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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. PMID:19299154

  2. Observations on the Chernobyl Disaster and LNT.

    PubMed

    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 ( 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. PMID:20585443

  3. 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

  4. Model Uncertainty via the Integration of Hormesis and LNT as the Default in Cancer Risk Assessment

    PubMed Central

    2015-01-01

    On June 23, 2015, the US Nuclear Regulatory Commission (NRC) issued a formal notice in the Federal Register that it would consider whether “it should amend its ‘Standards for Protection Against Radiation’ regulations from the linear non-threshold (LNT) model of radiation protection to the hormesis model.” The present commentary supports this recommendation based on the (1) flawed and deceptive history of the adoption of LNT by the US National Academy of Sciences (NAS) in 1956; (2) the documented capacity of hormesis to make more accurate predictions of biological responses for diverse biological end points in the low-dose zone; (3) the occurrence of extensive hormetic data from the peer-reviewed biomedical literature that revealed hormetic responses are highly generalizable, being independent of biological model, end point measured, inducing agent, level of biological organization, and mechanism; and (4) the integration of hormesis and LNT models via a model uncertainty methodology that optimizes public health responses at 10−4. Thus, both LNT and hormesis can be integratively used for risk assessment purposes, and this integration defines the so-called “regulatory sweet spot.” PMID:26740815

  5. Model Uncertainty via the Integration of Hormesis and LNT as the Default in Cancer Risk Assessment.

    PubMed

    Calabrese, Edward J

    2015-01-01

    On June 23, 2015, the US Nuclear Regulatory Commission (NRC) issued a formal notice in the Federal Register that it would consider whether "it should amend its 'Standards for Protection Against Radiation' regulations from the linear non-threshold (LNT) model of radiation protection to the hormesis model." The present commentary supports this recommendation based on the (1) flawed and deceptive history of the adoption of LNT by the US National Academy of Sciences (NAS) in 1956; (2) the documented capacity of hormesis to make more accurate predictions of biological responses for diverse biological end points in the low-dose zone; (3) the occurrence of extensive hormetic data from the peer-reviewed biomedical literature that revealed hormetic responses are highly generalizable, being independent of biological model, end point measured, inducing agent, level of biological organization, and mechanism; and (4) the integration of hormesis and LNT models via a model uncertainty methodology that optimizes public health responses at 10(-4). Thus, both LNT and hormesis can be integratively used for risk assessment purposes, and this integration defines the so-called "regulatory sweet spot." PMID:26740815

  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. PMID:20105434

  8. LNT--an apparent rather than a real controversy?

    PubMed

    Charles, M W

    2006-09-01

    Can the carcinogenic risks of radiation that are observed at high doses be extrapolated to low doses? This question has been debated through the whole professional life of the author--now nearing four decades. In its extreme form the question relates to a particular hypothesis (LNT) used widely by the international community for radiological protection applications. The linear no-threshold (LNT) hypothesis propounds that the extrapolation is linear and that it extends down to zero dose. The debate on the validity of LNT has increased dramatically in recent years. This is in no small part due to concern that exaggerated risks at low doses leads to undue amounts of societal resources being used to reduce man-made human exposure and because of the related growing public aversion to diagnostic and therapeutic medical exposures. The debate appears to be entering a new phase. There is a growing realisation of the limitations of fundamental data and the scientific approach to address this question at low doses. There also appears to be an increasing awareness that the assumptions necessary for a workable and acceptable system of radiological protection at low doses must necessarily be based on considerable pragmatism. Recent developments are reviewed and a historical perspective is given on the general nature of controversies in radiation protection over the years. All the protagonists in the debate will at the end of the day probably be able to claim that they were right! PMID:16926475

  9. 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.

  10. 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

  11. The Integration of LNT and Hormesis for Cancer Risk Assessment Optimizes Public Health Protection.

    PubMed

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2016-03-01

    This paper proposes a new cancer risk assessment strategy and methodology that optimizes population-based responses by yielding the lowest disease/tumor incidence across the entire dose continuum. The authors argue that the optimization can be achieved by integrating two seemingly conflicting models; i.e., the linear no-threshold (LNT) and hormetic dose-response models. The integration would yield the optimized response at a risk of 10 with the LNT model. The integrative functionality of the LNT and hormetic dose response models provides an improved estimation of tumor incidence through model uncertainty analysis and major reductions in cancer incidence via hormetic model estimates. This novel approach to cancer risk assessment offers significant improvements over current risk assessment approaches by revealing a regulatory sweet spot that maximizes public health benefits while incorporating practical approaches for model validation. PMID:26808876

  12. Activation of the NRF2-ARE signalling pathway by the Lentinula edodes polysaccharose LNT alleviates ROS-mediated cisplatin nephrotoxicity.

    PubMed

    Chen, Qian; Peng, Huixia; Dong, Lei; Chen, Lijuan; Ma, Xiaobin; Peng, Yuping; Dai, Shejiao; Liu, Qiang

    2016-07-01

    The nephrotoxicity of cisplatin (cis-DDP) limits its general clinical applications. Lentinan (LNT), a dextran extracted from the mushroom Lentinula edodes, has been shown to have multiple pharmacological activities. The primary objective of the current study was to determine whether and how LNT alleviates cis-DDP- induced cytotoxicity in HK-2 cells and nephrotoxicity in mice. LNT did not interfere with cisplatin's anti-tumour efficacy in vitro and functioned cooperatively with cis-DDP to inhibit activity in HeLa and A549 tumour cells. LNT alleviated the cis-DDP-induced decrease in HK-2 cell viability, caspase-3 activation and cleavage of the DNA repair enzyme PARP, decreased HK-2 cell apoptosis and inhibited reactive oxygen species (ROS) accumulation in HK-2 cells. The inhibitor of ROS (N-acetyl-L-cysteine, NAC) could decreased the apoptosis of HK-2 cell. In addition, LNT significantly prevented cis-DDP-induced kidney injury in vivo. LNT itself could not eliminate ROS levels in vitro. Further studies demonstrated that LNT induced NF-E2 p45-related factor 2 (Nrf2) protein and mRNA expression in a time- and dose-dependent manner. LNT promoted Nrf2 translocation to the nucleus and binding to the antioxidant-response element (ARE) sequence and induced the transcription and translation of heme oxygenase 1 (HO-1), aldo-keto reductases 1C1 and 1C2 (AKR1C), and NADP(H):quinone oxidoreductase 1 (NQO1). Finally, we used hNrf2 siRNA and an Nrf2 agonist (tBHQ) to inhibit or enhance Nrf2 expression. The results demonstrated that the LNT-mediated alleviation of cis-DDP-induced nephrotoxicity was achieved by preventing the accumulation of ROS in a manner that depended on the activation of the Nrf2-ARE signalling pathway. PMID:27093515

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

    PubMed

    Becker, Klaus

    2003-01-01

    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

  14. Rapid synthesis of Eu3+-doped LNT (Li-Nb-Ti-O) phosphor by millimeter-wave heating

    NASA Astrophysics Data System (ADS)

    Nakano, Hiromi; Ozono, Keita; Saji, Tasaburo; Miyake, Syoji; Hayashi, Hiroyuki

    2013-09-01

    We have been investigated a new phosphor containing the LNT (Li1+x-yNb1-x-3yTix+4yO3 (0.11 ⩽ x ⩽ 0.33, 0 ⩽ y ⩽ 0.09) with the superstructure as a host material. An Eu3+-doped LNT has prepared by sintering at 1373 K for 24 h by a conventional electric furnace before. A fast synthesizing technique that uses lower energy is required for application of the materials. In the present study, the Eu3+-doped LNT phosphor has been successfully synthesized by millimeter-wave (MM) heating at 1173 K for 1 h. A bright red emission was observed at an excitation wavelength of 398 nm. The maximum emission peak observed at around 625 nm is associated with the intra-4f shell 5D0-7F2 transition in Eu3+ ions. The photoluminescence (PL) intensity of the specimen by MM heating was nearly equivalent to that of the specimen obtained by electric furnace heating. MM radiation can therefore be considered to be a highly efficient, energy-saving method for the formation of Eu3+-doped LNT phosphors.

  15. Response to, "On the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith.".

    PubMed

    Beyea, Jan

    2016-07-01

    It is not true that successive groups of researchers from academia and research institutions-scientists who served on panels of the US National Academy of Sciences (NAS)-were duped into supporting a linear no-threshold model (LNT) by the opinions expressed in the genetic panel section of the 1956 "BEAR I" report. Successor reports had their own views of the LNT model, relying on mouse and human data, not fruit fly data. Nor was the 1956 report biased and corrupted, as has been charged in an article by Edward J. Calabrese in this journal. With or without BEAR I, the LNT model would likely have been accepted in the US for radiation protection purposes in the 1950's. PMID:26948286

  16. 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

  17. On the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith.

    PubMed

    Calabrese, Edward J

    2015-10-01

    This paper is an historical assessment of how prominent radiation geneticists in the United States during the 1940s and 1950s successfully worked to build acceptance for the linear no-threshold (LNT) dose-response model in risk assessment, significantly impacting environmental, occupational and medical exposure standards and practices to the present time. Detailed documentation indicates that actions taken in support of this policy revolution were ideologically driven and deliberately and deceptively misleading; that scientific records were artfully misrepresented; and that people and organizations in positions of public trust failed to perform the duties expected of them. Key activities are described and the roles of specific individuals are documented. These actions culminated in a 1956 report by a Genetics Panel of the U.S. National Academy of Sciences (NAS) on Biological Effects of Atomic Radiation (BEAR). In this report the Genetics Panel recommended that a linear dose response model be adopted for the purpose of risk assessment, a recommendation that was rapidly and widely promulgated. The paper argues that current international cancer risk assessment policies are based on fraudulent actions of the U.S. NAS BEAR I Committee, Genetics Panel and on the uncritical, unquestioning and blind-faith acceptance by regulatory agencies and the scientific community. PMID:26248082

  18. 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. PMID:24993953

  19. Telemonitoring in heart failure patients with clinical decision support to optimize medication doses based on guidelines.

