England, deposited asbestos containing fallout in an urban area. There was considerable community anxiety for months after the incident. Therefore an assessment of the long term health risks of this acute environmental incident were requested by the local health authority.
METHODS—The facts of the incident were gathered and appraised from unpublished and press reports, involved personnel, and further analysis of material collected at the time of the incident. The literature on the long term health risks of asbestos was reviewed, and combined with evidence on asbestos exposure to estimate community health risk.
RESULTS—Risk was almost entirely from exposure to fire fallout of chrysotile in asbestos bitumen paper covering the factory roof. Amosite was only detected in a few samples and in trace amounts. The number of people who lived in the area of fallout was 16 000 to 48 000. From a non-threshold model with assumptions likely to overestimate risk, the lung cancer risk is estimated to be undetectably small. Risk of mesothelioma from chrysotile exposure, and risks of lung cancer and mesothelioma from amosite exposure were based on observational studies and were estimated to be even lower than that of lung cancer risk from chrysotile exposure. Academically, there are assumptions that while reasonable cannot be proven, for example, the validity of extrapolating observed risk from much higher exposures to lower exposures, estimates of individual exposure, and that there is no threshold for asbestos to cause cancer.
CONCLUSIONS—The author is unaware of a similar study on long term health risks in a community exposed to asbestos in a fire. It is concluded that, using methods that do not underestimate risk, risk is undetectably small. Practical lessons from this methodology and approach to health risk assessment are discussed.


Keywords: asbestos; environmental pollutants; mesothelioma; health risk

  12. Arsenic accumulation in native plants of West Bengal, India: prospects for phytoremediation but concerns with the use of medicinal plants.

    PubMed

    Tripathi, Preeti; Dwivedi, Sanjay; Mishra, Aradhana; Kumar, Amit; Dave, Richa; Srivastava, Sudhakar; Shukla, Mridul Kumar; Srivastava, Pankaj Kumar; Chakrabarty, Debasis; Trivedi, Prabodh Kumar; Tripathi, Rudra Deo

    2012-05-01

    Arsenic (As) is a widespread environmental and food chain contaminant and class I, non-threshold carcinogen. Plants accumulate As due to ionic mimicry that is of importance as a measure of phytoremediation but of concern due to the use of plants in alternative medicine. The present study investigated As accumulation in native plants including some medicinal plants, from three districts [Chinsurah (Hoogly), Porbosthali (Bardhman), and Birnagar (Nadia)] of West Bengal, India, having a history of As pollution. A site-specific response was observed for Specific Arsenic Uptake (SAU; mg kg(-1) dw) in total number of 13 (8 aquatic and 5 terrestrial) collected plants. SAU was higher in aquatic plants (5-60 mg kg(-1) dw) than in terrestrial species (4-19 mg kg(-1) dw). The level of As was lower in medicinal plants (MPs) than in non-medicinal plants, however it was still beyond the WHO permissible limit (1 mg kg(-1) dw). The concentration of other elements (Cu, Zn, Se, and Pb) was found to be within prescribed limits in medicinal plants (MP). Among the aquatic plants, Marsilea showed the highest SAU (avg. 45 mg kg(-1) dw), however, transfer factor (TF) of As was the maximum in Centella asiatica (MP, avg. 1). Among the terrestrial plants, the maximum SAU and TF were demonstrated by Alternanthera ficoidea (avg. 15) and Phyllanthus amarus (MP, avg. 1.27), respectively. In conclusion, the direct use of MP or their by products for humans should not be practiced without proper regulation. In other way, one fern species (Marsilea) and some aquatic plants (Eichhornia crassipes and Cyperus difformis) might be suitable candidates for As phytoremediation of paddy fields.

  13. Important considerations in the development of public health advisories for arsenic and arsenic-containing compounds in drinking water.

    PubMed

    Tchounwou, P B; Wilson, B; Ishaque, A

    1999-01-01

    Drinking water contamination by arsenic remains a major public health problem. Acute and chronic arsenic exposure via drinking water has been reported in many countries of the world; especially in Argentina, Bangladesh, India, Mexico, Thailand, and Taiwan, where a large proportion of drinking water (ground water) is contaminated with a high concentration of arsenic. Research has also pointed out significantly higher standardized mortality ratios and cumulative mortality rates for cancers of the bladder, kidney, skin, liver, and colon in many areas of arsenic pollution. General health effects that are associated with arsenic exposure include cardiovascular and peripheral vascular disease, developmental anomalies, neurologic and neurobehavioral disorders, diabetes, hearing loss, portal fibrosis of the liver, lung fibrosis, hematologic disorders (anemia, leukopenia, and eosinophilia), and carcinoma. Although, the clinical manifestations of arsenic poisoning appear similar, the toxicity of arsenic compounds depends largely u[on the chemical species and the form of arsenic involved. On the basis of its high degree of toxicity to humans, and the non-threshold dose-response assumption, a zero level exposure is recommended for arsenic, even though this level is practically non-attainable. In this review, we provide and discuss important information on the physical and chemical properties, production and use, fate and transport, toxicokinetics, systemic and carcinogenic health effects, regulatory and health guidelines, analytical methods, and treatment technologies that are applied to arsenic pollution. Such information is critical in assisting the federal, state and local officials who are responsible for protecting public health in dealing with the problem of drinking water contamination by arsenic and arsenic-containing compounds.

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

    PubMed

    Hamada, Nobuyuki; Fujimichi, Yuki

    2014-07-01

    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.

  15. Genotoxicity assessment of 4-methylimidazole: regulatory perspectives.

    PubMed

    Morita, Takeshi; Uneyama, Chikako

    2016-01-01

    4-Methylimidazole (4-MI) is formed as a result of the Maillard reaction process, and therefore is found in many foods and beverages. It is also found in soft drinks (i.e., cola) as a by-product in the production of some caramel colors. NTP bioassays revealed clear evidence of lung carcinogenicity of 4-MI in male and female mice, but not in rats and then IARC classified 4-MI as group 2B carcinogen. Genotoxicity studies with 4-MI were negative in the Ames tests and in the erythrocyte micronucleus tests with mice or rats. US California EPA (CEPA) evaluated the testing has not been adequately comprehensive to rule out a genotoxic mode of action; as target tissue of the carcinogenicity of 4-MI was lung, the lung should be used as a source tissue for in vitro metabolic activation system. Thus, CEPA defined the No Significant Risk Level (NSRL) for 10(-5) lifetime risk level of cancer by 4-MI as 29 μg/day based on the non-threshold approach. As higher levels of 4-MI than the NSRL were identified in some kinds of cola, health concerns of 4-MI were drawn the attention. On the other hand, other regulatory bodies (e.g., European Food Safety Authority, EFSA) showed no concerns of 4-MI from the use of caramel colors in food. EFSA evaluated 4-MI is not genotoxic, so, non-observed adverse effect level of 4-MI was considered to be 80 mg/kg/day. In this paper, genotoxic assessments of 4-MI in different regulatory bodies are presented and the risk evaluation of 4-MI is discussed based on new genotoxicity data.

  16. Limited English proficient Asian Americans: Threshold language policy and access to mental health treatment.

    PubMed

    Snowden, Lonnie R; Masland, Mary C; Peng, Carol J; Wei-Mien Lou, Christine; Wallace, Neal T

    2011-01-01

    The importance of providing timely, effective mental health services is increasingly recognized worldwide, and language barriers are a formidable obstacle to achieving this objective. Threshold language policy is one response implemented by California and other states within the U.S., in accordance with Title VI of the Civil Rights Act of 1964, which prohibits discrimination on the basis of race, color, and national origin in programs receiving federal funding. This policy mandates language assistance services for Medicaid enrollees whose primary language is other than English once their population size reaches a designated level. Medicaid is the federal-state-funded health insurance program for specific classifications of low-income Americans. This study evaluated the impact of threshold language policy on Vietnamese, Cantonese, Hmong, and Cambodian limited English proficiency persons' use of public mental health services in California. Using random-effects regression on 247 observations, we regressed aggregate Vietnamese, Cantonese, Hmong, and Cambodian Medicaid mental health service penetration rates on an indicator of the threshold language policy's implementation, while controlling for a linear time trend and the effects of non-threshold language assistance programming. Immediately after implementation, threshold language policy requirements were associated with a penetration rate increase among this population. The penetration rate increase became greater after accounting for the impact of concurrent language assistance. However, this increase diminished over time. The findings indicate that, at least in the short run, language assistance measures requiring reasonable accommodations once populations of LEP persons reach a specified size have detectable effects on their mental health service use. These requirements increase the number of mental health consumers, but appear to provide declining benefit over time. California's threshold language policy provides

  17. Linear low-dose extrapolation for noncancer health effects is the exception, not the rule

    PubMed Central

    Rhomberg, Lorenz R; Goodman, Julie E; Haber, Lynne T; Dourson, Michael; Andersen, Melvin E; Klaunig, James E; Meek, Bette; Price, Paul S; McClellan, Roger O; Cohen, Samuel M

    2011-01-01

    The nature of the exposure-response relationship has a profound influence on risk analyses. Several arguments have been proffered as to why all exposure-response relationships for both cancer and noncarcinogenic end-points should be assumed to be linear at low doses. We focused on three arguments that have been put forth for noncarcinogens. First, the general “additivity-to-background” argument proposes that if an agent enhances an already existing disease-causing process, then even small exposures increase disease incidence in a linear manner. This only holds if it is related to a specific mode of action that has nonuniversal properties—properties that would not be expected for most noncancer effects. Second, the “heterogeneity in the population” argument states that variations in sensitivity among members ofthe target population tend to “flatten out and linearize” the exposure-response curve, but this actually only tends to broaden, not linearize, the dose-response relationship. Third, it has been argued that a review of epidemiological evidence shows linear or no-threshold effects at low exposures in humans, despite nonlinear exposure-response in the experimental dose range in animal testing for similar endpoints. It is more likely that this is attributable to exposure measurement error rather than a true non-threshold association. Assuming that every chemical is toxic at high exposures and linear at low exposures does not comport to modern-day scientific knowledge of biology. There is no compelling evidence-based justification for a general low-exposure linearity; rather, case-specific mechanistic arguments are needed. PMID:21226629

  18. Use of the nonavalent HPV vaccine in individuals previously fully or partially vaccinated with bivalent or quadrivalent HPV vaccines.

    PubMed

    Van Damme, Pierre; Bonanni, Paolo; Bosch, F Xavier; Joura, Elmar; Kjaer, Susanne Krüger; Meijer, Chris J L M; Petry, Karl-Ulrich; Soubeyrand, Benoit; Verstraeten, Thomas; Stanley, Margaret

    2016-02-03

    With the availability of the nonavalent human papillomavirus (HPV) vaccine, vaccinees, parents and healthcare providers need guidance on how to complete an immunization course started with the bi- or quadrivalent vaccine and whether to revaccinate individuals who have completed a full immunization course with the bi- or quadrivalent vaccine. To answer these questions three parameters should be considered: age at the start of vaccination (9 to 14 years of age versus 15 years and older, the cut-off for 2 or 3 doses schedule), the number of doses already received and the time interval between doses. Based on a number of scenarios, we propose that the 9-valent vaccine can be used to complete an incomplete vaccination regimen or might be added to a previous completed schedule to extend protection.

  19. Proposed changes for part N of suggested state regulations

    SciTech Connect

    Paris, R.

    1997-02-01

    This paper discusses proposed changes for Part N regulations regarding naturally occuring radioactive materials. It describes the work of the Commission on NORM of the Conference of Radiation Control Program Directors (CRCPD), toward adjusting the regulations. A set of questions was formulated and a review panel established to address these questions and come back with recommended actions. The panel recommended the distinction that the material being regulated is `Technologically Enhanced Naturally Occurring Radioactive Material` (TENORM). By this they mean `naturally occurring radioactive material not regulated under the Atomic Energy Act (AEA) whose radionuclide concentrations have been increased by or as a result of human practices.` Recommendations also include: using a dose based instead of concentration based standard; refined definition of exemptions from regulations; exclusion of radon from Total Effective Dose Equivalent (TEDE) calculations; provide states flexibility in implementation; inclusion of prospective remedial and operations aspects for TENORM; provision of institutional controls.

  20. Real-Time Statistical Modeling of Blood Sugar.

    PubMed

    Otoom, Mwaffaq; Alshraideh, Hussam; Almasaeid, Hisham M; López-de-Ipiña, Diego; Bravo, José

    2015-10-01

    Diabetes is considered a chronic disease that incurs various types of cost to the world. One major challenge in the control of Diabetes is the real time determination of the proper insulin dose. In this paper, we develop a prototype for real time blood sugar control, integrated with the cloud. Our system controls blood sugar by observing the blood sugar level and accordingly determining the appropriate insulin dose based on patient's historical data, all in real time and automatically. To determine the appropriate insulin dose, we propose two statistical models for modeling blood sugar profiles, namely ARIMA and Markov-based model. Our experiment used to evaluate the performance of the two models shows that the ARIMA model outperforms the Markov-based model in terms of prediction accuracy.

  1. Individual external dose monitoring of all citizens of Date City by passive dosimeter 5 to 51 months after the Fukushima NPP accident (series): 1. Comparison of individual dose with ambient dose rate monitored by aircraft surveys.

    PubMed

    Miyazaki, Makoto; Hayano, Ryugo

    2016-12-06

    Date (da'te) City in Fukushima Prefecture has conducted a population-wide individual dose monitoring program after the Fukushima Daiichi Nuclear Power Plant Accident, which provides a unique and comprehensive data set of the individual doses of citizens. The purpose of this paper, the first in the series, is to establish a method for estimating effective doses based on the available ambient dose rate survey data. We thus examined the relationship between the individual external doses and the corresponding ambient doses assessed from airborne surveys. The results show that the individual doses were about 0.15 times the ambient doses, the coefficient of 0.15 being a factor of 4 smaller than the value employed by the Japanese government, throughout the period of the airborne surveys used. The method obtained in this study could aid in the prediction of individual doses in the early phase of future radiological accidents involving large-scale contamination.

  2. Guidelines for acceptable soil concentrations in the Old F- and H-Area Retention Basins. Revision 1

    SciTech Connect

    Hamby, D.M.

    1994-04-18

    Concentration guidelines for residual radionuclides in soil at the sites of the Old F- and a Retention Basins (281-3F, 281-3H) have been calculated using a dose-based approach. The guidelines also are being applied to areas around the F-Basin`s Process Line. Estimation of these soil guidelines was completed using RESRAD 5.0 in accordance with the DOE RESRAD methodology specified in DOE/CH/8901 (Gi89). Guidelines are provided for the nuclides known to be present in the soils at each basin (Sc87). Soil and hydrologic characteristics specific to each basin are defined for the areas above, within, and beneath the contaminated zones.

  3. Guidelines for acceptable soil concentrations in the old F- and H-Area Retention Basins

    SciTech Connect

    Hamby, D.M.

    1994-04-18

    Concentration guidelines for residual radionuclides in soil at the sites of the Old F- and H-Area Retention Basins (281-3F, 281-3H) have been calculated using a dose-based approach. The guidelines also are being applied to areas around the F-Basin`s Process Line. Estimation of these soil guidelines was completed using RESRAD 5.0 in accordance with the DOE RESRAD methodology specified in DOE/CH/8901 (Gi89). Guidelines are provided for the nuclides known to be present in the soils at each basin (Sc87). Soil and hydrologic characteristics specific to each basin are defined for the areas above, within, and beneath the contaminated zones.

  4. Photodynamic therapy: superficial and interstitial illumination

    NASA Astrophysics Data System (ADS)

    Svanberg, Katarina; Bendsoe, Niels; Axelsson, Johan; Andersson-Engels, Stefan; Svanberg, Sune

    2010-07-01

    Photodynamic therapy (PDT) is reviewed using the treatment of skin tumors as an example of superficial lesions and prostate cancer as an example of deep-lying lesions requiring interstitial intervention. These two applications are among the most commonly studied in oncological PDT, and illustrate well the different challenges facing the two modalities of PDT-superficial and interstitial. They thus serve as good examples to illustrate the entire field of PDT in oncology. PDT is discussed based on the Lund University group's over 20 yr of experience in the field. In particular, the interplay between optical diagnostics and dosimetry and the delivery of the therapeutic light dose are highlighted. An interactive multiple-fiber interstitial procedure to deliver the required therapeutic dose based on the assessment of light fluence rate and sensitizer concentration and oxygen level throughout the tumor is presented.

  5. Phase I clinical trial of an injectable contraceptive for the male.

    PubMed

    Guha, S K; Singh, G; Anand, S; Ansari, S; Kumar, S; Koul, V

    1993-10-01

    Earlier studies on the rat and the monkey had demonstrated that an injection of styrene maleic anhydride (SMA) in a solvent vehicle of dimethyl sulphoxide (DMSO) into the lumen of the vas deferens is toxicologically safe and has contraceptive action. Phase I clinical trial was therefore undertaken on 38 male volunteers giving varying doses of SMA, ranging between 5 mg and 140 mg, into each vas deferens. A dose of 70 mg is the predicted therapeutic dose based on animal data. That the compound is within the vas deferens lumen during the period of the safety assessment is inferred from the effect on the spermatozoa count in ejaculates which reach azoospermic levels in the higher dose ranges. The treatment is well tolerated with only minimal side effects in a few cases and no long-term adverse effects.

  6. Discovery of phenyl acetamides as potent and selective GPR119 agonists.

    PubMed

    Zhu, Cheng; Wang, Liping; Zhu, Yuping; Guo, Zack Zhiqiang; Liu, Ping; Hu, Zhiyong; Szewczyk, Jason W; Kang, Ling; Chicchi, Gary; Ehrhardt, Anka; Woods, Andrea; Seo, Toru; Woods, Morgan; van Heek, Margaret; Dingley, Karen H; Pang, Jianmei; Salituro, Gino M; Powell, Joyce; Terebetski, Jenna L; Hornak, Viktor; Campeau, Louis-Charles; Orr, Robert K; Ujjainwalla, Feroze; Miller, Michael; Stamford, Andrew; Wood, Harold B; Kowalski, Timothy; Nargund, Ravi P; Edmondson, Scott D

    2017-03-01

    The paper describes the SAR/SPR studies that led to the discovery of phenoxy cyclopropyl phenyl acetamide derivatives as potent and selective GPR119 agonists. Based on a cis cyclopropane scaffold discovered previously, phenyl acetamides such as compound 17 were found to have excellent GPR119 potency and improved physicochemical properties. Pharmacokinetic data of compound 17 in rat, dog and rhesus will be described. Compound 17 was suitable for QD dosing based on its predicted human half-life, and its projected human dose was much lower than that of the recently reported structurally-related benzyloxy compound 2. Compound 17 was selected as a tool compound candidate for NHP (Non-Human Primate) efficacy studies.

  7. Consequences of meta-stable (177m)Lu admixture in (177)Lu for patient dosimetry.

    PubMed

    Konijnenberg, Mark W

    2015-01-01

    Lutetium-177 ((177)Lu) is a rare earth metal in the lanthanides series which decays by beta emission with a half life of 6.647 days to three excited states and the ground state of (177)Hf. When (177)Lu is produced by neutron capture in (176)Lu, inevitably an admixture is formed of the long-lived isomer (177)mLu. As its half-life of 160.4 days is so much longer than that of (177)Lu, concerns are raised on its possible enhancement in radiation dose to the patient treated with (177)Lu-DOTA-octreotate. This report evaluates this possible enhancement of the absorbed dose, based on the published pharmacokinetic profile of (177)Lu-DOTA-octreotate and assuming an admixture of 1 kBq (177)mLu /MBq (177)Lu (0.1%).

  8. High energy neutron response characteristics of a passive survey instrument for the determination of cosmic radiation fields in aircraft.

    PubMed

    Bartlett, D T; Tanner, R J; Hager, L G

    2002-01-01

    A passive survey instrument has been developed for the determination of cosmic radiation fields in aircraft. The instrument contains 30 TLDs and 36 PADC etched track detectors in order to obtain the required precision and an isotropic response. Two active electronic personal dosemeters are included to record the time profile of the field intensity. The instrument is robust and reliable, and is particularly useful to verify values of route doses based on calculations. The energy of the neutron component of the field to be determined extends to over 500 MeV, but with the majority of the dose equivalent below 200 MeV. The results are reported of measurements at Uppsala University and Physikalisch-Technische Bundesanstalt of the response characteristics of the instrument to quasi-monoenergetic neutrons in the energy range 60 to 180 MeV and for monoenergetic neutrons of energy from 70 keV to 14.7 MeV.

  9. Radiation-induced degradation of 4-chloroaniline in aqueous solution

    NASA Astrophysics Data System (ADS)

    Sánchez, M.; Wolfger, H.; Getoff, N.

    2002-12-01

    The radiation-induced decomposition of 4-chloroaniline (4-ClA) was studied under steady-state conditions using aqueous solutions saturated with air, pure oxygen, N 2O, argon and argon in the presence of t-Butanol. Using HPLC-method, the initial G-values of the substrate degradation as well as of a number of radiolytic products were determined. The formation of aminophenols, chlorophenols, aniline and phenol in addition to chloride, ammonia, formaldehyde and mixture of aldehydes as well as carboxylic acids was studied as a function of absorbed dose. Based on the experimental data, probable reaction mechanisms for the degradation of 4-ClA by γ-rays and the formation of the identified products are presented.

  10. Brachytherapy optimization using radiobiological-based planning for high dose rate and permanent implants for prostate cancer treatment

    NASA Astrophysics Data System (ADS)

    Seeley, Kaelyn; Cunha, J. Adam; Hong, Tae Min

    2017-01-01

    We discuss an improvement in brachytherapy--a prostate cancer treatment method that directly places radioactive seeds inside target cancerous regions--by optimizing the current standard for delivering dose. Currently, the seeds' spatiotemporal placement is determined by optimizing the dose based on a set of physical, user-defined constraints. One particular approach is the ``inverse planning'' algorithms that allow for tightly fit isodose lines around the target volumes in order to reduce dose to the patient's organs at risk. However, these dose distributions are typically computed assuming the same biological response to radiation for different types of tissues. In our work, we consider radiobiological parameters to account for the differences in the individual sensitivities and responses to radiation for tissues surrounding the target. Among the benefits are a more accurate toxicity rate and more coverage to target regions for planning high-dose-rate treatments as well as permanent implants.

  11. Prediction of multidimensional drug dose responses based on measurements of drug pairs

    PubMed Central

    Zimmer, Anat; Katzir, Itay; Dekel, Erez; Alon, Uri

    2016-01-01

    Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments. PMID:27562164

  12. Prediction of multidimensional drug dose responses based on measurements of drug pairs.

    PubMed

    Zimmer, Anat; Katzir, Itay; Dekel, Erez; Mayo, Avraham E; Alon, Uri

    2016-09-13

    Finding potent multidrug combinations against cancer and infections is a pressing therapeutic challenge; however, screening all combinations is difficult because the number of experiments grows exponentially with the number of drugs and doses. To address this, we present a mathematical model that predicts the effects of three or more antibiotics or anticancer drugs at all doses based only on measurements of drug pairs at a few doses, without need for mechanistic information. The model provides accurate predictions on available data for antibiotic combinations, and on experiments presented here on the response matrix of three cancer drugs at eight doses per drug. This approach offers a way to search for effective multidrug combinations using a small number of experiments.

  13. Environmental Monitoring Plan for the Oak Ridge Reservation, 2012

    SciTech Connect

    Thompson, Sharon D.

    2012-10-01

    The purpose of Oak Ridge Reservation (ORR) environmental surveillance is to characterize radiological and nonradiological conditions of the off-site environs and estimate public doses related to these conditions, confirm estimations of public dose based on effluent monitoring data, and, where appropriate, provide supplemental data to support compliance monitoring for applicable environmental regulations. This environmental monitoring plan (EMP) is intended to document the rationale, frequency, parameters, and analytical methods for the ORR environmental surveillance program and provides information on ORR site characteristics, environmental pathways, dose assessment methods, and quality management. ORR-wide environmental monitoring activities include a variety of media including air, surface water, vegetation, biota, and wildlife. In addition to these activities, site-specific effluent, groundwater, and best management monitoring programs are conducted at the Oak Ridge National Laboratory (ORNL), the Y-12 National Security Complex (Y-12), and the East Tennessee Technology Park (ETTP). This is revision 5.

  14. RESRAD soil concentration guidelines for the Old F-Area Retention Basin

    SciTech Connect

    Hamby, D.M.

    1994-02-24

    Concentration guidelines for residual radionuclides in soil at the site of the Old F-Area Retention Basin have been calculated using a dose-based approach. Estimation of these soil guidelines was completed using RESRAD 5.0 in accordance with the DOE RESRAD methodology specified in DOE/CH/8901. Guidelines are provided for the two predominant nuclides, Sr-90 and Cs-137, known to be present in the soil beneath the old basin. A guideline is also given for Pu-238 since it is known to exist at the H-Area Retention Basin. Site-specific soil characteristics are defined for the areas above, within, and beneath the contaminated zone.

  15. First results from electron-photon damage equivalence studies on a generic ethylene-propylene rubber

    SciTech Connect

    Buckalew, W.H.

    1986-04-01

    As part of a simulator adequacy assessment program, the relative effectiveness of electrons and photons to produce damage in a generic ethylene propylene rubber (EPR) has been investigated. The investigation was limited in extent in that a single EPR material, in three thickness, was exposed to Cobalt-60 photons and three electron beam energies. Basing material damage on changes in the EPR mechanical properties elongation and tensile strength, we observed that EPR damage was a smoothly varying function of absorbed energy and independent of irradiating particle type. EPR damage tracked equally well as a function of both incident particle energy and material front surface dose. Based on these preliminary data, we tentatively concluded that a correlation between particle, particle energy, and material damage (as measured by changes in material elongation and/or tensile strength) has been demonstrated. 14 figs.

  16. Resveratrol products resulting by free radical attack

    NASA Astrophysics Data System (ADS)

    Bader, Yvonne; Quint, R. M.; Getoff, Nikola

    2008-06-01

    Trans-resveratrol ( trans-3,4',5-trihydroxystilbene; RES), which is contained in red wine and many plants, is one of the most relevant and extensively investigated stilbenes with a broad spectrum of biological activities. Among other duties, RES has been reported to have anti-carcinogenetic activities, which could be attributed to its antioxidant properties. The degradation of RES was studied under various conditions. The products (aldehydes, carboxylic acids, etc.) generated from RES by the attack of free radicals were registered as a function of the radical concentration (absorbed radiation dose). Based on the obtained data it appears that the OH radicals are initiating the rather complicated process, which involves of the numerous consecutive reactions. A possible starting reaction mechanism is presented.

  17. "Visually clean" as a sole acceptance criterion for cleaning validation protocols.

    PubMed

    LeBlanc, Destin A

    2002-01-01

    The role of visual examination as the sole acceptance criterion in cleaning validation protocols is explored, including the proper definition of "visual limit" for a given residue. Such a visual limit is specific to the surface the residue is on, and is further defined by viewing conditions, such as lighting, distance, and angle of viewing. A visually clean standard may only be properly utilized if the visual limit is below any scientifically calculated residue limit, such as that determined by a traditional dose-based limit determination. While such an approach, properly applied, has scientific justification and appears to be accepted by the proposed Annex 15 to the European GMPs, the approach is still untested with regulatory authorities.

  18. Two years comparative studies on biological effects of environmental UV radiation

    NASA Astrophysics Data System (ADS)

    Grof, P.; Ronto, Gyorgyi; Gaspar, S.; Berces, A.; Szabo, Laszlo D.

    1994-07-01

    A method has been developed for determination of the biologically effective UV dose based on T7 phage as biosensor. In field experiments clockwork driven telescope has been used for determining doses from direct and global (direct plus diffuse) solar radiation. On fine summer days at mid-latitude this arrangement allowed the following comparisons: measured doses from direct and global radiation obtained at the same time and measuring site reflecting the biological importance of diffuse radiation; direct and global radiation obtained at the same time and measuring site reflecting the biological importance of diffuse radiation; direct and global doses obtained at the same time on different measuring sites (downtown, suburb, outside the town) reflecting the differences caused by air quality; direct and global doses obtained on the same measuring place, in summertime of two different years reflecting the importance of the long-term measurements for estimating the biological risk caused by increased UV-B radiation; measured data and model calculations.

  19. RESRAD for Radiological Risk Assessment. Comparison with EPA CERCLA Tools - PRG and DCC Calculators

    SciTech Connect

    Yu, C.; Cheng, J. -J.; Kamboj, S.

    2015-07-01

    The purpose of this report is two-fold. First, the risk assessment methodology for both RESRAD and the EPA’s tools is reviewed. This includes a review of the EPA’s justification for 2 using a dose-to-risk conversion factor to reduce the dose-based protective ARAR from 15 to 12 mrem/yr. Second, the models and parameters used in RESRAD and the EPA PRG and DCC Calculators are compared in detail, and the results are summarized and discussed. Although there are suites of software tools in the RESRAD family of codes and the EPA Calculators, the scope of this report is limited to the RESRAD (onsite) code for soil contamination and the EPA’s PRG and DCC Calculators also for soil contamination.

  20. Estimation of 1945 to 1957 food consumption

    SciTech Connect

    Anderson, D.M.; Bates, D.J.; Marsh, T.L.

    1993-03-01

    This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. The report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.

  1. Estimation of 1945 to 1957 food consumption. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Anderson, D.M.; Bates, D.J.; Marsh, T.L.

    1993-07-01

    This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. The report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.

  2. Estimation of 1945 to 1957 food consumption. Hanford Environmental Dose Reconstruction Project: Draft

    SciTech Connect

    Anderson, D.M.; Bates, D.J.; Marsh, T.L.

    1993-03-01

    This report details the methods used and the results of the study on the estimated historic levels of food consumption by individuals in the Hanford Environmental Dose Reconstruction (HEDR) study area from 1945--1957. This period includes the time of highest releases from Hanford and is the period for which data are being collected in the Hanford Thyroid Disease Study. These estimates provide the food-consumption inputs for the HEDR database of individual diets. This database will be an input file in the Hanford Environmental Dose Reconstruction Integrated Code (HEDRIC) computer model that will be used to calculate the radiation dose. The report focuses on fresh milk, eggs, lettuce, and spinach. These foods were chosen because they have been found to be significant contributors to radiation dose based on the Technical Steering Panel dose decision level.

  3. Slide Rule for Rapid Response Estimation of Radiological Dose from Criticality Accidents

    SciTech Connect

    Broadhead, B L; Childs, R L; Hopper, C M; Parks, C V

    1999-09-20

    This paper describes a functional slide rule that provides a readily usable "in-hand" method for estimating nuclear criticality accident information from sliding graphs, thereby permitting (1) the rapid estimation of pertinent criticality accident information without laborious or sophisticated calculations in a nuclear criticality emergency situation, (2) the appraisal of potential fission yields and external personnel radiation exposures for facility safety analyses, and (3) a technical basis for emergency preparedness and training programs at nonreactor nuclear facilities. The slide rule permits the estimation of neutron and gamma dose rates and integrated doses based upon estimated fission yields, distance from the fission source, and time-after criticality accidents for five different critical systems. Another sliding graph permits the estimation of critical solution fission yields based upon fissile material concentration, critical vessel geometry, and solution addition rate. Another graph provides neutron and gamma dose-reduction factors for water, steel, and concrete shields.

  4. GAMMA IRRADIATION TESTING OF MONTAN WAX FOR USE IN WASTE MANAGEMENT SYSTEMS

    SciTech Connect

    SOO,P.; HEISER,J.; HART,A.

    1996-09-08

    A field demonstration was funded by the US Department of Energy (DOE) to quantify the potential use of montan wax as a subsurface barrier material for nuclear waste management applications. As part of that demonstration, a study was completed to address some of the characteristics of the wax. Of particular interest is its resistance to chemical and structural changes that would influence its integrity as a barrier to minimize the migration of contaminants from their storage or disposal locations. Properties that were evaluated included hardness, melting point, molecular weight, and biodegradation as a function of gamma radiation dose. Based on the data obtained to date the wax is extremely resistant to radiation-induced change. Coupled with low permeability, the material shows promise as a subsurface barrier material.

  5. Quorum quenching analysis in Pseudomonas aeruginosa and Escherichia coli: network topology and inhibition mechanism effect on the optimized inhibitor dose.

    PubMed

    Barrios, Andrés Fernando González; Covo, Virginia; Medina, Luis Miguel; Vives-Florez, Martha; Achenie, Luke

    2009-06-01

    The discovery of quorum sensing as a mechanism for regulating specific phenotypes in bacteria based on population density has conveyed attention to find molecules capable of interfering quorum sensing networks (QSN) in a process coined quorum quenching. Here, we examined the dynamics of Escherichia coli AI-2 and Pseudomonas aeruginosa QSN exposed to signal degraders or competitors for binding transcriptional regulators. Stability analysis was performed for E. coli and P. aeruginosa finding no multistability in E. coli. However, our model allowed to discern that quenchers influence P. aeruginosa QSN multistability by reducing the interval of the amount of molecules of the extracellular signal that originate several steady states. We proposed a simulated annealing algorithm to optimize the quencher dose based on stochastic kinetics. E. coli QSN requires around 640 while P. aeruginosa QSN needs 253 quencher molecules per microorganism. This dose was found to be negatively influenced by the quencher-signal affinity.

  6. Personal dose-equivalent conversion coefficients for 1252 radionuclides.

    PubMed

    Otto, Thomas

    2016-01-01

    Dose conversion coefficients for radionuclides are useful for routine calculations in radiation protection in industry, medicine and research. They give a simple and often sufficient estimate of dose rates during production, handling and storage of radionuclide sources, based solely on the source's activity. The latest compilation of such conversion coefficients dates from 20 y ago, based on nuclear decay data published 30 y ago. The present publication provides radionuclide-specific conversion coefficients to personal dose based on the most recent evaluations of nuclear decay data for 1252 radionuclides and fluence-to-dose-equivalent conversion coefficients for monoenergetic radiations. It contains previously unknown conversion coefficients for >400 nuclides and corrects those conversion coefficients that were based on erroneous decay schemes. For the first time, estimates for the protection quantity Hp(3) are included.

  7. Large Cohort Dose-Volume Response Analysis of Parotid Gland Function After Radiotherapy: Intensity-Modulated Versus Conventional Radiotherapy

    SciTech Connect

    Dijkema, Tim Terhaard, Chris H.J.; Roesink, Judith M.; Braam, Petra M.; Gils, Carla H. van; Moerland, Marinus A.; Raaijmakers, Cornelis P.J.

    2008-11-15

    Purpose: To compare parotid gland dose-volume response relationships in a large cohort of patients treated with intensity-modulated (IMRT) and conventional radiotherapy (CRT). Methods and materials: A total of 221 patients (64 treated with IMRT, 157 with CRT) with various head-and-neck malignancies were prospectively evaluated. The distribution of tumor subsites in both groups was unbalanced. Stimulated parotid flow rates were measured before and 6 weeks, 6 months, and 1 year after radiotherapy. Parotid gland dose-volume histograms were derived from computed tomography-based treatment planning. The normal tissue complication probability (NTCP) model proposed by Lyman was fit to the data. A complication was defined as stimulated parotid flow ratio <25% of the pretreatment flow rate. The relative risk of complications was determined for IMRT vs. CRT and adjusted for the mean parotid gland dose using Poisson regression modeling. Results: One year after radiotherapy, NTCP curves for IMRT and CRT were comparable with a TD{sub 50} (uniform dose leading to a 50% complication probability) of 38 and 40 Gy, respectively. Until 6 months after RT, corrected for mean dose, different complication probabilities existed for IMRT vs. CRT. The relative risk of a complication for IMRT vs. CRT after 6 weeks was 1.42 (95% CI 1.21-1.67), after 6 months 1.41 (95% CI; 1.12-1.77), and at 1 year 1.21 (95% CI 0.87-1.68), after correcting for mean dose. Conclusions: One year after radiotherapy, no difference existed in the mean dose-based NTCP curves for IMRT and CRT. Early after radiotherapy (up to 6 months) mean dose based (Lyman) models failed to fully describe the effects of radiotherapy on the parotid glands.

  8. Different effects of lansoprazole and rabeprazole on the plasma voriconazole trough levels in allogeneic hematopoietic cell transplant recipients.

    PubMed

    Yasu, Takeo; Konuma, Takaaki; Kato, Seiko; Kurokawa, Yosuke; Takahashi, Satoshi; Tojo, Arinobu

    2016-10-01

    Voriconazole (VRC) is widely used as prophylaxis and in the treatment of invasive fungal disease (IFD) after allogeneic hematopoietic cell transplantation (HCT). We retrospectively examined the results of VRC therapeutic drug monitoring (TDM) in allogeneic HCT recipients. A total of 474 samples were obtained from 59 adult patients who received VRC during the first 100 days following HCT between 2009 and 2014 in our institute. Seventeen patients received VRC for prophylaxis of IFD, and 42 received VRC for the empirical or preemptive therapy for IFD. A total of 299 samples (63 %) were obtained during the administration of the intravenous form of VRC. The median VRC daily dose based on the actual body weight was 6.68 mg/kg/day (range, 1.92-10.41 mg/kg/day). The median VRC trough level was 0.99 mg/l (range, <0.09-5.45 mg/l). The multivariate analysis using a logistic regression model demonstrated significantly higher VRC trough levels (≥1.0 mg/l) in males (P < 0.001), empirical or preemptive therapy (P = 0.002), VRC daily dose based on the actual body weight ≥7 mg/kg/day (P < 0.001), and concomitant use of lansoprazole as compared to rabeprazole (P < 0.001). The concomitant use of calcineurin inhibitors and corticosteroids had no effects on VRC trough levels in multivariate analysis. These data suggest that lansoprazole and rabeprazole have different effects on the plasma VRC trough levels in the allogeneic HCT recipients.

  9. SU-E-T-109: An Investigation of Including Variable Relative Biological Effectiveness in Intensity Modulated Proton Therapy Planning Optimization for Head and Neck Cancer Patients

    SciTech Connect

    Cao, W; Zaghian, M; Lim, G; Randeniya, K; Mohan, R; Titt, U

    2015-06-15

    Purpose: The current practice of considering the relative biological effectiveness (RBE) of protons in intensity modulated proton therapy (IMPT) planning is to use a generic RBE value of 1.1. However, RBE is indeed a variable depending on the dose per fraction, the linear energy transfer, tissue parameters, etc. In this study, we investigate the impact of using variable RBE based optimization (vRBE-OPT) on IMPT dose distributions compared by conventional fixed RBE based optimization (fRBE-OPT). Methods: Proton plans of three head and neck cancer patients were included for our study. In order to calculate variable RBE, tissue specific parameters were obtained from the literature and dose averaged LET values were calculated by Monte Carlo simulations. Biological effects were calculated using the linear quadratic model and they were utilized in the variable RBE based optimization. We used a Polak-Ribiere conjugate gradient algorithm to solve the model. In fixed RBE based optimization, we used conventional physical dose optimization to optimize doses weighted by 1.1. IMPT plans for each patient were optimized by both methods (vRBE-OPT and fRBE-OPT). Both variable and fixed RBE weighted dose distributions were calculated for both methods and compared by dosimetric measures. Results: The variable RBE weighted dose distributions were more homogenous within the targets, compared with the fixed RBE weighted dose distributions for the plans created by vRBE-OPT. We observed that there were noticeable deviations between variable and fixed RBE weighted dose distributions if the plan were optimized by fRBE-OPT. For organs at risk sparing, dose distributions from both methods were comparable. Conclusion: Biological dose based optimization rather than conventional physical dose based optimization in IMPT planning may bring benefit in improved tumor control when evaluating biologically equivalent dose, without sacrificing OAR sparing, for head and neck cancer patients. The research

  10. Comparison of human growth hormone products' cost in pediatric and adult patients. A budgetary impact model.

    PubMed

    Bazalo, Gary R; Joshi, Ashish V; Germak, John

    2007-09-01

    We assessed the economic impact to the United States payer of recombinant human growth hormone (rhGH) utilization, comparing the relative dosage efficiency of marketed pen-based and vial-based products in a pediatric and in an adult population. A budgetary impact model calculated drug costs based on product waste and cost. Waste was the difference between prescribed dose, based on patient weight, and actual delivered dose, based on dosing increments and maximum deliverable dose for pens and a fixed-percent waste as derived from the literature for vials. Annual wholesale acquisition costs were calculated based upon total milligrams delivered, using a daily dose of 0.03 mg/kg for pediatric patients and 0.016 mg/kg for adults. Total annual drug costs were compared for two scenarios: 1) a product mix based on national market share and 2) restricting use to the product with lowest waste. Based on the literature, waste for each vial product was 23 percent. Among individual pens, waste was highest for Humatrope 24 mg (19.5 percent pediatric, 14.3 percent adult) and lowest for Norditropin Nordi-Flex 5 mg (1.1 percent pediatric, 1 percent adult). Restricting use to the brand with least waste (Norditropin), compared to national product share mix, resulted in a 10.2 percent reduction in annual pediatric patient cost from $19,026 to $17,089 and an 8 percent reduction in annual adult patient cost from $24,099 to $22,161. We concluded that pen delivery systems result in less waste than vial and syringe. Considering all approved delivery systems, Norditropin resulted in the least product waste and lower annual patient cost for both pediatric and adult populations.

  11. Chromosomal and carcinogenic effects of sequential HZE and low-LET irradiations

    NASA Astrophysics Data System (ADS)

    Simonson, Dustin Mark

    All persons are exposed to a natural background of ionizing radiations with different spatial patterns of energy deposition resulting in differential biologic response. Astronauts, aircrew and radioactive contamination clean-up personnel are exposed to particularly complex radiation spectra. The current method for calculating radiation-induced exposure limits in mixed radiation environments is based on the linear summation of non-threshold risks, a methodology grounded in the premise that each component of the radiation field acts independently of the presence of other components. The assumption of effect independence of in-vitro exposed samples was tested by evaluating the frequency of chromosome aberrations induced by sequential irradiation of immortalized human mammary epithelial cells with 1 GeV/nucleon 56Fe ions and 137Cs gamma-rays. Experimental response was found to be significantly less than calculated on the basis of effect independence, but only when 56Fe ions preceded the photon exposure. That there was order dependence is interpreted as evidence that response may not simply be a result of interactions between similar sublesions but rather may involve qualitatively different time-ordered parameters. The presence of this sub-additive response is phenomenologically similar to adaptive response, which had not been previously reported as a consequence to high-energy heavy ion irradiation. Calculations based on effect independence predict a significantly greater average number and lifetime cumulative incidence of breast cancers in female Sprague-Dawley rats irradiated with both 56Fe ions and 250 MeV protons than was experimentally observed. This finding supports the hypothesis that the presence of non-additive response is not exclusively an in vitro phenomenon. Results from an evaluation of mammary epithelial cell response induced in a rat cancer model are marginally consistent with the use of in vivo induced chromosome aberrations as a biomarker of breast

  12. Radiation protection issues in dynamic contrast-enhanced (perfusion) computed tomography.

    PubMed

    Brix, Gunnar; Lechel, Ursula; Nekolla, Elke; Griebel, Jürgen; Becker, Christoph

    2015-12-01

    Dynamic contrast-enhanced (DCE) CT studies are increasingly used in both medical care and clinical trials to improve diagnosis and therapy management of the most common life-threatening diseases: stroke, coronary artery disease and cancer. It is thus the aim of this review to briefly summarize the current knowledge on deterministic and stochastic radiation effects relevant for patient protection, to present the essential concepts for determining radiation doses and risks associated with DCE-CT studies as well as representative results, and to discuss relevant aspects to be considered in the process of justification and optimization of these studies. For three default DCE-CT protocols implemented at a latest-generation CT system for cerebral, myocardial and cancer perfusion imaging, absorbed doses were measured by thermoluminescent dosimeters at an anthropomorphic body phantom and compared with thresholds for harmful (deterministic) tissue reactions. To characterize stochastic radiation risks of patients from these studies, life-time attributable cancer risks (LAR) were estimated using sex-, age-, and organ-specific risk models based on the hypothesis of a linear non-threshold dose-response relationship. For the brain, heart and pelvic cancer studies considered, local absorbed doses in the imaging field were about 100-190 mGy (total CTDI(vol), 200 mGy), 15-30 mGy (16 mGy) and 80-270 mGy (140 mGy), respectively. According to a recent publication of the International Commission on Radiological Protection (ICRP Publication 118, 2012), harmful tissue reactions of the cerebro- and cardiovascular systems as well as of the lenses of the eye become increasingly important at radiation doses of more than 0.5 Gy. The LARs estimated for the investigated cerebral and myocardial DCE-CT scenarios are less than 0.07% for males and 0.1% for females at an age of exposure of 40 years. For the considered tumor location and protocol, the corresponding LARs are more than 6 times as high

  13. Precautionary principles: a jurisdiction-free framework for decision-making under risk.

    PubMed

    Ricci, Paolo F; Cox, Louis A; MacDonald, Thomas R

    2004-12-01

    relevance of new information, relative to the initial (and smaller) set of data on which the decision was based. We exemplify this seemingly simple situation using risk management of BSE. As an integral aspect of causal analysis under risk, the methods developed in this paper permit the addition of non-linear, hormetic dose-response models to the current set of regulatory defaults such as the linear, non-threshold models. This increase in the number of defaults is an important improvement because most of the variants of the precautionary principle require cost-benefit balancing. Specifically, increasing the set of causal defaults accounts for beneficial effects at very low doses. We also show and conclude that quantitative risk assessment dominates qualitative risk assessment, supporting the extension of the set of default causal models.

  14. Cancer and the environment: Ten topics in environmental cancer epidemiology in Canada.

    PubMed

    Huchcroft, Shirley A; Mao, Yang; Semenciw, Robert

    2010-01-01

    This Chronic Diseases in Canada supplement is a compilation of literature reviews by scientific experts. It was initiated as follow-up to the Green Plan, the federal government's environmental agenda in the 1990s. In recognizing that Canadians are concerned about the environment and its relationship to their health, this document attempts to address some of these concerns in relation to cancer by reviewing and summarizing the epidemiological literature for ten environmental exposures, and highlighting future research needs. The topics include three types of radiation exposure (ultraviolet, radon and electromagnetic (powerfrequency electromagnetic fields)), three classes of chemical exposure (organochlorines, disinfection by-products, and pesticides), two types of air pollution (environmental tobacco smoke and outdoor air pollution), and two industrial sources (pulp and paper milling, and metal mining and processing). This publication is intended to provide a base of information for researchers interested in environmental cancer epidemiology and to assist with the formulation of research priorities. The ten topics reviewed here were selected because concern about them has been expressed or because they involve known animal carcinogens. Complete elimination of exposures to carcinogens in the environment, synthetic or natural, is not technically feasible if cancer can potentially occur at any level of exposure (i.e., the linear non-threshold theory). Consequently, it is important to have an operational concept of safety which is more practical than that of zero risk. Such an approach uses the concept of acceptable or essentially negligible risk to determine the exposure levels at which carcinogens are regulated. Acceptable risk has been defined as one that is "so small, whose consequences are so slight, or whose associated benefits (perceived or real) are so great that persons or groups in society are willing to take or be subjected to that risk". The level of risk

  15. [Risk of postirradiation induction of cancer of the modern methods of radiotherapy (3D CRT and IMRT) head and neck cancer].

    PubMed

    Milecki, Piotr; Szyfter, Krzysztof; Skowronek, Janusz

    2004-01-01

    Ionizing radiation is a known "universal carcinogen" for a wide variety of tumors in man. Human populations are exposed to radiation coming from natural and industrial environment, and from medical sources. However, these are radiotherapy patients who receive the highest doses. Radiation both mutates and sterilizes cells (lethal effect). The risk of cancer induction from cells that have received very high doses of radiation (therapeutic dose about 2 Gy) is lower then from the cells with low doses, since the majority of them will have been sterilized. The epidemiological studies based on the population of atomic bomb survivors have indicated that the most acceptable model of carcinogenesis is the linear non-threshold model. The evaluation of clinical risk related to a wide range of radiation doses, which range from 0.01 Gy to 2 Gy, is connected with many methodological problems such as: differences in treatment factors (dose range, irradiated volume, anatomical site), unknown epidemiological data (smoking abuse, comorbidity), shortening of the follow-up (short lifespan, migration), evaluation of small groups of patients. The most important difficulty is lack of the sufficient knowledge of genetic background which is probably most significant in carcinogenesis process. The introduction into clinical practice of a new sophisticated method of irradiation such as the three-dimensional conformal radiotherapy (3D CRT) or intensity modulated radiotherapy (IMRT) leads to the increase of low irradiation dose for very large volume of normal tissue. Thus, the evaluation of these new methods in the context of carcinogenesis is a very important objective in the future. Today, we can only introduce the most important questions concerned with the risk of carcinogenesis induction which await answers: what is the risk of induction of cancer due to the implementation of these new methods of treatment, and how important is this risk for clinical practice, especially in the case of

  16. Method for Implementing Subsurface Solid Derived Concentration Guideline Levels (DCGL) - 12331

    SciTech Connect

    Lively, J.W.

    2012-07-01

    The U.S. Nuclear Regulatory Commission (NRC) and other federal agencies currently approve the Multi-Agency Radiation Site Survey and Investigation Manual (MARSSIM) as guidance for licensees who are conducting final radiological status surveys in support of decommissioning. MARSSIM provides a method to demonstrate compliance with the applicable regulation by comparing residual radioactivity in surface soils with derived concentration guideline levels (DCGLs), but specifically discounts its applicability to subsurface soils. Many sites and facilities undergoing decommissioning contain subsurface soils that are potentially impacted by radiological constituents. In the absence of specific guidance designed to address the derivation of subsurface soil DCGLs and compliance demonstration, decommissioning facilities have attempted to apply DCGLs and final status survey techniques designed specifically for surface soils to subsurface soils. The decision to apply surface soil limits and surface soil compliance metrics to subsurface soils typically results in significant over-excavation with associated cost escalation. MACTEC, Inc. has developed the overarching concepts and principles found in recent NRC decommissioning guidance in NUREG 1757 to establish a functional method to derive dose-based subsurface soil DCGLs. The subsurface soil method developed by MACTEC also establishes a rigorous set of criterion-based data evaluation metrics (with analogs to the MARSSIM methodology) that can be used to demonstrate compliance with the developed subsurface soil DCGLs. The method establishes a continuum of volume factors that relate the size and depth of a volume of subsurface soil having elevated concentrations of residual radioactivity with its ability to produce dose. The method integrates the subsurface soil sampling regime with the derivation of the subsurface soil DCGL such that a self-regulating optimization is naturally sought by both the responsible party and regulator

  17. Historical Doses from Tritiated Water and Tritiated Hydrogen Gas Released to the Atmosphere from Lawrence Livermore National Laboratory (LLNL). Part 3. Routine Releases, 1973 - 2005

    SciTech Connect

    Peterson, S

    2007-08-15

    Annual mean concentrations of tritium in air moisture, calculated from data obtained from an air tritium sampler near the LLNL Discovery Center, were compared with annual mean air moisture concentrations predicted from atmospheric releases of tritium for the years 1973 through 2005. The 95% confidence intervals on the predictions and observations usually overlapped. When the distributions of predictions and observations were different, predictions were higher. Using both the observed and predicted air concentrations as input to the tritium dose model, DCART, annual doses to a hypothetical adult, child (age 10) and infant (age 6 months to 1 year) assumed to be living at LLNL's Discovery Center were calculated. Although the doses based on predicted air concentrations tended to be higher, they were nevertheless indistinguishable from doses based on observed air concentrations when uncertainties were taken into account. Annual doses, calculated by DCART and based on observed and predicted air concentrations, were compared with historical tritium doses reported annually by LLNL. Although the historical doses were calculated using various assumptions over the years, their agreement with the DCART predictions is remarkable. The Discovery Center was not the location of the site-wide maximally exposed individual (SWMEI) from 1974 through 1978. However, doses at the location of the SW-MEI for those years were indistinguishable from those at the Discovery Center when uncertainties were taken into account. The upper confidence limits for all doses were always well below the current regulatory limit for dose to a member of the public (100 {micro}Sv or 10 mrem per year) from atmospheric releases (40 CFR Part 61, Subpart H). Based on observed air concentrations, the 97.5% confidence limit on the cumulative dose to the hypothetical person born in 1973 and living through 2005 at the Discovery Center was 150 {micro}Sv (15 mrem), while that of the hypothetical adult who spent his

  18. Assessment of normal tissue complications following prostate cancer irradiation: Comparison of radiation treatment modalities using NTCP models

    SciTech Connect

    Takam, Rungdham; Bezak, Eva; Yeoh, Eric E.; Marcu, Loredana

    2010-09-15

    Purpose: Normal tissue complication probability (NTCP) of the rectum, bladder, urethra, and femoral heads following several techniques for radiation treatment of prostate cancer were evaluated applying the relative seriality and Lyman models. Methods: Model parameters from literature were used in this evaluation. The treatment techniques included external (standard fractionated, hypofractionated, and dose-escalated) three-dimensional conformal radiotherapy (3D-CRT), low-dose-rate (LDR) brachytherapy (I-125 seeds), and high-dose-rate (HDR) brachytherapy (Ir-192 source). Dose-volume histograms (DVHs) of the rectum, bladder, and urethra retrieved from corresponding treatment planning systems were converted to biological effective dose-based and equivalent dose-based DVHs, respectively, in order to account for differences in radiation treatment modality and fractionation schedule. Results: Results indicated that with hypofractionated 3D-CRT (20 fractions of 2.75 Gy/fraction delivered five times/week to total dose of 55 Gy), NTCP of the rectum, bladder, and urethra were less than those for standard fractionated 3D-CRT using a four-field technique (32 fractions of 2 Gy/fraction delivered five times/week to total dose of 64 Gy) and dose-escalated 3D-CRT. Rectal and bladder NTCPs (5.2% and 6.6%, respectively) following the dose-escalated four-field 3D-CRT (2 Gy/fraction to total dose of 74 Gy) were the highest among analyzed treatment techniques. The average NTCP for the rectum and urethra were 0.6% and 24.7% for LDR-BT and 0.5% and 11.2% for HDR-BT. Conclusions: Although brachytherapy techniques resulted in delivering larger equivalent doses to normal tissues, the corresponding NTCPs were lower than those of external beam techniques other than the urethra because of much smaller volumes irradiated to higher doses. Among analyzed normal tissues, the femoral heads were found to have the lowest probability of complications as most of their volume was irradiated to lower

  19. Corrective Action Decision Document for Corrective Action Unit 536: Area 3 Release Site, Nevada Test Site, Nevada, Revision 0 with Errata

    SciTech Connect

    Boehlecke, Robert

    2004-11-01

    corrective action investigation (CAI). Record of Technical Change No. 1 to the CAIP documents changes to the PALs agreed to by the Nevada Division of Environmental Protection (NDEP) and DOE, National Nuclear Security Administration Nevada Site Office (NNSA/NSO). This ROTC provides the justification for changing from background-based to dose-based radiological PALs. This ROTC was approved and the dose-based PAL comparison implemented on March 9, 2004.

  20. A Pilot Study of Retail ‘Vape Shops’ in the San Francisco Bay Area

    PubMed Central

    Burbank, Andrea D; Thrul, Johannes; Ling, Pamela M

    2016-01-01

    INTRODUCTION The use of electronic cigarettes or vape devices is increasing, and products are evolving rapidly. This study assessed retail vape shops in the San Francisco Bay Area to describe store characteristics, products offered, advertisements and health claims, as well as employees’ perceptions of their customers’ demographics, and practices to support smoking cessation. METHODS We conducted store audits of shops that exclusively sell vape devices with physical addresses in San Francisco and Alameda counties (n=23, response rate 72%) and interviewed vape shop owners/employees. RESULTS While all stores carried second and third generation vape devices, 83% of stores did not carry first generation devices. Employees estimated the majority of their customers bought devices for smoking cessation or to replace tobacco, and a small minority purchased for first-time recreational use. Employees most frequently recommended dosing nicotine based on usual cigarette consumption, adjusting doses based on “throat hit” or cravings, use of a second or third generation e-cigarette, and encouraged customers to experiment and customize to “whatever works for you” as smoking cessation advice. CONCLUSIONS Vape shops report a significant number of their customers are interested in smoking cessation, and employees are giving smoking cessation advice. A subpopulation of customers includes some nicotine novices. Studies of vape shops should include both observations and interviews with employees in order to detect important informal practices that may differ from posted signs or printed advertising. These practices include cessation counseling, product claims, and custom discount prices or bargaining.

  1. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, Kevin M.; Doyle, Barney L.

    1996-01-01

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue.

  2. Dose-related effect of fly ash on edaphic properties in laterite cropland soil.

    PubMed

    Roy, Gourab; Joy, Vadakepuram Chacko

    2011-05-01

    Short-term laboratory and field studies showed dose-based effect of coal fly ash on chemical and microbial properties of laterite cropland soil. Sandy loam soil mixed with farmyard manure (10% w/w) and amended with fly ash at 5%, 10%, 20%, 40% w/w (50-400 t ha(-1)) was incubated in the laboratory and added to field plots. The pH, EC, PO(4), Ca and Na of soil increased with dose and time, but OC, NO(3) and K decreased. There was temporary inhibition of bacteria, fungi and actinomycetes populations at 5% and 10% doses, but 20% and 40% were harmful. Activities of major soil enzymes declined at higher doses. Amylase, cellulase and invertase recovered in 5% and 10%, these doses did not affect dehydrogenase but benefited phosphatase and arylsulphatase activities. The above assessments showed that up to 100 t ha(-1) fly ash is apparently safe to microbial characteristics of tropical red laterite soil.

  3. Radioactive waste management complex low-level waste radiological composite analysis

    SciTech Connect

    McCarthy, J.M.; Becker, B.H.; Magnuson, S.O.; Keck, K.N.; Honeycutt, T.K.

    1998-05-01

    The composite analysis estimates the projected cumulative impacts to future members of the public from the disposal of low-level radioactive waste (LLW) at the Idaho National Engineering and Environmental Laboratory (INEEL) Radioactive Waste Management Complex (RWMC) and all other sources of radioactive contamination at the INEEL that could interact with the LLW disposal facility to affect the radiological dose. Based upon the composite analysis evaluation, waste buried in the Subsurface Disposal Area (SDA) at the RWMC is the only source at the INEEL that will significantly interact with the LLW facility. The source term used in the composite analysis consists of all historical SDA subsurface disposals of radionuclides as well as the authorized LLW subsurface disposal inventory and projected LLW subsurface disposal inventory. Exposure scenarios evaluated in the composite analysis include all the all-pathways and groundwater protection scenarios. The projected dose of 58 mrem/yr exceeds the composite analysis guidance dose constraint of 30 mrem/yr; therefore, an options analysis was conducted to determine the feasibility of reducing the projected annual dose. Three options for creating such a reduction were considered: (1) lowering infiltration of precipitation through the waste by providing a better cover, (2) maintaining control over the RWMC and portions of the INEEL indefinitely, and (3) extending the period of institutional control beyond the 100 years assumed in the composite analysis. Of the three options investigated, maintaining control over the RWMC and a small part of the present INEEL appears to be feasible and cost effective.

  4. Genetic damage induced by a food coloring dye (sunset yellow) on meristematic cells of Brassica campestris L.

    PubMed

    Dwivedi, Kshama; Kumar, Girjesh

    2015-01-01

    We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny.

  5. DEPDOSE: An interactive, microcomputer based program to calculate doses from exposure to radionuclides deposited on the ground. Volume 1, User`s manual

    SciTech Connect

    Beres, D.A.; Hull, A.P.

    1991-12-01

    DEPDOSE is an interactive, menu driven, microcomputer based program designed to rapidly calculate committed dose from radionuclides deposited on the ground. The program is designed to require little or no computer expertise on the part of the user. The program consisting of a dose calculation section and a library maintenance section. These selections are available to the user from the main menu. The dose calculation section provides the user with the ability to calculate committed doses, determine the decay time needed to reach a particular dose, cross compare deposition data from separate locations, and approximate a committed dose based on a measured exposure rate. The library maintenance section allows the user to review and update dose modifier data as well as to build and maintain libraries of radionuclide data, dose conversion factors, and default deposition data. The program is structured to provide the user easy access for reviewing data prior to running the calculation. Deposition data can either be entered by the user or imported from other databases. Results can either be displayed on the screen or sent to the printer.

  6. Opioid antagonists and the sexual satiation phenomenon.

    PubMed

    Rodríguez-Manzo, G; Fernández-Guasti, A

    1995-11-01

    This study evaluates the effects of the IP injection of naloxone (0.3, 3 and 30 mg/kg) and naltrexone (0.2, 2 and 20 mg/kg) on the sexual satiation phenomenon. It was found that both antagonists exert a dose-based biphasic effect on the proportion of sexually exhausted rats displaying copulation. The intermediate doses of both opioid antagonists were more effective than the low and high doses in increasing the percentage of animals engaged in copulation. The analysis of the specific sexual behaviour parameters revealed that naloxone produces a slight inhibitory effect at the lowest dose, evidenced as an increase in the intromission number. The higher doses of this compound facilitated copulation reflected as a shortening of the ejaculation latency and the interintromission interval (III) and an increase in the copulatory rate. Naltrexone treatment had only facilitatory effects at the lower doses by reducing the III. The higher doses of naloxone (3 and 30 mg/kg) and the intermediate dose of naltrexone (2 mg/kg) decreased the spontaneous ambulatory behaviour of sexually satiated rats without impairing sexual behaviour execution. Data suggest a participation of the endogenous opioid systems in the sexual inhibition resulting from sexual exhaustion.

  7. Dosimetry and Risk Assessment: Fundamental Concepts

    SciTech Connect

    Fisher, Darrell R.

    2005-12-29

    Radiation dosimetry is important for characterizing radiation exposures and for risk assessment. In a medical setting, dosimetry is important for evaluating the safety of administered radiopharmaceuticals and for planning the safe administration of therapeutic radionuclides. Environmental dosimetry helps establish the safety of radionuclide releases from electric power production and other human activities. Internal and external dosimetry help us understand the consequences of radiation exposure. The absorbed dose is the fundamental quantity in radiation dosimetry from which all other operational values in radiation protection are obtained. Equivalent dose to tissue and effective dose to the whole body are derivatives of absorbed dose and constructs of risk. Mathematical systems supported by computer software facilitate dose calculations and make it possible to estimate internal dose based on bioassay or other biokinetic data. Risk coefficients for radiation-induced cancer rely primarily on data from animal studies and long-term observations of the Hiroshima and Nagasaki bomb survivors. Low-dose research shows that mechanisms of radiation interactions with tissue are dose-dependent, but the resulting biological effects are not necessarily linear with absorbed dose. Thus, the analysis of radiation effects and associated risks must account for the influences of microscopic energy distributions at the cellular level, dose-rate, cellular repair of sub-lethal radiation damage, and modifying factors such as bystander effects, adaptive response, and genomic instability.

  8. Pharmacokinetic and toxicology assessment of INTERCEPT (S-59 and UVA treated) platelets.

    PubMed

    Ciaravi, V; McCullough, T; Dayan, A D

    2001-10-01

    The pathogen inactivation process developed by Cerus and Baxter Healthcare Corporations uses the psoralen, S-59 (amotosalen) in an ex vivo photochemical treatment (PCT) process to inactivate viruses, bacteria, protozoans, and leukocytes in platelet concentrates and plasma. Studies were performed by intravenous infusion of S-59 PCT formulations +/- compound adsorption device (CAD) treatment and with non-UVA illuminated S-59, using doses that were multiples of potential clinical exposures. The studies comprised full pharmacokinetic, single- and repeated-dose (up to 13 weeks duration) toxicity, safety pharmacology (CNS, renal, and cardiovascular), reproductive toxicity, genotoxicity, carcinogenicity testing in the p53(+/-) mouse, vein irritation, and phototoxicity. No specific target organ toxicity (clinical or histopathological), reproductive toxicity, or carcinogenicity was observed. S-59 and/or PCT formulations demonstrated CNS, ECG, and phototoxicity only at supraclinical doses. Based on the extremely large safety margins (>30,000-fold expected clinical exposures), the CNS and ECG observations are not considered to have any toxicological relevance. Additionally, after a complete assessment, mutagenicity and phototoxicity results are not considered relevant for the proposed use of INTERCEPT platelets. Thus, the results of an extensive series of in vitro and in vivo studies have not demonstrated any toxicologically relevant effects of platelet concentrates prepared by the INTERCEPT system.

  9. Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy.

    PubMed

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-21

    We propose the use of the Auger electron and positron-emitting generator 134Ce/134La (half-lives 3.16 d and 6.45 min) for radionuclide therapy. It combines emission of high-energy beta particles with Auger electrons. The high-energy beta particles have similar energies as those emitted by 90Y. Many cancer patients receiving radionuclide therapy have both bulk tumours, which are best treated with high-energy beta particles, and single spread cells or micrometastasis, which are preferably treated with low-energy electrons such as Auger and conversion electrons. Furthermore, the positron-emitting 134La can be used to study kinetics and dosimetry using PET. Production and PET performance were investigated and theoretical dosimetry calculations were made. PET resolution, recovery and quantitative accuracy were slightly degraded for 134La compared to 18F. 134Ce/134La absorbed doses to single cells were higher than absorbed doses from 90Y and 111In. Absorbed doses to spheres representing bulk tumours were almost as high as for 90Y, and a factor 10 higher than for 111In. Whole-body absorbed doses, based on kinetics of the somatostatin analogue octreotide, were higher for 134Ce/134La than for 90Y because of the 134La annihilation photons. This initial study of the therapeutic possibilities of 134Ce/134La is encouraging and justifies further investigations.