    PubMed

    Kropf, Martin; Modre-Osprian, Robert; Hayn, Dieter; Fruhwald, Friedrich; Schreier, Günter

    2014-01-01

    The European Society of Cardiology guidelines for heart failure management are based on strong evidence that adherence to optimal medication is beneficial for heart failure patients. Telemonitoring with integrated clinical decision support enables physicians to adapt medication dose based on up to date vital parameters and reduces the number of hospital visits needed solely for up-titration of heart failure medication. Although keeping track of weight and blood pressure changes is recommended during unstable phases, e.g. post-discharge and during up-titration of medication, guidelines are rather vague regarding telehealth aspects. In this paper, we focus on the evaluation of a clinical decision support system for adaption of heart failure medication and for detecting early deteriorations through monitoring of blood pressure, heart rate and weight changes. This clinical decision support system is currently used in INTENSE-HF, a large scale telemonitoring trial with heart failure patients. The aim of this paper was to apply the decision support algorithm to an existing telemonitoring dataset, to assess the ability of the decision support concept to adhere to the guidelines and to discuss its limitations and potential improvements. PMID:25570663

  20. Changes in the planning target volume and liver volume dose based on the selected respiratory phase in respiratory-gated radiation therapy for a hepatocellular carcinoma

    NASA Astrophysics Data System (ADS)

    Lee, Jae-Seung; Im, In-Chul; Kang, Su-Man; Goo, Eun-Hoe; Baek, Seong-Min

    2013-11-01

    The aim of this study was to quantitatively analyze the changes in the planning target volume (PTV) and liver volume dose based on the respiratory phase to identify the optimal respiratory phase for respiratory-gated radiation therapy for a hepatocellular carcinoma (HCC). Based on the standardized procedure for respiratory-gated radiation therapy, we performed a 4-dimensional computed tomography simulation for 0 ˜ 90%, 30 ˜ 70%, and 40 ˜ 60% respiratory phases to assess the respiratory stability (S R ) and the defined PTV i for each respiratory phase i. A treatment plan was established, and the changes in the PTV i and dose volume of the liver were quantitatively analyzed. Most patients (91.5%) passed the respiratory stability test (S R = 0.111 ± 0.015). With standardized respiration training exercises, we were able to minimize the overall systematic error caused by irregular respiration. Furthermore, a quantitative analysis to identify the optimal respiratory phase revealed that when a short respiratory phase (40 ˜ 60%) was used, the changes in the PTV were concentrated inside the center line; thus, we were able to obtain both a PTV margin accounting for respiration and a uniform radiation dose within the PTV.

  1. 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.

  2. Cancer risk assessment: Optimizing human health through linear dose-response models.

    PubMed

    Calabrese, Edward J; Shamoun, Dima Yazji; Hanekamp, Jaap C

    2015-07-01

    This paper proposes that generic cancer risk assessments be based on the integration of the Linear Non-Threshold (LNT) and hormetic dose-responses since optimal hormetic beneficial responses are estimated to occur at the dose associated with a 10(-4) risk level based on the use of a LNT model as applied to animal cancer studies. The adoption of the 10(-4) risk estimate provides a theoretical and practical integration of two competing risk assessment models whose predictions cannot be validated in human population studies or with standard chronic animal bioassay data. This model-integration reveals both substantial protection of the population from cancer effects (i.e. functional utility of the LNT model) while offering the possibility of significant reductions in cancer incidence should the hormetic dose-response model predictions be correct. The dose yielding the 10(-4) cancer risk therefore yields the optimized toxicologically based "regulatory sweet spot". PMID:25916915

  3. 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.

  4. 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).

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

    PubMed Central

    Becker, Klaus

    2003-01-01

    Among the various “natural laboratories” of high natural or technical enhanced natural radiation environments in the world such as Kerala (India), Brazil, Ramsar (Iran), etc., the areas in and around the Central European Ore Mountains (Erzgebirge) in the southern parts of former East Germany, but also including parts of Thuringia, northern Bohemia (now Czech Republic), and northeastern Bavaria, are still relatively little known internationally. Although this area played a central role in the history of radioactivity and radiation effects on humans over centuries, most of the valuable earlier results have not been published in English or quotable according to the current rules in the scientific literature and therefore are not generally known internationally. During the years 1945 to 1989, this area was one of the world’s most important uranium mining areas, providing the former Soviet Union with 300,000 tons of uranium for its military programs. Most data related to health effects of radon and other carcinogenic agents on miners and residents became available only during the years after German reunification. Many of the studies are still unpublished, or more or less internal reports. By now, substantial studies have been performed on the previously unavailable data about the miners and the population, providing valuable insights that are, to a large degree, in disagreement with the opinion of various international bodies assuming an increase of lung cancer risk in the order of 10% for each 100 Bq/m3 (or doubling for 1000 Bq/m3), even for small residential radon concentrations. At the same time, other studies focusing on never-smokers show little or no effects of residential radon exposures. Experiments in medical clinics using radon on a large scale as a therapeutic against various rheumatic and arthritic disease demonstrated in randomized double-blind studies the effectiveness of such treatments. The main purpose of this review is to critically examine, including some historical references, recent results primarily in three areas, namely the possible effects of the inhalation of very high radon concentrations on miners; the effect of increased residential radon concentrations on the population; and the therapeutic use of radon. With many of the results still evolving and/or under intense discussion among the experts, more evidence is emerging that radon, which has been inhaled at extremely high concentrations in the multimillion Bq/m3 range by many of older miners (however, with substantial confounders, and large uncertainties in retrospective dosimetry), was perhaps an important but not the dominating factor for an increase in lung cancer rates. Other factors such as smoking, inhalation of quartz and mineral dust, arsenic, nitrous gases, etc. are likely to be more serious contributors to increased miner lung cancer rates. An extrapolation of miner data to indoor radon situations is not feasible. Concerning indoor radon studies, the by far dominating effect of smoking on the lung cancer incidence makes the results of some studies, apparently showing a positive dose-response relationship, questionable. According to recent studies in several countries, there are no, or beneficial, residential radon effects below about 600 to 1000 Bq/m3 (the extensive studies in the U.S., in particular by B. Cohen, and the discussions about these data, will not be part of this review, because they have already been discussed in detail in the U.S. literature). As a cause of lung cancer, radon seems to rank — behind active and passive smoking, and probably also air pollution in densely populated and/or industrial areas (diesel exhaust soot, etc.) — as a minor contributor in cases of extremely high residential radon levels, combined with heavy smoking of the residents. As demonstrated in an increasing number of randomized double-blind clinical studies for various painful inflammatory joint diseases such as rheumatism, arthritic problems, and Morbus Bechterew, radon treatments are beneficial, with the positiv

  6. 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. PMID:25271928

  7. Uses and Abuses of Models in Radiation Risk Management

    SciTech Connect

    Strom, Daniel J.

    1998-12-10

    This paper is a high-level overview of managing risks to workers, public, and the environment. It discusses the difference between a model and a hypothesis. The need for models in risk assessment is justified, and then it is shown that radiation risk models that are useable in risk management are highly simplistic. The weight of evidence is considered for and against the linear non-threshold (LNT) model for carcinogenesis and heritable ill-health that is currently the basis for radiation risk management. Finally, uses and misuses of this model are considered. It is concluded that the LNT model continues to be suitable for use as the basis for radiation protection.

  8. 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.

  9. 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.

  10. 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. PMID:27131569

  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. A Mathematical Model for Estimating Biological Damage Caused by Radiation

    NASA Astrophysics Data System (ADS)

    Manabe, Yuichiro; Ichikawa, Kento; Bando, Masako

    2012-10-01

    We propose a mathematical model for estimating biological damage caused by low-dose irradiation. We understand that the linear non threshold (LNT) hypothesis is realized only in the case of no recovery effects. In order to treat the realistic living objects, our model takes into account various types of recovery as well as proliferation mechanism, which may change the resultant damage, especially for the case of lower dose rate irradiation. It turns out that the lower the radiation dose rate, the safer the irradiated system of living object (which is called symbolically ``tissue'' hereafter) can have chances to survive, which can reproduce the so-called dose and dose-rate effectiveness factor (DDREF).

  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. Review of Chinese Environmental Risk Assessment Regulations and Case Studies

    PubMed Central

    Meng, Xiaojie; Zhang, Yan; Zhao, Yuchao; Lou, In Chio; Gao, Jixi

    2012-01-01

    Environmental risk assessment is an essential step in the development of solutions for pollution problems and new environmental regulations. An assessment system for environmental risks has been developed in China in recent decades. However, many of the Chinese technical guidelines, standards, and regulations were directly adapted from those of developed countries, and were not based on the Chinese environmental and socioeconomic context. Although existing environmental regulations for pollutants are usually obtained by extrapolations from high-dose toxicological data to low-dose scenarios using linear-non-threshold (LNT) models, toxicologists have argued that J-shaped or inverse J-shaped curves may dominate the dose–response relationships for environmental pollutants at low doses because low exposures stimulate biological protective mechanisms that are ineffective at higher doses. The costs of regulations based on LNT and J-shaped models could therefore be dramatically different. Since economic factors strongly affect the decision-making process, particularly for developing countries, it is time to strengthen basic research to provide more scientific support for Chinese environmental regulations. In this paper, we summarize current Chinese environmental policies and standards and the application of environmental risk assessment in China, and recommend a more scientific approach to the development of Chinese regulations. PMID:22740787

  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. PMID:23220609

  17. Dose-based duration adjustments for the effects of inhaled trichloroethylene on rat visual function.

    PubMed

    Boyes, William K; Bercegeay, Mark; Ali, Joseph S; Krantz, Todd; McGee, John; Evans, Marina; Raymer, James H; Bushnell, Philip J; Simmons, Jane Ellen

    2003-11-01

    Risk assessments often must consider exposures that vary over time or for which the exposure duration of concern differs from the available data, and a variety of extrapolation procedures have been devised accordingly. The present experiments explore the relationship(s) between exposure concentration (C) and time (t) to investigate procedures for assessing the risks of short-term solvent exposures. The first hypothesis tested was that the product of C x t would produce a constant health effect (Haber's rule). The second hypothesis tested was that exposure conditions produce effects in proportion to the tissue concentrations created. Awake, adult, male Long-Evans (LE) rats were exposed to trichloroethylene (TCE) vapor in a head-only exposure chamber while pattern onset/offset visual evoked potentials (VEPs) were recorded. Exposure conditions were designed to provide C x t products of 0 ppm/h (0 ppm for 4 h) or 4000 ppm/h created through four exposure scenarios: 1000 ppm for 4 h; 2000 ppm for 2 h; 3000 ppm for 1.3 h; or 4000 ppm for 1h (n = 9-10/concentration). The amplitude of the VEP frequency double component (F2) was decreased significantly by exposure; this decrease was related to C but not to t or to the C x t product, indicating that Haber's rule did not hold. The mean amplitude (+/- SEM in muV) of the F2 component in the control and treatment groups measured 4.4 +/- 0.5 (0 ppm/4 h), 3.1 +/- 0.5 (1000 ppm/4 h), 3.1 +/- 0.4 (2000 ppm/2 h), 2.3 +/- 0.3 (3000 ppm/1.3 h), and 1.9 +/- 0.4 (4000 ppm/1 h). A physiologically based pharmacokinetic (PBPK) model was used to estimate the concentrations of TCE in the brain achieved during each exposure condition. The F2 amplitude of the VEP decreased monotonically as a function of the estimated peak brain concentration but was not related to the area under the curve (AUC) of the brain TCE concentration. In comparison to estimates from the PBPK model, extrapolations based on Haber's rule yielded approximately a 6-fold error in estimated exposure duration when extrapolating across only a 4-fold change in exposure concentration. These results indicate that the use of a linear form of Haber's rule will not predict accurately the risks of acute exposure to TCE, nor will an estimate of AUC of brain TCE. However, an estimate of the brain TCE concentration at the time of VEP testing predicted the effects of TCE across exposure concentrations and durations. PMID:12915717