  10. Amine modification of nonporous silica nanoparticles reduces inflammatory response following intratracheal instillation in murine lungs.

    PubMed

    Morris, Angie S; Adamcakova-Dodd, Andrea; Lehman, Sean E; Wongrakpanich, Amaraporn; Thorne, Peter S; Larsen, Sarah C; Salem, Aliasger K

    2016-01-22

    Amorphous silica nanoparticles (NPs) possess unique material properties that make them ideal for many different applications. However, the impact of these materials on human and environmental health needs to be established. We investigated nonporous silica NPs both bare and modified with amine functional groups (3-aminopropyltriethoxysilane (APTES)) in order to evaluate the effect of surface chemistry on biocompatibility. In vitro data showed there to be little to no cytotoxicity in a human lung cancer epithelial cell line (A549) for bare silica NPs and amine-functionalized NPs using doses based on both mass concentration (below 200μg/mL) and exposed total surface area (below 14m(2)/L). To assess lung inflammation, C57BL/6 mice were administered bare or amine-functionalized silica NPs via intra-tracheal instillation. Two doses (0.1 and 0.5mg NPs/mouse) were tested using the in vivo model. At the higher dose used, bare silica NPs elicited a significantly higher inflammatory response, as evidence by increased neutrophils and total protein in bronchoalveolar lavage (BAL) fluid compared to amine-functionalized NPs. From this study, we conclude that functionalization of nonporous silica NPs with APTES molecules reduces murine lung inflammation and improves the overall biocompatibility of the nanomaterial.

  11. Comparison of Capillary and Venous Drug Concentrations After Administration of a Single Dose of Risperidone, Paliperidone, Quetiapine, Olanzapine, or Aripiprazole

    PubMed Central

    De Meulder, Marc; Weiner, Sveta; Savitz, Adam

    2016-01-01

    Abstract Risperidone, paliperidone, quetiapine, olanzapine, and aripiprazole are antipsychotic drugs approved for treating various psychiatric disorders, including schizophrenia. The objective of this randomized, parallel‐group, open‐label study was to compare finger‐stick‐based capillary with corresponding venous whole‐blood and plasma concentrations for these drugs after administration of a single dose to healthy volunteers. All whole‐blood and plasma drug concentrations were measured with validated liquid chromatography–tandem mass spectrometry methods. Capillary and venous concentrations (both in plasma and whole blood) were in close agreement, although a time‐dependent difference was observed, most obviously for olanzapine and paliperidone, with slightly higher capillary versus venous drug concentrations during the first hours after administering a single dose. The observed difference between capillary and venous plasma drug concentrations is expected not to be relevant in clinical practice, considering the wide window of therapeutic concentrations and the wide range of drug concentrations in the patient population for a given dose. Based on these results, finger‐stick‐based capillary drug concentrations have been shown to approximate venous drug concentrations. PMID:27365164

  12. Near Infrared Optical Proteolytic Beacons for In Vivo Imaging of Matrix Metalloproteinase Activity

    PubMed Central

    McIntyre, J. Oliver; Scherer, Randy L.; Matrisian, Lynn M.

    2010-01-01

    The exuberant expression of proteinases by tumor cells has long been associated with the breakdown of the extracellular matrix, tumor invasion, and metastasis to distant organs. There is both epidemiological and experimental data that support a causative role for proteinases of the matrix metalloproteinase (MMP) family in tumor progression. Optical imaging techniques provide an extraordinary opportunity for non-invasive “molecular imaging” of tumor-associated proteolytic activity. The application of optical proteolytic beacons for the detection of specific proteinase activities associated with tumors has several potential purposes: 1) Detection of small, early-stage tumors with increased sensitivity due to the catalytic nature of proteolytic activity, 2) Diagnosis and Prognosis to distinguished tumors that require particularly aggressive therapy or those that will not benefit from therapy, 3) Identification of tumors appropriate for specific anti-proteinase therapeutics and optimization of drug and dose based on determination of target modulation, and 4) as an indicator of efficacy of proteolytically-activated pro-drugs. This chapter describes the synthesis, characterization, and application of reagents that use visible and near infrared fluorescence resonance energy transfer (FRET) fluorophore pairs to detect and measure MMP-referable proteolytic activity in tumors in mouse models of cancer. PMID:20135290

  13. Novel Parameter Predicting Grade 2 Rectal Bleeding After Iodine-125 Prostate Brachytherapy Combined With External Beam Radiation Therapy

    SciTech Connect

    Shiraishi, Yutaka; Hanada, Takashi; Ohashi, Toshio; Yorozu, Atsunori; Toya, Kazuhito; Saito, Shiro; Shigematsu, Naoyuki

    2013-09-01

    Purpose: To propose a novel parameter predicting rectal bleeding on the basis of generalized equivalent uniform doses (gEUD) after {sup 125}I prostate brachytherapy combined with external beam radiation therapy and to assess the predictive value of this parameter. Methods and Materials: To account for differences among radiation treatment modalities and fractionation schedules, rectal dose–volume histograms (DVHs) of 369 patients with localized prostate cancer undergoing combined therapy retrieved from corresponding treatment planning systems were converted to equivalent dose-based DVHs. The gEUDs for the rectum were calculated from these converted DVHs. The total gEUD (gEUD{sub sum}) was determined by a summation of the brachytherapy and external-beam radiation therapy components. Results: Thirty-eight patients (10.3%) developed grade 2+ rectal bleeding. The grade 2+ rectal bleeding rate increased as the gEUD{sub sum} increased: 2.0% (2 of 102 patients) for <70 Gy, 10.3% (15 of 145 patients) for 70-80 Gy, 15.8% (12 of 76 patients) for 80-90 Gy, and 19.6% (9 of 46 patients) for >90 Gy (P=.002). Multivariate analysis identified age (P=.024) and gEUD{sub sum} (P=.000) as risk factors for grade 2+ rectal bleeding. Conclusions: Our results demonstrate gEUD to be a potential predictive factor for grade 2+ late rectal bleeding after combined therapy for prostate cancer.

  14. Assessment of the estrogenic activity of phytoestrogens isolated from bourbon and beer.

    PubMed

    Rosenblum, E R; Stauber, R E; Van Thiel, D H; Campbell, I M; Gavaler, J S

    1993-12-01

    Phytoestrogenic substances have previously been isolated and identified in two alcoholic beverages: bourbon and beer. To delineate the relative potencies of the estrogenic substances of plant origin thus far identified in these commonly consumed alcoholic beverages, we evaluated the ability of biochanin A, beta-sitosterol, genistein, and daidzein to bind to cytosolic estrogen receptor binding sites. The in vitro studies demonstrated that each of the contained substances was capable of effectively competing for cytosolic estrogen receptor binding sites of rat liver and uterus. Further, the two phytoestrogenic constituents of bourbon, beta-sitosterol and biochanin A, were less potent than those present in beer. Given the high concentration of beta-sitosterol in bourbon, we chose to evaluate the estrogenicity of beta-sitosterol in vivo using ovariectomized rats. beta-sitosterol was administered either daily or intermittently at 3 doses, based on amounts previously determined to be present in bourbon. The in vivo studies demonstrated that beta-sitosterol is capable of producing a weak estrogenic effect only at the lowest dose (6.2 micrograms/dl) administered intermittently. These responses suggest that beta-sitosterol may be weakly estrogenic at low doses, but is unable to maintain such an effect at higher doses.

  15. An Extrusion Spheronization Approach to Enable a High Drug Load Formulation of a Poorly Soluble Drug with a Low Melting Surfactant.

    PubMed

    Tatavarti, Aditya; Kesisoglou, Filippos

    2015-11-01

    Vitamin E tocopherol polyethylene glycol succinate (TPGS) is a non-ionic surface active agent, known to enhance the bioavailability of lipophilic compounds via wettability, solubility, and in some cases permeability enhancement. MK-0536 is an anti-retroviral drug with poor wettability and solubility and a high dose. Based on pharmacokinetic studies in dogs and humans, use of vitamin E TPGS in oral solid formulations of MK-0536 provides desired PK characteristics. The use of vitamin E TPGS, however, in solid dosage forms is limited because of the processing challenges resulting from its waxy nature and low melting temperature (∼37°C). The current study, for the first time, demonstrates the use of an alternative low pressure extrusion and spheronization approach to enable high loadings of the poorly soluble, poorly compactable drug and relatively high levels of vitamin E TPGS. This approach not only aided in mitigating processing challenges arising from most high energy process steps such as milling, compression, and coating, but also enabled a higher drug load formulation that provided superior bioperformance relative to a conventional high shear wet granulated formulation. An encapsulated dosage form consisting of pellets prepared by extrusion spheronization with 75% (w/w) MK-0536 and 10% (w/w) vitamin E TPGS was developed.

  16. Influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets.

    PubMed

    Vranić, Edina; Uzunović, Alija

    2007-11-01

    Dose-related adverse effects of medications are a major problem in modern medical practice. The "correct" dose, based on drug company guidelines in package inserts, may not be correct for many patients. Tablet splitting or dividing has been an accepted practice for many years as a means of obtaining the prescribed dose of medication. As model tablets for this investigation, two batches of lisinopril- hydrochlorothiazide scored tablets labeled to contain 20/12.5 mg were used. The aim of this study was to establish possible influence of tablet splitting on content uniformity of lisinopril/hydrochlorthiazide tablets. Determination of the content uniformity of lisinopril and hydrochlorthiazide in our batches, was carried out by HPLC method. The results of content uniformity studies for halves of tablets containing combination of lisinopril-hydrochlorthiazide (supposed to contain 50% of stated 20/12.5 mg in the whole tablet) were: 49.60 +/-3.29% and 49.29+/-0.60 % (lisinopril); 50.33+/-3.50% and 50.69+/-1.95% (hydrochlorthiazide) for batch I and II, respectively. We can conclude that the results obtained in this study support an option of tablet splitting, which is very important for obtaining the required dosage when a dosage form of the required strength is unavailable, and for better individualization of the therapy.

  17. Evaluation of organ doses and effective dose according to the ICRP Publication 110 reference male/female phantom and the modified ImPACT CT patient dosimetry.

    PubMed

    Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Matsunaga, Yuta; Kawaguchi, Ai; Katada, Kazuhiro; Toyama, Hiroshi; Koshida, Kichiro; Suzuki, Shouichi

    2014-09-07

    We modified the Imaging Performance Assessment of CT scanners (ImPACT) to evaluate the organ doses and the effective dose based on the International Commission on Radiological Protection (ICRP) Publication 110 reference male/female phantom with the Aquilion ONE ViSION Edition scanner. To select the new CT scanner, the measurement results of the CTDI100,c and CTDI100,p for the 160 (head) and the 320 (body) mm polymethylmethacrylate phantoms, respectively, were entered on the Excel worksheet. To compute the organ doses and effective dose of the ICRP reference male/female phantom, the conversion factors obtained by comparison between the organ doses of different types of phantom were applied. The organ doses and the effective dose were almost identical for the ICRP reference male/female and modified ImPACT. The results of this study showed that, with the dose assessment of the ImPACT, the difference in sex influences only testes and ovaries. Because the MIRD-5 phantom represents a partially hermaphrodite adult, the phantom has the dimensions of the male reference man including testes, ovaries, and uterus but no female breasts, whereas the ICRP male/female phantom includes whole-body male and female anatomies based on high-resolution anatomical datasets. The conversion factors can be used to estimate the doses of a male and a female accurately, and efficient dose assessment can be performed with the modified ImPACT.

  18. Treatment of urban runoff at Lake Tahoe: low-intensity chemical dosing.

    PubMed

    Trejo-Gaytan, Julieta; Bachand, Philip; Darby, Jeannie

    2006-12-01

    A systematic investigation of the effect of coagulant type and dose and temperature, mixing, and water quality on subsequent charge neutralization and removal of phosphorus and fine particles from urban and/or stormwater runoff entering Lake Tahoe (Sierra Nevada mountains, western United States) was conducted. Dosing based on streaming current values resulted in turbidities of less than 10.9 +/- 0.35 NTU and filterable and total phosphorus concentrations of less than 9.83 +/- 0.54 and 25.6 +/- 5.71 microg/L, respectively. Inadequate slow mixing could be partially compensated for by increased settling time; however, such quiescent conditions are difficult to obtain in natural systems. For prehydrolyzed forms of aluminum, high intensity rapid mixing was counterproductive. Several classes of coagulants responded robustly to water quality and temperature changes. However, polyaluminum chlorides modified with silica or sulfate, with low to medium basicity, were consistently the best performers in these tests, in terms of simultaneously removing phosphorus and fine particles under a wide range of operating conditions with low doses.

  19. SU-E-T-335: Transit Dosimetry for Verification of Dose Delivery Using Electronic Portal Imaging Device (EPID)

    SciTech Connect

    Baek, T; Chung, E; Lee, S; Yoon, M

    2014-06-01

    Purpose: To evaluate the effectiveness of transit dose, measured with an electronic portal imaging device (EPID), in verifying actual dose delivery to patients. Methods: Plans of 5 patients with lung cancer, who received IMRT treatment, were examined using homogeneous solid water phantom and inhomogeneous anthropomorphic phantom. To simulate error in patient positioning, the anthropomorphic phantom was displaced from 5 mm to 10 mm in the inferior to superior (IS), superior to inferior (SI), left to right (LR), and right to left (RL) directions. The transit dose distribution was measured with EPID and was compared to the planed dose using gamma index. Results: Although the average passing rate based on gamma index (GI) with a 3% dose and a 3 mm distance-to-dose agreement tolerance limit was 94.34 % for the transit dose with homogeneous phantom, it was reduced to 84.63 % for the transit dose with inhomogeneous anthropomorphic phantom. The Result also shows that the setup error of 5mm (10mm) in IS, SI, LR and SI direction can Result in the decrease in values of GI passing rates by 1.3% (3.0%), 2.2% (4.3%), 5.9% (10.9%), and 8.9% (16.3%), respectively. Conclusion: Our feasibility study suggests that the transit dose-based quality assurance may provide information regarding accuracy of dose delivery as well as patient positioning.

  20. Penetration of biologically effective ultraviolet radiation in the eastern Pacific Ocean

    SciTech Connect

    Wones, A.G.; Gucinski, H. ); Behrenfeld, M. )

    1990-01-09

    There is evidence that marine plankton appear to be at their threshold level for damage or reduction in productivity at present levels of solar UV-B (290-320 nm). Increases of solar UV-B from projected stratospheric ozone depletion may there for lead to such effects, but depend on the distribution of radiant energy in the water column. Because of instrumental and environmental difficulties in taking underwater IV-B measurements at sea, relatively few studies of the penetration of UV-B in the sea have been done. Measurements taken in the eastern Pacific Ocean from 12[degrees] north to 58[degrees] south latitude show considerable variation in UV-B attenuation. The depth of 10% transmittance of DNA effective radiation (normalized to 300 nm) ranged from 9.2 m at 8[degrees] north to 33.1 m at 28[degrees] south latitude. Penetration depths of biologically significant daily UV-B doses (based on UV-B exposure studies), are given for present day (measured) irradiance and modeled irradiance expected with ozone depletion.

  1. Galactic and solar radiation exposure to aircrew during a solar cycle.

    PubMed

    Lewis, B J; Bennett, L G I; Green, A R; McCall, M J; Ellaschuk, B; Butler, A; Pierre, M

    2002-01-01

    An on-going investigation using a tissue-equivalent proportional counter (TEPC) has been carried out to measure the ambient dose equivalent rate of the cosmic radiation exposure of aircrew during a solar cycle. A semi-empirical model has been derived from these data to allow for the interpolation of the dose rate for any global position. The model has been extended to an altitude of up to 32 km with further measurements made on board aircraft and several balloon flights. The effects of changing solar modulation during the solar cycle are characterised by correlating the dose rate data to different solar potential models. Through integration of the dose-rate function over a great circle flight path or between given waypoints, a Predictive Code for Aircrew Radiation Exposure (PCAIRE) has been further developed for estimation of the route dose from galactic cosmic radiation exposure. This estimate is provided in units of ambient dose equivalent as well as effective dose, based on E/H x (10) scaling functions as determined from transport code calculations with LUIN and FLUKA. This experimentally based treatment has also been compared with the CARI-6 and EPCARD codes that are derived solely from theoretical transport calculations. Using TEPC measurements taken aboard the International Space Station, ground based neutron monitoring, GOES satellite data and transport code analysis, an empirical model has been further proposed for estimation of aircrew exposure during solar particle events. This model has been compared to results obtained during recent solar flare events.

  2. Polyethylene glycol-polyvinyl alcohol grafted copolymer: study of the bioavailability after oral administration to rats.

    PubMed

    Heuschmid, Franziska F; Schuster, Paul; Lauer, Birthe; Fabian, Eric; Leibold, Edgar; van Ravenzwaay, Bennard

    2013-07-01

    The absorption, urinary excretion, and the biliary excretion of a single oral dose of 10 or 1000 mg/kg bw of (14)C-polyethylene glycol-polyvinyl alcohol (PEG-PVA) grafted copolymer were studied in adult male and female rats. In a balance/excretion experiment, the total excretion of ingested radioactivity was determined over a period of 168 h and residual radioactivity was detected in selected tissues and the carcass. In a biliary excretion experiment, excretion of radioactivity via the bile duct was determined over a period of 48 h after administration of the substance to cannulated rats. Most, if not all, of the radioactivity (>100%) was excreted within 48 h via the feces regardless of sex or dose. Urinary excretion was very limited: 0.45-0.50% of dose at the low dose and 0.22-0.27% of dose at the high dose. At both dose levels, residual radioactivity in the carcass and all organs and tissues after 168 h was ≤ 0.02% of dose. Biliary excretion was 0.01-0.02% of dose. Based on these findings, the bioavailability of PEG-PVA grafted copolymer was determined to be <1% demonstrating that absorption was virtually negligible following a single oral administration to male and female rats.

  3. HEMODOSE: A Biodosimetry Tool Based on Multi-type Blood Cell Counts

    PubMed Central

    Hu, Shaowen; Blakely, William F.; Cucinotta, Francis A.

    2015-01-01

    Abstract Peripheral blood cell counts are important biomarkers of radiation exposure. In this work, a simplified compartmental modeling approach is applied to simulate the perturbation of the hematopoiesis system in humans after radiation exposure, and HemoDose software is reported to estimate individuals’ absorbed doses based on multi-type blood cell counts. Testing with patient data in some historical accidents indicates that either single or serial granulocyte, lymphocyte, leukocyte, and platelet counts after exposure can be robust indicators of the absorbed doses. In addition, such correlation exists not only in the early time window (1 or 2 d) but also in the late phase (up to 4 wk) after exposure, when the four types of cell counts are combined for analysis. These demonstrate the capability of HemoDose as a rapid point-of-care diagnostic or centralized high-throughput assay system for personnel exposed to unintended high doses of radiation, especially in large-scale nuclear/radiological disaster scenarios involving mass casualties. PMID:26011498

  4. Inactivation of Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes in ready-to-bake cookie dough by gamma and electron beam irradiation.

    PubMed

    Jeong, Seul-Gi; Kang, Dong-Hyun

    2017-06-01

    This study was conducted to investigate the efficacy of gamma and electron beam irradiation to inactivate foodborne pathogens in ready-to-bake cookie dough and to determine the effect on quality by measuring color and texture changes. Cookie dough inoculated with Escherichia coli O157:H7, Salmonella Typhimurium, or Listeria monocytogenes was subjected to gamma and electron beam irradiation, with doses ranging from 0 to 3 kGy. As the radiation dose increased, the inactivation effect increased among all tested pathogens. After 3.0 kGy of gamma and electron beam irradiation, numbers of inoculated pathogens were reduced to below the detection limit (1 log CFU/g). The D10-values of E. coli O157:H7, S. Typhimurium, and L. monocytogenes in cookie dough treated with gamma rays were 0.53, 0.51, and 0.71 kGy, respectively, which were similar to those treated by electron beam with the same dose. Based on the D10-value of pathogens in cookie dough, L. monocytogenes showed more resistance to both treatments than did E. coli O157:H7 and S. Typhimurium. Color values and textural characteristics of irradiated cookie dough were not significantly (P > 0.05) different from the control. These results suggest that irradiation can be applied to control pathogens in ready-to-bake cookie dough products without affecting quality.

  5. Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model.

    PubMed

    Swartling, Johannes; Höglund, Odd V; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

    2016-02-01

    Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30  J/cm2.

  6. 210Po, 210Pb, 40K and 137Cs in edible wild berries and mushrooms and ingestion doses to man from high consumption rates of these wild foods.

    PubMed

    Gwynn, Justin P; Nalbandyan, Anna; Rudolfsen, Geir

    2013-02-01

    This paper discusses activity concentrations of (210)Po, (210)Pb, (40)K and (137)Cs in edible wild berries and mushrooms collected from Øvre Dividalen national park, Northern Norway and derives committed effective ingestion doses to man based on high consumption rates of these wild foods. Edible wild berries and mushrooms accumulated similar levels of (210)Pb, but mushrooms accumulated higher levels of (210)Po and (40)K than berries. There appears to be a clear difference in the ability of Leccinum spp. of fungi to accumulate (210)Po and/or translocate (210)Po to mushrooms compared to Russula spp. of fungi. Activity concentrations of (137)Cs in edible wild berries and mushrooms from Øvre Dividalen national park reflected the lower levels of fallout of this radionuclide in Northern Norway compared to more central areas following the Chernobyl accident. For mushrooms, ingestion doses are dominated by (210)Po, while for berries, (40)K is typically the main contributor to dose. Based on high consumption rates, ingestion doses arising from the combination of (210)Po, (210)Pb and (40)K were up to 0.05 mSv/a for berries and 0.50 mSv/a for mushrooms. Consumption of such wild foods may result in a significant contribution to total annual doses when consumed in large quantities, particularly when selecting mushrooms species that accumulate high activity concentrations of (210)Po.

  7. Radiocesium concentrations in wild mushrooms collected in Kawauchi Village after the accident at the Fukushima Daiichi Nuclear Power Plant

    PubMed Central

    Nakashima, Kanami; Orita, Makiko; Fukuda, Naoko; Taira, Yasuyuki; Hayashida, Naomi; Matsuda, Naoki

    2015-01-01

    It is well known from the experience after the 1986 accident at the Chernobyl Nuclear Power Plant that radiocesium tends to concentrate in wild mushrooms. In this study, we collected wild mushrooms from the Kawauchi Village of Fukushima Prefecture, located within 30 km of the Fukushima Daiichi Nuclear Power Plant, and evaluated their radiocesium concentrations to estimate the risk of internal radiation exposure in local residents. We found that radioactive cesium exceeding 100 Bq/kg was detected in 125 of 154 mushrooms (81.2%). We calculated committed effective doses based on 6,278 g per year (age > 20 years, 17.2 g/day), the average intake of Japanese citizens, ranging from doses of 0.11–1.60 mSv, respectively. Although committed effective doses are limited even if residents eat contaminated foods several times, we believe that comprehensive risk-communication based on the results of the radiocesium measurements of food, water, and soil is necessary for the recovery of Fukushima after this nuclear disaster. PMID:26623189

  8. Radiation-associated lung cancer: a comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki.

    PubMed

    Land, C E; Shimosato, Y; Saccomanno, G; Tokuoka, S; Auerbach, O; Tateishi, R; Greenberg, S D; Nambu, S; Carter, D; Akiba, S

    1993-05-01

    A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

  9. Radiation-associated lung cancer: A comparison of the histology of lung cancers in uranium miners and survivors of the atomic bombings of Hiroshima and Nagasaki

    SciTech Connect

    Land, C.E.; Shimosato, Y.; Saccomanno, G.; Tokuoka, S.; Auerbach, O.; Tateishi, R.; Greenberg, S.D.; Nambu, S.; Carter, D.; Akiba, S. )

    1993-05-01

    A binational panel of Japanese and American pulmonary pathologists reviewed tissue slides of lung cancer cases diagnosed among Japanese A-bomb survivors and American uranium miners and classified the cases according to histological subtype. Blind reviews were completed on slides from 92 uranium miners and 108 A-bomb survivors, without knowledge of population, sex, age, smoking history, or level of radiation exposure. Consensus diagnoses were obtained with respect to principal subtype, including squamous-cell cancer, small-cell cancer, adenocarcinoma, and less frequent subtypes. The results were analyzed in terms of population, radiation dose, and smoking history. As expected, the proportion of squamous-cell cancer was positively related to smoking history in both populations. The relative frequencies of small-cell cancer and adenocarcinoma were very different in the two populations, but this difference was accounted for adequately by differences in radiation dose or, more specifically, dose-based relative risk estimates based on published data. Radiation-induced cancers appeared more likely to be of the small-cell subtype, and less likely to be adenocarcinomas, in both populations. The data appeared to require no additional explanation in terms of radiation quality (alpha particles vs gamma rays), uniform or local irradiation, inhaled vs external radiation source, or other population difference.

  10. Methylmercury Concentration in Fish and Risk-Benefit Assessment of Fish Intake among Pregnant versus Infertile Women in Taiwan.

    PubMed

    Hsi, Hsing-Cheng; Hsu, You-Wen; Chang, Tien-Chin; Chien, Ling-Chu

    2016-01-01

    This study examined methylmercury (MeHg) concentrations in fish, the daily MeHg exposure dose, and the risk-benefit of MeHg, ω-3 polyunsaturated fatty acid (ω-3 PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) related to fish intake among pregnant and infertile women in Taiwan. The measured MeHg concentrations in fish did not exceed the Codex guideline level of 1 mg/kg. Swordfish (0.28 ± 0.23 mg/kg) and tuna (0.14 ± 0.13 mg/kg) had the highest MeHg concentrations. The MeHg concentration in the hair of infertile women (1.82 ± 0.14 mg/kg) was significantly greater than that of pregnant women (1.24 ± 0.18 mg/kg). In addition, 80% of infertile women and 68% of pregnant women had MeHg concentrations in hair that exceeded the USEPA reference dose (1 mg/kg). The MeHg concentrations in hair were significantly and positively correlated with the estimated daily MeHg exposure dose. Based on the risk-benefit evaluation results, this paper recommends consumption of fish species with a low MeHg concentration and high concentrations of DHA + EPA and ω-3 PUFA (e.g., salmon, mackerel, and greater amberjack).

  11. Methylmercury Concentration in Fish and Risk-Benefit Assessment of Fish Intake among Pregnant versus Infertile Women in Taiwan

    PubMed Central

    Hsi, Hsing-Cheng; Hsu, You-Wen; Chang, Tien-Chin; Chien, Ling-Chu

    2016-01-01

    This study examined methylmercury (MeHg) concentrations in fish, the daily MeHg exposure dose, and the risk–benefit of MeHg, ω-3 polyunsaturated fatty acid (ω-3 PUFA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) related to fish intake among pregnant and infertile women in Taiwan. The measured MeHg concentrations in fish did not exceed the Codex guideline level of 1 mg/kg. Swordfish (0.28 ± 0.23 mg/kg) and tuna (0.14 ± 0.13 mg/kg) had the highest MeHg concentrations. The MeHg concentration in the hair of infertile women (1.82 ± 0.14 mg/kg) was significantly greater than that of pregnant women (1.24 ± 0.18 mg/kg). In addition, 80% of infertile women and 68% of pregnant women had MeHg concentrations in hair that exceeded the USEPA reference dose (1 mg/kg). The MeHg concentrations in hair were significantly and positively correlated with the estimated daily MeHg exposure dose. Based on the risk–benefit evaluation results, this paper recommends consumption of fish species with a low MeHg concentration and high concentrations of DHA + EPA and ω-3 PUFA (e.g., salmon, mackerel, and greater amberjack). PMID:27187161

  12. Incorporation of physiologically based pharmacokinetic modeling in the evaluation of solubility requirements for the salt selection process: a case study using phenytoin.

    PubMed

    Chiang, Po-Chang; Wong, Harvey

    2013-10-01

    In the pharmaceutical industry, salt is commonly used to improve the oral bioavailability of poorly soluble compounds. Currently, there is a limited understanding on the solubility requirement for salts that will translate to improvement in oral exposure. Despite the obvious need, there is very little research reported in this area mainly due to the complexity of such a system. To our knowledge, no report has been published to guide this important process and salt solubility requirement still remains unanswered. Physiologically based pharmacokinetic (PBPK) modeling offers a means to dynamically integrate the complex interplay of the processes determining oral absorption. A sensitivity analysis was performed using a PBPK model describing phenytoin to determine a solubility requirement for phenytoin salts needed to achieve optimal oral bioavailability for a given dose. Based on the analysis, it is predicted that phenytoin salts with solubility greater than 0.3 mg/mL would show no further increases in oral bioavailability. A salt screen was performed using a variety of phenytoin salts. The piperazine and sodium salts showed the lowest and highest aqueous solubility and were tested in vivo. Consistent with our analysis, we observed no significant differences in oral bioavailability for these two salts despite an approximate 60 fold difference in solubility. Our study illustrates that higher solubility salts sometimes provide no additional improvements in oral bioavailability and PBPK modeling can be utilized as an important tool to provide guidance to the salt selection and define a salt solubility requirement.

  13. Patient-specific organ dose estimation during transcatheter arterial embolization using Monte Carlo method and adaptive organ segmentation

    NASA Astrophysics Data System (ADS)

    Tsai, Hui-Yu; Lin, Yung-Chieh; Tyan, Yeu-Sheng

    2014-11-01

    The purpose of this study was to evaluate organ doses for individual patients undergoing interventional transcatheter arterial embolization (TAE) for hepatocellular carcinoma (HCC) using measurement-based Monte Carlo simulation and adaptive organ segmentation. Five patients were enrolled in this study after institutional ethical approval and informed consent. Gafchromic XR-RV3 films were used to measure entrance surface dose to reconstruct the nonuniform fluence distribution field as the input data in the Monte Carlo simulation. XR-RV3 films were used to measure entrance surface doses due to their lower energy dependence compared with that of XR-RV2 films. To calculate organ doses, each patient's three-dimensional dose distribution was incorporated into CT DICOM images with image segmentation using thresholding and k-means clustering. Organ doses for all patients were estimated. Our dose evaluation system not only evaluated entrance surface doses based on measurements, but also evaluated the 3D dose distribution within patients using simulations. When film measurements were unavailable, the peak skin dose (between 0.68 and 0.82 of a fraction of the cumulative dose) can be calculated from the cumulative dose obtained from TAE dose reports. Successful implementation of this dose evaluation system will aid radiologists and technologists in determining the actual dose distributions within patients undergoing TAE.

  14. The use of estimated glomerular filtration rate for dose adjustment of medications in the elderly.

    PubMed

    Elinder, Carl-Gustaf; Bárány, Peter; Heimbürger, Olof

    2014-07-01

    Adverse drug effects as a consequence of inappropriate dosage are a common cause of hospitalization among the elderly. Older individuals are at a particular risk of overdosing because their kidney function decreases with advancing age and the elderly are often prescribed several pharmaceutical drugs. In addition, serum creatinine levels decrease owing to a reduction in muscle mass with age. Therefore, drug dosing based on the serum creatinine level only, instead of using assessment of the renal function, may result in overdosing of frail elderly patients. Renal function, i.e., the glomerular filtration rate can, with simple formulas, be estimated from analysis of creatinine and/or plasma cystatin C (eGFR). Such estimations performed with modern and validated formulas, as a rule present renal function normalized to the body surface area (mL/min/1.73 m(2)). A good estimation of how much the normal dosing interval should be prolonged, or the dose reduced, to obtain a desired plasma concentration of drugs that are mainly eliminated by glomerular filtration can be obtained by calculating the ratio between the patient's eGFR and the normal renal function (about 90-125 mL/min/1.73 m(2)). Increased knowledge and use of eGFR by prescribing physicians will reduce the risk of overdosing drugs in the elderly.

  15. Reconstruction and forecast of doses due to ingestion of 137Cs and 90Sr after the Chernobyl accident.

    PubMed

    Kravets, A P; Pavlenko, Yu A

    2008-04-01

    The assessment doses due to ingestion of (137)Cs and (90)Sr for the population suffering from the Chernobyl accident was performed on the basis of the new mechanistic ecological model for assessment of radiological consequences of agricultural lands contamination (EMARC). The EMARC model allows estimation of internal doses based on ecological factors influencing the contamination of foodstuff, for the post-accidental years in the countries of the former Soviet Union. The EMARC model allows estimation of all quantities required in radiation hygiene practice. For example, the proposed analytical method may be used for both retrospective dose reconstruction and prospective estimates of annual dose and integrated "life-time" dose, for different age intervals. According to the EMARC model, estimated reference "life-time" doses for adults are between 7 and 269 microSv kBq(-1) m(2) for (137)Cs, and between 25 and 235 microSv kBq(-1) m(2) for (90)Sr. Maximal doses were estimated for persons who were 3, 9 and 11 years old, at the time of the accident and these doses exceed those for adults by a factors of 1, 5 for (90)Sr, and 1.4 for (137)Cs.

  16. Estimated Fluoride Doses from Toothpastes Should be Based on Total Soluble Fluoride

    PubMed Central

    Oliveira, Maria José L.; Martins, Carolina C.; Paiva, Saul M.; Tenuta, Livia M. A.; Cury, Jaime A.

    2013-01-01

    The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride—TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children’s toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children’s toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children’s toothpaste is used. PMID:24189183

  17. Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry

    PubMed Central

    Macaeva, Ellina; Saeys, Yvan; Tabury, Kevin; Janssen, Ann; Michaux, Arlette; Benotmane, Mohammed A.; De Vos, Winnok H.; Baatout, Sarah; Quintens, Roel

    2016-01-01

    Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice. PMID:26763932

  18. DEPDOSE: An interactive, microcomputer based program to calculate doses from exposure to radionuclides deposited on the ground

    SciTech Connect

    Beres, D.A.; Hull, A.P.

    1991-12-01

    DEPDOSE is an interactive, menu driven, microcomputer based program designed to rapidly calculate committed dose from radionuclides deposited on the ground. The program is designed to require little or no computer expertise on the part of the user. The program consisting of a dose calculation section and a library maintenance section. These selections are available to the user from the main menu. The dose calculation section provides the user with the ability to calculate committed doses, determine the decay time needed to reach a particular dose, cross compare deposition data from separate locations, and approximate a committed dose based on a measured exposure rate. The library maintenance section allows the user to review and update dose modifier data as well as to build and maintain libraries of radionuclide data, dose conversion factors, and default deposition data. The program is structured to provide the user easy access for reviewing data prior to running the calculation. Deposition data can either be entered by the user or imported from other databases. Results can either be displayed on the screen or sent to the printer.

  19. Captan fungicide exposures of strawberry harvesters using THPI as a urinary biomarker.

    PubMed

    Krieger, R I; Dinoff, T M

    2000-04-01

    Clothing affords harvesters considerable protection against the elements and can retain substantial amounts of pesticide residue from treated crops. Normal work clothing of female harvesters was supplemented with rubber latex gloves and facial scarves to determine whether those measures reduced exposure. Captan fungicide exposures in female strawberry harvesters were assessed by determining urine clearance rates of tetrahydrophalimide (THPI). Clean rubber gloves were supplied to the 41 harvesters for the 3 days of the study period in October 1995. The workers were divided into two groups consisting of either bare-handed or gloved workers, and 24-h urine specimens were collected each day. Female harvesters who worked bare-handed cleared 5.3 microg captan equivalents as THPI with a range of 0.4 to 13.8 microg/person/day. Harvesters who worked wearing rubber latex gloves cleared only 2.0 microg captan equivalents with a range of 0.9 to 4.3 microg/person/day. In this case clean rubber latex gloves reduced absorbed dose by 38%, compared to the dose absorbed by bare-handed workers. These results additionally indicate that when a pesticide is avidly retained by rubber latex gloves and not readily absorbed dermally as captan, estimates of absorbed dose based on passive dosimetry data may be less reliable than exposure estimates derived from urine biomonitoring.

  20. Dose estimation based on a behavior survey of residents around the JCO facility.

    PubMed

    Fujimoto, K; Yonehara, H; Yamaguchi, Y; Endo, A

    2001-09-01

    The NIRS staff interviewed the residents in the evacuated zone around the JCO facility in Tokai-mura on 19 and 20 November, 1999, to obtain the following parameters every 30 minutes starting from 10:35 A.M. on 30 September to 6:15 A.M. on 1 October: the distance from the precipitation tank, the type of the house, positions in the house, wall materials and their thickness in order to estimate individual doses due to the accident. The ambient dose equivalents were obtained based on monitoring data during the accident. In addition, computer calculations were conducted to evaluate the conversion factor from ambient dose equivalent to effective dose equivalent as well as the shielding effect of the house or factory to estimate the effective dose equivalent to the residents. The estimated individual doses based on the behavior survey were in the range from zero to 21 mSv. The individual doses were reported to the residents during the second visit to each house and factory at the end of January, 2000.

  1. Jingzhaotoxin-II, a novel tarantula toxin preferentially targets rat cardiac sodium channel.

    PubMed

    Wang, Meichi; Liu, Qingping; Luo, Haiyong; Li, Jiang; Tang, Jianzhou; Xiao, Yucheng; Liang, Songping

    2008-12-15

    Naturally occurring toxins are invaluable tools for exploration of the structure and function relationships of voltage-gated sodium channels (VGSCs). In this study, we isolated and characterized a novel VGSC toxin named jingzhaotoxin-II (JZTX-II) from the tarantula Chilobrachys jingzhao venom. JZTX-II consists of 32 amino acid residues including two acidic and two basic residues. Cloned and sequenced using 3'- and 5'-rapid amplification of the cDNA ends, the full-length cDNA for JZTX-II was found to encode a 63-residue precursor which contained a signal peptide of 21 residues, a propeptide of 10 residues and a mature peptide of 32 residues. Under whole-cell voltage-clamp conditions, JZTX-II significantly slowed rapid inactivation of TTX-resistant (TTX-R) VGSC on cardiac myocytes with the IC50=0.26+/-0.09 microM. In addition, JZTX-II had no effect on TTX-R VGSCs on rat dorsal root ganglion neurons but exerted a concentration-dependent reduction in tetrodotoxin-sensitive (TTX-S) VGSCs accompanied by a slowing of sodium current inactivation similar to delta-ACTXs. It is notable that TTX-S VGSCs on cultured rat hippocampal neurons were resistant to JZTX-II at high dose. Based on its high selectivity for mammalian VGSC subtypes, JZTX-II might be an important ligand for discrimination of VGSC subtypes and for exploration of the distribution and modulation mechanisms of VGSCs.

  2. A Comparison of Dose Metrics to Predict Local Tumor Control for Photofrin-mediated Photodynamic Therapy.

    PubMed

    Qiu, Haixia; Kim, Michele M; Penjweini, Rozhin; Finlay, Jarod C; Busch, Theresa M; Wang, Tianhao; Guo, Wensheng; Cengel, Keith A; Simone, Charles B; Glatstein, Eli; Zhu, Timothy C

    2017-01-13

    This preclinical study examines light fluence, photodynamic therapy (PDT) dose and "apparent reacted singlet oxygen," [(1) O2 ]rx , to predict local control rate (LCR) for Photofrin-mediated PDT of radiation-induced fibrosarcoma (RIF) tumors. Mice bearing RIF tumors were treated with in-air fluences (50-250 J cm(-2) ) and in-air fluence rates (50-150 mW cm(-2) ) at Photofrin dosages of 5 and 15 mg kg(-1) and a drug-light interval of 24 h using a 630-nm, 1-cm-diameter collimated laser. A macroscopic model was used to calculate [(1) O2 ]rx and PDT dose based on in vivo explicit dosimetry of the drug concentration, light fluence and tissue optical properties. PDT dose and [(1) O2 ]rx were defined as a temporal integral of drug concentration and fluence rate, and singlet oxygen concentration consumed divided by the singlet oxygen lifetime, respectively. LCR was stratified for different dose metrics for 74 mice (66 + 8 control). Complete tumor control at 14 days was observed for [(1) O2 ]rx ≥ 1.1 mm or PDT dose ≥1200 μm J cm(-2) but cannot be predicted with fluence alone. LCR increases with increasing [(1) O2 ]rx and PDT dose but is not well correlated with fluence. Comparing dosimetric quantities, [(1) O2 ]rx outperformed both PDT dose and fluence in predicting tumor response and correlating with LCR.

  3. Preliminary experience on the implementation of computed tomography (CT)-based image guided brachytherapy (IGBT) of cervical cancer using high-dose-rate (HDR) Cobalt-60 source in University of Malaya Medical Centre (UMMC)

    NASA Astrophysics Data System (ADS)

    Jamalludin, Z.; Min, U. N.; Ishak, W. Z. Wan; Malik, R. Abdul

    2016-03-01

    This study presents our preliminary work of the computed tomography (CT) image guided brachytherapy (IGBT) implementation on cervical cancer patients. We developed a protocol in which patients undergo two Magnetic Resonance Imaging (MRI) examinations; a) prior to external beam radiotherapy (EBRT) and b) prior to intra-cavitary brachytherapy for tumour identification and delineation during IGBT planning and dosimetry. For each fraction, patients were simulated using CT simulator and images were transferred to the treatment planning system. The HR-CTV, IR-CTV, bladder and rectum were delineated on CT-based contouring for cervical cancer. Plans were optimised to achieve HR-CTV and IR-CTV dose (D90) of total EQD2 80Gy and 60Gy respectively, while limiting the minimum dose to the most irradiated 2cm3 volume (D2cc) of bladder and rectum to total EQD2 90Gy and 75Gy respectively. Data from seven insertions were analysed by comparing the volume-based with traditional point- based doses. Based on our data, there were differences between volume and point doses of HR- CTV, bladder and rectum organs. As the number of patients having the CT-based IGBT increases from day to day in our centre, it is expected that the treatment and dosimetry accuracy will be improved with the implementation.

  4. Genetic Damage Induced by a Food Coloring Dye (Sunset Yellow) on Meristematic Cells of Brassica campestris L.

    PubMed Central

    Dwivedi, Kshama; Kumar, Girjesh

    2015-01-01

    We have performed the present piece of work to evaluate the effect of synthetic food coloring azo dye (sunset yellow) on actively dividing root tip cells of Brassica campestris L. Three doses of azo dye were administered for the treatment of actively dividing root tip cells, namely, 1%, 3%, and 5%, for 6-hour duration along with control. Mitotic analysis clearly revealed the azo dye induced endpoint deviation like reduction in the frequency of normal divisions in a dose dependent manner. Mitotic divisions in the control sets were found to be perfectly normal while dose based reduction in MI was registered in the treated sets. Azo dye has induced several chromosomal aberrations (genotoxic effect) at various stages of cell cycle such as stickiness of chromosomes, micronuclei formation, precocious migration of chromosome, unorientation, forward movement of chromosome, laggards, and chromatin bridge. Among all, stickiness of chromosomes was present in the highest frequency followed by partial genome elimination as micronuclei. The present study suggests that extensive use of synthetic dye should be forbidden due to genotoxic and cytotoxic impacts on living cells. Thus, there is an urgent need to assess potential hazardous effects of these dyes on other test systems like human and nonhuman biota for better scrutiny. PMID:25954313

  5. Treatment against coccidiosis in Norwegian lambs and potential risk factors for development of anticoccidial resistance-a questionnaire-based study.

    PubMed

    Odden, Ane; Enemark, Heidi L; Robertson, Lucy J; Ruiz, Antonio; Hektoen, Lisbeth; Stuen, Snorre

    2017-02-11

    The objectives of this study were to investigate the use of anticoccidials in Norwegian sheep flocks and identify farms with management procedures likely to select for drug resistance. Data were obtained by a questionnaire sent to all members of the Norwegian Sheep Recording System in October 2015. The data set consisted of 1215 answers, corresponding to 8.5% of Norwegian sheep flocks. Anticoccidials were used in 82.7% of flocks. Main treatment was at turnout (38.6% of treated flocks) or 1 week after turnout (32.4%). Interestingly, clinical signs possibly related to coccidiosis were observed by almost 40% of the farmers after treatment, which might be an indication of drug resistance. Correlations between the apparently reduced anticoccidial efficacy and management conditions, such as the size of the farms, were found. From the farmers' perspective, metaphylactic treatment was used in 88.5% of treated flocks, of which approximately one third had no history of clinical coccidiosis. Even though farmers seem aware of the importance of good drenching routines based on reliable estimates of weights and calibration of drench guns, drench gun used for anticoccidial administration was never calibrated in 12.1% of the flocks. Finally, dose estimation was made by visual appraisal in 27.5% of the flocks, which can lead to incorrect dosing. Based on the present study, it cannot be determined whether the apparent treatment failure was related to management practises, incorrect administration of the drug, other infections or actual anticoccidial drug resistance.

  6. Estimation of parameters for the elimination of an orally administered test substance with unknown absorption.

    PubMed

    Vogt, Josef A; Denzer, Christian

    2013-04-01

    Assessment of the elimination of an oral test dose based on plasma concentration values requires correction for the effect of gastric release and absorption. Irregular uptake processes should be described 'model independently', which requires estimation of a large number of absorption parameters. To limit the associated computational effort a new approach is developed with a reduced number of unknown parameters. A marginalized and regularized absorption approach (MRA) is defined, which uses for the uptake just one parameter to control rigidity of the uptake curve. For validation, elimination and absorption were reproduced using published IVIVC data and a synthetic data set for comparison with approaches using a 'model-free'--staircase function or mechanistic models to describe absorption. MRA performed almost as accurate as well specified mechanistic models, which gave the best reproduction. MRA demonstrated a 50fold increase in computational efficiency compared to other approaches. The absorption estimated for the IVIVC study demonstrated an in vivo-in vitro correlation comparable to published values. The newly developed MRA approach can be used to efficiently and accurately estimate elimination and absorption with a restricted number of adaptive parameters and with automatic adjustment of the complexity of the uptake.

  7. Spatial Prediction of Coxiella burnetii Outbreak Exposure via Notified Case Counts in a Dose-Response Model.

    PubMed

    Brooke, Russell J; Kretzschmar, Mirjam E E; Hackert, Volker; Hoebe, Christian J P A; Teunis, Peter F M; Waller, Lance A

    2017-01-01

    We develop a novel approach to study an outbreak of Q fever in 2009 in the Netherlands by combining a human dose-response model with geostatistics prediction to relate probability of infection and associated probability of illness to an effective dose of Coxiella burnetii. The spatial distribution of the 220 notified cases in the at-risk population are translated into a smooth spatial field of dose. Based on these symptomatic cases, the dose-response model predicts a median of 611 asymptomatic infections (95% range: 410, 1,084) for the 220 reported symptomatic cases in the at-risk population; 2.78 (95% range: 1.86, 4.93) asymptomatic infections for each reported case. The low attack rates observed during the outbreak range from (Equation is included in full-text article.)to (Equation is included in full-text article.). The estimated peak levels of exposure extend to the north-east from the point source with an increasing proportion of asymptomatic infections further from the source. Our work combines established methodology from model-based geostatistics and dose-response modeling allowing for a novel approach to study outbreaks. Unobserved infections and the spatially varying effective dose can be predicted using the flexible framework without assuming any underlying spatial structure of the outbreak process. Such predictions are important for targeting interventions during an outbreak, estimating future disease burden, and determining acceptable risk levels.

  8. The measurement of radiation levels in Australian zircon milling plants.

    PubMed

    Hartley, B M

    2001-01-01

    The processing of zircon often involves grinding it to a fine powder known as zircon flour. As the resulting particles are small they may be inhaled if they become airborne and, since they contain some uranium and thorium, deliver radiation doses to workers. Theoretical estimates and measured radiation exposure in Australian zircon milling plants are reported in this paper. Theoretical doses, calculated in this work, indicate a potential maximum dose to workers of 5.5 mSv y(-1). Measured doses, based on normal work practices, vary in different plants from 0.66 mSv to 1.03 mSv y(-1) and suggest that in the dustiest Australian zircon milling plants the maximum dose would be of the order of 1 mSv y(-1). Measurements, which focused on the dustiest operations, indicate an upper limit of dose of about 3 mSv y(-1). Based on the theoretical and measured doses not exceeding 6 mSv y(-1), workers would not be designated as Category A workers, and probably would not be designated Category B workers, exceeding 1 mSv y(-1), under the guidelines of a EURATOM Directive.

  9. A manual for applying the allowable residual contamination level method for decommissioning facilities on the Hanford Site

    SciTech Connect

    Napier, B.A.; Piepel, G.F.; Kennedy, W.E. Jr.; Schreckhise, R.G.

    1988-08-01

    This report describes the modifications that have been made to enhance the original Allowable Residual Contamination Level (ARCL) method to make it more applicable to site-specific analyses. This version considers the mixture of radionuclides present at the time of site characterization, the elapsed time after decommissioning when exposure to people could occur, and includes a calculation of the upper confidence limit of the potential dose based on sampling statistics that are developed during the site characterization efforts. The upper confidence limit of potential exposure can now be used for comparison against applicable radiation dose limits (i.e., 25 mrem/yr at Hanford). The level of confidence can be selected by the user. A wide range of exposure scenarios were evaluated; the rationale used to select the most limiting scenarios is explained. The radiation dose factors used for the inhalation and ingestion pathways were also updated to correspond with the radiation dosimetry methods utilized in the International Commission of Radiological Protection Publications 26 and 30 (ICRP 1977; 1979a,b, 1980, 1981, 1982a,b). This simplifies the calculations, since ''effective whole body'' doses are now calculated, and also brings the dosimetry methods used in the ARCL method in conformance with the rationale used by DOE in developing the 25 mrem/yr limit at Hanford. 46 refs., 21 figs., 15 tabs.

  10. A simplified technique for delivering total body irradiation (TBI) with improved dose homogeneity

    SciTech Connect

    Yao Rui; Bernard, Damian; Turian, Julius; Abrams, Ross A.; Sensakovic, William; Fung, Henry C.; Chu, James C. H.

    2012-04-15

    Purpose: Total body irradiation (TBI) with megavoltage photon beams has been accepted as an important component of management for a number of hematologic malignancies, generally as part of bone marrow conditioning regimens. The purpose of this paper is to present and discuss the authors' TBI technique, which both simplifies the treatment process and improves the treatment quality. Methods: An AP/PA TBI treatment technique to produce uniform dose distributions using sequential collimator reductions during each fraction was implemented, and a sample calculation worksheet is presented. Using this methodology, the dosimetric characteristics of both 6 and 18 MV photon beams, including lung dose under cerrobend blocks was investigated. A method of estimating midplane lung doses based on measured entrance and exit doses was proposed, and the estimated results were compared with measurements. Results: Whole body midplane dose uniformity of {+-}10% was achieved with no more than two collimator-based beam modulations. The proposed model predicted midplane lung doses 5% to 10% higher than the measured doses for 6 and 18 MV beams. The estimated total midplane doses were within {+-}5% of the prescribed midplane dose on average except for the lungs where the doses were 6% to 10% lower than the prescribed dose on average. Conclusions: The proposed TBI technique can achieve dose uniformity within {+-}10%. This technique is easy to implement and does not require complicated dosimetry and/or compensators.

  11. A CONCEPTUAL FRAMEWORK FOR MANAGING RADIATION DOSE TO PATIENTS IN DIAGNOSTIC RADIOLOGY USING REFERENCE DOSE LEVELS.

    PubMed

    Almén, Anja; Båth, Magnus

    2016-06-01

    The overall aim of the present work was to develop a conceptual framework for managing radiation dose in diagnostic radiology with the intention to support optimisation. An optimisation process was first derived. The framework for managing radiation dose, based on the derived optimisation process, was then outlined. The outset of the optimisation process is four stages: providing equipment, establishing methodology, performing examinations and ensuring quality. The optimisation process comprises a series of activities and actions at these stages. The current system of diagnostic reference levels is an activity in the last stage, ensuring quality. The system becomes a reactive activity only to a certain extent engaging the core activity in the radiology department, performing examinations. Three reference dose levels-possible, expected and established-were assigned to the three stages in the optimisation process, excluding ensuring quality. A reasonably achievable dose range is also derived, indicating an acceptable deviation from the established dose level. A reasonable radiation dose for a single patient is within this range. The suggested framework for managing radiation dose should be regarded as one part of the optimisation process. The optimisation process constitutes a variety of complementary activities, where managing radiation dose is only one part. This emphasises the need to take a holistic approach integrating the optimisation process in different clinical activities.

  12. A Combined Tissue Kinetics and Dosimetric Model of Respiratory Tissue Exposed to Radiation

    SciTech Connect

    John R. Ford

    2005-11-01

    Existing dosimetric models of the radiation response of tissues are essentially static. Consideration of changes in the cell populations over time has not been addressed realistically. For a single acute dose this is not a concern, but for modeling chronic exposures or fractionated acute exposures, the natural turnover and progression of cells could have a significant impact on a variety of endpoints. This proposal addresses the shortcomings of current methods by combining current dose-based calculation techniques with information on the cell turnover for a model tissue. The proposed model will examine effects at the single-cell level for an exposure of a section of human bronchiole. The cell model will be combined with Monte Carlo calculations of doses to cells and cell nuclei due to varying dose-rates of different radiation qualities. Predictions from the model of effects on survival, apoptosis rates, and changes in the number of cycling and differentiating cells will be tested experimentally. The availability of dynamic dosimetric models of tissues at the single-cell level will be useful for analysis of low-level radiation exposures and in the development of new radiotherapy protocols.

  13. An updated nuclear criticality slide rule

    SciTech Connect

    Hopper, C.M.; Broadhead, B.L.

    1998-04-01

    This Volume 2 contains the functional version of the updated nuclear criticality slide rule (more accurately, sliding graphs) that is referenced in An Updated Nuclear Criticality Slide Rule: Technical Basis, NUREG/CR-6504, Vol. 1 (ORNL/TM-13322/V1). This functional slide rule provides a readily usable {open_quotes}in-hand{close_quotes} method for estimating pertinent nuclear criticality accident information from sliding graphs, thereby permitting (1) the rapid estimation of pertinent criticality accident information without laborious or sophisticated calculations in a nuclear criticality emergency situation, (2) the appraisal of potential fission yields and external personnel radiation exposures for facility safety analyses, and (3) a technical basis for emergency preparedness and training programs at nonreactor nuclear facilities. The slide rule permits the estimation of neutron and gamma dose rates and integrated doses based upon estimated fission yields, distance from the fission source, and time-after criticality accidents for five different critical systems. Another sliding graph permits the estimation of critical solution fission yields based upon fissile material concentration, critical vessel geometry, and solution addition rate. Another graph provides neutron and gamma dose-reduction factors for water, steel, and concrete. Graphs from historic documents are provided as references for estimating critical parameters of various fissile material systems. Conversion factors for various English and metric units are provided for quick reference.

  14. Online dosimetry for temoporfin-mediated interstitial photodynamic therapy using the canine prostate as model

    NASA Astrophysics Data System (ADS)

    Swartling, Johannes; Höglund, Odd V.; Hansson, Kerstin; Södersten, Fredrik; Axelsson, Johan; Lagerstedt, Anne-Sofie

    2016-02-01

    Online light dosimetry with real-time feedback was applied for temoporfin-mediated interstitial photodynamic therapy (PDT) of dog prostate. The aim was to investigate the performance of online dosimetry by studying the correlation between light dose plans and the tissue response, i.e., extent of induced tissue necrosis and damage to surrounding organs at risk. Light-dose planning software provided dose plans, including light source positions and light doses, based on ultrasound images. A laser instrument provided therapeutic light and dosimetric measurements. The procedure was designed to closely emulate the procedure for whole-prostate PDT in humans with prostate cancer. Nine healthy dogs were subjected to the procedure according to a light-dose escalation plan. About 0.15 mg/kg temoporfin was administered 72 h before the procedure. The results of the procedure were assessed by magnetic resonance imaging, and gross pathology and histopathology of excised tissue. Light dose planning and online dosimetry clearly resulted in more focused effect and less damage to surrounding tissue than interstitial PDT without dosimetry. A light energy dose-response relationship was established where the threshold dose to induce prostate gland necrosis was estimated from 20 to 30 J/cm2.

  15. Removal of pharmaceutical residues using ozonation as intermediate process step at Linköping WWTP, Sweden.

    PubMed

    Baresel, Christian; Malmborg, Jonas; Ek, Mats; Sehlén, Robert

    2016-01-01

    Pilot tests as basis for the design, implementation and operation of a future full-scale oxidation plant completing the existing sewage treatment in Linköping, Sweden, were performed. Using an ozonation step between bio-sedimentation and post-denitrification processes, the primary goal was the removal of the highest priority substances to effluent water levels that will not cause adverse effects in the recipient considering the natural dilution. The study included initial emission screenings, dose control trials, treatment performance studies and eco-toxicity studies. At an ozone dose of 5 mg O3/L, most substances could be removed. Ecotoxicological tests showed no negative effect for the tested ozone doses. High levels of oxygen into the denitrification could be rapidly reduced in the biology. The number of bacteria in the treated water could be significantly reduced even at relatively low ozone doses. Based on these results, the planning for the full-scale implementation of the treatment system was initiated in 2015.

  16. Ion-induced nuclear radiotherapy

    DOEpatents

    Horn, K.M.; Doyle, B.L.

    1996-08-20

    Ion-induced Nuclear Radiotherapy (INRT) is a technique for conducting radiosurgery and radiotherapy with a very high degree of control over the spatial extent of the irradiated volume and the delivered dose. Based upon the concept that low energy, ion induced atomic and nuclear reactions can be used to produce highly energetic reaction products at the site of a tumor, the INRT technique is implemented through the use of a conduit-needle or tube which conducts a low energy ion beam to a position above or within the intended treatment area. At the end of the conduit-needle or tube is a specially fabricated target which, only when struck by the ion beam, acts as a source of energetic radiation products. The inherent limitations in the energy, and therefore range, of the resulting reaction products limits the spatial extent of irradiation to a pre-defined volume about the point of reaction. Furthermore, since no damage is done to tissue outside this irradiated volume, the delivered dose may be made arbitrarily large. INRT may be used both as a point-source of radiation at the site of a small tumor, or as a topical bath of radiation to broad areas of diseased tissue. 25 figs.

  17. Probability Estimates of Solar Particle Event Doses During a Period of Low Sunspot Number for Thinly-Shielded Spacecraft and Short Duration Missions

    NASA Technical Reports Server (NTRS)

    Atwell, William; Tylka, Allan J.; Dietrich, William; Rojdev, Kristina; Matzkind, Courtney

    2016-01-01

    In an earlier paper (Atwell, et al., 2015), we investigated solar particle event (SPE) radiation exposures (absorbed dose) to small, thinly-shielded spacecraft during a period when the sunspot number (SSN) was less than 30. These SPEs contain Ground Level Events (GLE), sub-GLEs, and sub-sub-GLEs (Tylka and Dietrich, 2009, Tylka and Dietrich, 2008, and Atwell, et al., 2008). GLEs are extremely energetic solar particle events having proton energies extending into the several GeV range and producing secondary particles in the atmosphere, mostly neutrons, observed with ground station neutron monitors. Sub-GLE events are less energetic, extending into the several hundred MeV range, but do not produce secondary atmospheric particles. Sub-sub GLEs are even less energetic with an observable increase in protons at energies greater than 30 MeV, but no observable proton flux above 300 MeV. In this paper, we consider those SPEs that occurred during 1973-2010 when the SSN was greater than 30 but less than 50. In addition, we provide probability estimates of absorbed dose based on mission duration with a 95% confidence level (CL). We also discuss the implications of these data and provide some recommendations that may be useful to spacecraft designers of these smaller spacecraft.

  18. A phase I, open-label, dose-escalation, multicenter study of the JAK2 inhibitor NS-018 in patients with myelofibrosis

    PubMed Central

    Verstovsek, S; Talpaz, M; Ritchie, E; Wadleigh, M; Odenike, O; Jamieson, C; Stein, B; Uno, T; Mesa, R A

    2017-01-01

    NS-018 is a Janus-activated kinase 2 (JAK2)-selective inhibitor, targeting the JAK–signal transducer and activator of transcription (STAT) pathway that is deregulated in myelofibrosis. In this phase I, dose-escalation portion of a phase I/II study, patients with myelofibrosis received oral NS-018 in continuous 28-day cycles. The primary study objective was to evaluate safety, tolerability and clinically active dose of NS-018. Forty-eight patients were treated; 23 (48%) had previously received a JAK inhibitor (JAKi). The most common drug-related adverse events were thrombocytopenia (27%)/anemia (15%) for hematologic events, and dizziness (23%)/nausea (19%) for non-hematologic events. Once daily NS-018 at 300 mg was chosen as the phase II study dose based on improved tolerability compared with higher doses. A ⩾50% reduction in palpable spleen size was achieved in 56% of patients (47% of patients with prior JAKi treatment), and improvements were observed in myelofibrosis-associated symptoms. Bone marrow fibrosis grade (local assessment) improved from baseline in 11/30 evaluable patients (37%) after 3 cycles of NS-018. JAK2 allele burden was largely unchanged. Changes in cytokine/protein levels were noted after 4 weeks of treatment. NS-018 reached peak plasma concentration in 1–2 h and did not accumulate with multiple dosing. NS-018 will be assessed in patients with previous JAKi exposure in the phase II portion. PMID:27479177

  19. The fate of p21CDKN1A in cells surviving UV-irradiation.

    PubMed

    Itoh, Toshiki; Linn, Stuart

    2005-12-08

    p21(CDKN1A) is a critical regulator of cell cycle progression in response to DNA damage. There are conflicting conclusions as to whether p21(CDKN1A) levels increase or decrease after ultraviolet (UV)-irradiation and recently it was even reported to disappear entirely following 2.5-30 Jm(-2) of UV-irradiation in the presence of growth medium. The latter would suggest an alternative mechanism for cell cycle arrest after UV-irradiation, since p21(CDKN1A) induction has been considered to be the major mediator of p53-mediated cell cycle arrest after DNA damage. Using physiological UV doses based on cell-killing, we previously observed and here verify that low doses (1.2-6 Jm(-2)) induce p21(CDKN1A) immediately after UV-irradiation, though higher doses cause a latency during which p21(CDKN1A) levels remain fairly constant before increasing. As expected, p53 induction preceded p21(CDKN1A) induction at all doses. Thus, p21(CDKN1A) levels after low doses of UV-irradiation may be controlled in a p53-dependent manner without severe reduction. We propose that physiological relevant UV doses should be determined for each target cell type prior to studying UV-induced responses and that p21(CDKN1A) is indeed critical for cell cycle arrest in cells that survive UV-irradiation.

  20. Concurrent 2,4-D and triclopyr biomonitoring of backpack applicators, mixer/loader and field supervisor in forestry.

    PubMed

    Zhang, Xiaofei; Acevedo, Sandra; Chao, Yingfu; Chen, Zhenshan; Dinoff, Travis; Driver, Jeffrey; Ross, John; Williams, Ryan; Krieger, Robert

    2011-01-01

    Two herbicides, 2,4-D and triclopyr esters (application ratio 1.6:1 acid equivalents) were applied as a tank mix by a crew of 8 backpack sprayer applicators, a mixer/loader, and a field supervisor. The crew was employed in a conifer release program in northern California during the summer of 2002. Biomonitoring (urine, 24 h) utilized 2,4-D and triclopyr (a.e.) as rapidly excreted exposure biomarkers. The absorbed dosages of 2,4-D and triclopyr were calculated based upon cotton whole body suits and biomonitoring. Dosages based upon accumulation of the herbicides on body suits averaged 42.6 μg (a.e.) 2,4-D/kg-d and 8.0 μg (a.e.) triclopyr/kg-d. Six consecutive days of concurrent urine collections showed that backpack applicators excreted an average of 11.0 μg (a.e.) 2,4-D/kg-d and 18.9 μg (a.e.) triclopyr/kg-d. Estimates based upon curve fitting were 17.1 and 29.3 μg (a.e.)/kg-d, respectively. Results suggest that passive dosimetry for 2,4-D consistently overestimated the dosage measured using biomonitoring by a factor of 2-3 fold, while for triclopyr, passive dosimetry underestimated the absorbed dose based on biomonitoring by a factor of 2-4 fold.

  1. Stereotactic Body Radiation Therapy Boost in Locally Advanced Pancreatic Cancer

    SciTech Connect

    Seo, Young Seok; Kim, Mi-Sook; Yoo, Sung Yul; Cho, Chul Koo; Yang, Kwang Mo; Yoo, Hyung Jun; Choi, Chul Won; Lee, Dong Han; Kim, Jin; Kim, Min Suk; Kang, Hye Jin; Kim, YoungHan

    2009-12-01

    Purpose: To investigate the clinical application of a stereotactic body radiation therapy (SBRT) boost in locally advanced pancreatic cancer patients with a focus on local efficacy and toxicity. Methods and Materials: We retrospectively reviewed 30 patients with locally advanced and nonmetastatic pancreatic cancer who had been treated between 2004 and 2006. Follow-up duration ranged from 4 to 41 months (median, 14.5 months). A total dose of 40 Gy was delivered in 20 fractions using a conventional three-field technique, and then a single fraction of 14, 15, 16, or 17 Gy SBRT was administered as a boost without a break. Twenty-one patients received chemotherapy. Overall and local progression-free survival were calculated and prognostic factors were evaluated. Results: One-year overall survival and local progression-free survival rates were 60.0% and 70.2%, respectively. One patient (3%) developed Grade 4 toxicity. Carbohydrate antigen 19-9 response was found to be an independent prognostic factor for survival. Conclusions: Our findings indicate that a SBRT boost provides a safe means of increasing radiation dose. Based on the results of this study, we recommend that a well controlled Phase II study be conducted on locally advanced pancreatic cancer.