  18. A randomized trial of initial warfarin dosing based on simple clinical criteria.

    PubMed

    Shine, Daniel; Patel, Jeetendra; Kumar, Juhi; Malik, Aamir; Jaeger, Joseph; Maida, Mahamadu; Ord, Linda; Burrows, Grover

    2003-02-01

    Warfarin induction is accomplished by titrating dosage to coagulation test results. Algorithms can guide this process but not identify the starting dose. We hypothesized that an initial warfarin dose approximating the maintenance value would safely enhance rapidity of induction. In a randomized trial we compared a fixed-dose to a maintenance-dose strategy for beginning warfarin therapy. To predict the maintenance dose among patients with differing warfarin requirements we performed regression analysis on clinical factors derived from chart review. Four community hospitals supplied records for retrospective analysis. The prospective trial was conducted in one, a 350-bed teaching institution. A sample of inpatients anticoagulated during 1998 formed the development set for retrospective study; a 1999 sample formed the validation set. A one year trial recruited consecutive eligible inpatients initiated on warfarin. We randomly assigned patients to a first warfarin dose calculated using our regression formula or fixed at 5 mg. All patients' subsequent doses were determined (as a percentage of initial) from coagulation testing. We compared days to anticoagulation, hospitalized hours, complications, and activity of factor II and protein C in a patient sample at intervals after induction. Weight, age, serum albumin, and presence of malignancy explained 25-30% of variance in maintenance dose. Ninety patients (44 calculated-dose and 46 standard-dose) evaluated in the clinical trial. Mean time to anticoagulation (among patients achieving anticoagulation) was 4.2 and 5.0 days, respectively (p = 0.007). We observed no significant differences in other endpoints. Individualized initial dosing may safely hasten warfarin induction. PMID:12574810

  19. Evaluation of target dose based on water-equivalent thickness in external beam radiotherapy

    PubMed Central

    Moghaddam, Behnaz Ghanbar; Vahabi-Moghaddam, Masoud; Sadremomtaz, Alireza

    2013-01-01

    In vivo dosimetry was carried out for 152 patients receiving external beam radiotherapy and the treatment sites were divided into two main groups: Thorax, Abdomen, and Pelvic (120 fields) and Head and Neck (52 fields). Combined entrance and exit dose measurements were performed using LiF: Mg, Cu, P thermoluminescent dosimeters (TLDs). Water-equivalent (effective) thicknesses and target dose were evaluated using dose transmission data. The ratio of measured to expected value for each quantity was considered as an indicator for the accuracy of the parameter. The average ratio of the entrance dose was evaluated as 1.01 ± 0.07. In the diameter measurement, the mean ratio of effective depth divided by the contour depth is 1.00 ± 0.13 that shows a wide distribution which reflects the influence of contour inaccuracies as well as tissue inhomogeneities. At the target level, the mean ratio of measured to the prescribed dose is 1.00 ± 0.07. According to our findings, the difference between effective depth and patient depth has a direct relation to target dose discrepancies. There are some inevitable sources which may cause the difference. Evaluation and application of effective diameter in treatment calculations would lead to a more reliable target dose, especially for fields which involve Thorax, Abdomen, and Pelvic. PMID:23532059

  20. Rapid method for thermal dose-based safety supervision during MR scans.

    PubMed

    Neufeld, Esra; Fuetterer, Maximilian; Murbach, Manuel; Kuster, Niels

    2015-07-01

    To maximize diagnostic accuracy and minimize costs, magnetic resonance imaging (MRI) scanners expose patients to electromagnetic exposure levels well above the established maximum, but in a well-controlled environment. In this paper, we discuss a novel safety assessment model that offers maximum flexibility while ensuring no local tissue damage due to radiofrequency induced heating occurs. This model is based on the cumulative equivalent minutes at 43 °C (CEM43) thermal dose concept, which naturally considers exposure duration, tissue sensitivity and the transient nature of heating, and permits rapid assessment of exposure safety of a given MRI scan using information about the transient specific absorption rate (SAR). It builds upon theoretical considerations (e.g., relating peak temperatures in the presence and absence of local thermoregulation) as well as data extracted from simulations involving anatomical models (e.g., to determine the characteristic time of temperature changes). The model is capable of predicting CEM43 for patients with either uncompromised thermoregulation or absent thermoregulation. The model predictions approximate detailed simulations well and results illustrate the importance of adequately considering changes in perfusion. The model presented herein offers an MRI safety assessment approach that overcomes problems associated with traditional SAR-based limits. Its limitations and the associated uncertainties are discussed together with remaining open questions. PMID:25962894

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

    PubMed

    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 cm(3). 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

  2. 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

  3. 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.

  4. NOx Storage-Reduction Characteristics of Ba-Based Lean NOx Trap Catalysts Subjected to Simulated Road Aging

    SciTech Connect

    Ji, Yaying; Fisk, Courtney; Easterling, Vencon; Graham, Uschi; Poole, Adam; Crocker, Mark; Choi, Jae-Soon; Partridge Jr, William P; Wilson, Karen

    2010-01-01

    Although Lean NO{sub x} Trap (LNT) catalyst technology has made significant strides in recent years, the issue of LNT durability remains problematic. Following on from our previous research concerning the effect of ceria addition on LNT preformance, in this study we focus on the role of ceria in ameliorating the deterioration of Ba-based LNT catalysts during aging. Indeed, we have observed that spectacular improvements in LNT durability can be achieved through the incorporation of CeO{sub 2}-ZrO{sub 2} into the LNT formulation, and, to a lesser extent, La-stabilized ceria.

  5. American Society for Pain Management Nursing Position Statement: Prescribing and Administering Opioid Doses Based Solely on Pain Intensity.

    PubMed

    Pasero, Chris; Quinlan-Colwell, Ann; Rae, Diana; Broglio, Kathleen; Drew, Debra

    2016-06-01

    The foundation of safe and effective pain management is an individualized, comprehensive pain assessment, which includes, but is not limited to, determining the intensity of pain if the patient is able to report it. An unforeseen consequence of the widespread use of pain intensity rating scales is the practice of prescribing specific doses of opioid analgesics based solely on specific pain intensity. Many factors in addition to pain intensity influence opioid requirements, and there is no research showing that a specific opioid dose will relieve pain of a specific intensity in all patients. The American Society for Pain Management Nursing (ASPMN) holds the position that the practice of prescribing doses of opioid analgesics based solely on a patient's pain intensity should be prohibited because it disregards the relevance of other essential elements of assessment and may contribute to untoward patient outcomes. PMID:27108082

  6. Exogenous Calcium Alleviates Low Night Temperature Stress on the Photosynthetic Apparatus of Tomato Leaves

    PubMed Central

    Ni, Yang; Meng, Zhaojuan; Lu, Tao; Li, Tianlai

    2014-01-01

    The effect of exogenous CaCl2 on photosystem I and II (PSI and PSII) activities, cyclic electron flow (CEF), and proton motive force of tomato leaves under low night temperature (LNT) was investigated. LNT stress decreased the net photosynthetic rate (Pn), effective quantum yield of PSII [Y(II)], and photochemical quenching (qP), whereas CaCl2 pretreatment improved Pn, Y(II), and qP under LNT stress. LNT stress significantly increased the non-regulatory quantum yield of energy dissipation [Y(NO)], whereas CaCl2 alleviated this increase. Exogenous Ca2+ enhanced stimulation of CEF by LNT stress. Inhibition of oxidized PQ pools caused by LNT stress was alleviated by CaCl2 pretreatment. LNT stress reduced zeaxanthin formation and ATPase activity, but CaCl2 pretreatment reversed both of these effects. LNT stress caused excess formation of a proton gradient across the thylakoid membrane, whereas CaCl2 pretreatment decreased the said factor under LNT. Thus, our results showed that photoinhibition of LNT-stressed plants could be alleviated by CaCl2 pretreatment. Our findings further revealed that this alleviation was mediated in part by improvements in carbon fixation capacity, PQ pools, linear and cyclic electron transports, xanthophyll cycles, and ATPase activity. PMID:24828275

  7. 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.

  8. 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

    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

  9. 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

  10. 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.

  11. Genomic rearrangements and signatures of breeding in the allo-octoploid strawberry as revealed through an allele dose based SSR linkage map

    PubMed Central

    2014-01-01

    Background Breeders in the allo-octoploid strawberry currently make little use of molecular marker tools. As a first step of a QTL discovery project on fruit quality traits and resistance to soil-borne pathogens such as Phytophthora cactorum and Verticillium we built a genome-wide SSR linkage map for the cross Holiday x Korona. We used the previously published MADCE method to obtain full haplotype information for both of the parental cultivars, facilitating in-depth studies on their genomic organisation. Results The linkage map incorporates 508 segregating loci and represents each of the 28 chromosome pairs of octoploid strawberry, spanning an estimated length of 2050 cM. The sub-genomes are denoted according to their sequence divergence from F. vesca as revealed by marker performance. The map revealed high overall synteny between the sub-genomes, but also revealed two large inversions on LG2C and LG2D, of which the latter was confirmed using a separate mapping population. We discovered interesting breeding features within the parental cultivars by in-depth analysis of our haplotype data. The linkage map-derived homozygosity level of Holiday was similar to the pedigree-derived inbreeding level (33% and 29%, respectively). For Korona we found that the observed homozygosity level was over three times higher than expected from the pedigree (13% versus 3.6%). This could indicate selection pressure on genes that have favourable effects in homozygous states. The level of kinship between Holiday and Korona derived from our linkage map was 2.5 times higher than the pedigree-derived value. This large difference could be evidence of selection pressure enacted by strawberry breeders towards specific haplotypes. Conclusion The obtained SSR linkage map provides a good base for QTL discovery. It also provides the first biologically relevant basis for the discernment and notation of sub-genomes. For the first time, we revealed genomic rearrangements that were verified in a separate mapping population. We believe that haplotype information will become increasingly important in identifying marker-trait relationships and regions that are under selection pressure within breeding material. Our attempt at providing a biological basis for the discernment of sub-genomes warrants follow-up studies to streamline the naming of the sub-genomes among different octoploid strawberry maps. PMID:24581289

  12. Spontaneous nematic alignment of a lipid nanotube in aqueous solutions.

    PubMed

    Ding, Wuxiao; Minamikawa, Hiroyuki; Kameta, Naohiro; Wada, Momoyo; Masuda, Mitsutoshi; Shimizu, Toshimi

    2015-01-27

    The dispersibility and liquid crystal formation of a self-assembled lipid nanotube (LNT) was investigated in a variety of aqueous solutions. As the lipid component, we chose a bipolar lipid with glucose and tetraglycine headgroups, which self-assembled into an LNT with a small outer diameter of 16 to 17 nm and a high axial ratio of more than 310. The LNT gave a stable colloidal dispersion in its dilute solutions and showed spontaneous liquid crystal (LC) alignment at relatively low concentrations and in a pH region including neutral pH. The LNT samples with shorter length distributions were prepared by sonication, and the relationship between the LNT axial ratio and the minimum LC formation concentration was examined. The robustness of the LNT made the liquid crystal stable in mixed solvents of water/ethanol, water/acetone, and water/tetrahydrofuran (1:1 by volume) and at a temperature of up to 90 °C in water. The observed colloidal behavior of the LNT was compared to those of similar 1D nanostructures such as a phospholipid tubule. PMID:25548876

  13. Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism.