  2. Estimated UV doses to psoriasis patients during climate therapy at Gran Canaria in March 2006

    NASA Astrophysics Data System (ADS)

    Nilsen, L. T. N.; Søyland, E.; Krogstad, A. L.

    2008-01-01

    Psoriasis is a chronic inflammatory disease involving about 2-3% of the Norwegian population. Sun exposure has a positive effect on most psoriasis lesions, but ultraviolet (UV) radiation also causes a direct DNA damage in the skin cells and comprises a carcinogenic potential. UV exposure on the skin causes a local as well as a systemic immune suppressive effect, but the relation between sun exposure and these biological effects is not well known. In March 2006 a study was carried out to investigate possible therapeutic outcome mechanisms in 20 psoriasis patients receiving climate therapy at Gran Canaria. This paper presents estimates of their individual skin UV-doses based on UV measurements and the patients' diaries with information on time spent in the sun. On the first day of exposure the patients received on average 5.1 Standard Erythema Doses (SED: median=4.0 SED, range 2.6-10.3 SED) estimated to the skin. During the 15 days study they received 165.8 SED (range 104.3-210.1 SED). The reduction in PASI score was 72.8% on average, but there was no obvious relation between the improvement and the UV dose. The UV doses were higher than those found from climate therapy studies at other locations. It seems beneficial to use more strict exposure schedules that consider the available UV irradiance, depending on time of the day, time of the year and weather conditions.

  3. Assessment of Digoxin-Specific Fab Fragment Dosages in Digoxin Poisoning.

    PubMed

    Nordt, Sean Patrick; Clark, Richard F; Machado, Carol; Cantrell, F Lee

    2016-01-01

    Digoxin poisoning still remains a common cause of morbidity and mortality. Fortunately, digoxin-specific Fab fragments are commercially available as an antidote. However, these Fab fragments are several thousand dollars per vial. There is a standardized formula to calculate appropriate Fab fragment dosage based on the serum digoxin concentration. This can greatly reduce the amount of Fab fragment administered. There is also an empiric dosing guideline recommending 6-10 vials be given; however, this may result in higher amounts of Fab fragments being administered than required. We performed this study to assess the amounts of digoxin-specific Fab fragments administered in the treatment of digoxin poisonings recorded in a poison control system database from January 1, 2000, to December 31, 2009, in which digoxin serum concentrations were available. This was a retrospective study of 278 patients, 107 with acute poisonings (group A) and 171 following chronic poisoning (group B). In group A, the calculated Fab dose was higher than the calculated dose based on available concentrations in 39 (36%) of group A and 15 (9%) of group B patients. The average wholesale price cost of the excessive dosages ranged from $4818 to as high as $50,589 per patient. Our data suggests that clinician education on digoxin poisoning and the use of the standardized formula to calculate the Fab dose may decrease over utilization and decrease costs associated with the administration of digoxin-specific Fab fragments in the treatment of digoxin poisonings.

  4. Summary of the environmental dose models used at DOE nuclear sites in 1979

    SciTech Connect

    Kennedy, W.E. Jr.; Mueller, M.A.

    1982-09-01

    Methods for assessing public exposure to radiation from normal operations at DOE facilities are reviewed in this report. This review includes a summary of the methods used in 1979 as described in annual environmental reports submitted by Department of Energy (DOE) contractors. The methods used ranged from estimating public doses based on environmental measurements and comparison to the DOE concentration guides, to complex methods using environmental pathway modeling and estimated radionuclide releases. No two sites used the same combination of measurements and pathway models in their analysis. While most sites used an atmospheric dispersion model to predict air concentrations of radioactive material, only about half of the sites provided enough information about the model used to permit proper model evaluation. The waterborne pathways related to drinking water or ingestion of fish were generally well described, while the external exposure or terrestrial food pathways were often not considered. The major recommendation resulting from this review was that complete documentations of the models used should be included either within the annual reports or as separate readily available documents. In addition, most sites could make better use of graphics (i.e., tables and figures) to better communicate the findings of their analyses.

  5. Application of Adaptive Design Methodology in Development of a Long-Acting Glucagon-Like Peptide-1 Analog (Dulaglutide): Statistical Design and Simulations

    PubMed Central

    Skrivanek, Zachary; Berry, Scott; Berry, Don; Chien, Jenny; Geiger, Mary Jane; Anderson, James H.; Gaydos, Brenda

    2012-01-01

    Background Dulaglutide (dula, LY2189265), a long-acting glucagon-like peptide-1 analog, is being developed to treat type 2 diabetes mellitus. Methods To foster the development of dula, we designed a two-stage adaptive, dose-finding, inferentially seamless phase 2/3 study. The Bayesian theoretical framework is used to adaptively randomize patients in stage 1 to 7 dula doses and, at the decision point, to either stop for futility or to select up to 2 dula doses for stage 2. After dose selection, patients continue to be randomized to the selected dula doses or comparator arms. Data from patients assigned the selected doses will be pooled across both stages and analyzed with an analysis of covariance model, using baseline hemoglobin A1c and country as covariates. The operating characteristics of the trial were assessed by extensive simulation studies. Results Simulations demonstrated that the adaptive design would identify the correct doses 88% of the time, compared to as low as 6% for a fixed-dose design (the latter value based on frequentist decision rules analogous to the Bayesian decision rules for adaptive design). Conclusions This article discusses the decision rules used to select the dula dose(s); the mathematical details of the adaptive algorithm—including a description of the clinical utility index used to mathematically quantify the desirability of a dose based on safety and efficacy measurements; and a description of the simulation process and results that quantify the operating characteristics of the design. PMID:23294775

  6. 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.

  7. Evaluation of exposure pathways to man from disposal of radioactive materials into sanitary sewer systems

    SciTech Connect

    Kennedy, W.E. Jr.; Parkhurst, M.A.; Aaberg, R.L.; Rhoads, K.C.; Hill, R.L.; Martin, J.B.

    1992-05-01

    In accordance with 10 CFR 20, the US Nuclear Regulatory Commission (NRC) regulates licensees` discharges of small quantities of radioactive materials into sanitary sewer systems. This generic study was initiated to examine the potential radiological hazard to the public resulting from exposure to radionuclides in sewage sludge during its treatment and disposal. Eleven scenarios were developed to characterize potential exposures to radioactive materials during sewer system operations and sewage sludge treatment and disposal activities and during the extended time frame following sewage sludge disposal. Two sets of deterministic dose calculations were performed; one to evaluate potential doses based on the radionuclides and quantities associated with documented case histories of sewer system contamination and a second, somewhat more conservative set, based on theoretical discharges at the maximum allowable levels for a more comprehensive list of 63 radionuclides. The results of the stochastic uncertainty and sensitivity analysis were also used to develop a collective dose estimate. The collective doses for the various radionuclides and scenarios range from 0.4 person-rem for {sup 137}Cs in Scenario No. 5 (sludge incinerator effluent) to 420 person-rem for {sup 137}Cs in Scenario No. 3 (sewage treatment plant liquid effluent). None of the 22 scenario/radionuclide combinations considered have collective doses greater than 1000 person-rem/yr. However, the total collective dose from these 22 combinations was found to be about 2100 person-rem.

  8. Improving Glycemic Control and Insulin Ordering Efficiency for Hospitalized Patients With Diabetes Through Carbohydrate Counting.

    PubMed

    Pearson, Kristina K; Reiland, Sarah A; Meara, John G O; Brown, Julie K; Fedraw, Leslie A; Mapes, David L

    2016-01-01

    Glycemic control in hospitalized patients is challenging but important for optimal outcomes. Insulin dosing through carbohydrate counting may address patient, provider, and institutional factors that complicate hospital glycemic management. On two surgical units at a tertiary care teaching hospital, we pilot tested postmeal insulin dosing based on carbohydrate counting (plus basal insulin) rather than the current process of ordering scheduled premeal insulin without knowledge of the patient's consumption. Analysis assessed hyperglycemia, hypoglycemia, insulin orders, and nurse and provider satisfaction and confidence. On general surgery, mean glucose level improved from 188 to 137 mg/dl (p < .001). On cardiovascular surgery, mean glucose improved only mildly from 177 to 175 mg/dl (p < .28). No hypoglycemia was reported. Efficiency of mealtime insulin dosing improved through reduced average number of insulin orders per meal from 1.1 to 0.09. Process satisfaction improved for providers (preintervention, 60%; postintervention, 100%), general surgery nurses (preintervention, 72%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 69%; postintervention, 84%). Confidence in insulin dose accuracy improved for providers (preintervention, 50%; postintervention, 100%), general surgery nurses (preintervention, 59%; postintervention, 100%), and cardiovascular surgery nurses (preintervention, 48%; postintervention, 84%). Carbohydrate counting is effective and efficient and improved staff satisfaction and confidence in hospital mealtime insulin dosing.

  9. High Prevalence of Obesity in Acute Promyelocytic Leukemia (APL): Implications for Differentiating Agents in APL and Metabolic Syndrome

    PubMed Central

    Tedesco, Jason; Qualtieri, Julianne; Head, David; Savani, Bipin N.; Reddy, Nishitha

    2011-01-01

    Background: Between January 1999 and December 2008, 469 patients treated for acute myeloid leukemia (AML) were included in this single-institution study. Methods: We performed a case-control analysis to study the rate of obesity among patients with acute promyelocytic leukemia (APL) and non-APL AML. Results: A total of 81% of APL patients analyzed were obese compared with 41.7% in the non-APL group (p < 0.001). Body mass index (BMI) >30 was seen in 57% of APL patients compared with 31% for the non-APL group (p = 0.01). Neither obesity nor the chemotherapy dosing based on ideal body weight affected survival. Conclusions: Our findings generate the hypothesis that APL and metabolic syndromes may share a common pathogenic pathway via retinoic acid receptors (RARs), the ligand-controlled transcription factors that function as heterodimers with retinoid X receptors (RXRs) to regulate cell growth and survival. If this link is confirmed in larger studies, our data will instigate further studies using RXR and RAR modulators as a preventive strategy among obese individuals. PMID:23556085

  10. Biodosimetry of heavy ions by interphase chromosome painting

    NASA Astrophysics Data System (ADS)

    Durante, M.; Kawata, T.; Nakano, T.; Yamada, S.; Tsujii, H.

    1998-11-01

    We report measurements of chromosomal aberrations in peripheral blood lymphocytes from cancer patients undergoing radiotherapy treatment. Patients with cervix or esophageal cancer were treated with 10 MV X-rays produced at a LINAC accelerator, or high-energy carbon ions produced at the HIMAC accelerator at the National Institute for Radiological Sciences (NIRS) in Chiba. Blood samples were obtained before, during, and after the radiation treatment. Chromosomes were prematurely condensed by incubation in calyculin A. Aberrations in chromosomes 2 and 4 were scored after fluorescence in situ hybridization with whole-chromosome probes. Pre-treatment samples were exposed in vitro to X-rays, individual dose-response curves for the induction of chromosomal aberrations were determined, and used as calibration curves to calculate the effective whole-body dose absorbed during the treatment. This calculated dose, based on the calibration curve relative to the induction of reciprocal exchanges, has a sharp increase after the first few fractions of the treatment, then saturates at high doses. Although carbon ions are 2-3 times more effective than X-rays in tumor sterilization, the effective dose was similar to that of X-ray treatment. However, the frequency of complex-type chromosomal exchanges was much higher for patients treated with carbon ions than X-ray.

  11. Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments

    PubMed Central

    Hinshaw, Ling; Mallad, Ashwini; Dalla Man, Chiara; Cobelli, Claudio; Carter, Rickey E.; Kudva, Yogish C.; Basu, Ananda

    2015-01-01

    Glucagon use in artificial pancreas for type 1 diabetes (T1D) is being explored for prevention and rescue from hypoglycemia. However, the relationship between glucagon stimulation of endogenous glucose production (EGP) viz., hepatic glucagon sensitivity, and prevailing glucose concentrations has not been examined. To test the hypothesis that glucagon sensitivity is increased at hypoglycemia vs. euglycemia, we studied 29 subjects with T1D randomized to a hypoglycemia or euglycemia clamp. Each subject was studied at three glucagon doses at euglycemia or hypoglycemia, with EGP measured by isotope dilution technique. The peak EGP increments and the integrated EGP response increased with increasing glucagon dose during euglycemia and hypoglycemia. However, the difference in dose response based on glycemia was not significant despite higher catecholamine concentrations in the hypoglycemia group. Knowledge of glucagon's effects on EGP was used to develop an in silico glucagon action model. The model-derived output fitted the obtained data at both euglycemia and hypoglycemia for all glucagon doses tested. Glucagon clearance did not differ between glucagon doses studied in both groups. Therefore, the glucagon controller of a dual hormone control system may not need to adjust glucagon sensitivity, and hence glucagon dosing, based on glucose concentrations during euglycemia and hypoglycemia. PMID:26152766

  12. Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery.

    PubMed

    Elkomy, Mohammed H; Drover, David R; Glotzbach, Kristi L; Galinkin, Jeffery L; Frymoyer, Adam; Su, Felice; Hammer, Gregory B

    2016-01-01

    The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children without cardiac abnormalities of similar age. Children 1-6 months of age need higher morphine doses per kilogram to achieve an area under concentration-time curve comparable to that in older children. Pediatric patients with renal failure receiving morphine therapy are at increased risk of developing opioid toxicity due to accumulation of morphine metabolites.

  13. Effect of dry mycelium of Penicillium chrysogenum fertilizer on soil microbial community composition, enzyme activities and snap bean growth.

    PubMed

    Wang, Bing; Liu, Huiling; Cai, Chen; Thabit, Mohamed; Wang, Pu; Li, Guomin; Duan, Ziheng

    2016-10-01

    The dry mycelium fertilizer (DMF) was produced from penicillin fermentation fungi mycelium (PFFM) following an acid-heating pretreatment to degrade the residual penicillin. In this study, it was applied into soil as fertilizer to investigate its effects on soil properties, phytotoxicity, microbial community composition, enzyme activities, and growth of snap bean in greenhouse. As the results show, pH, total nitrogen, total phosphorus, total potassium, and organic matter of soil with DMF treatments were generally higher than CON treatment. In addition, the applied DMF did not cause heavy metal and residual drug pollution of the modified soil. The lowest GI values (<0.3) were recorded at DMF8 (36 kg DMF/plat) on the first days after applying the fertilizer, indicating that severe phytotoxicity appeared in the DMF8-modified soil. Results of microbial population and enzyme activities illustrated that DMF was rapidly decomposed and the decomposition process significantly affected microbial growth and enzyme activities. The DMF-modified soil phytotoxicity decreased at the late fertilization time. DMF1 was considered as the optimum amount of DMF dose based on principal component analysis scores. Plant height and plant yield of snap bean were remarkably enhanced with the optimum DMF dose.

  14. Need of UV protection and evaluation of efficacy of sunscreens.

    PubMed

    Kaur, Anoopinder; Thatai, Purva; Sapra, Bharti

    2014-01-01

    Sun exposure has been coupled with numerous types of acute and chronic reactions in skin, for example, sun burns, photoimmune suppression, photoaging, and skin cancer. In scrutiny of growing understanding of the potentially unfavorable long-term side effects of solar irradiation, there is a universal call for harmless and effective photoprotectants. Photoprotective agents are used for protection against ultraviolet (UV) radiations. In support of best photoprotective measures, now sunscreens are in great demand. Safeguard from UVB is quantified as a minimal erythema dose-based sun protection factor (SPF). UVA protection testing methods include evaluation of persistent pigment darkening (PPD) and critical wavelength. The rationale of this review is to present the contemporary information on the cutaneous pathophysiology of photooxidative stress, to study different UV filters with their UV spectrum and various commercially available sunscreens, with special emphasis on their active ingredients and SPFs. The characterization of different parameters to evaluate the efficacy of sunscreens, for example, SPF, immune suppression factor, photostability, and water resistance, have been described on the basis of findings from different researchers.

  15. Clinical efficacy and safety evaluation of tailoring iron chelation practice in thalassaemia patients from Asia-Pacific: a subanalysis of the EPIC study of deferasirox.

    PubMed

    Viprakasit, Vip; Ibrahim, Hishamshah; Ha, Shau-Yin; Ho, Phoebe Joy; Li, Chi-Kong; Chan, Lee-Lee; Chiu, Chang-Fang; Sutcharitchan, Pranee; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Xue, Hong-Ling; Bowden, Donald K; Lin, Kai-Hsin

    2011-03-01

    Although thalassaemia is highly prevalent in the Asia-Pacific region, clinical data on efficacy and safety profiles of deferasirox in patients from this region are rather limited. Recently, data from the multicentre Evaluation of Patients' Iron Chelation with Exjade (EPIC) study in 1744 patients with different anaemias has provided an opportunity to analyse 1115 thalassaemia patients, of whom 444 patients were from five countries in the Asia-Pacific region (AP) for whom thalassaemia management and choice of iron chelators were similar. Compared to the rest of the world (ROW), baseline clinical data showed that the AP group appeared to be more loaded with iron (3745.0 vs. 2822.0 ng/ml) and had a higher proportion on deferoxamine monotherapy prior to the study (82.9 vs. 58.9%). Using a starting deferasirox dose based on transfusional iron intake and tailoring it to individual patient response, clinical efficacy based on serum ferritin reduction in AP and ROW thalassaemia patients was similar. Interestingly, the AP group developed a higher incidence of drug-related skin rash compared to ROW (18.0 vs. 7.2%), which may indicate different pharmacogenetic backgrounds in the two populations. Our analysis confirms that, with appropriate adjustment of dose, deferasirox can be clinically effective across different regions, with manageable side effects.

  16. Dosing of praziquantel by height in sub-Saharan African adults.

    PubMed

    Palha De Sousa, Chiquita A; Brigham, Tracy; Chasekwa, Bernard; Mbuya, Mduduzi N N; Tielsch, James M; Humphrey, Jean H; Prendergast, Andrew J

    2014-04-01

    The cornerstone of schistosomiasis control is mass praziquantel treatment in high prevalence areas. Adults are an important target population, given increasing recognition of the burden of male and female genital schistosomiasis. However, use of weighing scales to calculate praziquantel dosing in rural areas can be challenging. For school-age children, the World Health Organization (WHO) has approved a dose pole to simplify praziquantel dosing based on height. We modified the pediatric dose pole by adding two height categories and incorporating a simple overweight/obesity adjustment, for simplified mass treatment of adults in sub-Saharan Africa. Using the rural Zimbabwean Demographic and Health Survey data, we show that the modified dose pole with body mass index adjustment would result in > 98% of adults receiving an acceptable dose (30-60 mg/kg), with only 1.4% and 0.3% receiving an inadequate dose (< 30 mg/kg) or high dose (> 60 mg/kg), respectively. An adult dose pole may provide a more feasible alternative to weighing scales in community-based praziquantel treatment programs.

  17. Comparison of template-matching and singular-spectrum-analysis methods for imaging implanted brachytherapy seeds.

    PubMed

    Alam, S Kaisar; Mamou, Jonathan; Feleppa, Ernest J; Kalisz, Andrew; Ramachandran, Sarayu

    2011-11-01

    Brachytherapy using small implanted radioactive seeds is becoming an increasingly popular method for treating prostate cancer, in which a radiation oncologist implants seeds in the prostate transperineally under ultrasound guidance. Dosimetry software determines the optimal placement of seeds for achieving the prescribed dose based on ultrasonic determination of the gland boundaries. However, because of prostate movement and distortion during the implantation procedure, some seeds may not be placed in the desired locations; this causes the delivered dose to differ from the prescribed dose. Current ultrasonic imaging methods generally cannot depict the implanted seeds accurately. We are investigating new ultrasonic imaging methods that show promise for enhancing the visibility of seeds and thereby enabling real-time detection and correction of seed-placement errors during the implantation procedure. Real-time correction of seed-placement errors will improve the therapeutic radiation dose delivered to target tissues. In this work, we compare the potential performance of a template-matching method and a previously published method based on singular spectrum analysis for imaging seeds. In particular, we evaluated how changes in seed angle and position relative to the ultrasound beam affect seed detection. The conclusion of the present study is that singular spectrum analysis has better sensitivity but template matching is more resistant to false positives; both perform well enough to make seed detection clinically feasible over a relevant range of angles and positions. Combining the information provided by the two methods may further reduce ambiguities in determining where seeds are located.

  18. Charging for hospital pharmaceutical services: flat free based on the medication record.

    PubMed

    Wyatt, B K

    1979-03-01

    A 200-bed hospital's change in pricing drug products from a cost-plus-fee system to a flat fee per dose based on the medication administration record (MAR) is described. With the flat-fee system, drug charges are not recorded when the drug is dispensed by the pharmacy; data for charging doses are obtained directly from the MAR forms generated by the nursing staff. Charges are 55 cents per oral or suppository dose and $3.00 per injection dose. Drugs administered intravenously, topical drugs, injections costing more than $10.00 per dose, and miscellaneous nondrug items are still charged on a cost-plus-fee basis. Man-hours are saved in the pharmacy department because of the elimination of the pricing function and maintenance of price lists. The need for nursing staff to charge for any doses administered from emergency or Schedule II floor-stock supplies is eliminated. The workload for business office personnel is reduced because the number of individual charges is less than with the cost-plus charging system. The system is accepted by patients and third-party payers and has made a complete unit dose drug distribution system possible at lower cost.

  19. A review of human exposure to polybrominated diphenyl ethers (PBDEs) in China.

    PubMed

    Ni, Kun; Lu, Yonglong; Wang, Tieyu; Kannan, Kurunthachalam; Gosens, Jorrit; Xu, Li; Li, Qiushuang; Wang, Lin; Liu, Shijie

    2013-11-01

    This paper reviews recent studies on human exposure to polybrominated diphenyl ethers (PBDEs) in China, with particular focus on external exposure routes (e.g. diet and dust ingestion, inhalation of air) and internal doses based on biomonitoring studies of PBDEs (e.g. breast milk, blood and hair). PBDE concentrations reported for fish samples collected from electronic waste (e-waste) recycling sites, PBDE manufacturing sites, local markets in selected cities and estuarine areas in China have been compiled. House dust has been a significant contributor to human exposure to PBDEs in many countries. This is especially true for toddlers, who are exposed to significantly higher doses of PBDEs than adults. Infants are also exposed to high levels of PBDEs via breast-feeding. The general population's inhalation exposure to PBDEs from household products is likely a less significant source into the indoor environment. In addition, the contribution of several exposure pathways to PBDEs among various age groups was analyzed. We found that house dust contributed most to the daily exposure to PBDEs for both toddlers and adults in urban areas of China. Furthermore, workers and residents in and around electronic recycling and PBDE manufacturing sites are exposed to the highest PBDE levels among all populations studied thus far. For the occupationally exposed populations, BDE209 was the dominant congener, in most cases. Rigorous pollution prevention and occupational protection measures are needed in China to mitigate potential health effects associated with PBDE exposures.

  20. Risk assessment of soils identified on firefighter turnout gear.

    PubMed

    Easter, Elizabeth; Lander, Deborah; Huston, Tabitha

    2016-09-01

    The purpose of this research was to identify the composition of soils on firefighter turnout gear and to determine the dermal exposure risks associated with the soils. Nine used Nomex hoods from the Philadelphia fire department were analyzed for the presence of trace metals and seven sets of used turnout gear were analyzed for semi-volatile organics. Turnout gear samples were removed from areas of the gear known to have high levels of dermal absorption including the collar, armpit, wrist, and crotch areas, from either the outer shell or thermal liner layers. The following compounds were detected: polycyclic aromatic hydrocarbons (PAHs), phthalate plasticizers, and polybrominated diphenyl ether flame retardants (PBDEs). A screening risk assessment was conducted by converting the measured concentrations to an estimated dermally absorbed dose based on estimates for the permeation coefficient (Kp) and an assumed firefighting exposure scenario. Benzo(a) pyrene had the highest dermal exposure risk based on carcinogenic effects and PBDE-99 had the highest dermal exposure risk based on non-carcinogenic effects. For the metals, arsenic had the highest dermal exposure risk for the use hoods.

  1. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease

    PubMed Central

    Rey, Martial; Yang, Menglin; Lee, Linda; Zhang, Ye; Sheff, Joey G.; Sensen, Christoph W.; Mrazek, Hynek; Halada, Petr; Man, Petr; McCarville, Justin L; Verdu, Elena F.; Schriemer, David C.

    2016-01-01

    Celiac disease is triggered by partially digested gluten proteins. Enzyme therapies that complete protein digestion in vivo could support a gluten-free diet, but the barrier to completeness is high. Current options require enzyme amounts on the same order as the protein meal itself. In this study, we evaluated proteolytic components of the carnivorous pitcher plant (Nepenthes spp.) for use in this context. Remarkably low doses enhance gliadin solubilization rates, and degrade gliadin slurries within the pH and temporal constraints of human gastric digestion. Potencies in excess of 1200:1 (substrate-to-enzyme) are achieved. Digestion generates small peptides through nepenthesin and neprosin, the latter a novel enzyme defining a previously-unknown class of prolyl endoprotease. The digests also exhibit reduced TG2 conversion rates in the immunogenic regions of gliadin, providing a twin mechanism for evading T-cell recognition. When sensitized and dosed with enzyme-treated gliadin, NOD/DQ8 mice did not show intestinal inflammation, when compared to mice challenged with only pepsin-treated gliadin. The low enzyme load needed for effective digestion suggests that gluten detoxification can be achieved in a meal setting, using metered dosing based on meal size. We demonstrate this by showing efficient antigen processing at total substrate-to-enzyme ratios exceeding 12,000:1. PMID:27481162

  2. Kevlar® as a Potential Accident Radiation Dosimeter for First Responders, Law Enforcement and Military Personnel.

    PubMed

    Romanyukha, Alexander; Trompier, François; Benevides, Luis A

    2016-08-01

    Today the armed forces and law enforcement personnel wear body armor, helmets, and flak jackets composed substantially of Kevlar® fiber to prevent bodily injury or death resulting from physical, ballistic, stab, and slash attacks. Therefore, there is a high probability that during a radiation accident or its aftermath, the Kevlar®-composed body armor will be irradiated. Preliminary study with samples of Kevlar® foundation fabric obtained from body armor used by the U.S. Marine Corps has shown that all samples evaluated demonstrated an EPR signal, and this signal increased with radiation dose. Based on these results, the authors predict that, with individual calibration, exposure at dose above 1 Gy can be reliably detected in Kevlar® samples obtained from body armor. As a result of these measurements, a post-event reconstruction of exposure dose can be obtained by taking various samples throughout the armor body and helmet worn by the same irradiated individual. The doses can be used to create a whole-body dose map that would be of vital importance in a case of a partial body or heterogeneous exposure.

  3. [Estimation of the Average Glandular Dose Using the Mammary Gland Image Analysis in Mammography].

    PubMed

    Otsuka, Tomoko; Teramoto, Atsushi; Asada, Yasuki; Suzuki, Shoichi; Fujita, Hiroshi; Kamiya, Satoru; Anno, Hirofumi

    2016-05-01

    Currently, the glandular dose is evaluated quantitatively on the basis of the measured data using phantom, and not in a dose based on the mammary gland structure of an individual patient. However, mammary gland structures of the patients are different from each other and mammary gland dose of an individual patient cannot be obtained by the existing methods. In this study, we present an automated estimation method of mammary gland dose by means of mammary structure which is measured automatically using mammogram. In this method, mammary gland structure is extracted by Gabor filter; mammary region is segmented by the automated thresholding. For the evaluation, mammograms of 100 patients diagnosed with category 1 were collected. Using these mammograms we compared the mammary gland ratio measured by proposed method and visual evaluation. As a result, 78% of the total cases were matched. Furthermore, the mammary gland ratio and average glandular dose among the patients with same breast thickness was matched well. These results show that the proposed method may be useful for the estimation of average glandular dose for the individual patients.

  4. Quantitative structure - mesothelioma potency model ...

    EPA Pesticide Factsheets

    Cancer potencies of mineral and synthetic elongated particle (EP) mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. A unique and comprehensive rat intra-pleural (IP) dose characterization data set with a wide variety of EP size, shape, crystallographic, chemical, and bio-durability properties facilitated extensive statistical analyses of 50 rat IP exposure test results for evaluation of alternative dose pleural mesothelioma response models. Utilizing logistic regression, maximum likelihood evaluations of thousands of alternative dose metrics based on hundreds of individual EP dimensional variations within each test sample, four major findings emerged: (1) data for simulations of short-term EP dose changes in vivo (mild acid leaching) provide superior predictions of tumor incidence compared to non-acid leached data; (2) sum of the EP surface areas (ÓSA) from these mildly acid-leached samples provides the optimum holistic dose response model; (3) progressive removal of dose associated with very short and/or thin EPs significantly degrades resultant ÓEP or ÓSA dose-based predictive model fits, as judged by Akaike’s Information Criterion (AIC); and (4) alternative, biologically plausible model adjustments provide evidence for reduced potency of EPs with length/width (aspect) ratios 80 µm. Regar

  5. Radionuclide concentrations in soils and produce from Cochiti, Jemez, Taos, and San Ildefonso Pueblo Gardens

    SciTech Connect

    Fresquez, P.R.; Armstrong, D.R.; Salazar, J.G.

    1995-05-01

    Radionuclide ({sup 3}H, {sup 90}Sr, {sup 137}Cs, {sup 238}Pu, {sup 239}Pu, and total uranium) concentrations were determined in soils and produce collected from Cochiti, Jemez, Taos, and San Ildefonso Pueblo gardens. All radionuclides in soils from Pueblo areas were within or just above regional statistical (natural and/or worldwide fallout) reference levels. Similarily, the average levels of radionuclides in produce collected from Cochiti, Jemez, Taos, and San Ildefonso Pueblo gardens were not significantly different in produce collected from regional (background) locations. The effective (radiation) dose equivalent from consuming 352 lb of produce from Cochiti, Jemez, Taos, and San Ildefonso, after natural background has been subtracted, was 0.036 ({+-}0.016), 0.072 ({+-}0.051), 0.012 ({+-}0.027), and 0.110 ({+-}0.102) mrem/yr, respectively. The highest calculated dose, based on the mean + 2 std dev (95% confidence level), was 0.314 mrem/yr; this was <0.4% of the International Commission on Radiological Protection permissible dose limit for protecting members of the public.

  6. Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry.

    PubMed

    Macaeva, Ellina; Saeys, Yvan; Tabury, Kevin; Janssen, Ann; Michaux, Arlette; Benotmane, Mohammed A; De Vos, Winnok H; Baatout, Sarah; Quintens, Roel

    2016-01-14

    Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice.

  7. Radioisotope tracer study in a sludge hygienization research irradiator (SHRI).

    PubMed

    Pant, H J; Thýn, J; Zitný, R; Bhatt, B C

    2001-01-01

    A radioisotope tracer study has been carried out in a batch type sludge hygienization research irradiator with flow from top to bottom, the objective being to measure flow rate, circulation and mixing times and to investigate the hydrodynamic behaviour of the irradiator for identifying the cause(s) of malfunction. A stimulus-response technique with NH4(82)Br as a tracer was used to measure the above parameters. Experiments were carried out at three different flow rates, i.e 1.0, 0.64 and 0.33 m3/min. Three combined models based on a set of differential equations are proposed and used to simulate the measured tracer concentration curves. The obtained parameters were used to estimate dead volume and analyse hydrodynamic behaviour of the irradiator. The nonlinear regression problem of model parameter estimation was solved using the Marquardt-Levenberg method. The measured flow rate was found to be in good agreement with the values shown by the flow meter. The circulation times were found to be half of the mixing times. A simple approach for estimation of dose based on a known vertical dose-rate profile inside the irradiator is presented. About one-fourth of the volume of the irradiator was found to be dead at lower flow rates and this decreased with increase in flow rate. At higher flow rates, a semi stagnant volume was found with slow exchange of flow between the active and dead volumes.