    PubMed

    Xu, Hui; Zou, Siwei; Xu, Xiaojuan; Zhang, Lina

    2016-01-01

    β-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro, and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors. PMID:27353254

  14. Anti-tumor effect of β-glucan from Lentinus edodes and the underlying mechanism

    PubMed Central

    Xu, Hui; Zou, Siwei; Xu, Xiaojuan; Zhang, Lina

    2016-01-01

    β-Glucans are well known for its various bioactivities, but the underlying mechanism has not been fully understood. This study focuses on the anti-tumor effect and the potential mechanism of a branched β-(1, 3)-glucan (LNT) extracted from Lentinus edodes. The in vivo data indicated that LNT showed a profound inhibition ratio of ~75% against S-180 tumor growth, even significantly higher than the positive control of Cytoxan (~54%). Interestingly, LNT sharply promoted immune cells accumulation into tumors accompanied by cell apoptosis and inhibition of cell proliferation during tumor development. Furthermore, LNT not only up-regulated expressions of the tumor suppressor p53, cell cycle arrestin p21 and pro-apoptotic proteins of Bax and caspase 3/9, but also down-regulated PARP1 and anti-apoptotic protein Bcl-2 expressions in tumor tissues. It was first found that LNT initiated p53-dependent signaling pathway to suppress cell proliferation in vitro, and the caspase-dependent pathway to induce cell apoptosis in vivo. The underlying anti-tumor mechanism was proposed that LNT activated immune responses to induce cell apoptosis through caspase 3-dependent signaling pathway and to inhibit cell proliferation possibly via p53-dependent signaling pathway in vivo. Besides, LNT inhibited angiogenesis by suppressing VEGF expression, leading to slow progression of tumors. PMID:27353254

  15. 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

  16. 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

  17. Electric moulding of dispersed lipid nanotubes into a nanofluidic device

    PubMed Central

    Frusawa, Hiroshi; Manabe, Tatsuhiko; Kagiyama, Eri; Hirano, Ken; Kameta, Naohiro; Masuda, Mitsutoshi; Shimizu, Toshimi

    2013-01-01

    Hydrophilic nanotubes formed by lipid molecules have potential applications as platforms for chemical or biological events occurring in an attolitre volume inside a hollow cylinder. Here, we have integrated the lipid nanotubes (LNTs) by applying an AC electric field via plug-in electrode needles placed above a substrate. The off-chip assembly method has the on-demand adjustability of an electrode configuration, enabling the dispersed LNT to be electrically moulded into a separate film of parallel LNT arrays in one-step. The fluorescence resonance energy transfer technique as well as the digital microscopy visualised the overall filling of gold nanoparticles up to the inner capacity of an LNT film by capillary action, thereby showing the potential of this flexible film for use as a high-throughput nanofluidic device where not only is the endo-signalling and product in each LNT multiplied but also the encapsulated objects are efficiently transported and reacted. PMID:23835525

  18. 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. PMID:26849459

  19. 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

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

    PubMed

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

    2015-03-01

    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. PMID:25498656

  1. The cooperative effect of p53 and Rb in local nanotherapy in a rabbit VX2 model of hepatocellular carcinoma

    PubMed Central

    Dong, Shengli; Tang, Qibin; Long, Miaoyun; Guan, Jian; Ye, Lu; Li, Gaopeng

    2013-01-01

    Background/aim A local nanotherapy (LNT) combining the therapeutic efficacy of trans-arterial embolization, nanoparticles, and p53 gene therapy has been previously presented. The study presented here aimed to further improve the incomplete tumor eradication and limited survival enhancement and to elucidate the molecular mechanism of the LNT. Methods In a tumor-targeting manner, recombinant expressing plasmids harboring wild-type p53 and Rb were either co-transferred or transferred separately to rabbit hepatic VX2 tumors in a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex and Lipiodol® (Guerbet, Villepinte, France) emulsion via the hepatic artery. Subsequent co-expression of p53 and Rb proteins within the treated tumors was investigated by Western blotting and in situ analysis by laser-scanning confocal microscopy. The therapeutic effect was evaluated by the tumor growth velocity, apoptosis and necrosis rates, their sensitivity to Adriamycin® (ADM), mitomycin C, and fluorouracil, the microvessel density of tumor tissue, and the survival time of animals. Eventually, real-time polymerase chain reaction and enhanced chemiluminescence Western blotting were used to investigate the expressive changes of important genes related to the therapy. Results The administration procedure proved safe for the rabbits’ liver function, the p53 plus Rb LNT showed significantly better antitumoral effect and lower expression of malignant genes than the p53 or Rb LNT, although no significant difference was observed in animal survival when the p53 plus Rb LNT was compared with the p53 LNT. Conclusion Rb works synergistically with p53 in combined therapy mediated by a poly-L-lysine-modified hydroxyapatite nanoparticle nanoplex to augment the antitumoral effect through the downregulated expression of important genes related to apoptosis, necrosis, growth, differentiation and multidrug resistance of tumor cells. LNT with p53 and Rb is potentially an effective antitumor

  2. [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. PMID:26521869

  3. 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.

  4. β-Glucan from Lentinus edodes Inhibits Nitric Oxide and Tumor Necrosis Factor-α Production and Phosphorylation of Mitogen-activated Protein Kinases in Lipopolysaccharide-stimulated Murine RAW 264.7 Macrophages*

    PubMed Central

    Xu, Xiaojuan; Yasuda, Michiko; Nakamura-Tsuruta, Sachiko; Mizuno, Masashi; Ashida, Hitoshi

    2012-01-01

    Lentinan (LNT), a β-glucan from the fruiting bodies of Lentinus edodes, is well known to have immunomodulatory activity. NO and TNF-α are associated with many inflammatory diseases. In this study, we investigated the effects of LNT extracted by sonication (LNT-S) on the NO and TNF-α production in LPS-stimulated murine RAW 264.7 macrophages. The results suggested that treatment with LNT-S not only resulted in the striking inhibition of TNF-α and NO production in LPS-activated macrophage RAW 264.7 cells, but also the protein expression of inducible NOS (iNOS) and the gene expression of iNOS mRNA and TNF-α mRNA. It is surprising that LNT-S enhanced LPS-induced NF-κB p65 nuclear translocation and NF-κB luciferase activity, but severely inhibited the phosphorylation of JNK1/2 and ERK1/2. The neutralizing antibodies of anti-Dectin-1 and anti-TLR2 hardly affected the inhibition of NO production. All of these results suggested that the suppression of LPS-induced NO and TNF-α production was at least partially attributable to the inhibition of JNK1/2 and ERK1/2 activation. This work discovered a promising molecule to control the diseases associated with overproduction of NO and TNF-α. PMID:22102286

  5. Characterization of Lean NOx Trap Catalysts with In-Cylinder Regeneration Strategies

    SciTech Connect

    Parks, II, James E; Huff, Shean P; Swartz, Matthew M; West, Brian H

    2008-01-01

    Lean NOx trap (LNT) catalysts with different formulations have been characterized on a light-duty diesel engine platform. Two in-cylinder regeneration strategies were used during the study. The reductant chemistry differed for both strategies with one strategy having high levels of CO and H2 and the other strategy having a higher hydrocarbon component. The matrix of LNT catalysts that were characterized included LNTs with various sorbate loads and varying ceria content; the sorbate was Ba. Intra-catalyst measurements of exhaust gas composition were obtained at one quarter, one half, and three quarters of the length of the catalysts to better understand the affect of formulation on performance. Exhaust analysis with FTIR allowed measurement of NH3 and thereby, a measurement of N2 selectivity for the catalysts. Although overall NOx conversion increased with increasing sorbate load, the formation of NH3 increased as well. Interestingly, the presence of ceria in the LNT allowed NH3 to be oxidized to N2 in the downstream half of the LNT, thereby greatly reducing the tailpipe NH3 level. Despite different capacities for NOx sorption, a similar pattern for NOx adsorption as a function of the length of the catalyst was observed for catalysts with 8% and 20% Ba load. Results from these engine based experiments will be discussed relative to the body of literature concerning fundamental and model LNT studies.

  6. 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.

  7. 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.

  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. 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

  10. Time to Reject the Linear-No Threshold Hypothesis and Accept Thresholds and Hormesis: A Petition to the U.S. Nuclear Regulatory Commission.

    PubMed

    Marcus, Carol S

    2015-07-01

    On February 9, 2015, I submitted a petition to the U.S. Nuclear Regulatory Commission (NRC) to reject the linear-no threshold (LNT) hypothesis and ALARA as the bases for radiation safety regulation in the United States, using instead threshold and hormesis evidence. In this article, I will briefly review the history of LNT and its use by regulators, the lack of evidence supporting LNT, and the large body of evidence supporting thresholds and hormesis. Physician acceptance of cancer risk from low dose radiation based upon federal regulatory claims is unfortunate and needs to be reevaluated. This is dangerous to patients and impedes good medical care. A link to my petition is available: http://radiationeffects.org/wp-content/uploads/2015/03/Hormesis-Petition-to-NRC-02-09-15.pdf, and support by individual physicians once the public comment period begins would be extremely important. PMID:26018704

  11. Low-Temperature Sintering Behavior and Dielectric Properties of Li2O-Nb2O5-TiO2 Ceramics with Li-B-Si-O Glass

    NASA Astrophysics Data System (ADS)

    Li, Enzhu; Zhang, Peng; Mi, Yuean; Wang, Jing; Yuan, Ying; Zhou, Xiaohua

    2015-11-01

    This paper reports an investigation of the low-temperature sintering behaviors, microstructures, and microwave dielectric properties of Li1.0Nb0.6Ti0.5O3 (LNT) ceramics fired with addition of different amounts of Li2O-B2O3-SiO2 (LBS) glass. The results suggest that addition of LBS glass can effectively reduce the sintering temperature of LNT ceramic from 1100°C to 900°C without detriment of its microwave dielectric properties. However, addition of excess LBS glass leads to rapid grain growth and therefore decreases the density and microwave dielectric properties of the LNT ceramic. Optimized specimens with 1.0 wt.% LBS glass sintered at 900°C possessed excellent microwave dielectric properties of ɛ r ≈ 66.17, Q × f ≈ 5170 GHz ( f = 4.32 GHz), and τ f ≈ 19.2 ppm/°C.

  12. 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.

  13. 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

  14. 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

  15. Neural networks for tracking of unknown SISO discrete-time nonlinear dynamic systems.

    PubMed

    Aftab, Muhammad Saleheen; Shafiq, Muhammad

    2015-11-01

    This article presents a Lyapunov function based neural network tracking (LNT) strategy for single-input, single-output (SISO) discrete-time nonlinear dynamic systems. The proposed LNT architecture is composed of two feedforward neural networks operating as controller and estimator. A Lyapunov function based back propagation learning algorithm is used for online adjustment of the controller and estimator parameters. The controller and estimator error convergence and closed-loop system stability analysis is performed by Lyapunov stability theory. Moreover, two simulation examples and one real-time experiment are investigated as case studies. The achieved results successfully validate the controller performance. PMID:26456201

  16. 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…

  17. 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...

  18. 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...

  19. 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. PMID:24910586

  20. 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.

  1. High permittivity and near-zero τɛ dielectrics Ca0.36Sr0.64TiO3-Li0.5Nd0.5TiO3 for multilayer ceramic capacitors

    NASA Astrophysics Data System (ADS)

    Wang, Xiaochuan; Liu, Yawen; Wang, Xiaohong; Lu, Wenzhong

    2015-11-01

    The microstructure and dielectric properties of (1 - x)Ca0.36Sr0.64TiO3-xLi0.5Nd0.5TiO3 (0 ≤ x ≤ 1) [abbreviated as (1 - x)CST-xLNT] solid solutions were investigated in this study. X-ray diffraction results showed that the samples exhibited a single cubic phase with x ≤ 0.5, whereas increasing LNT content resulted in a structural change from cubic to tetragonal phase in when x > 0.5. The permittivity (ɛr) decreased with increasing x, while the dielectric loss (tan δ) increased and then decreased at x = 1.0. The temperature dependence of ɛr and tan δ at 1 MHz for the (1 - x)CST-xLNT ceramics was also investigated. The temperature coefficient of the permittivity (τɛ) increased from highly negative values to positive values with increasing x. A near-zero τɛ was achieved at x = 0.57. Optimised dielectric properties were estimated to be ɛr = 227, tan δ = 0.043 and τɛ = 12 ppm/°C. Therefore, the 0.43CST-0.57LNT ceramic is proposed as a promising candidate material for multilayer ceramic capacitors with good temperature stability and high capacitance.

  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

    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.

  3. 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.

  4. 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.

  5. 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...

  6. 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...

  7. 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. PMID:26580818

  8. Contributions of the specialized conduction system to the activation sequence in the canine pulmonary conus.

    PubMed

    Pollard, A E; Spitzer, K W; Burgess, M J

    1997-07-01

    This study was designed to characterize the relative contributions of the specialized conduction system and the myocardial architecture to the ventricular activation sequence. In animal experiments, the activation sequence within a 14 x 14-mm region on each surface of the pulmonary conus from isolated canine hearts was determined from electrograms recorded during ventricular drives applied at the periphery of the measurement region. Recordings were obtained simultaneously from electrode arrays mounted on the endocardium and epicardium. Activation sequences were determined before and after the right ventricular cavity was bathed with a dilute Lugol-normal Tyrode (LNT) solution that selectively inhibited excitation of Purkinje cells. Simulations of action potential propagation in three-dimensional models (14.4 mm long x 7.2 mm wide x 3.6 mm thick) that included the major features of the midwall architecture were performed to aid in the interpretation of the experimental findings. During endocardial pacing (7 animals, 43 total drives), LNT application markedly prolonged the endocardial (13.7 +/- 1.3 ms) and epicardial (5.7 +/- 1.0 ms) activation sequences. However, epicardial isochrone maps constructed with electrograms recorded before LNT application showed no signs of multiple breakthrough sites and, with the exception of overall timing, closely resembled isochrone maps constructed with electrograms recorded after LNT application. During epicardial pacing (9 animals, 55 total drives), LNT application prolonged the endocardial (3.7 +/- 0.6 ms) and epicardial (1.9 +/- 0.6 ms) activation sequences much less dramatically than during endocardial pacing, suggesting a primary contribution of myocardial architecture. However, in those instances where nonuniform anisotropy slowed epicardial expansion of the depolarization wavefront, the specialized conduction system contributed to the activation sequence to a greater extent. PMID:9249520

  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. 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.

  11. Lentinan mitigates therarubicin-induced myelosuppression by activating bone marrow-derived macrophages in an MAPK/NF-κB-dependent manner.

    PubMed

    Liu, Qiang; Dong, Lei; Li, Hong; Yuan, Jia; Peng, Yuping; Dai, Shejiao

    2016-07-01

    Bone marrow (BM) suppression (also known as myelosuppression) is the most common and most severe side-effect of therarubicin (THP) and thereby limits the clinical application of this anticancer agent. Lentinan (LNT), a glucan extracted from dried shiitake mushrooms (Lentinula edodes), exhibits a variety of pharmacological activities. The objectives of the present study were to determine the effect of LNT on the myelosuppression of THP-treated mice and to examine the pharmacological mechanism of these effects. In vivo experiments indicated that non-cytotoxic levels of LNT strongly increased blood myeloperoxidase (MPO) activity; improved BM structural injuries; increased the numbers of leukocytes and neutrophils in the blood and BM; elevated the blood levels of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF) and macrophage colony-stimulating factor (M-CSF); and reduced the self-healing period in THP-treated mice. In vitro experiments indicated that LNT increased the viability of BM-derived macrophages (BMDMs) in a time- and dose-dependent manner without toxic side-effects and markedly increased the release of G-CSF, GM-CSF and M-CSF by BMDMs. Further analyses revealed that LNT activated the NF-κB and MAPK signalling pathways and promoted the nuclear import of p65 and that BAY 11-7082 (a specific inhibitor of NF-κB) suppressed the release of G-CSF, GM-CSF and M-CSF. Furthermore, we found that U0126, SB203580 and SP600125 (specific inhibitors of ERK, p38 and JNK, respectively) markedly inhibited the IKK/IκB/NF-κB-dependent release of G-CSF, GM-CSF and M-CSF. In conclusion, LNT induces the production of G-CSF, GM-CSF and M-CSF by activating the MAPK/NF-κB signalling pathway in BM cells, thereby mitigating THP-induced myelosuppression. PMID:27121155

  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. 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

  14. Ceramics

    NASA Astrophysics Data System (ADS)

    Li, Enzhu; Zou, Mengying; Duan, Shuxin; Xu, Ning; Yuan, Ying; Zhou, Xiaohua

    2014-11-01

    The effects of excess Li content on the phase structure and microwave dielectric properties, especially on the temperature coefficient, of LiNb0.6 Ti0.5O3 (LNT) ceramics were studied. The results show that small amounts of Li effectively enhanced the sintering process due to the compensation of high volatility of Li, leading to a densification and homogenous microstructure, and therefore enhanced the dielectric properties. However, too much Li leads to a secondary phase and cause abnormal grain growth. The LNT + 5 wt.% Li ceramic sintered at 1075°C in the air shows the best properties of ɛ r = 69.73, Q × f = 5543 GHz, and τ f = -4.4 ppm/°C.

  15. 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.

  16. 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.

  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. 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.

  19. Effect of Ceria on the Storage and Regeneration Behavior of a Model Lean NOx Trap Catalyst

    SciTech Connect

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

    2007-01-01

    In this study the effect of ceria addition on the performance of a model Ba-based lean NO{sub x} trap (LNT) catalyst was examined. The presence of ceria improved NO{sub x} storage capacity in the temperature range 200-400 C under both continuous lean and lean-rich cycling conditions. Temperature-programmed experiments showed that NO{sub x} stored in the ceria-containing catalyst was thermally less stable and more reactive to reduction with both H{sub 2} and CO as reductants, albeit at the expense of additional reductant consumed by reduction of the ceria. These findings demonstrate that the incorporation of ceria in LNTs not only improves NO{sub x} storage efficiency but also positively impacts LNT regeneration behavior.

  20. A more flexible lipoprotein sorting pathway.

    PubMed

    Chahales, Peter; Thanassi, David G

    2015-05-01

    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

  1. Mechanics of lipid bilayer junctions affecting the size of a connecting lipid nanotube

    NASA Astrophysics Data System (ADS)

    Karlsson, Roger; Kurczy, Michael; Grzhibovskis, Richards; Adams, Kelly L.; Ewing, Andrew G.; Cans, Ann-Sofie; Voinova, Marina V.

    2011-06-01

    In this study we report a physical analysis of the membrane mechanics affecting the size of the highly curved region of a lipid nanotube (LNT) that is either connected between a lipid bilayer vesicle and the tip of a glass microinjection pipette (tube-only) or between a lipid bilayer vesicle and a vesicle that is attached to the tip of a glass microinjection pipette (two-vesicle). For the tube-only configuration (TOC), a micropipette is used to pull a LNT into the interior of a surface-immobilized vesicle, where the length of the tube L is determined by the distance of the micropipette to the vesicle wall. For the two-vesicle configuration (TVC), a small vesicle is inflated at the tip of the micropipette tip and the length of the tube L is in this case determined by the distance between the two interconnected vesicles. An electrochemical method monitoring diffusion of electroactive molecules through the nanotube has been used to determine the radius of the nanotube R as a function of nanotube length L for the two configurations. The data show that the LNT connected in the TVC constricts to a smaller radius in comparison to the tube-only mode and that tube radius shrinks at shorter tube lengths. To explain these electrochemical data, we developed a theoretical model taking into account the free energy of the membrane regions of the vesicles, the LNT and the high curvature junctions. In particular, this model allows us to estimate the surface tension coefficients from R( L) measurements.

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

    USGS Publications Warehouse

    Marion, J.L.; Reid, S.

    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.

  3. 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 .

  4. 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

  5. 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. PMID:26895326

  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. Radiation chemical effects on polybutadiene polymers, styrene-butadiene block copolymers, and isotactic polypropylene

    SciTech Connect

    Basheer, R.A.