  8. Estimated fluoride doses from toothpastes should be based on total soluble fluoride.

    PubMed

    Oliveira, Maria José L; Martins, Carolina C; Paiva, Saul M; Tenuta, Livia M A; Cury, Jaime A

    2013-11-01

    The fluoride dose ingested by young children may be overestimated if based on levels of total fluoride (TF) rather than levels of bioavailable fluoride (total soluble fluoride-TSF) in toothpaste. The aim of the present study was to compare doses of fluoride intake based on TF and TSF. Fluoride intake in 158 Brazilian children aged three and four years was determined after tooth brushing with their usual toothpaste (either family toothpaste (n = 80) or children's toothpaste (n = 78)). The estimated dose (mg F/day/Kg of body weight) of TF or TSF ingested was calculated from the chemical analysis of the toothpastes. Although the ingested dose of TF from the family toothpastes was higher than that from the children's toothpastes (0.074 ± 0.007 and 0.039 ± 0.003 mg F/day/Kg, respectively; p < 0.05), no difference between types of toothpaste was found regarding the ingested dose based on TSF (0.039 ± 0.005 and 0.039 ± 0.005 mg F/day/Kg, respectively; p > 0.05). The fluoride dose ingested by children from toothpastes may be overestimated if based on the TF of the product. This finding suggests that the ingested dose should be calculated based on TSF. Dose of TSF ingested by children is similar whether family or children's toothpaste is used.

  9. Six-Dimensional Correction of Intra-Fractional Prostate Motion with CyberKnife Stereotactic Body Radiation Therapy.

    PubMed

    Lei, Siyuan; Piel, Nathaniel; Oermann, Eric K; Chen, Viola; Ju, Andrew W; Dahal, Kedar N; Hanscom, Heather N; Kim, Joy S; Yu, Xia; Zhang, Guowei; Collins, Brian T; Jha, Reena; Dritschilo, Anatoly; Suy, Simeng; Collins, Sean P

    2011-01-01

    Large fraction radiation therapy offers a shorter course of treatment and radiobiological advantages for prostate cancer treatment. The CyberKnife is an attractive technology for delivering large fraction doses based on the ability to deliver highly conformal radiation therapy to moving targets. In addition to intra-fractional translational motion (left-right, superior-inferior, and anterior-posterior), prostate rotation (pitch, roll, and yaw) can increase geographical miss risk. We describe our experience with six-dimensional (6D) intra-fraction prostate motion correction using CyberKnife stereotactic body radiation therapy (SBRT). Eighty-eight patients were treated by SBRT alone or with supplemental external radiation therapy. Trans-perineal placement of four gold fiducials within the prostate accommodated X-ray guided prostate localization and beam adjustment. Fiducial separation and non-overlapping positioning permitted the orthogonal imaging required for 6D tracking. Fiducial placement accuracy was assessed using the CyberKnife fiducial extraction algorithm. Acute toxicities were assessed using Common Toxicity Criteria v3. There were no Grade 3, or higher, complications and acute morbidity was minimal. Ninety-eight percent of patients completed treatment employing 6D prostate motion tracking with intra-fractional beam correction. Suboptimal fiducial placement limited treatment to 3D tracking in two patients. Our experience may guide others in performing 6D correction of prostate motion with CyberKnife SBRT.

  10. Patient-Specific Thresholds and Doses of Intracranial Hypertension in Severe Traumatic Brain Injury.

    PubMed

    Lazaridis, Christos; Smielewski, Peter; Menon, David K; Hutchinson, Peter; Pickard, John D; Czosnyka, Marek

    2016-01-01

    Based on continuous monitoring of the pressure reactivity index (PRx), we defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. We hypothesized that an "ICP dose" based on individually assessed ICP thresholds might correlate more closely with 6-month outcome compared with ICP doses derived from the recommended universal thresholds of 20 and 25 mmHg. Data from 327 patients with severe traumatic brain injury (TBI) were analyzed. ICP doses were computed as the cumulative area under the curve above the defined thresholds in graphing ICP versus time. The term Dose 20 (D20) was used to refer to an ICP threshold of 20 mm Hg. The markers D25 and DPRx were calculated similarly. The discriminative ability of each dose with regard to mortality was assessed by receiver operating characteristics analysis using fivefold cross-validation (CV). DPRx was found to be the best discriminator of mortality, despite the fact that D20 was twice as large as DPRx. Individualized doses of intracranial hypertension were stronger predictors of mortality than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method of individualizing the ICP threshold.

  11. A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

    PubMed

    Zang, Yong; Lee, J Jack

    2017-01-15

    We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Assessment of knowledge and awareness among radiology personnel regarding current computed tomography technology and radiation dose

    NASA Astrophysics Data System (ADS)

    Karim, M. K. A.; Hashim, S.; Bradley, D. A.; Bahruddin, N. A.; Ang, W. C.; Salehhon, N.

    2016-03-01

    In this paper, we evaluate the level of knowledge and awareness among 120 radiology personnel working in 7 public hospitals in Johor, Malaysia, concerning Computed Tomography (CT) technology and radiation doses based on a set of questionnaires. Subjects were divided into two groups (Medical profession (Med, n=32) and Allied health profession (AH, n=88). The questionnaires are addressed: (1) demographic data (2) relative radiation dose and (3) knowledge of current CT technology. One-third of respondents from both groups were able to estimate relative radiation dose for routine CT examinations. 68% of the allied health profession personnel knew of the Malaysia regulations entitled ‘Basic Safety Standard (BSS) 2010’, although notably 80% of them had previously attended a radiation protection course. No significant difference (p < 0.05) in mean scores of CT technology knowledge detected between the two groups, with the medical professions producing a mean score of (26.7 ± 2.7) and the allied health professions a mean score of (25.2 ± 4.3). This study points to considerable variation among the respondents concerning their understanding of knowledge and awareness of risks of radiation and CT optimization techniques.

  13. System for interstitial photodynamic therapy with online dosimetry: first clinical experiences of prostate cancer

    NASA Astrophysics Data System (ADS)

    Swartling, Johannes; Axelsson, Johan; Ahlgren, Göran; Kälkner, Karl Mikael; Nilsson, Sten; Svanberg, Sune; Svanberg, Katarina; Andersson-Engels, Stefan

    2010-09-01

    The first results from a clinical study for Temoporfin-mediated photodynamic therapy (PDT) of low-grade (T1c) primary prostate cancer using online dosimetry are presented. Dosimetric feedback in real time was applied, for the first time to our knowledge, in interstitial photodynamic therapy. The dosimetry software IDOSE provided dose plans, including optical fiber positions and light doses based on 3-D tissue models generated from ultrasound images. Tissue optical property measurements were obtained using the same fibers used for light delivery. Measurements were taken before, during, and after the treatment session. On the basis of these real-time measured optical properties, the light-dose plan was recalculated. The aim of the treatment was to ablate the entire prostate while minimizing exposure to surrounding organs. The results indicate that online dosimetry based on real-time tissue optical property measurements enabled the light dose to be adapted and optimized. However, histopathological analysis of tissue biopsies taken six months post-PDT treatment showed there were still residual viable cancer cells present in the prostate tissue sections. The authors propose that the incomplete treatment of the prostate tissue could be due to a too low light threshold dose, which was set to 5 J/cm2.

  14. Doxylamine pharmacokinetics following single dose oral administration in children ages 2-17 years.

    PubMed

    Balan, Guhan; Thompson, Gary A; Gibb, Roger; Li, Lijuan; Hull, David; Seeck, Molly

    2013-11-01

    To characterize doxylamine pharmacokinetics in children. This study was conducted in 41 subjects, ages 2-17 years. Doxylamine succinate doses based on age/weight ranged from 3.125 to 12.5 mg. A single oral dose was administered with 2 to 4 oz. of water or decaffeinated beverages ∼2 hours after a light breakfast. Plasma samples were obtained before and for 72 hours after dosing and analyzed for doxylamine using HPLC MS/MS. Pharmacokinetic parameters were estimated using non-compartmental methods and relationships with age were assessed using linear regression. Over the fourfold dose range, Cmax was similar while AUC increased only 60%, although not statistically significant (P-value = 0.0517). As expected due to increasing body size, CLo and Vz /F increased with age. Due to a similar increase with age for Clo and Vz /F, no age-related differences in t1/2,z were observed (∼16 hours). Allometric scaling indicated no maturation related changes in CLo ; although Vz /F remained age-dependent, the predicted range decreased ∼70%. Overall, the single doses were well tolerated. Somnolence was the most common reported AE with no apparent differences in incidence noted with age. An age/weight dosing nomogram utilizing a fourfold range of doses achieves similar Cmax , whereas AUC increases only 60%.

  15. Pharmacokinetics of cyclosporine after renal transplant in children.

    PubMed

    Mochon, M; Cooney, G; Lum, B; Caputo, G C; Dunn, S; Goldsmith, B; Baluarte, H J; Polinsky, M S; Kaiser, B A

    1996-07-01

    The pharmacokinetics of cyclosporine and the relationship between blood levels and average drug concentration were prospectively evaluated in 18 children 1 month after renal transplantation. All children had normal renal function and no hepatic or gastrointestinal dysfunction. Cyclosporine was administered after an overnight fast, and serial blood samples were drawn over a 24-hour period. Analysis of cyclosporine levels was performed by means of monoclonal radio immunoassay on whole blood. Children were divided into three age groups for comparison: 2-5 years, 5-10 years, and > 10 years. There were no differences between age groups in serum protein, serum lipids, or hemoglobin levels, or in the pharmacokinetic parameters of cyclosporine except as follows: significant differences were noted in cyclosporine dose based on body weight, apparent steady-state volume of distribution, and apparent blood clearance, with the youngest children (2-5) requiring higher doses, a relative greater distribution, and exhibiting more rapid drug clearance than those > 10 years of age. In addition, we observed diurnal variation in trough levels, with morning levels (0 hr) significantly higher than those obtained in the evening (12 hours after administration of cyclosporine). Trough levels demonstrated a fair correlation with area under the concentration-time curve (AUC) and average concentration (Cav), but an abbreviated kinetic profile using cyclosporine levels 1 and 3.5 hours after administration accurately predicted AUC.

  16. An automated voxelized dosimetry tool for radionuclide therapy based on serial quantitative SPECT/CT imaging

    SciTech Connect

    Jackson, Price A.; Kron, Tomas; Beauregard, Jean-Mathieu; Hofman, Michael S.; Hogg, Annette; Hicks, Rodney J.

    2013-11-15

    Purpose: To create an accurate map of the distribution of radiation dose deposition in healthy and target tissues during radionuclide therapy.Methods: Serial quantitative SPECT/CT images were acquired at 4, 24, and 72 h for 28 {sup 177}Lu-octreotate peptide receptor radionuclide therapy (PRRT) administrations in 17 patients with advanced neuroendocrine tumors. Deformable image registration was combined with an in-house programming algorithm to interpolate pharmacokinetic uptake and clearance at a voxel level. The resultant cumulated activity image series are comprised of values representing the total number of decays within each voxel's volume. For PRRT, cumulated activity was translated to absorbed dose based on Monte Carlo-determined voxel S-values at a combination of long and short ranges. These dosimetric image sets were compared for mean radiation absorbed dose to at-risk organs using a conventional MIRD protocol (OLINDA 1.1).Results: Absorbed dose values to solid organs (liver, kidneys, and spleen) were within 10% using both techniques. Dose estimates to marrow were greater using the voxelized protocol, attributed to the software incorporating crossfire effect from nearby tumor volumes.Conclusions: The technique presented offers an efficient, automated tool for PRRT dosimetry based on serial post-therapy imaging. Following retrospective analysis, this method of high-resolution dosimetry may allow physicians to prescribe activity based on required dose to tumor volume or radiation limits to healthy tissue in individual patients.

  17. Assessment of MLC tracking performance during hypofractionated prostate radiotherapy using real-time dose reconstruction

    NASA Astrophysics Data System (ADS)

    Fast, M. F.; Kamerling, C. P.; Ziegenhein, P.; Menten, M. J.; Bedford, J. L.; Nill, S.; Oelfke, U.

    2016-02-01

    By adapting to the actual patient anatomy during treatment, tracked multi-leaf collimator (MLC) treatment deliveries offer an opportunity for margin reduction and healthy tissue sparing. This is assumed to be especially relevant for hypofractionated protocols in which intrafractional motion does not easily average out. In order to confidently deliver tracked treatments with potentially reduced margins, it is necessary to monitor not only the patient anatomy but also the actually delivered dose during irradiation. In this study, we present a novel real-time online dose reconstruction tool which calculates actually delivered dose based on pre-calculated dose influence data in less than 10 ms at a rate of 25 Hz. Using this tool we investigate the impact of clinical target volume (CTV) to planning target volume (PTV) margins on CTV coverage and organ-at-risk dose. On our research linear accelerator, a set of four different CTV-to-PTV margins were tested for three patient cases subject to four different motion conditions. Based on this data, we can conclude that tracking eliminates dose cold spots which can occur in the CTV during conventional deliveries even for the smallest CTV-to-PTV margin of 1 mm. Changes of organ-at-risk dose do occur frequently during MLC tracking and are not negligible in some cases. Intrafractional dose reconstruction is expected to become an important element in any attempt of re-planning the treatment plan during the delivery based on the observed anatomy of the day.

  18. Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science – Addressing the ODWAC New Recommendation

    PubMed Central

    Dingwall, S.; Mills, C.E.; Phan, N.; Taylor, K.; Boreham, D.R.

    2011-01-01

    Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered. The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from

  19. Air pollution and health in urban areas.

    PubMed

    Schwela, D

    2000-01-01

    In this paper, recent reviews of the World Health Organization, other review papers, and more recent literature on the human health effects of current air pollution trends in urban areas are reviewed and summarized as follows: Sulphur dioxide. Some studies, but not others, found associations between sulphur dioxide (SO2) exposure and daily mortality and morbidity. Single-pollutant correlations sometimes disappeared when other pollutants, especially suspended particulate matter (SPM), were included. Cross-sectional studies with asthmatics revealed significant, non-threshold relations between SO2 and decrements of the forced expiratory volume in 1 second (FEV1). Nitrogen dioxide. Weak associations between short-term nitrogen dioxide (NO2) exposure from gas cooking and respiratory symptoms and a decrement in lung function parameters were found in children, but not consistently in exposed women. With long-term exposure, children, but not adults, exhibit increased respiratory symptoms, decreased lung function, and increased incidences of chronic cough, bronchitis, and conjunctivitis. A causal relationship between NO2 exposure and adverse health effects has not yet been established. Carbon monoxide. Binding of CO in the lungs with hemoglobin in the blood forms carboxyhemoglobin (COHb), which impairs the transport of oxygen. The health effects of CO include hypoxia, neurological deficits and neurobehavioral changes, and increases in daily mortality and hospital admissions for cardiovascular diseases. The latter persists even at very low CO levels, indicating no threshold for the onset of these effects. Whether the relation between daily mortality and exposure to CO are causal or whether CO might act as a proxy for SPM is still an open question. Ambient CO may have even more serious health consequences than does COHb formation and at lower levels than that mediated through elevated COHb levels. Ozone. Short-term acute effects of O3 include pulmonary function decrements

  20. Human Health and the Biological Effects of Tritium in Drinking Water: Prudent Policy Through Science - Addressing the ODWAC New Recommendation.

    PubMed

    Dingwall, S; Mills, C E; Phan, N; Taylor, K; Boreham, D R

    2011-02-22

    Tritium is a radioactive form of hydrogen and is a by-product of energy production in Canadian Deuterium Uranium (CANDU) reactors. The release of this radioisotope into the environment is carefully managed at CANDU facilities in order to minimize radiation exposure to the public. However, under some circumstances, small accidental releases to the environment can occur. The radiation doses to humans and non-human biota from these releases are low and orders of magnitude less than doses received from naturally occurring radioisotopes or from manmade activities, such as medical imaging and air travel. There is however a renewed interest in the biological consequences of low dose tritium exposures and a new limit for tritium levels in Ontario drinking water has been proposed. The Ontario Drinking Water Advisory Council (ODWAC) issued a formal report in May 2009 in response to a request by the Minister of the Environment, concluding that the Ontario Drinking Water Quality Standard for tritium should be revised from the current 7,000 Bq/L level to a new, lower 20 Bq/L level. In response to this recommendation, an international scientific symposium was held at McMaster University to address the issues surrounding this change in direction and the validity of a new policy. Scientists, regulators, government officials, and industrial stakeholders were present to discuss the potential health risks associated with low level radiation exposure from tritium. The regulatory, economic, and social implications of the new proposed limit were also considered.The new recommendation assumed a linear-no-threshold model to calculate carcinogenic risk associated with tritium exposure, and considered tritium as a non-threshold chemical carcinogen. Both of these assumptions are highly controversial given that recent research suggests that low dose exposures have thresholds below which there are no observable detrimental effects. Furthermore, mutagenic and carcinogenic risk calculated from

  1. Corrective Action Investigation Plan for Corrective Action Unit 104: Area 7 Yucca Flat Atmospheric Test Sites, Nevada National Security Site, Nevada, Revision 0

    SciTech Connect

    Patrick Matthews

    2011-08-01

    of the total effective dose (TED) to the dose-based final action level (FAL). The presence of TED exceeding the FAL is considered a radiological contaminant of concern (COC). Anything identified as a COC will require corrective action. The TED will be calculated as the total of separate estimates of internal and external dose. Results from the analysis of soil samples will be used to calculate internal radiological dose. Thermoluminescent dosimeters will be used to measure external radiological dose. Based on process knowledge of the releases associated with the nuclear tests and radiological survey information about the location and shape of the resulting contamination plume, it was determined that the releases from the nuclear tests are co-located and will be investigated concurrently. A field investigation will be performed to define areas where TED exceeds the FAL and to determine whether other COCs are present at the site. The investigation will also collect information to determine the presence and nature of contamination associated with migration and excavation, as well as any potential releases discovered during the investigation. Appendix A provides a detailed discussion of the DQO methodology and the DQOs specific to each CAS.

  2. Validation of a deformable image registration technique for cone beam CT-based dose verification

    SciTech Connect

    Moteabbed, M. Sharp, G. C.; Wang, Y.; Trofimov, A.; Efstathiou, J. A.; Lu, H.-M.

    2015-01-15

    Purpose: As radiation therapy evolves toward more adaptive techniques, image guidance plays an increasingly important role, not only in patient setup but also in monitoring the delivered dose and adapting the treatment to patient changes. This study aimed to validate a method for evaluation of delivered intensity modulated radiotherapy (IMRT) dose based on multimodal deformable image registration (DIR) for prostate treatments. Methods: A pelvic phantom was scanned with CT and cone-beam computed tomography (CBCT). Both images were digitally deformed using two realistic patient-based deformation fields. The original CT was then registered to the deformed CBCT resulting in a secondary deformed CT. The registration quality was assessed as the ability of the DIR method to recover the artificially induced deformations. The primary and secondary deformed CT images as well as vector fields were compared to evaluate the efficacy of the registration method and it’s suitability to be used for dose calculation. PLASTIMATCH, a free and open source software was used for deformable image registration. A B-spline algorithm with optimized parameters was used to achieve the best registration quality. Geometric image evaluation was performed through voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric evaluation, IMRT treatment plans were created and optimized on the original CT image and recomputed on the two warped images to be compared. The dose volume histograms were compared for the warped structures that were identical in both warped images. This procedure was repeated for the phantom with full, half full, and empty bladder. Results: The results indicated mean HU differences of up to 120 between registered and ground-truth deformed CT images. However, when the CBCT intensities were calibrated using a region of interest (ROI)-based calibration curve, these differences were reduced by up to 60%. Similarly, the mean differences in average vector field

  3. Measuring and Modeling Naturally Occurring Radioactive Material: Interpreting the Relationship Between the Natural Radionuclides Present

    SciTech Connect

    Lombardo, A.J.; Mucha, A.F.

    2008-07-01

    decay series radionuclides, the resulting TENORM source term may contain several smaller decay chains, each headed by a different longer lived member of the original series. This paper presents the anatomy of common TENORM source terms and the pitfalls of measuring, interpreting and modeling these source terms. Modeling TENORM with common software such as RESRAD is discussed. In summary: RESRAD modeling (dose assessments) to derive single radionuclide, dose based acceptance criteria, requires a good understanding of the physical, chemical and biological factors/input parameters applicable to the selected exposure scenario(s). When NORM or TENORM source terms are modeled, an additional understanding of the status of equilibrium, is necessary to accurately perform a dose assessment in support of dose based acceptance criteria. Historical information about the site processes/ores, selection of appropriate analytical analyses to identify key decay series radionuclide and a comprehensive review of the characterization data are needed to understand the equilibrium status of the decay series present. Once the source term has been characterized (in regards to relative activities of the radionuclides within a decay series) the source term must be input into RESRAD to reflect that status of equilibrium at time zero, or at the time since placement, if the characterization data reflects the equilibrium status of dated material. When the RESRAD output file is reviewed, depending on the time of maximum dose, DCGL values may be artificially high in value. Sum of fraction calculations, based on the status of equilibrium of each decay series, can also be used to assess the RESRAD results and develop an appropriate MARSSIM final status survey protocol. (authors)

  4. Corrective Action Investigation Plan for Corrective Action Unit 366: Area 11 Plutonium Valley Dispersion Sites, Nevada National Security Site, Nevada, Revision 0

    SciTech Connect

    Patrick Matthews

    2011-09-01

    Corrective Action Unit 366 comprises the six corrective action sites (CASs) listed below: (1) 11-08-01, Contaminated Waste Dump No.1; (2) 11-08-02, Contaminated Waste Dump No.2; (3) 11-23-01, Radioactively Contaminated Area A; (4) 11-23-02, Radioactively Contaminated Area B; (5) 11-23-03, Radioactively Contaminated Area C; and (6) 11-23-04, Radioactively Contaminated Area D. These sites are being investigated because existing information on the nature and extent of potential contamination is insufficient to evaluate and recommend corrective action alternatives (CAAs). Additional information will be obtained by conducting a corrective action investigation before evaluating CAAs and selecting the appropriate corrective action for each CAS. The results of the field investigation will support a defensible evaluation of CAAs that will be presented in the Corrective Action Decision Document. The sites will be investigated based on the data quality objectives (DQOs) developed July 6, 2011, by representatives of the Nevada Division of Environmental Protection and the U.S. Department of Energy (DOE), National Nuclear Security Administration Nevada Site Office. The DQO process was used to identify and define the type, amount, and quality of data needed to develop and evaluate appropriate corrective actions for CAU 366. The presence and nature of contamination at CAU 366 will be evaluated based on information collected from a field investigation. Radiological contamination will be evaluated based on a comparison of the total effective dose (TED) at sample locations to the dose-based final action level (FAL). The TED will be calculated by summing the estimates of internal and external dose. Results from the analysis of soil samples collected from sample plots will be used to calculate internal radiological dose. Thermoluminescent dosimeters placed at each sample location will be used to measure external radiological dose. Based on historical documentation of the releases

  5. Characterization of the homogeneous tissue mixture approximation in breast imaging dosimetry

    SciTech Connect

    Sechopoulos, Ioannis; Bliznakova, Kristina; Qin Xulei; Fei Baowei; Feng, Steve Si Jia

    2012-08-15

    Purpose: To compare the estimate of normalized glandular dose in mammography and breast CT imaging obtained using the actual glandular tissue distribution in the breast to that obtained using the homogeneous tissue mixture approximation. Methods: Twenty volumetric images of patient breasts were acquired with a dedicated breast CT prototype system and the voxels in the breast CT images were automatically classified into skin, adipose, and glandular tissue. The breasts in the classified images underwent simulated mechanical compression to mimic the conditions present during mammographic acquisition. The compressed thickness for each breast was set to that achieved during each patient's last screening cranio-caudal (CC) acquisition. The volumetric glandular density of each breast was computed using both the compressed and uncompressed classified images, and additional images were created in which all voxels representing adipose and glandular tissue were replaced by a homogeneous mixture of these two tissues in a proportion corresponding to each breast's volumetric glandular density. All four breast images (compressed and uncompressed; heterogeneous and homogeneous tissue) were input into Monte Carlo simulations to estimate the normalized glandular dose during mammography (compressed breasts) and dedicated breast CT (uncompressed breasts). For the mammography simulations the x-ray spectra used was that used during each patient's last screening CC acquisition. For the breast CT simulations, two x-ray spectra were used, corresponding to the x-ray spectra with the lowest and highest energies currently being used in dedicated breast CT prototype systems under clinical investigation. The resulting normalized glandular dose for the heterogeneous and homogeneous versions of each breast for each modality was compared. Results: For mammography, the normalized glandular dose based on the homogeneous tissue approximation was, on average, 27% higher than that estimated using the

  6. Validation of a deformable image registration technique for cone beam CT-based dose verification

    PubMed Central

    Moteabbed, M.; Sharp, G. C.; Wang, Y.; Trofimov, A.; Efstathiou, J. A.; Lu, H.-M.

    2015-01-01

    Purpose: As radiation therapy evolves toward more adaptive techniques, image guidance plays an increasingly important role, not only in patient setup but also in monitoring the delivered dose and adapting the treatment to patient changes. This study aimed to validate a method for evaluation of delivered intensity modulated radiotherapy (IMRT) dose based on multimodal deformable image registration (dir) for prostate treatments. Methods: A pelvic phantom was scanned with CT and cone-beam computed tomography (CBCT). Both images were digitally deformed using two realistic patient-based deformation fields. The original CT was then registered to the deformed CBCT resulting in a secondary deformed CT. The registration quality was assessed as the ability of the dir method to recover the artificially induced deformations. The primary and secondary deformed CT images as well as vector fields were compared to evaluate the efficacy of the registration method and it’s suitability to be used for dose calculation. plastimatch, a free and open source software was used for deformable image registration. A B-spline algorithm with optimized parameters was used to achieve the best registration quality. Geometric image evaluation was performed through voxel-based Hounsfield unit (HU) and vector field comparison. For dosimetric evaluation, IMRT treatment plans were created and optimized on the original CT image and recomputed on the two warped images to be compared. The dose volume histograms were compared for the warped structures that were identical in both warped images. This procedure was repeated for the phantom with full, half full, and empty bladder. Results: The results indicated mean HU differences of up to 120 between registered and ground-truth deformed CT images. However, when the CBCT intensities were calibrated using a region of interest (ROI)-based calibration curve, these differences were reduced by up to 60%. Similarly, the mean differences in average vector field

  7. Development of PET imaging-based dose-painting prescriptions

    NASA Astrophysics Data System (ADS)

    Bowen, Stephen R.

    Historically, prescriptions in radiation therapy are based on physician experience drawn from the results of extensive clinical trials in order to establish standard-of-care guidelines. The doses of radiation are generally uniform across target volumes to reflect a fixed level of local neoplastic disease control of the population mean. However, inter-patient and intra-tumor variation in response to uniform doses can result in diminished tumor control and poor clinical outcome for certain patients. Recent research endeavors are emphasizing the need to individualize prescriptions by incorporating patient-specific biological markers with prognostic and predictive value. Quantitative imaging with positron emission tomography (PET) of tumor glucose metabolism, cell proliferation, and hypoxia has been suggested as a sensitive and specific technique to tailor patient prescriptions in a manner that may significantly improve clinical outcome. The concept of prescribing and delivering non-uniform dose based on molecular imaging, termed dose painting, hinges on the establishment of a dose-response relationship at the image voxel scale that optimizes a particular clinical endpoint. This doctoral thesis presented two methods of defining dose-painting prescriptions based on PET imaging: the first was a heuristic model derivation of hypoxia dose-painting prescriptions in head-and-neck cancer patients; the second was an empirical imaging surrogate endpoint derivation of prescriptions in veterinary sinonasal cancer patients. The clinical implementation of these dose painting prescriptions was investigated, which emphasized treatment planning and delivery solutions. Lastly, a summary and discussion of the future of dose painting to forge links between tumor biology and clinical outcome was presented. The compelling dose painting concept is fast becoming a clinical reality that may positively impact cancer patient lives.

  8. The Safety Evaluation of Salvianolic Acid B and Ginsenoside Rg1 Combination on Mice

    PubMed Central

    Zhao, Qun; Yang, Min; Deng, Yanping; Yu, Haitao; Wang, Linlin; Teng, Fukang; Cho, Kenka; Ma, Hongmei; Wu, Peng; Li, Xue; Wu, Wanying; Liu, Xuan; Xu, Feng; Jiang, Baohong; Guo, De-An

    2015-01-01

    Our previous study indicated that the combination of salvianolic acid B (SalB) and ginsenoside Rg1 (Rg1), the main components of Salvia miltiorrhizae and Panax notoginseng, improves myocardium structure and ventricular function in rats with ischemia/reperfusion injury. The present study aimed to determine the safety of the combined SalB and Rg1 (SalB-Rg1) in mice. The safety of SalB-Rg1 was evaluated through acute toxicity and repeated-dose toxicity. In the acute toxicity study, the up and down procedure was carried out firstly, and then, the Bliss method was applied. In the toxicity study for seven-day repeated treatment of SalB-Rg1, forty Kunming mice were randomly divided into four groups. The intravenous median lethal dose (LD50) of the SalB-Rg1 combination was 1747 mg/kg using the Bliss method. For both the acute toxicity study and the seven-day repeated toxicity study, SalB-Rg1 did not induce significant abnormality on brain, heart, kidney, liver and lung structure at any dose based on H&E stain. There were no significant changes related to the SalB-Rg1 toxicity detected on biochemical parameters for two kinds of toxicity studies. The LD50 in mice was 1747 mg/kg, which was more than one hundred times higher than the effective dose. Both studies of acute toxicity and seven-day repeated dose toxicity indicated the safety of the SalB-Rg1 combination. PMID:26690140

  9. The development of the plutonium lung clearance model for exposure estimation of the Mayak production association, nuclear plant workers.

    PubMed

    Khokhryakov, Valentin F; Suslova, Klara G; Vostrotin, Vadim V; Romanov, Sergey A; Menshikh, Zoya S; Kudryavtseva, Tamara I; Filipy, Ronald E; Miller, Scott C; Krahenbuhl, Melinda P

    2002-04-01

    The purpose of this study was to develop a biokinetic model that uses urinary plutonium excretion rate data to estimate the plutonium accumulation in the human respiratory tract after occupational exposure. The model is based on autopsy and urinalysis data, specifically the plutonium distribution between the respiratory tract and the remainder of the body, taken from 543 former workers of a radiochemical facility at the Mayak Production Association (MPA) plant. The metabolism of plutonium was represented with a compartmental model, which considers individual exposure histories and the inherent solubility properties of industrial plutonium aerosols. The transport properties of plutonium-containing aerosols were estimated by experimentally defining their in vitro solubility. The in vitro solubilities were found by dialysis in a Ringer's solution. Analysis of the autopsy data indicated that a considerable fraction of the inhaled plutonium is systemically redistributed rapidly after inhalation. After the initial dynamic period, a three-compartment model describes the retention in the respiratory tract. One compartment describes the nuclide retained in the lungs, the second compartment describes a plutonium lung concentration that exponentially decreases with time, and the third compartment describes the concentration in the pulmonary lymph nodes. The model parameters were estimated by minimizing sum squared of the error between the tissue and bioassay data and the model results. The parameters reflect the inverse relationship between plutonium retention in lungs and the experimentally derived aerosol transportability. The model was validated by comparing the autopsy results with in vivo data for 347 cases. The validation indicates that the model parameters are unbiased. This model is being used to estimate individual levels of nuclide accumulation and to compute radiation doses based upon the urinary excretion rates.

  10. Molecular imaging-based dose painting: a novel paradigm for radiation therapy prescription.

    PubMed

    Bentzen, Søren M; Gregoire, Vincent

    2011-04-01

    Dose painting is the prescription of a nonuniform radiation dose distribution to the target volume based on functional or molecular images shown to indicate the local risk of relapse. Two prototypical strategies for implementing this novel paradigm in radiation oncology are reviewed: subvolume boosting and dose painting by numbers. Subvolume boosting involves the selection of a "target within the target," defined by image segmentation on the basis of the quantitative information in the image or morphologically, and this is related to image-based target volume selection and delineation. Dose painting by numbers is a voxel-level prescription of dose based on a mathematical transformation of the image intensity of individual pixels. The quantitative use of images to decide both where and how to delivery radiation therapy in an individual case is also called theragnostic imaging. Dose painting targets are imaging surrogates for cellular or microenvironmental phenotypes associated with poor radioresponsiveness. In this review, the focus is on the following positron emission tomography tracers: FDG and choline as surrogates for tumor burden, fluorothymidine as a surrogate for proliferation (or cellular growth fraction) and hypoxia-sensitive tracers, including [(18)F] fluoromisonidazole, EF3, EF5, and (64)Cu-labeled copper(II) diacetyl-di(N(4)-methylthiosemicarbazone) as surrogates of cellular hypoxia. Research advances supporting the clinicobiological rationale for dose painting are reviewed as are studies of the technical feasibility of optimizing and delivering realistic dose painted radiation therapy plans. Challenges and research priorities in this exciting research field are defined and a possible design for a randomized clinical trial of dose painting is presented.