    1981-01-01

    Electron spin resonance (ESR) of the free radical structure resulting from high energy gamma LNT irradiation of the polymers revealed the presence of allylic free radicals of the type approx. CH.CH = CH.CH/sub 2/ approx. The presence of chemically trapped electrons in polybutadiene and styrene-butadiene (SB) block copolymers irradiated in the absence of light at LNT was determined by ESR measurements, and the trapping sites were shown to be impurities or additive molecules which were imbedded in between the polymer chains and which had not been completely removed by purification. Reaction kinetic studies of free radical decay indicated that the decay followed the equation derived for the case in which some free radicals decay by a second order mechanism in the presence of nondecaying free radicals. The same reaction scheme was found to describe the kinetics of alkyl free radical decay in LNT irradiated quenched and annealed isotactic polypropylene with the decay rate of quenched samples being higher than for annealed samples. Results of studies of radiation-induced crosslinking of the elastomers are also included. (BLM)

  8. 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.

  9. “Protective Bystander Effects Simulated with the State-Vector Model”—HeLa x Skin Exposure to 137Cs Not Protective Bystander Response But Mammogram and Diagnostic X-Rays Are

    PubMed Central

    Leonard, Bobby E.

    2008-01-01

    The recent Dose Response journal article “Protective Bystander Effects Simulated with the State-Vector Model” (Schollnberger and Eckl 2007) identified the suppressive (below natural occurring, zero primer dose, spontaneous level) dose response for HeLa x skin exposure to 137Cs gamma rays (Redpath et al 2001) as a protective Bystander Effect (BE) behavior. I had previously analyzed the Redpath et al (2001) data with a Microdose Model and conclusively showed that the suppressive response was from Adaptive Response (AR) radio-protection (Leonard 2005, 2007a). The significance of my microdose analysis has been that low LET radiation induced single (i.e. only one) charged particle traversals through a cell can initiate a Poisson distributed activation of AR radio-protection. The purpose of this correspondence is to clarify the distinctions relative to the BE and the AR behaviors for the Redpath groups 137Cs data, show conversely however that the Redpath group data for mammography (Ko et al 2004) and diagnostic (Redpath et al 2003) X-rays do conclusively reflect protective bystander behavior and also herein emphasize the need for radio-biologist to apply microdosimetry in planning and analyzing their experiments for BE and AR. Whether we are adamantly pro-LNT, adamantly anti-LNT or, like most of us, just simple scientists searching for the truth in radio-biology, it is important that we accurately identify our results, especially when related to the LNT hypothesis controversy. PMID:18846260

  10. 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. PMID:22696531

  11. Linear No-Threshold model and standards for protection against radiation.

    PubMed

    Shamoun, Dima Yazji

    2016-06-01

    In response to the three petitions by Carol S. Marcus, Mark L. Miller, and Mohan Doss, dated February 9, February 13, and February 24, 2015, respectively, the Nuclear Regulatory Commission (NRC or the Commission) has announced that it is considering assessing its choice of dose-response model, the Linear No-Threshold (LNT) model, for exposure to ionizing radiation. This comment is designed to assist the Commission in evaluating the merits of a review of the default dose-response model it uses as the basis for the Standards for Protection against Radiation regulations. It extends the petitioners' argument in favor of reexamining the default hypothesis (LNT) and taking consideration of low-dose hormesis for two main reasons: 1) Failure to review the LNT hypothesis may jeopardize the NRC's mission to protect public health and safety; and 2) The National Research Council's guidelines for choosing adequate defaults indicate that the choice of low-dose default model is due for a reevaluation. PMID:26924276

  12. 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.

  13. 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).

  14. Polymorphonuclear leucocyte sequestration in the lungs and liver following soft-tissue trauma: an in vivo study

    SciTech Connect

    Thoerne, J.B.; Blomquist, S.; Elmer, O.; Grafstroem, G.M.; Martensson, L.

    1989-04-01

    Neutrophils are thought to sequestrate in the lungs and the liver in association with shock. Indications for this have previously been demonstrated in different in vitro studies. In this experiment an in vivo technique for dynamic studies of pulmonary and liver neutrophil sequestration (PNT and LNT, respectively) is described. Autologous neutrophils from ten pigs were labelled with indium-111 oxine. The pigs were placed under a scintillation camera for continuous recording of the activity distribution in the pigs during 105 minutes. Following a steady-state period of 15 minutes seven pigs were subjected to a standardized soft-tissue trauma. Three pigs were used as controls and not traumatized. Within 1-3 minutes after trauma the radioactivity over the lungs increased dramatically, indicating PNT. This was followed by a fast decrease but 90 minutes after trauma PNT levels were still significantly elevated. LNT showed a similar pattern, although the immediate increase was less dramatic. This study shows that PNT and LNT occur immediately after soft-tissue trauma and can be studied dynamically in vivo.

  15. Freely drawn single lipid nanotube patterns.

    PubMed

    Sugihara, Kaori; Rustom, Amin; Spatz, Joachim P

    2015-03-14

    LNTs are unique 3D structures made only of safe and abundant biomaterials by self-assembly. The current bottleneck for developing applications using LNTs is the lack of an easy technique to pattern them on substrates. We report a method to free-draw single lipid nanotube (LNT) patterns in any shape on surfaces with 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) that takes an inverted hexagonal (HII) phase. We used pre-self-assembled LNTs or HII lipid blocks as a lipid reservoir from which new LNTs were pulled by applying a point load with a micromanipulator. The extreme simplicity of our technique originates from the fundamental nature of DOPE lipids that prefer a HII phase, while all the conventional approaches use PC lipids that form a lamellar phase. By adjusting the surface properties with polyelectrolyte multilayers, the created single LNT objects are able to remain adhered to the surface for over a week. Importantly, it could be shown that two vesicles loaded with caged fluorescent molecules were able to fuse well with a LNT, enabling diffusive transport of uncaged fluorescent molecules from one vesicle to the other. PMID:25626419

  16. 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. PMID:26405667

  17. Amphoteric substitutionality and lattice distortion of Ge in InP

    SciTech Connect

    Yu, K.M.; Moll, A.J.; Walukiewicz, W. ); Derhacobian, N.; Rossington, C. )

    1994-03-21

    We have studied the electrical and structural properties of InP implanted with Ge ions (2[times]10[sup 15]/cm[sup 2]). The implantation was performed at both room temperature (RT) and liquid nitrogen temperature (LNT). After annealing at 850 [degree]C for 5 s, both sets of samples exhibited [ital n]-type conductivity. The [ital n]-type activation efficiency in the RT implanted sample was about a factor of 2 higher than that in the LNT sample (15% and 8%, respectively). Extended x-ray absorption fine structure spectroscopy (EXAFS) shows direct evidence of the amphoteric substitutionality of the Ge atoms in InP for both samples. The ratios of Ge on In sites to Ge on P sites, derived from the EXAFS results, are consistent with the electrical behavior of the samples. The EXAFS results also reveal that the Ge---In and Ge---P bond lengths in the RT sample are very similar to their theoretical values, but are very different from the original In---P bond length. A relaxation in the Ge---In bond is observed in the LNT sample, resulting in a Ge---In bond length very similar to the original In---P bond length.

  18. Enhanced high temperature performance of MgAl2O4-supported Pt-BaO lean NOx trap catalysts

    SciTech Connect

    Kwak, Ja Hun; Kim, Do Heui; Szanyi, Janos; Cho, Sung June; Peden, Charles HF

    2012-03-05

    The structural and chemical characteristics of Pt/BaO lean-NO{sub x} trap (LNT) catalysts supported on {gamma}-Al{sub 2}O{sub 3} and MgAl{sub 2}O{sub 4} are compared in this study. The Pt-BaO/MgAl{sub 2}O{sub 4} sample shows relatively low NO{sub x} uptake at temperatures below 300 C, and the temperature of maximum NO{sub x} uptake (T{sub max}) is shifted to 350 C in comparison to that of Pt-BaO/Al{sub 2}O{sub 3} (T{sub max} {approx}250 C). More importantly, the NO{sub x} uptake over the MgAl{sub 2}O{sub 4}-supported catalyst at 350 C is twice that of the alumina-based one. The shift toward the higher temperature NO{sub x} uptake is explained by the larger interfacial area between Pt and BaO, due to smaller Pt clusters as evidenced by TEM and Pt L3 EXAFS. In situ TR-XRD results demonstrate that the formation of a BaAl{sub 2}O{sub 4} phase in the BaO/MgAl{sub 2}O{sub 4} LNT catalyst occurs at a temperature about 100 C higher than on BaO/Al{sub 2}O{sub 3}, which may also represent a beneficial attribute of the BaO/MgAl{sub 2}O{sub 4} LNT with respect to catalyst stability.

  19. Carbonates-based noble metal-free lean NOx trap catalysts MOx-K2CO3/K2Ti8O17 (M = Ce, Fe, Cu, Co) with superior catalytic performance

    NASA Astrophysics Data System (ADS)

    Zhang, Yuxia; You, Rui; Liu, Dongsheng; Liu, Cheng; Li, Xingang; Tian, Ye; Jiang, Zheng; Zhang, Shuo; Huang, Yuying; Zha, Yuqing; Meng, Ming

    2015-12-01

    A series of base metal-based lean NOx trap (LNT) catalysts MOx-K2CO3/K2Ti8O17 (M = Ce, Fe, Cu, Co) were synthesized by successive impregnations and employed for the storage and reduction of NOx in the emissions of lean-burn engines at 350 °C. The XRD and XANES/EXAFS results reveal that the active phases in the corresponding catalysts exist as CeO2, Fe2O3, CuO and Co3O4, respectively. Among all the catalysts, CoOx-K2CO3/K2Ti8O17 exhibits the best performance, which cannot only trap the NOx quickly and completely at lean condition, giving the highest storage capacity (3.32 mmol/g) reported so far, but also reduce the NOx at rich condition, showing a NOx reduction percentage as high as 99.0%. Meanwhile, this catalyst displays an ultralow NOx to N2O selectivity (0.3%) during NOx reduction. The excellent performance of CoOx-K2CO3/K2Ti8O17 results from its largest amount of surface active oxygen species as revealed by XPS, O2-TPD and NO-TPD. HRTEM, FT-IR and CO2-TPD results illustrate that several kinds of K species such as sbnd OK groups, K2O, surface carbonates and bulk or bulk-like carbonates coexist in the catalysts. Based upon the in situ DRIFTS results, the participation of K2CO3 in NOx storage is confirmed, and the predominant NOx storage species is revealed as bidentate nitrites formed via multiple kinetic pathways. The low cost and high catalytic performance of the CoOx-based LNT catalyst make it most promising for the substitution of noble metal-based LNT catalysts.

  20. 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.

  1. 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.

  2. Future of Radiation Protection Regulations.

    PubMed

    Doss, Mohan

    2016-03-01

    THERE IS considerable disagreement in the scientific community regarding the carcinogenicity of low-dose radiation (LDR), with publications supporting opposing points of view. However, major flaws have been identified in many of the publications claiming increased cancer risk from LDR. The data generally recognized as the most important for assessing radiation effects in humans, the atomic bomb survivor data, are often cited to raise LDR cancer concerns. However, these data no longer support the linear no-threshold (LNT) model after the 2012 update but are consistent with radiation hormesis. Thus, a resolution of the controversy regarding the carcinogenicity of LDR appears to be imminent, with the rejection of the LNT model and acceptance of radiation hormesis. Hence, for setting radiation protection regulations, an alternative approach to the present one based on the LNT model is needed. One approach would be to determine the threshold dose for the carcinogenic effect of radiation from existing data and establish regulations to ensure radiation doses are kept well below the threshold dose. This can be done by setting dose guidelines specifying safe levels of radiation doses, with the requirement that these safe levels, referred to as guidance levels, not be exceeded significantly. Using this approach, a dose guidance level of 10 cGy for acute radiation exposures and 10 cGy y for exposures over extended periods of time are recommended. The concept of keeping doses as low as reasonably achievable, known as ALARA, would no longer be required for low-level radiation exposures not expected to exceed the dose guidance levels significantly. These regulations would facilitate studies using LDR for prevention and treatment of diseases. Results from such studies would be helpful in refining dose guidance levels. The dose guidance levels would be the same for the public and radiation workers to ensure everyone's safety. PMID:26808881

  3. Complete lymph flow reconstruction: A free vascularized lymph node true perforator flap transfer with efferent lymphaticolymphatic anastomosis.

    PubMed

    Yamamoto, Takumi; Yoshimatsu, Hidehiko; Yamamoto, Nana

    2016-09-01

    Treatment of primary lower extremity lymphedema (LEL) is challenging, and lymph node transfer (LNT) can be a choice of treatment for progressive LEL. However, LNT has a risk of donor site lymphedema and possible lymph node (LN) sclerosis due to efferent lymphatic vessel (ELV) obstruction. Here, we report the first case of complete lymph flow reconstruction with true perforator LNT with efferent lymphaticolymphatic anastomosis (ELLA) for a patient with primary LEL and severe lymphosclerosis. A 49-year-old female suffered from primary progressive unilateral left LEL refractory to conservative treatments with frequent episodes of cellulitis. A true perforator LN flap was selectively harvested from the left lateral thoracic region under indocyanine green (ICG) lymphography navigation and transferred to the left groin with perforator-to-perforator anastomosis. The ELV of the transplanted LN was supermicrosurgically anastomosed to the contralateral iliac lymphatic vessel that was subcutaneously transferred to the left groin. Postoperatively, the patient experienced no episode of cellulitis with reduced degree of compression treatment, and lymphedematous volume decreased from 306 to 264 in terms of LEL index. Postoperative ICG lymphography showed evidence of reconstructed lymph flow from the left foot to the left groin and to the right inguinal LN through the transplanted LN flap and the ELLA. There were no subjective or objective findings of donor site lymphedema of the left arm or the right back and the lower extremity. True perforator LN flap with ELLA is a safe and effective treatment and has the potential to be a useful therapeutic option for primary unilateral LEL. PMID:27449876

  4. 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. PMID:22437350

  5. Amphoteric behavior and precipitation of Ge dopants in InP

    SciTech Connect

    Yu, K.M.; Moll, A.J.; Walukiewicz, W.

    1996-11-01

    We have directly correlated the electrical behavior, the impurity lattice site location, ion damage, and the local bonding environments of Ge-dopant ions implanted into InP. We have found that after rapid thermal annealing the free electron concentration in the samples implanted at room temperature (RT) are always higher than those implanted at liquid nitrogen temperature (LNT). Although the macroscopic structure seems to be insensitive to the implantation temperature, significantly more local disorder is created in the LNT implanted amorphous layers. Moreover, the amphoteric bonding structure of the Ge atoms is found to be well established already in the as-implanted amorphous InP. After high temperature annealing ({approx_gt}800{degree}C), the Ge atoms rearrange locally with more of the Ge substituting the In site than the P site resulting in {ital n}-type conductivity. The solid solubility of Ge in the InP is measured to be {approximately}1.4{endash}1.6{times}10{sup 20}/cm{sup 3} while the free electron concentration is estimated to saturate at {approximately}3.4{times}10{sup 19}/cm{sup 3}. The relatively low electron concentration can be explained by Ge precipitation and the compensation of Ge{sub In} donors by Ge{sub P} acceptors in the RT implanted case. The further reduction in electron concentration in the LNT implanted samples is believed to be related to the high residual damage found in these samples. The high solubility of Ge in InP can be attributed to the availability of two possible sublattice sites for the dopant and the compensation of the local strains due to the amphoteric substitution of the Ge. The concentration ratio of the Ge{sub In} to Ge{sub P} determined in the heavily implanted material has been used to estimate the difference in the formation energy of Ge substituting those two different sites.

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

    DOE PAGESBeta

    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. 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.

  8. 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.

  9. Theoretical model of granular compaction

    SciTech Connect

    Ben-Naim, E.; Knight, J.B.; Nowak, E.R. |; Jaeger, H.M.; Nagel, S.R.

    1997-11-01

    Experimental studies show that the density of a vibrated granular material evolves from a low density initial state into a higher density final steady state. The relaxation towards the final density follows an inverse logarithmic law. As the system approaches its final state, a growing number of beads have to be rearranged to enable a local density increase. A free volume argument shows that this number grows as N = {rho}/(1 {minus} {rho}). The time scale associated with such events increases exponentially e{sup {minus}N}, and as a result a logarithmically slow approach to the final state is found {rho} {infinity} {minus}{rho}(t) {approx_equal} 1/lnt.

  10. 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

  11. 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.

  12. 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.

  13. Vibrational study and spectra-structure correlations in ammonium saccharinate: comparison with the alkali saccharinates.

    PubMed

    Naumov, P; Jovanovski, G

    2000-06-01

    The FT IR spectra, at temperatures from liquid-nitrogen boiling (LNT) up to room temperature (RT), as well as the RT Raman solid-state spectra of protonated and deuterated ammonium saccharinate and of a series of alkali (Na, K, Rb, Cs) saccharinates are studied. The spectral assignments are aided with ab initio calculations on the free saccharinato anion at the HF/6-31 + + G(d,p) level. Attention is paid to the ND, CO and SO2 stretching regions. Correlation splitting is believed to be responsible for the presence of a v(CO) doublet. The averaged v(CO) frequency in (purely ionic) ammonium saccharinate is found to be the lowest in the so far studied saccharinates, along with the assumptions that the v(CO) frequency (or the corresponding averaged value) can have predictive value for the type of the metal-to-saccharinato ligand/ion bonding. The appreciably higher contribution of the dominating internal coordinate in the corresponding normal vibration in case of v(as)(SO2) than in v(s)(SO2) makes it suitable for spectra-structure correlations. Contrary to RT, even though no phase transitions were observed in the studied temperature range, some polycentered character is prescribed to the hydrogen bonds in which the ammonium ions of effective symmetry C8 participate at LNT. Certain structural predictions about the saccharinates of K, Rb and Cs are made. PMID:10888436

  14. Material recognition with the Medipix photon counting colour X-ray system

    NASA Astrophysics Data System (ADS)

    Norlin, B.; Manuilskiy, A.; Nilsson, H.-E.; Fröjdh, C.

    2004-09-01

    An energy sensitive imaging system like Medipix1 has proved to be promising in distinguishing different materials in an X-ray image of an object. We propose a general method utilising X-ray energy information for material recognition. For objects where the thickness of the materials is unknown, a convenient material parameter to identify is K=α1/α2, which is the ratio of the logarithms of the measured transmissions ln(t1)/ln(t2). If a database of the parameter K for different materials and energies is created, this method can be used for material recognition independent of the thickness of the materials.Series of images of an object consisting of aluminium and silicon were taken with different energy thresholds. The X-ray absorption for silicon and aluminium is very similar for the range 40-60keV and only differs for lower energies. The results show that it is possible to distinguish between aluminium and silicon on images achieved by Medipix1 using a standard dental source. By decreasing the spatial resolution a better contrast between the materials was achieved. The resolution of contrasts shown by the histograms was close to the limit of the system due to the statistical noise of the signal.

  15. Thermoluminescence analysis of co-doped NaCl at low temperature irradiations.

    PubMed

    Cruz-Zaragoza, E; Ortiz, A; Furetta, C; Flores, C; Hernández, J; Murrieta, H

    2011-02-01

    The thermoluminescent response and kinetics parameters of NaCl, doubly activated by Ca-Mn and Cd-Mn ions, exposed to gamma radiation are analyzed. The doped NaCl samples were irradiated at relative low temperature, i.e. at the liquid nitrogen temperature (LNT) and at dry ice temperature (DIT), and the glow curves obtained after 2 Gy of gamma irradiation were analyzed using the computerized glow curve deconvolution (CGCD). An evident variation in the glow curve structure after LNT and DIT was observed. It seems that different kinds of trapping levels are activated at relative low temperature. The original two prominent peaks in compositions A (Ca,Mn) and B (Ca,Mn) have been changed in only one main peak with satellites in the low temperature side of the glow curves. In compositions C (Cd,Mn) and D (Cd,Mn), low temperature peaks become stronger and prominent than the high temperature peaks; this effect could be explained considering that the trapping probability for low temperature traps, the one very close to the conduction band, is enhanced by low temperatures during irradiation. PMID:21093275

  16. Origin of the infrared to visible upconversion mechanisms in Nd 3+-doped potassium lead chloride crystal

    NASA Astrophysics Data System (ADS)

    Mendioroz, A.; Balda, R.; Al-Saleh, M.; Fernández, J.

    2005-10-01

    The infrared to visible upconversion mechanisms of Nd3+ ions in potassium lead chloride crystal have been investigated at liquid nitrogen temperature (LNT). We have observed upconversion luminescence when pumping into both 4F3/2 and 4F5/2 bands and off-resonance, at 851 and 856 nm. The main bands appearing in the emission spectra are two blue bands located at 420 and 435 nm, corresponding to transitions 4D3/2 → 4I13/2 and 2P1/2 → 4I9/2 respectively, and green, orange and red emissions, located at 535, 595 and 668 nm, corresponding to 4G7/2-4G9/2 → 4I9/2, 4I11/2, 4I13/2 transitions, respectively. The results show that, upon excitation of either the 4F3/2 or 4F5/2 band at LNT, two- and three-body energy transfer upconversion process are responsible for the emissions coming from levels 4G7/2-4G9/2 (535, 595, and 668 nm) and 4D3/2 (420 nm), respectively. However, the experimental data indicate that the mechanisms leading to the luminescence coming from level 2P1/2 depend on the pumping wavelength and sample temperature.

  17. Anomalous ion damage behavior in ZnSe

    SciTech Connect

    Yu, K.M.; Bourret-Courchesne, E.D.