  11. SU-E-T-789: Validation of 3DVH Accuracy On Quantifying Delivery Errors Based On Clinical Relevant DVH Metrics

    SciTech Connect

    Ma, T; Kumaraswamy, L

    2015-06-15

    Purpose: Detection of treatment delivery errors is important in radiation therapy. However, accurate quantification of delivery errors is also of great importance. This study aims to evaluate the 3DVH software’s ability to accurately quantify delivery errors. Methods: Three VMAT plans (prostate, H&N and brain) were randomly chosen for this study. First, we evaluated whether delivery errors could be detected by gamma evaluation. Conventional per-beam IMRT QA was performed with the ArcCHECK diode detector for the original plans and for the following modified plans: (1) induced dose difference error up to ±4.0% and (2) control point (CP) deletion (3 to 10 CPs were deleted) (3) gantry angle shift error (3 degree uniformly shift). 2D and 3D gamma evaluation were performed for all plans through SNC Patient and 3DVH, respectively. Subsequently, we investigated the accuracy of 3DVH analysis for all cases. This part evaluated, using the Eclipse TPS plans as standard, whether 3DVH accurately can model the changes in clinically relevant metrics caused by the delivery errors. Results: 2D evaluation seemed to be more sensitive to delivery errors. The average differences between ECLIPSE predicted and 3DVH results for each pair of specific DVH constraints were within 2% for all three types of error-induced treatment plans, illustrating the fact that 3DVH is fairly accurate in quantifying the delivery errors. Another interesting observation was that even though the gamma pass rates for the error plans are high, the DVHs showed significant differences between original plan and error-induced plans in both Eclipse and 3DVH analysis. Conclusion: The 3DVH software is shown to accurately quantify the error in delivered dose based on clinically relevant DVH metrics, where a conventional gamma based pre-treatment QA might not necessarily detect.

  12. Median infectious dose (ID₅₀) of porcine reproductive and respiratory syndrome virus isolate MN-184 via aerosol exposure.

    PubMed

    Cutler, Timothy D; Wang, Chong; Hoff, Steven J; Kittawornrat, Apisit; Zimmerman, Jeffrey J

    2011-08-05

    The median infectious dose (ID(50)) of porcine reproductive and respiratory syndrome (PRRS) virus isolate MN-184 was determined for aerosol exposure. In 7 replicates, 3-week-old pigs (n=58) respired 10l of airborne PRRS virus from a dynamic aerosol toroid (DAT) maintained at -4°C. Thereafter, pigs were housed in isolation and monitored for evidence of infection. Infection occurred at virus concentrations too low to quantify by microinfectivity assays. Therefore, exposure dose was determined using two indirect methods ("calculated" and "theoretical"). "Calculated" virus dose was derived from the concentration of rhodamine B monitored over the exposure sequence. "Theoretical" virus dose was based on the continuous stirred-tank reactor model. The ID(50) estimate was modeled on the proportion of pigs that became infected using the probit and logit link functions for both "calculated" and "theoretical" exposure doses. Based on "calculated" doses, the probit and logit ID(50) estimates were 1 × 10(-0.13)TCID(50) and 1 × 10(-0.14)TCID(50), respectively. Based on "theoretical" doses, the probit and logit ID(50) were 1 × 10(0.26)TCID(50) and 1 × 10(0.24)TCID(50), respectively. For each point estimate, the 95% confidence interval included the other three point estimates. The results indicated that MN-184 was far more infectious than PRRS virus isolate VR-2332, the only other PRRS virus isolate for which ID(50) has been estimated for airborne exposure. Since aerosol ID(50) estimates are available for only these two isolates, it is uncertain whether one or both of these isolates represent the normal range of PRRS virus infectivity by this route.

  13. SU-E-T-596: P3DVHStats - a Novel, Automatic, Institution Customizable Program to Compute and Report DVH Quantities On Philips Pinnacle TPS

    SciTech Connect

    Wu, C

    2015-06-15

    Purpose: To implement a novel, automatic, institutional customizable DVH quantities evaluation and PDF report tool on Philips Pinnacle treatment planning system (TPS) Methods: An add-on program (P3DVHStats) is developed by us to enable automatic DVH quantities evaluation (including both volume and dose based quantities, such as V98, V100, D2), and automatic PDF format report generation, for EMR convenience. The implementation is based on a combination of Philips Pinnacle scripting tool and Java language pre-installed on each Pinnacle Sun Solaris workstation. A single Pinnacle script provide user a convenient access to the program when needed. The activated script will first export DVH data for user selected ROIs from current Pinnacle plan trial; a Java program then provides a simple GUI interface, utilizes the data to compute any user requested DVH quantities, compare with preset institutional DVH planning goals; if accepted by users, the program will also generate a PDF report of the results and export it from Pinnacle to EMR import folder via FTP. Results: The program was tested thoroughly and has been released for clinical use at our institution (Pinnacle Enterprise server with both thin clients and P3PC access), for all dosimetry and physics staff, with excellent feedback. It used to take a few minutes to use MS-Excel worksheet to calculate these DVH quantities for IMRT/VMAT plans, and manually save them as PDF report; with the new program, it literally takes a few mouse clicks in less than 30 seconds to complete the same tasks. Conclusion: A Pinnacle scripting and Java language based program is successfully implemented, customized to our institutional needs. It is shown to dramatically reduce time and effort needed for DVH quantities computing and EMR reporting.

  14. Treatment Planning for MRI Assisted Brachytherapy of Gynecologic Malignancies Based on Total Dose Constraints

    SciTech Connect

    Lang, Stefan Kirisits, Christian; Dimopoulos, Johannes; Georg, Dietmar; Poetter, Richard

    2007-10-01

    Purpose: To develop a method for treatment planning and optimization of magnetic resonance imaging (MRI)-assisted gynecologic brachytherapy that includes biologically weighted total dose constraints. Methods and Materials: The applied algorithm is based on the linear-quadratic model and includes dose, dose rate, and fractionation of the whole radiotherapy setting, consisting of external beam therapy plus high-dose-rate (HDR), low-dose-rate (LDR) or pulsed-dose rate (PDR) brachytherapy. Biologically effective doses (BED) are converted to more familiar isoeffective (equivalent) doses in 2-Gy fractions. For individual treatment planning of each brachytherapy fraction, the algorithm calculates the physical dose per brachytherapy fraction that corresponds to a predefined isoeffective total dose constraint. Achieved target dose and sparing of organs at risk of already delivered brachytherapy fractions are incorporated. Results: Since implementation for use in clinical routine in 2001, MRI assisted treatment plans of 216 gynecologic patients (161 HDR, 55 PDR brachytherapy) were prospectively optimized taking into account isoeffective dose-volume histogram-based total dose constraints for high-risk clinical target volume (HR CTV) and organs at risk (bladder, rectum, sigmoid). The algorithm is implemented in a spreadsheet and the procedure is fast and efficient. An uncertainty analysis of the isoeffective total doses based on variations of tissue parameters shows that confidence intervals are larger for PDR compared with HDR brachytherapy. For common treatment schedules, overall uncertainties of high-risk clinical target volume and organs at risk are within 8 Gy, except for the bladder when using the PDR technique. Conclusion: The presented method to respect total dose constraints is reliable and efficient and an essential tool when aiming to increase local control and minimize side effects.

  15. Phase I, multicenter, open-label, dose-escalation study of sonidegib in Asian patients with advanced solid tumors.

    PubMed

    Minami, Hironobu; Ando, Yuichi; Ma, Brigette Buig Yue; Hsiang Lee, Jih-; Momota, Hiroyuki; Fujiwara, Yutaka; Li, Leung; Fukino, Koichi; Ito, Koji; Tajima, Takeshi; Mori, Asuka; Lin, Chia-Chi

    2016-10-01

    Sonidegib is a selective inhibitor of Smoothened receptor, which is a key regulator of the Hedgehog signaling pathway. The purpose of this study was to determine the maximum tolerated dose based on dose-limiting toxicity (DLT) and the recommended dose (RD) of sonidegib in Asian patients with advanced solid tumors. This was an open-label, single-arm, multicenter, two-group, parallel, dose-escalation, phase I study undertaken in Asian patients; group 1 included patients from Japan and group 2 included patients from Hong Kong and Taiwan. Dose escalation was guided by a Bayesian logistic regression model dependent on DLTs in cycle 1 and other safety findings. A total of 45 adult Asian patients with confirmed advanced solid tumors were enrolled. Group 1 included 21 patients (12 treated with 400 mg q.d. [once daily] and 9 treated with 600 mg q.d.) and group 2 included 24 patients (12 treated with 400 mg q.d., 8 treated with 600 mg q.d., and 4 treated with 800 mg q.d.). Elevation in creatine kinase was the DLT in both groups. The most common adverse events suspected to be related to sonidegib in both patient groups were increase in creatine kinase levels, myalgia, fatigue, and abnormal hepatic function. The RD of 400 mg q.d. was defined in both groups. Difference in tolerability was noted between the East Asian patients and Western population. The RD in East Asian patients (400 mg q.d.) was lower than in patients from Europe and the USA (800 mg q.d. and 250 mg twice daily). (Registered with Clinicaltrials.gov: NCT01208831.).

  16. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization.

    PubMed

    Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

    2015-01-01

    6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP's widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient's ability to metabolize the drug instead of the traditional standard-dose-for-all approach.

  17. Model-Based Individualized Treatment of Chemotherapeutics: Bayesian Population Modeling and Dose Optimization

    PubMed Central

    Jayachandran, Devaraj; Laínez-Aguirre, José; Rundell, Ann; Vik, Terry; Hannemann, Robert; Reklaitis, Gintaras; Ramkrishna, Doraiswami

    2015-01-01

    6-Mercaptopurine (6-MP) is one of the key drugs in the treatment of many pediatric cancers, auto immune diseases and inflammatory bowel disease. 6-MP is a prodrug, converted to an active metabolite 6-thioguanine nucleotide (6-TGN) through enzymatic reaction involving thiopurine methyltransferase (TPMT). Pharmacogenomic variation observed in the TPMT enzyme produces a significant variation in drug response among the patient population. Despite 6-MP’s widespread use and observed variation in treatment response, efforts at quantitative optimization of dose regimens for individual patients are limited. In addition, research efforts devoted on pharmacogenomics to predict clinical responses are proving far from ideal. In this work, we present a Bayesian population modeling approach to develop a pharmacological model for 6-MP metabolism in humans. In the face of scarcity of data in clinical settings, a global sensitivity analysis based model reduction approach is used to minimize the parameter space. For accurate estimation of sensitive parameters, robust optimal experimental design based on D-optimality criteria was exploited. With the patient-specific model, a model predictive control algorithm is used to optimize the dose scheduling with the objective of maintaining the 6-TGN concentration within its therapeutic window. More importantly, for the first time, we show how the incorporation of information from different levels of biological chain-of response (i.e. gene expression-enzyme phenotype-drug phenotype) plays a critical role in determining the uncertainty in predicting therapeutic target. The model and the control approach can be utilized in the clinical setting to individualize 6-MP dosing based on the patient’s ability to metabolize the drug instead of the traditional standard-dose-for-all approach. PMID:26226448

  18. In vivo measurement of 241Am in the lungs confounded by activity deposited in other organs.

    PubMed

    Lobaugh, Megan L; Spitz, Henry B; Glover, Samuel E

    2015-01-01

    Radioactive material deposited in multiple organs of the body is likely to confound a result of an in vivo measurement performed over the lungs, the most frequently monitored organ for occupational exposure. The significance of this interference was evaluated by measuring anthropometric torso phantoms containing lungs, liver, skeleton, and axillary lymph nodes, each with a precisely known quantity of 241Am uniformly distributed in the organs. Arrays of multiple high-resolution germanium detectors were positioned over organs within the torso phantom containing 241Am or over proximal organs without activity to determine the degree of measurement confounding due to photons emitted from other source organs. A set of four mathematical response functions describes the measured count rate with detectors positioned over each of the relevant organs and 241Am contained in the measured organ or one of the other organs selected as a confounder. Simultaneous solution of these equations by matrix algebra, where the diagonal terms of the matrix are calibration factors for a direct measurement of activity in an organ and the off-diagonal terms reflect the contribution (i.e., interference or cross-talk) produced by 241Am in a confounding organ, yields the activity deposited in each of the relevant organs. The matrix solution described in this paper represents a method for adjusting a result of 241Am measured directly in one organ for interferences that may arise from 241Am deposited elsewhere and represents a technically valid procedure to aid in evaluating internal dose based upon in vivo measurements for those radioactive materials known to deposit in multiple organs.

  19. Predictors of mortality in patients with extensively drug-resistant Acinetobacter baumannii pneumonia receiving colistin therapy.

    PubMed

    Choi, Ik Sung; Lee, Yu Ji; Wi, Yu Mi; Kwan, Byung Soo; Jung, Kae Hwa; Hong, Woong Pyo; Kim, June Myong

    2016-08-01

    The ratio of the area under the free (unbound) concentration-time curve to minimum inhibitory concentration (fAUC/MIC) was proposed to be the pharmacokinetic/pharmacodynamic index most strongly linked to the antibacterial effect of colistin against Acinetobacter baumannii. A retrospective study of patients who received colistin to treat pneumonia caused by extensively drug-resistant (XDR) A. baumannii over a 4-year period was performed to assess the impact of the colistin MIC on mortality. A total of 227 patients were included in the analysis. The 7-day and 14-day mortality rates of patients with XDR A. baumannii pneumonia receiving colistin therapy were 15.0% and 23.8%, respectively. In the multivariate analysis, Acute Physiology and Chronic Health Evaluation (APACHE) II score, days from index culture to first dose of colistin, underlying tumour and septic shock at presentation were independent predictors of mortality in patients with XDR A. baumannii pneumonia receiving colistin therapy. In the univariate analysis, the colistin dose based on ideal body weight (IBW) correlated with patient outcome. Therefore, the use of IBW appeared to be more appropriate to calculate the colistin dosage. In addition, these results highlight the clinical significance of colistin MIC in patients with XDR A. baumannii pneumonia receiving colistin therapy. Although MICs were in the 'susceptible' range, patients infected with isolates with high colistin MICs showed a poorer clinical response rate than patients infected with isolates with low colistin MICs. Further clinical studies are needed to evaluate the roles of colistin MIC for predicting mortality in XDR A. baumannii pneumonia with a high colistin MIC.

  20. Decommissioning of the Hematite Former Fuel Cycle Facility using a decision flow logic based work control process

    SciTech Connect

    Anderson, Keith D.

    2013-07-01

    The remediation and decommissioning of the Hematite Former Fuel Cycle Facility (FFCF), the Hematite Facility, is currently being carried out by Westinghouse Electric Company LLC under the Hematite Decommissioning Project (HDP). The Hematite Facility is located near the town of Hematite, Missouri, USA. The Hematite Facility consists of 228 acres of land with primary operations historically being conducted within the central portion of the property that is roughly 10 acres including Burial Pits and the Site Pond area. Decommissioning and remediation activities are being performed with the eventual objective of the release of the property. Primary contaminants include the legacy disposal and contamination of natural and enriched uranium from the nuclear fuel cycle, as well as chemicals used during the facility operations. Two major regulatory bodies, the U.S. Nuclear Regulatory Commission (NRC) and the Missouri Department of Natural Resources (MDNR), provide critical roles in the approval and oversight of the current regulatory path to remediation, decommissioning and eventual release. Further, remediation and decommissioning activities are performed under the implementing policies, plans, and procedures under the Hematite Decommissioning Plan (DP) and the Record of Decision (ROD). Remediation and decommissioning tasks at the Hematite Former Fuel Cycle Facility, referred to as the Hematite Facility, are performed against a disciplined decision logic flow that applies accumulated technical and monitoring data to determine each step of the excavation, exhumation, and removal of wastes from the Burial Pits and the remaining Areas of Concern (AOC). Decision flow logic is based upon the nuclear criticality safety controls and threshold conditions, relative level of radioactive and chemical contamination, security protocol, and final waste stream disposition. The end result is to remediate the residual radioactive and chemical contamination to approved dose-based and risk

  1. Management of iron deficiency anemia: A survey of pediatric hematology/oncology specialists

    PubMed Central

    Powers, Jacquelyn M.; McCavit, Timothy L.; Buchanan, George R.

    2015-01-01

    Background Iron deficiency anemia (IDA) is the most common hematologic condition in children and adolescents in the United States (US). No prior reports have described the management of IDA by a large cohort of pediatric hematology-oncology specialists. Procedure A 20-question electronic survey that solicited responses to two hypothetical cases of IDA was sent to active members of the American Society of Pediatric Hematology/Oncology (ASPHO) in the United States. Results Of 1,217 recipients, 398 (32.7%) reported regularly treating IDA and completed the survey. In a toddler with nutritional IDA, 15% (N=61) of respondents reported ordering no diagnostic test beyond a complete blood count. Otherwise, wide variability in laboratory testing was reported. For treatment, most respondents would prescribe ferrous sulfate (N=335, 84%) dosed at 6 mg/kg/day (N=248, 62%) divided twice daily (N=272, 68%). The recommended duration of iron treatment after resolution of anemia and normalized serum ferritin varied widely from 0 months to 3 months. For an adolescent with heavy menstrual bleeding and IDA, most respondents recommended ferrous sulfate (N=327, 83%), with dosing based on the number of tablets daily. For IDA refractory to oral treatment, intravenous iron therapy was recommended most frequently, 48% (N=188) using iron sucrose, 17% (n=68) ferric gluconate, and 15% (N=60) low molecular weight iron dextran. Conclusion The approach to diagnosis and treatment of IDA in childhood was widely variable among responding ASPHO members. Given the lack of an evidence base to guide clinical decision making, further research investigating IDA management is needed. PMID:25663613

  2. Quantitative structure-mesothelioma potency model optimization for complex mixtures of elongated particles in rat pleura: A retrospective study.

    PubMed

    Cook, Philip M; Swintek, Joseph; Dawson, Timothy D; Chapman, David; Etterson, Mathew A; Hoff, Dale

    2016-01-01

    Cancer potencies of mineral and synthetic elongated particle mixtures, including asbestos fibers, are influenced by changes in fiber dose composition, bioavailability, and biodurability in combination with relevant cytotoxic dose-response relationships. An extensive rat intrapleural dose characterization data set with a wide variety of elongated particles physicochemical properties facilitated statistical analyses of pleural mesothelioma response data combined from several studies for evaluation of alternative dose-response models. Utilizing logistic regression of individual elongated particle dimensional variations within each test sample, four major findings emerged: (1) Mild acid leaching provides superior prediction of tumor incidence compared to samples that were not leached; (2) sum of the elongated particle surface areas from mildly acid-leached samples provides the optimum holistic dose-response model; (3) progressive removal of dose associated with very short and/or thin elongated particles significantly degrades the resultant particle count and surface area dose-based predictive model fits; and (4) alternative biologically plausible model adjustments provide evidence for reduced potency of elongated particles with aspect ratios less than 8 and lengths greater than 80 µm. Regardless of these adjustments, the optimum predictive models strongly incorporate potency attributable to abundant short elongated particles in proportion to their surface area. Transmission electron microscopy analyses of low-temperature-ashed pleural membrane and lung tissues 5.5 mo post intrapleural exposures do not support hypotheses that short elongated particles that reach the pleural space are rapidly eliminated. Low-aspect-ratio elongated particles were still abundant in pleural membrane tissues but may have reduced potencies due to aggregation tendencies and therefore lower potential for intracellular presence.

  3. Safe Implementation of Computerized Provider Order Entry for Adult Oncology

    PubMed Central

    Kaemingk, D.; Frieze, D.; Hendrie, P.; Payne, T.H.

    2015-01-01

    Summary Background Oncology has lagged in CPOE adoption due to the narrow therapeutic index of chemotherapy drugs, individualized dosing based on weight and height, regimen complexity, and workflows that include hard stops where safety checks are performed and documented. Objectives We sought to establish CPOE for chemotherapy ordering and administration in an academic teaching institution using a commercially available CPOE system. Methods A commercially available CPOE system was implemented throughout the hospital. A multidisciplinary team identified key safety gaps that required the development of a customized complex order display and a verification documentation workflow. Staff reported safety events were monitored for two years and compared to the year prior to go live. Results A workflow was enabled to capture real-time provider verification status during the time from ordering to the administration of chemotherapy. A customized display system was embedded in the EMR to provide a single screen view of the relevant parameters of chemotherapy doses including current and previous patient measurements of height and weight, dose adjustments, provider verifications, prior chemotherapy regimens, and a synopsis of the standard regimen for reference. Our system went live with 127 chemotherapy plans and has been expanded to 189. Staff reported safety events decreased following implementation, particularly in the area of prescribing and transcribing by the second year of use. Conclusions We observed reduced staff reported safety events following implementation of CPOE for inpatient chemotherapy using an electronic verification workflow and an embedded custom clinical decision support page. This implementation demonstrates that CPOE can be safely used for inpatient chemotherapy, even in an extremely complex environment. PMID:26767061

  4. State of play of pharmacogenetics and personalized medicine in heart failure.

    PubMed

    Parry, Helen M; Doney, Alex S F; Palmer, Colin N A; Lang, Chim C

    2013-12-01

    Heart failure is a common disease with high levels of morbidity and mortality. A large body of evidence guiding treatment shows prognostic benefit with beta-blockers and angiotensin-converting enzyme inhibitors, while diuretics are commonly prescribed for symptomatic benefit. Wide variation in drug response between clinically similar patients is a significant problem. Evidence suggests this may have a genetic component. Variation in candidate genes including the beta-1, beta-2, and alpha-2 adrenergic receptors, the renin-angiotensin-aldosterone pathway and genes involved in renal electrolyte handling with diuretics may be important. Single-nucleotide polymorphisms (SNPs) potentially influencing drug response include the Arg 389 Gly variant and the Ser 49 Gly variant in the beta-1 adrenergic receptor, the Arg 16 Gly, Gln 27 Glu, and Thr 164 Ile polymorphisms within the beta-2 adrenergic receptor, an insertion at the 287th base pair in the angiotensin-converting enzyme and the Gly 264 Ala mutation in the sodium chloride co-transporter. However, research addressing the clinical significance of these polymorphisms has yielded conflicting results that have had no influence on clinical practice. Genome-wide association studies may provide an alternative approach to discovering genetic variations influencing drug response, a relatively unchartered area in heart failure management. If future work in this area produces a strong case that variation in drug response has a specific and clinically meaningful genetic component, this could be used to guide drug dosing based on genotype; a step forward in the journey toward personally tailored medicine.

  5. Measurement of emission fluxes from Technical Area 54, Area G and L. Final report

    SciTech Connect

    Eklund, B.

    1995-03-15

    The emission flux (mass/time-area) of tritiated water from TA-54 was measured to support the characterization of radioactive air emissions from waste sites for the Radioactive Air Emissions Management (RAEM) program and for the Area G Performance Assessment. Measurements were made at over 180 locations during the summers of 1993 and 1994, including randomly selected locations across Area G, three suspected areas of contamination at Area G, and the property surrounding TA-54. The emission fluxes of radon were measured at six locations and volatile organic compounds (VOCs) at 30 locations. Monitoring was performed at each location over a several-hour period using the U.S. EPA flux chamber approach. Separate samples for tritiated water, radon, and VOCs were collected and analyzed in off-site laboratories. The measured tritiated water emission fluxes varied over several orders of magnitude, from background levels of about 3 pCi/m{sup 2}-min to 9.69 x 10{sup 6} pCi/m{sup 2}-min near a disposal shaft. Low levels of tritiated water were found to have migrated into Pajarito Canyon, directly south of Area G. The tritium flux data were used to generate an estimated annual emission rate of 14 Curies/yr for all of Area G, with the majority of this activity being emitted from relatively small areas adjacent to several disposal shafts. The estimated total annual release is less than 1% of the total tritium release from all LANL in 1992 and results in a negligible off-site dose. Based on the limited data available, the average emission flux of radon from Area G is estimated to be 8.1 pCi/m{sup 2}-min. The measured emission fluxes of VOCs were < 100 {mu}g/m{sup 2}-min, which is small compared with fluxes typically measured at hazardous waste landfills. The air quality impacts of these releases were evaluated in a separate report.

  6. Evaluation of administered dose using portal images in craniospinal irradiation of pediatric patients.

    PubMed

    Coelho, Carina Marques; Calçada, Raquel; Rodrigues, Sofia; Barragán, Juan Antonio; Sá, Ana Cravo; Macedo, Ana Paula; de Fátima Monsanto, Maria

    2017-03-21

    This study aimed to assess the administered dose based on portal imaging in craniospinal pediatric irradiation by evaluating cases in which portal images did or did not account for the total administered dose. We also intended to calculate the mean increase in total administered dose. Data were collected from General University Hospital Gregorio Marañón; we evaluated the total dose administered, total dose planned, number of portal images per treatment and corresponding monitor units of two different groups: one in which the dose from portal images is deducted from the total administered dose (D), and another in which it was not (N). We used descriptive statistics to analyze the collected data, including the mean and respective standard deviation. We used the Shapiro-Wilk and Spearman rank correlation coefficient tests and estimated the linear regression coefficients. Patients in group D received a mean dose of 29.00 ± 10.28 cGy based on the verification portal images, a quantity that was deducted from the planned dose to match the total administered dose. Patients in group N received a mean dose of 41.50 ± 30.53 cGy, which was not deducted from the planned dose, evidencing a mean increase of 41.50 ± 30.55 cGy over the total administered dose. The acquisition of the set-up verification portal images, without their inclusion in the total administered dose, reflects an average increase in total dose for craniospinal irradiation of pediatric patients. Subtraction of the monitor units used to acquire the verification images is recommended.

  7. Benefit of therapeutic drug monitoring of protease inhibitors in HIV-infected patients depends on PI used in HAART regimen--ANRS 111 trial

    PubMed Central

    Duval, Xavier; Mentré, France; Rey, Elisabeth; Auleley, Solange; Peytavin, Gilles; Biour, Michel; Métro, Annie; Goujard, Cecile; Taburet, Anne-Marie; Lascoux, Cecile; Panhard, Xaviere; Tréluyer, Jean-Marc; Salmon-Céron, Dominique

    2009-01-01

    Due to high inter-patient variability, and efficacy-concentration and toxicity-concentration relationships, optimization of HIV-protease inhibitor doses based on plasma concentrations could be beneficial. During a 48-week open prospective non-randomized interventional study of 115 protease inhibitor-naïve patients initiating an indinavir/ritonavir or lopinavir/ritonavir or nelfinavir containing therapy, protease inhibitor dose was modified when plasma trough concentrations (Ctrough) at week 2, 8, 16 and 24 were outside predefined optimal concentration ranges. Failure of the strategy was defined as the proportions of patients with HIV-RNA above 200 copies/ml from week 24 to 48 and/or experiencing grade 2, 3 or 4 PI-related adverse events during the study; proportion of patients with last Ctrough measurement outside the concentration range was determined at each visit. Virological failure and/or occurrence of adverse event were observed in 37/94 assessable patients (39% CI95%: 29.4–50.0). In the on-treatment analysis, failure of the strategy was noted in 16% of indinavir/r or lopinavir/r treated patients (8/51; CI95% 7.0–28.6; virological failure: 2; adverse event: 6) but in 44% of nelfinavir-treated patients (11/25; CI95%: 24.4–65.1; virological failure: 10; adverse event: 1); Ctrough concentrations outside the range were less frequent at the last measurement than at W2 (41% versus 66%; p < 0.05) with proportions of 35% for indinavir/r or lopinavir/r treated patients, but 57% for nelfinavir treated patients. The proposed strategy of therapeutic drug monitoring may be beneficial to indinavir/r and lopinavir/r-treated patients, but for nelfinavir failed to move concentrations into the predefined range and to produce the expected virological success. PMID:19709326

  8. SU-E-J-186: Using 4DCT-Based Motion Modeling to Predict Motion and Duty Cycle On Successive Days of Gated Radiotherapy

    SciTech Connect

    Myronakis, M; Cai, W; Dhou, S; Cifter, F; Lewis, J

    2015-06-15

    Purpose: To determine if 4DCT-based motion modeling and external surrogate motion measured during treatment simulation can enhance prediction of residual tumor motion and duty cycle during treatment delivery. Methods: This experiment was conducted using simultaneously recorded tumor and external surrogate motion acquired over multiple fractions of lung cancer radiotherapy. These breathing traces were combined with the XCAT phantom to simulate CT images. Data from the first day was used to estimate the residual tumor motion and duty cycle both directly from the 4DCT (the current clinical standard), and from external-surrogate based motion modeling. The accuracy of these estimated residual tumor motions and duty cycles are evaluated by comparing to the measured internal/external motions from other treatment days. Results: All calculations were done for 25% and 50% duty cycles. The results indicated that duty cycle derived from 4DCT information alone is not enough to accurately predict duty cycles during treatment. Residual tumor motion was determined from the recorded data and compared with the estimated residual tumor motion from 4DCT. Relative differences in residual tumor motion varied from −30% to 55%, suggesting that more information is required to properly predict residual tumor motion. Compared to estimations made from 4DCT, in three out of four patients examined, the 30 seconds of motion modeling data was able to predict the duty cycle with better accuracy than 4DCT. No improvement was observed in prediction of residual tumor motion for this dataset. Conclusion: Motion modeling during simulation has the potential to enhance 4DCT and provide more information about target motion, duty cycles, and delivered dose. Based on these four patients, 30 seconds of motion modeling data produced improve duty cycle estimations but showed no measurable improvement in residual tumor motion prediction. More patient data is needed to verify this Result. I would like to

  9. Plasma and CSF oxytocin levels after intranasal and intravenous oxytocin in awake macaques.

    PubMed

    Freeman, Sara M; Samineni, Sridhar; Allen, Philip C; Stockinger, Diane; Bales, Karen L; Hwa, Granger G C; Roberts, Jeffrey A

    2016-04-01

    Oxytocin (OT) is a neuropeptide that mediates a variety of complex social behaviors in animals and humans. Intranasal OT has been used as an experimental therapeutic for human conditions characterized by deficits in social functioning, especially autism spectrum disorder and schizophrenia. However, it is currently under intense debate whether intranasal delivery of OT reaches the central nervous system. In this study, four female rhesus macaques were implanted with chronic intrathecal catheters and used to investigate the pharmacokinetic profile of OT in the central nervous system and the peripheral vasculature following intravenous (IV) and intranasal (IN) administration of OT. In a randomized, crossover design, OT was given to four awake monkeys at three different doses based on body weight (0.1 IU/kg; 1 IU/kg; 5 IU/kg). A time course of concurrent cerebrospinal fluid (CSF) and plasma samples were taken following administration. We found a dose-dependent effect of IV OT treatment on plasma OT levels, which peaked at 5 min post-dose and gradually returned to baseline by 120 min. In contrast, a change in CSF OT was only observed at the highest IV dose (5 IU/kg) at 15 min post-dose and gradually returned to baseline by 120 min. After IN administration, there was no significant change in plasma OT at any of the three doses. However, at the highest dose level, we found a significant increase in CSF OT at 15-30 min post- dose. The results of this study in light of recent, similar publications highlight the importance of methodological consistency across studies. This study also establishes a non-human primate model that can provide a stable platform for carrying out serial sampling from the central nervous system and peripheral vasculature concurrently.

  10. A phase 2 study of eliglustat tartrate (Genz-112638), an oral substrate reduction therapy for Gaucher disease type 1

    PubMed Central

    Lukina, Elena; Watman, Nora; Arreguin, Elsa Avila; Banikazemi, Maryam; Dragosky, Marta; Iastrebner, Marcelo; Rosenbaum, Hanna; Phillips, Mici; Pastores, Gregory M.; Rosenthal, Daniel I.; Kaper, Mathilde; Singh, Tejdip; Puga, Ana Cristina; Bonate, Peter L.

    2010-01-01

    Eliglustat tartrate (Genz-112638), a specific inhibitor of glucosylceramide synthase, is under development as an oral substrate reduction therapy for Gaucher disease type 1 (GD1). A multinational, open-label, single-arm phase 2 study of 26 GD1 patients (16 female, 10 male; mean age, 34 years) evaluated the efficacy, safety, and pharmacokinetics of eliglustat tartrate administered twice daily by mouth at 50- or 100-mg doses based on plasma drug concentrations. Entry criteria required splenomegaly with thrombocytopenia and/or anemia. The composite primary efficacy end point required improvement after 52 weeks in at least 2 of these 3 disease manifestations and was met by 77% (95% confidence interval [CI] = 58%-89%) of all patients and 91% (95% CI = 72%-98%) of the 22 patients completing 52 weeks. Statistically significant improvements occurred in mean hemoglobin level (1.62 g/dL; 95% CI =1.05-2.18 g/dL), platelet count (40.3%; 95% CI = 23.7-57.0 g/dL), spleen volume (−38.5%; 95% CI = −43.5%-−33.5%), liver volume (−17.0%; 95% CI = −21.6%-12.3%), and lumbar spine bone mineral density (0.31 Z-score; 95% CI = 0.09-0.53). Elevated biomarkers (chitotriosidase; chemokine CCL18; angiotensin-converting enzyme; tartrate-resistant acid phosphatase) decreased by 35% to 50%. Plasma glucosylceramide and ganglioside GM3 normalized. Eliglustat tartrate was well tolerated: 7 mild, transient adverse events in 6 patients were considered treatment-related. Individual pharmacokinetics varied; mean time to maximal observed concentration was 2.3 hours and mean half-life was 6.8 hours. Eliglustat tartrate appears to be a promising oral treatment for GD1. This study is registered at www.clinicaltrials.gov as #NCT00358150. PMID:20439622

  11. Multivariable Adaptive Closed-Loop Control of an Artificial Pancreas Without Meal and Activity Announcement

    PubMed Central

    Turksoy, Kamuran; Bayrak, Elif Seyma; Quinn, Lauretta; Littlejohn, Elizabeth

    2013-01-01

    Abstract Background Accurate closed-loop control is essential for developing artificial pancreas (AP) systems that adjust insulin infusion rates from insulin pumps. Glucose concentration information from continuous glucose monitoring (CGM) systems is the most important information for the control system. Additional physiological measurements can provide valuable information that can enhance the accuracy of the control system. Proportional-integral-derivative control and model predictive control have been popular in AP development. Their implementations to date rely on meal announcements (e.g., bolus insulin dose based on insulin:carbohydrate ratios) by the user. Adaptive control techniques provide a powerful alternative that do not necessitate any meal or activity announcements. Materials and Methods Adaptive control systems based on the generalized predictive control framework are developed by extending the recursive modeling techniques. Physiological signals such as energy expenditure and galvanic skin response are used along with glucose measurements to generate a multiple-input–single-output model for predicting future glucose concentrations used by the controller. Insulin-on-board (IOB) is also estimated and used in control decisions. The controllers were tested with clinical studies that include seven cases with three different patients with type 1 diabetes for 32 or 60 h without any meal or activity announcements. Results The adaptive control system kept glucose concentration in the normal preprandial and postprandial range (70–180 mg/dL) without any meal or activity announcements during the test period. After IOB estimation was added to the control system, mild hypoglycemic episodes were observed only in one of the four experiments. This was reflected in a plasma glucose value of 56 mg/dL (YSI 2300 STAT; Yellow Springs Instrument, Yellow Springs, OH) and a CGM value of 63 mg/dL). Conclusions Regulation of blood glucose concentration with an AP

  12. Folate receptor-targeted liposomes loaded with a diacid metabolite of norcantharidin enhance antitumor potency for H22 hepatocellular carcinoma both in vitro and in vivo.

    PubMed

    Liu, Min-Chen; Liu, Lin; Wang, Xia-Rong; Shuai, Wu-Ping; Hu, Ying; Han, Min; Gao, Jian-Qing

    2016-01-01

    The diacid metabolite of norcantharidin (DM-NCTD) is clinically effective against hepatocellular carcinoma (HCC), but is limited by its short half-life and high incidence of adverse effects at high doses. We developed a DM-NCTD-loaded, folic acid (FA)-modified, polyethylene glycolated (DM-NCTD/FA-PEG) liposome system to enhance the targeting effect and antitumor potency for HCC at a moderate dose based on our previous study. The DM-NCTD/FA-PEG liposome system produced liposomes with regular spherical morphology, with mean particle size approximately 200 nm, and an encapsulation efficiency >80%. MTT cytotoxicity assays demonstrated that the DM-NCTD/FA-PEG liposomes showed significantly stronger cytotoxicity effects on the H22 hepatoma cell line than did PEG liposomes without the FA modification (P<0.01). We used liquid chromatography-mass spectrometry for determination of DM-NCTD in tissues and tumors, and found it to be sensitive, rapid, and reliable. In addition, the biodistribution study showed that DM-NCTD liposomes improved tumor-targeting efficiency, and DM-NCTD/FA-PEG liposomes exhibited the highest efficiency of the treatments (P<0.01). Meanwhile, the results indicated that although the active liposome group had an apparently increased tumor-targeting efficiency of DM-NCTD, the risk to the kidney was higher than in the normal liposome group. With regard to in vivo antitumor activity, DM-NCTD/FA-PEG liposomes inhibited tumors in H22 tumor-bearing mice better than either free DM-NCTD or DM-NCTD/PEG liposomes (P<0.01), and induced considerably more significant cellular apoptosis in the tumors, with no obvious toxicity to the tissues of model mice or the liver tissue of normal mice, as shown by histopathological examination. All these results demonstrate that DM-NCTD-loaded FA-modified liposomes might have potential application for HCC-targeting therapy.

  13. NUNDO: a numerical model of a human torso phantom and its application to effective dose equivalent calculations for astronauts at the ISS.

    PubMed

    Puchalska, Monika; Bilski, Pawel; Berger, Thomas; Hajek, Michael; Horwacik, Tomasz; Körner, Christine; Olko, Pawel; Shurshakov, Vyacheslav; Reitz, Günther

    2014-11-01

    The health effects of cosmic radiation on astronauts need to be precisely quantified and controlled. This task is important not only in perspective of the increasing human presence at the International Space Station (ISS), but also for the preparation of safe human missions beyond low earth orbit. From a radiation protection point of view, the baseline quantity for radiation risk assessment in space is the effective dose equivalent. The present work reports the first successful attempt of the experimental determination of the effective dose equivalent in space, both for extra-vehicular activity (EVA) and intra-vehicular activity (IVA). This was achieved using the anthropomorphic torso phantom RANDO(®) equipped with more than 6,000 passive thermoluminescent detectors and plastic nuclear track detectors, which have been exposed to cosmic radiation inside the European Space Agency MATROSHKA facility both outside and inside the ISS. In order to calculate the effective dose equivalent, a numerical model of the RANDO(®) phantom, based on computer tomography scans of the actual phantom, was developed. It was found that the effective dose equivalent rate during an EVA approaches 700 μSv/d, while during an IVA about 20 % lower values were observed. It is shown that the individual dose based on a personal dosimeter reading for an astronaut during IVA results in an overestimate of the effective dose equivalent of about 15 %, whereas under an EVA conditions the overestimate is more than 200 %. A personal dosemeter can therefore deliver quite good exposure records during IVA, but may overestimate the effective dose equivalent received during an EVA considerably.

  14. Evaluation of patient dose using a virtual CT scanner: Applications to 4DCT simulation and Kilovoltage cone-beam imaging

    NASA Astrophysics Data System (ADS)

    DeMarco, J. J.; McNitt-Gray, M. F.; Cagnon, C. H.; Angel, E.; Agazaryan, N.; Zankl, M.

    2008-02-01

    This work evaluates the effects of patient size on radiation dose from simulation imaging studies such as four-dimensional computed tomography (4DCT) and kilovoltage cone-beam computed tomography (kV-CBCT). 4DCT studies are scans that include temporal information, frequently incorporating highly over-sampled imaging series necessary for retrospective sorting as a function of respiratory phase. This type of imaging study can result in a significant dose increase to the patient due to the slower table speed as compared with a conventional axial or helical scan protocol. Kilovoltage cone-beam imaging is a relatively new imaging technique that requires an on-board kilovoltage x-ray tube and a flat-panel detector. Instead of porting individual reference fields, the kV tube and flat-panel detector are rotated about the patient producing a cone-beam CT data set (kV-CBCT). To perform these investigations, we used Monte Carlo simulation methods with detailed models of adult patients and virtual source models of multidetector computed tomography (MDCT) scanners. The GSF family of three-dimensional, voxelized patient models, were implemented as input files using the Monte Carlo code MCNPX. The adult patient models represent a range of patient sizes and have all radiosensitive organs previously identified and segmented. Simulated 4DCT scans of each voxelized patient model were performed using a multi-detector CT source model that includes scanner specific spectra, bow-tie filtration, and helical source path. Standard MCNPX tally functions were applied to each model to estimate absolute organ dose based upon an air-kerma normalization measurement for nominal scanner operating parameters.

  15. A framework for organ dose estimation in x-ray angiography and interventional radiology based on dose-related data in DICOM structured reports

    NASA Astrophysics Data System (ADS)

    Omar, Artur; Bujila, Robert; Fransson, Annette; Andreo, Pedro; Poludniowski, Gavin

    2016-04-01

    Although interventional x-ray angiography (XA) procedures involve relatively high radiation doses that can lead to deterministic tissue reactions in addition to stochastic effects, convenient and accurate estimation of absorbed organ doses has traditionally been out of reach. This has mainly been due to the absence of practical means to access dose-related data that describe the physical context of the numerous exposures during an XA procedure. The present work provides a comprehensive and general framework for the determination of absorbed organ dose, based on non-proprietary access to dose-related data by utilizing widely available DICOM radiation dose structured reports. The framework comprises a straightforward calculation workflow to determine the incident kerma and reconstruction of the geometrical relation between the projected x-ray beam and the patient’s anatomy. The latter is difficult in practice, as the position of the patient on the table top is unknown. A novel patient-specific approach for reconstruction of the patient position on the table is presented. The proposed approach was evaluated for 150 patients by comparing the estimated position of the primary irradiated organs (the target organs) with their position in clinical DICOM images. The approach is shown to locate the target organ position with a mean (max) deviation of 1.3 (4.3), 1.8 (3.6) and 1.4 (2.9) cm for neurovascular, adult and paediatric cardiovascular procedures, respectively. To illustrate the utility of the framework for systematic and automated organ dose estimation in routine clinical practice, a prototype implementation of the framework with Monte Carlo simulations is included.

  16. A framework for organ dose estimation in x-ray angiography and interventional radiology based on dose-related data in DICOM structured reports.

    PubMed

    Omar, Artur; Bujila, Robert; Fransson, Annette; Andreo, Pedro; Poludniowski, Gavin

    2016-04-21

    Although interventional x-ray angiography (XA) procedures involve relatively high radiation doses that can lead to deterministic tissue reactions in addition to stochastic effects, convenient and accurate estimation of absorbed organ doses has traditionally been out of reach. This has mainly been due to the absence of practical means to access dose-related data that describe the physical context of the numerous exposures during an XA procedure. The present work provides a comprehensive and general framework for the determination of absorbed organ dose, based on non-proprietary access to dose-related data by utilizing widely available DICOM radiation dose structured reports. The framework comprises a straightforward calculation workflow to determine the incident kerma and reconstruction of the geometrical relation between the projected x-ray beam and the patient's anatomy. The latter is difficult in practice, as the position of the patient on the table top is unknown. A novel patient-specific approach for reconstruction of the patient position on the table is presented. The proposed approach was evaluated for 150 patients by comparing the estimated position of the primary irradiated organs (the target organs) with their position in clinical DICOM images. The approach is shown to locate the target organ position with a mean (max) deviation of 1.3 (4.3), 1.8 (3.6) and 1.4 (2.9) cm for neurovascular, adult and paediatric cardiovascular procedures, respectively. To illustrate the utility of the framework for systematic and automated organ dose estimation in routine clinical practice, a prototype implementation of the framework with Monte Carlo simulations is included.

  17. SU-E-T-427: Feasibility Study for Evaluation of IMRT Dose Distribution Using Geant4-Based Automated Algorithms

    SciTech Connect

    Choi, H; Shin, W; Testa, M; Min, C; Kim, J

    2015-06-15

    Purpose: For intensity-modulated radiation therapy (IMRT) treatment planning validation using Monte Carlo (MC) simulations, a precise and automated procedure is necessary to evaluate the patient dose distribution. The aim of this study is to develop an automated algorithm for IMRT simulations using DICOM files and to evaluate the patient dose based on 4D simulation using the Geant4 MC toolkit. Methods: The head of a clinical linac (Varian Clinac 2300 IX) was modeled in Geant4 along with particular components such as the flattening filter and the multi-leaf collimator (MLC). Patient information and the position of the MLC were imported from the DICOM-RT interface. For each position of the MLC, a step- and-shoot technique was adopted. PDDs and lateral profiles were simulated in a water phantom (50×50×40 cm{sup 3}) and compared to measurement data. We used a lung phantom and MC-dose calculations were compared to the clinical treatment planning used at the Seoul National University Hospital. Results: In order to reproduce the measurement data, we tuned three free parameters: mean and standard deviation of the primary electron beam energy and the beam spot size. These parameters for 6 MV were found to be 5.6 MeV, 0.2378 MeV and 1 mm FWHM respectively. The average dose difference between measurements and simulations was less than 2% for PDDs and radial profiles. The lung phantom study showed fairly good agreement between MC and planning dose despite some unavoidable statistical fluctuation. Conclusion: The current feasibility study using the lung phantom shows the potential for IMRT dose validation using 4D MC simulations using Geant4 tool kits. This research was supported by Korea Institute of Nuclear safety and Development of Measurement Standards for Medical Radiation funded by Korea research Institute of Standards and Science. (KRISS-2015-15011032)

  18. Robust plan optimization using edge-enhanced intensity for intrafraction organ deformation in prostate intensity-modulated radiation therapy

    PubMed Central

    Kizaki, Hisao; Aboshi, Keiko; Tsujii, Mari; Yamada, Yuji; Tamari, Keisuke; Seo, Yuji; Isohashi, Fumiaki; Yoshioka, Yasuo; Ogawa, Kazuhiko

    2017-01-01

    This study evaluated a method for prostate intensity-modulated radiation therapy (IMRT) based on edge-enhanced (EE) intensity in the presence of intrafraction organ deformation using the data of 37 patients treated with step-and-shoot IMRT. On the assumption that the patient setup error was already accounted for by image guidance, only organ deformation over the treatment course was considered. Once the clinical target volume (CTV), rectum, and bladder were delineated and assigned dose constraints for dose optimization, each voxel in the CTV derived from the DICOM RT-dose grid could have a stochastic dose from the different voxel location according to the probability density function as an organ deformation. The stochastic dose for the CTV was calculated as the mean dose at the location through changing the voxel location randomly 1000 times. In the EE approach, the underdose region in the CTV was delineated and optimized with higher dose constraints that resulted in an edge-enhanced intensity beam to the CTV. This was compared to a planning target volume (PTV) margin (PM) approach in which a CTV to PTV margin equivalent to the magnitude of organ deformation was added to obtain an optimized dose distribution. The total monitor units, number of segments, and conformity index were compared between the two approaches, and the dose based on the organ deformation of the CTV, rectum, and bladder was evaluated. The total monitor units, number of segments, and conformity index were significantly lower with the EE approach than with the PM approach, while maintaining the dose coverage to the CTV with organ deformation. The dose to the rectum and bladder were significantly reduced in the EE approach compared with the PM approach. We conclude that the EE approach is superior to the PM with regard to intrafraction organ deformation. PMID:28282417

  19. Disposition and interaction of biotherapeutics in pediatric populations.

    PubMed

    Yanni, Souzan

    2012-09-01

    Human development of an individual from a fertilized ovum to maturity alters the body anatomy and physiology. Changes of size and function, from birth onwards, cause significant alterations in the pharmacokinetics (PK) of drugs and subsequently their response pharmacodynamics (PD) in infants and children from those in adults. During the last three decades, hundreds of mechanistic and clinical pharmacology studies have been conducted to investigate the age-mediated changes of absorption, distribution, metabolism and excretion processes of drugs, which subsequently affect the pharmacology response and the safety in pediatric patients compared to adults. The practice of determining pediatric dose based on simplistic scaling of an adult dose assuming linear relationship between postnatal age and body weight or surface area that may lead to under prediction of therapeutic dose or over prediction of the dose is now under scrutiny. By understanding the disposition mechanism of therapeutic agents thoroughly, their potential drug interactions and their PK/PD relationships can be better determined in pediatric populations. As such, dosing regimens can be estimated based on actual clearance and exposure and not just by simplistic scaling of an adult dose. Accurate prediction of clearance in pediatrics is so critical that extensive translational research is warranted to improve our ability to estimate safe and efficacious doses in different pediatric populations from retrospective clinical studies in adults. Biotherapeutics, proteins and peptides-based drugs, generally depend on absorption (A), distribution (D), metabolism (M), and excretion (E) in their disposition as small molecules, but the underlying mechanisms and potential drug interaction propensity can be very different. In this article, the factors that alter pediatric and adult PK parameters are compared, and pediatric and adult PK parameters and potential drug interactions for selected biotherapeutics are summarized

  20. Identification of Granulocyte Colony-Stimulating Factor and Interleukin-6 as Candidate Biomarkers of CBLB502 Efficacy as a Medical Radiation Countermeasure

    PubMed Central

    Krivokrysenko, Vadim I.; Shakhov, Alexander N.; Singh, Vijay K.; Bone, Frederick; Kononov, Yevgeniy; Shyshynova, Inna; Cheney, Alec; Maitra, Ratan K.; Purmal, Andrei; Whitnall, Mark H.; Feinstein, Elena

    2012-01-01

    Given an ever-increasing risk of nuclear and radiological emergencies, there is a critical need for development of medical radiation countermeasures (MRCs) that are safe, easily administered, and effective in preventing and/or mitigating the potentially lethal tissue damage caused by acute high-dose radiation exposure. Because the efficacy of MRCs for this indication cannot be ethically tested in humans, development of such drugs is guided by the Food and Drug Administration's Animal Efficacy Rule. According to this rule, human efficacious doses can be projected from experimentally established animal efficacious doses based on the equivalence of the drug's effects on efficacy biomarkers in the respective species. Therefore, identification of efficacy biomarkers is critically important for drug development under the Animal Efficacy Rule. CBLB502 is a truncated derivative of the Salmonella flagellin protein that acts by triggering Toll-like receptor 5 (TLR5) signaling and is currently under development as a MRC. Here, we report identification of two cytokines, granulocyte colony-stimulating factor (G-CSF) and interleukin-6 (IL-6), as candidate biomarkers of CBLB502's radioprotective/mitigative efficacy. Induction of both G-CSF and IL-6 by CBLB502 1) is strictly TLR5-dependent, 2) occurs in a CBLB502 dose-dependent manner within its efficacious dose range in both nonirradiated and irradiated mammals, including nonhuman primates, and 3) is critically important for the ability of CBLB502 to rescue irradiated animals from death. After evaluation of CBLB502 effects on G-CSF and IL-6 levels in humans, these biomarkers will be useful for accurate prediction of human efficacious CBLB502 doses, a key step in the development of this prospective radiation countermeasure. PMID:22837010

  1. Role of Quantitative Clinical Pharmacology in Pediatric Approval and Labeling.

    PubMed

    Mehrotra, Nitin; Bhattaram, Atul; Earp, Justin C; Florian, Jeffry; Krudys, Kevin; Lee, Jee Eun; Lee, Joo Yeon; Liu, Jiang; Mulugeta, Yeruk; Yu, Jingyu; Zhao, Ping; Sinha, Vikram

    2016-07-01

    Dose selection is one of the key decisions made during drug development in pediatrics. There are regulatory initiatives that promote the use of model-based drug development in pediatrics. Pharmacometrics or quantitative clinical pharmacology enables development of models that can describe factors affecting pharmacokinetics and/or pharmacodynamics in pediatric patients. This manuscript describes some examples in which pharmacometric analysis was used to support approval and labeling in pediatrics. In particular, the role of pharmacokinetic (PK) comparison of pediatric PK to adults and utilization of dose/exposure-response analysis for dose selection are highlighted. Dose selection for esomeprazole in pediatrics was based on PK matching to adults, whereas for adalimumab, exposure-response, PK, efficacy, and safety data together were useful to recommend doses for pediatric Crohn's disease. For vigabatrin, demonstration of similar dose-response between pediatrics and adults allowed for selection of a pediatric dose. Based on model-based pharmacokinetic simulations and safety data from darunavir pediatric clinical studies with a twice-daily regimen, different once-daily dosing regimens for treatment-naïve human immunodeficiency virus 1-infected pediatric subjects 3 to <12 years of age were evaluated. The role of physiologically based pharmacokinetic modeling (PBPK) in predicting pediatric PK is rapidly evolving. However, regulatory review experiences and an understanding of the state of science indicate that there is a lack of established predictive performance of PBPK in pediatric PK prediction. Moving forward, pharmacometrics will continue to play a key role in pediatric drug development contributing toward decisions pertaining to dose selection, trial designs, and assessing disease similarity to adults to support extrapolation of efficacy.

  2. Quantifying the image quality and dose reduction of respiratory triggered 4D cone-beam computed tomography with patient-measured breathing

    NASA Astrophysics Data System (ADS)

    Cooper, Benjamin J.; O'Brien, Ricky T.; Kipritidis, John; Shieh, Chun-Chien; Keall, Paul J.

    2015-12-01

    Respiratory triggered four dimensional cone-beam computed tomography (RT 4D CBCT) is a novel technique that uses a patient’s respiratory signal to drive the image acquisition with the goal of imaging dose reduction without degrading image quality. This work investigates image quality and dose using patient-measured respiratory signals for RT 4D CBCT simulations. Studies were performed that simulate a 4D CBCT image acquisition using both the novel RT 4D CBCT technique and a conventional 4D CBCT technique. A set containing 111 free breathing lung cancer patient respiratory signal files was used to create 111 pairs of RT 4D CBCT and conventional 4D CBCT image sets from realistic simulations of a 4D CBCT system using a Rando phantom and the digital phantom, XCAT. Each of these image sets were compared to a ground truth dataset from which a mean absolute pixel difference (MAPD) metric was calculated to quantify the degradation of image quality. The number of projections used in each simulation was counted and was assumed as a surrogate for imaging dose. Based on 111 breathing traces, when comparing RT 4D CBCT with conventional 4D CBCT, the average image quality was reduced by 7.6% (Rando study) and 11.1% (XCAT study). However, the average imaging dose reduction was 53% based on needing fewer projections (617 on average) than conventional 4D CBCT (1320 projections). The simulation studies have demonstrated that the RT 4D CBCT method can potentially offer a 53% saving in imaging dose on average compared to conventional 4D CBCT in simulation studies using a wide range of patient-measured breathing traces with a minimal impact on image quality.

  3. Childhood leukemia around French nuclear power plants--the Geocap study, 2002-2007.

    PubMed

    Sermage-Faure, Claire; Laurier, Dominique; Goujon-Bellec, Stéphanie; Chartier, Michel; Guyot-Goubin, Aurélie; Rudant, Jérémie; Hémon, Denis; Clavel, Jacqueline

    2012-09-01

    The aim of this work is to study the risk of childhood acute leukemia (AL) around French nuclear power plants (NPPs). The nationwide Geocap case-control study included the 2,753 cases diagnosed in mainland France over 2002-2007 and 30,000 contemporaneous population controls. The last addresses were geocoded and located around the 19 NPPs. The study used distance to NPPs and a dose-based geographic zoning (DBGZ), based on the estimated dose to bone marrow related to NPP gaseous discharges. An odds ratio (OR) of 1.9 [1.0-3.3], based on 14 cases, was evidenced for children living within 5 km of NPPs compared to those living 20 km or further away, and a very similar association was observed in the concomitant incidence study (standardized incidence ratio (SIR)=1.9 [1.0-3.2]). These results were similar for all the 5-year-age groups. They persisted after stratification for several contextual characteristics of the municipalities of residence. Conversely, using the DBGZ resulted in OR and SIR close to one in all of the dose categories. There was no increase in AL incidence over 1990-2001 and over the entire 1990-2007 period. The results suggest a possible excess risk of AL in the close vicinity of French NPPs in 2002-2007. The absence of any association with the DBGZ may indicate that the association is not explained by NPP gaseous discharges. Overall, the findings call for investigation for potential risk factors related to the vicinity of NPP and collaborative analysis of multisite studies conducted in various countries.

  4. Magnetic hyperthermia dosimetry by biomechanical properties revealed in magnetomotive optical coherence elastography (MM-OCE) (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Huang, Pin-Chieh; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris M.; Boppart, Stephen A.

    2016-03-01

    Magnetic nanoparticles (MNPs) have been utilized in magnetic hyperthermia to treat solid tumors. Under an appropriate AC magnetic field, energy can be transferred to the MNPs to heat up the intended tissue target while sparing non-targeted healthy tissue. However, a sensitive monitoring technique for the dose of MNP thermal therapy is desirable in order to prevent over-treatment and collateral injury. Typical hyperthermia dosimetry often relies on changes in imaging properties or temperature measurements based on the thermal distribution. Alternative dosimetric indicators can include the biomechanical properties of the tissue, reflecting the changes due to protein denaturation, coagulation, and tissue dehydration during hyperthermia treatments. Tissue stiffness can be probed by elastography modalities including MRI, ultrasound imaging, and optical coherence elastography (OCE), with OCE showing the highest displacement sensitivity (tens of nanometers). Magnetomotive optical coherence elastography (MM-OCE) is one type of OCE that utilizes MNPs as internal force transducers to probe the tissue stiffness. Therefore, we examined the feasibility of evaluating the hyperthermia dose based on the elasticity changes revealed by MM-OCE. Superparamagnetic MNPs were applied to ex vivo tissue specimens for both magnetic hyperthermia and MM-OCE experiments, where temperature and elastic modulus were obtained. A correlation between temperature rise and measured stiffness was observed. In addition, we found that with repetitive sequential treatments, tissue stiffness increased, while temperature rise remained relatively constant. These results potentially suggest that MM-OCE could indicate the irreversible changes the tissue undergoes during thermal therapy, which supports the idea for MM-OCE-based hyperthermia dosage control in future applications.

  5. CD19 CAR–T cells of defined CD4+:CD8+ composition in adult B cell ALL patients

    PubMed Central

    Turtle, Cameron J.; Hanafi, Laïla-Aïcha; Berger, Carolina; Gooley, Theodore A.; Cherian, Sindhu; Hudecek, Michael; Sommermeyer, Daniel; Melville, Katherine; Pender, Barbara; Budiarto, Tanya M.; Robinson, Emily; Steevens, Natalia N.; Chaney, Colette; Soma, Lorinda; Chen, Xueyan; Li, Daniel; Cao, Jianhong; Heimfeld, Shelly; Jensen, Michael C.; Riddell, Stanley R.; Maloney, David G.

    2016-01-01

    BACKGROUND. T cells that have been modified to express a CD19-specific chimeric antigen receptor (CAR) have antitumor activity in B cell malignancies; however, identification of the factors that determine toxicity and efficacy of these T cells has been challenging in prior studies in which phenotypically heterogeneous CAR–T cell products were prepared from unselected T cells. METHODS. We conducted a clinical trial to evaluate CD19 CAR–T cells that were manufactured from defined CD4+ and CD8+ T cell subsets and administered in a defined CD4+:CD8+ composition to adults with B cell acute lymphoblastic leukemia after lymphodepletion chemotherapy. RESULTS. The defined composition product was remarkably potent, as 27 of 29 patients (93%) achieved BM remission, as determined by flow cytometry. We established that high CAR–T cell doses and tumor burden increase the risks of severe cytokine release syndrome and neurotoxicity. Moreover, we identified serum biomarkers that allow testing of early intervention strategies in patients at the highest risk of toxicity. Risk-stratified CAR–T cell dosing based on BM disease burden decreased toxicity. CD8+ T cell–mediated anti-CAR transgene product immune responses developed after CAR–T cell infusion in some patients, limited CAR–T cell persistence, and increased relapse risk. Addition of fludarabine to the lymphodepletion regimen improved CAR–T cell persistence and disease-free survival. CONCLUSION. Immunotherapy with a CAR–T cell product of defined composition enabled identification of factors that correlated with CAR–T cell expansion, persistence, and toxicity and facilitated design of lymphodepletion and CAR–T cell dosing strategies that mitigated toxicity and improved disease-free survival. TRIAL REGISTRATION. ClinicalTrials.gov NCT01865617. FUNDING. R01-CA136551; Life Science Development Fund; Juno Therapeutics; Bezos Family Foundation. PMID:27111235

  6. Determination of neutron dose from criticality accidents with bioassays for sodium-24 in blood and phosphorus-32 in hair

    SciTech Connect

    Feng, Y.; Miller, L.F.; Brown, K.S.; Casson, W.H.; Mei, G.T.; Thein, M.

    1993-06-01

    A comprehensive review of accident neutron dosimetry using blood and hair analysis was performed and is summarized in this report. Experiments and calculations were conducted at Oak Ridge National Laboratory (ORNL) and the University of Tennessee (UT) to develop measurement techniques for the activity of {sup 24}Na in blood and {sup 32}P in hair for nuclear accident dosimetry. An operating procedure was established for the measurement of {sup 24}Na in blood using an HPGe detector system. The sensitivity of the measurement for a 20-mL sample is 0.01-0.02 Gy of total neutron dose for hard spectra and below 0.005 Gy for soft spectra based on a 30- to 60-min counting time. The operating procedures for direct counting of hair samples are established using a liquid scintillation detector. Approximately 0.06-0.1 Gy of total neutron dose can be measured from a 1-g hair sample using this procedure. Detailed procedures for chemical dissolution and ashing of hair samples are also developed. A method is proposed to use blood and hair analysis for assessing neutron dose based on a collection of 98 neutron spectra. Ninety-eight blood activity-to-dose conversion factors were calculated. The calculated results for an uncollided fission spectrum compare favorably with previously published data for fission neutrons. This nuclear accident dosimetry system makes it possible to estimate an individual`s neutron dose within a few hours after an accident if the accident spectrum can be approximated from one of 98 tabulated neutron spectrum descriptions. If the information on accident and spectrum description is not available, the activity ratio of {sup 32}P in hair and {sup 24}Na in blood can provide information related to the neutron spectrum for dose assessment.

  7. Genetic toxicity evaluation of iodotrifluoromethane (Cf{sub 3}I). Volume 2. Results of in vivo mouse bone marrow erythrocyte micronucleus testing. Final report, March-December 1994

    SciTech Connect

    Mitchell, A.D.

    1995-01-01

    Under subcontract to ManTech Environmental Technology, Incorporated, Genesys Research, Incorporated, examined the potential of odotrifluoromethane (CF3I) to induce structural chromosomes aberrations in erythropoietic cells of the bone marrow. Genesys used the mouse micronucleus test which measures the clastogenic (chromosomes breaking) action of chemicals by the induction of micronuclei in bone marrow cells, as observed in erythrocytes from the peripheral blood of male and female mice obtained approximately 24 hours after steady-state dosing. Based on preliminary toxicity information obtained by ManTech, a mouse bone marrow micronucleus test of CF3I was conducted using 2.6, 5.0, and 7.5% CF3I administered to male and female Swiss Webster mice by inhalation for six hours on each of three consecutive days. Bone marrow cells were obtained from the mice sacrificed 24 hours after the third exposure. Erythrocytes from mice exposed to the test material, and to the negative and positive controls, were evaluated for toxicity and the presence of micronuclei. The positive control, 0.4 mg triethylenemelamine (TEM)/kg (administered intraperitonealy) significantly (p

  8. Method to Calculate the Protamine Dose Necessary for Reversal of Heparin as a Function of Activated Clotting Time in Patients Undergoing Cardiac Surgery

    PubMed Central

    Cuenca, Javier Suárez; Diz, Pilar Gayoso; Sampedro, Francisco Gude; Zincke, J. Marcos Gómez; Acuña, Helena Rey; Fontanillo, M. Manuela Fontanillo

    2013-01-01

    Abstract: Activated clotting time (ACT) has been used to monitor coagulation and guide management of anticoagulation control in patients undergoing cardiac surgery for decades. However, reversal of heparin with protamine is typically empirically based on total heparin administered. Dose-related adverse effects of protamine are well described. The aim of this study was to evaluate a heparin reversal strategy based on calculation of the protamine dose based on ACT measurements. We present a method using a mathematical formula based on the dose–response line (1). To check the formula, we performed a retrospective observational cohort study of 177 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB). The study group of 80 patients was administered the dose of protamine obtained using our formula, and the control group of 97 patients was administered the empirically calculated dose. The ACT returned to normal values in patients who were given doses of protamine that were calculated using our formula; all but two had a final ACT of 141. The application of the formula resulted in a significant reduction in the dose of protamine (p < .023). The formula we present is a valid method for calculating the dose of protamine necessary to neutralize heparin. This same method can be used working with a target ACT to adjust the dose of heparin. As a result of its functionality, it allows application on a daily basis standardizing the process. We believe that the formula we developed can be applied in all those procedures in which it is necessary to anticoagulate patients with heparin and later neutralization (cardiac surgery with or without CPB, vascular surgery, procedures of interventional cardiology, and extracorporeal depuration procedures). PMID:24649571

  9. A Cholera Conjuga