    1996-09-01

    The structural properties of ZnSe damaged by 180 keV Zn ions are studied for a wide range of ion dose (10{sup 13}{endash}10{sup 16}/cm{sup 2}) using ion channeling techniques. We found that ZnSe cannot be rendered amorphous by implantation at either room temperature (RT) or liquid nitrogen temperature (LNT) in the range of doses investigated. For lower ion doses (10{sup 13}{endash}10{sup 14}/cm{sup 2}), ZnSe samples implanted at LNT result in less damage than those implanted at RT by as much as an order of magnitude. Moreover, no simple point defect or amorphous clusters are found in the implanted ZnSe. For high implant doses ({approx_gt}10{sup 14}/cm{sup 2}), the samples are still monocrystalline but become highly defective with extended defects. Our results also suggests that point defects in the ZnSe created during implantation may be mobile at or below RT and that they may migrate rapidly under ion irradiation. {copyright} {ital 1996 American Institute of Physics}

  18. Risk management for plausibly hormetic environmental carcinogens: the case of radon.

    PubMed

    Bogen, K T; Layton, D W

    1998-08-01

    Risk management typically involves efforts to reduce human exposures by establishing regulations that limit the concentration of the substance in environmental media. In cases where a substance is widely used in commerce or is naturally occurring in the environment, compliance costs can be substantial because of nationwide requirements to add expensive control technologies. Uncertainties in a dose-response function further impact risk management decisions because they may correspond to large differences in health benefit per unit exposure reduction. These problems are highlighted in the case of plausibly hormetic environmental carcinogens, for which a linear-no-threshold (LNT) dose-response model has been the traditional regulatory default assumption. In this case, model uncertainty is pivotal, and risk management is consequently inherently controversial. However, marginal cost functions that arise for plausibly hormetic carcinogens are expected to possess a common analytic feature that may be particularly useful for this type of risk management problem. Specifically, marginal cost functions in this context are expected to have roots reflecting contaminant concentration values above which regulatory goals may be optimally placed subject to cost constraints. Here we illustrate this heuristic feature in the case of residential radon, using both a LNT model and a biologically plausible hormetic model to predict associated risks of lung cancer mortality. PMID:9756142

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

    PubMed

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

    2016-02-01

    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

  20. 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.

  1. 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.

  2. Urgent Change Needed to Radiation Protection Policy.

    PubMed

    Cuttler, Jerry M

    2016-03-01

    Although almost 120 y of medical experience and data exist on human exposure to ionizing radiation, advisory bodies and regulators claim there are still significant uncertainties about radiation health risks that require extreme precautions be taken. Decades of evidence led to recommendations in the 1920s for protecting radiologists by limiting their daily exposure. These were shown in later studies to decrease both their overall mortality and cancer mortality below those of unexposed groups. In the 1950s, without scientific evidence, the National Academy of Sciences Biological Effects of Atomic Radiation (BEAR) Committee and the NCRP recommended that the linear no-threshold (LNT) model be used to assess the risk of radiation-induced mutations in germ cells and the risk of cancer in somatic cells. This policy change was accepted by the regulators of every country without a thorough review of its basis. Because use of the LNT model has created extreme public fear of radiation, which impairs vital medical applications of low-dose radiation in diagnostics and therapy and blocks nuclear energy projects, it is time to change radiation protection policy back into line with the data. PMID:26808879

  3. 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.

  4. 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.

  5. 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

  6. Lack of nontargeted effects in murine bone marrow after low-dose in vivo X irradiation.

    PubMed

    Zyuzikov, Nikolay A; Coates, Philip J; Parry, John M; Lorimore, Sally A; Wright, Eric G

    2011-03-01

    Exposure to high doses of ionizing radiation unequivocally produces adverse health effects including malignancy. At low doses the situation is much less clear, because effects are generally too small to be estimated directly by epidemiology, and extrapolation of risk and establishment of international rules and standards rely on the linear no-threshold (LNT) concept. Claims that low doses are more damaging than would be expected from LNT have been made on the basis of in vitro studies of nontargeted bystander effects and genomic instability, but relevant investigations of primary cells and tissues are limited. Here we show that after low-dose low-LET in vivo radiation exposures in the 0-100-mGy range of murine bone marrow there is no evidence of a bystander effect, assessed by p53 pathway signaling, nor is there any evidence for longer-term chromosomal instability in the bone marrow at doses below 1000 mGy. The data are not consistent with speculations based on in vitro nontargeted effects that low-dose X radiation is more damaging than would be expected from linear extrapolation. PMID:21388275

  7. 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.

  8. 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

  9. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs.

    PubMed

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27-87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  10. PTK7 as a potential prognostic and predictive marker of response to adjuvant chemotherapy in breast cancer patients, and resistance to anthracycline drugs

    PubMed Central

    Ataseven, Beyhan; Gunesch, Angela; Eiermann, Wolfgang; Kates, Ronald E; Högel, Bernhard; Knyazev, Pjotr; Ullrich, Axel; Harbeck, Nadia

    2014-01-01

    Biomarkers predicting resistance to particular chemotherapy regimens could play a key role in optimally individualized treatment concepts. PTK7 (protein tyrosine kinase 7) belongs to the receptor tyrosine kinase family involved in several physiological, but also malignant, cell behaviors. Recent studies in acute myeloid leukemia have associated PTK7 expression with resistance to anthracycline therapy. PTK7 mRNA expression in primary tumor tissue (PTT) and corresponding lymph node tissue (LNT) were retrospectively measured in 117 patients with early breast cancer; PTK7 expression was available in 103 PTT and 108 LNT samples. Median age was 60 years (range, 27–87 years). At a median follow-up of 28.5 months, 6 deaths and 16 recurrences had occurred. PTK7 expression correlations with clinicopathological features were computed and PTK7 expression effects on patient outcome were analyzed in three cohorts defined by adjuvant treatment: anthracycline-based treatment, other chemotherapy regimens (including taxane or other substances), or no chemotherapy. Association of PTK7 expression with clinicopathological features was seen only for age in PTT and nodal stage in LNT. High LN PTK7 was associated with poorer disease-free survival (DFS) in the total population (3-year DFS: low [81.7%] versus high [70.4%]; P=0.016) and in patients without adjuvant chemotherapy (3-year DFS: low [91.7%] versus high [22.3%]; P<0.001), but not in patients receiving adjuvant chemotherapy (P=0.552). DFS stratified by PTK7 expression was compared in treatment cohorts: In patients with low LN PTK7 expression, neither chemotherapy cohort showed significantly better survival than the no-chemotherapy cohort. In patients with high LN PTK7 expression, those receiving chemotherapy, including substances other than anthracyclines, but not those receiving only anthracycline-based chemotherapy, showed significantly better DFS than those receiving no chemotherapy (P=0.001). Our results support earlier

  11. Effect of Aging on the NOx Storage and Regeneration Characteristics of Fully Formulated Lean NOx Trap Catalysts

    SciTech Connect

    Ji, Yaying; Easterling, Vencon; Graham, Uschi; Fisk, Courtney; Crocker, Mark; Choi, Jae-Soon

    2011-01-01

    In order to elucidate the effect of washcoat composition on lean NO{sub x} trap (LNT) aging characteristics, fully formulated monolithic LNT catalysts containing varying amounts of Pt, Rh and BaO were subjected to accelerated aging on a bench reactor. Subsequent catalyst evaluation revealed that in all cases aging resulted in deterioration of the NO{sub x} conversion as a consequence of impaired NO{sub x} storage and NO{sub x} reduction functions, while increased selectivity to NH{sub 3} was observed in the temperature range 250--450 C. Elemental analysis, H{sub 2} chemisorption and TEM data revealed two main changes which account for the degradation in LNT performance. First, residual sulfur in the catalysts, associated with the Ba phase, decreased catalyst NO{sub x} storage capacity. Second, sintering of the precious metals in the washcoat occurred, resulting in decreased contact between the Pt and Ba, and hence in less efficient NO{sub x} spillover from Pt to Ba during NO{sub x} adsorption, as well as decreased rates of reductant spillover from Pt to Ba and reverse NO{sub x} spillover during catalyst regeneration. For the aged catalysts, halving the Pt loading from 100 to 50 g/ft{sup 3} was found to result in a significant decrease in overall NO{sub x} conversion, while for catalysts with the same 100 g/ft{sup 3} Pt loading, increasing the relative amount of Pt on the NO{sub x} storage components (BaO and La-stabilized CeO{sub 2}), as opposed to an Al{sub 2}O{sub 3} support material (where it was co-located with Rh), was found to be beneficial. The effect of Rh loading on aged catalyst performance was found to be marginal within the range studied (10--20 g/ft{sup 3}), as was the effect of BaO loading in the range 30--45 g/L.

  12. 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

  13. Maxima of two random walks: universal statistics of lead changes

    NASA Astrophysics Data System (ADS)

    Ben-Naim, E.; Krapivsky, P. L.; Randon-Furling, J.

    2016-05-01

    We investigate statistics of lead changes of the maxima of two discrete-time random walks in one dimension. We show that the average number of lead changes grows as {π }-1{ln}t in the long-time limit. We present theoretical and numerical evidence that this asymptotic behavior is universal. Specifically, this behavior is independent of the jump distribution: the same asymptotic underlies standard Brownian motion and symmetric Lévy flights. We also show that the probability to have at most n lead changes behaves as {t}-1/4{({ln}t)}n for Brownian motion and as {t}-β (μ ){({ln}t)}n for symmetric Lévy flights with index μ. The decay exponent β \\equiv β (μ ) varies continuously with the Lévy index when 0\\lt μ \\lt 2, and remains constant β =1/4 for μ \\gt 2.

  14. Qubit dephasing due to quasiparticle tunneling

    NASA Astrophysics Data System (ADS)

    Zanker, Sebastian; Marthaler, Michael

    2015-05-01

    We study dephasing of a superconducting qubit due to quasiparticle tunneling through a Josephson junction. While qubit decay due to tunneling processes is well understood within a golden rule approximation, pure dephasing due to BCS quasiparticles gives rise to a divergent golden rule rate. We calculate qubit dephasing due to quasiparticle tunneling beyond lowest-order approximation in coupling between qubit and quasiparticles. Summing up a certain class of diagrams, we show that qubit dephasing due to purely longitudinal coupling to quasiparticles leads to dephasing ˜exp[-x (t )] where x (t ) ∝t3 /2 for short-time scales and x (t )∝t ln(t ) for long-time scales.

  15. 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.

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

    PubMed Central

    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/m3. The US Environmental Protection Agency should consider raising its radon action level from 150 to at least 1000 Bq/m3. PMID:26740812

  17. A Fast Method of Transforming Relaxation Functions Into the Frequency Domain

    PubMed Central

    Mopsik, Frederick I.

    1999-01-01

    The limits to the error due to truncation of the numeric integration of the one-sided Laplace transform of a relaxation function in the time domain into its equivalent frequency domain are established. Separate results are given for large and small ω. These results show that, for a given ω, only a restricted range of time samples is needed to perform the computation to a given accuracy. These results are then combined with a known error estimate for integration by cubic splines to give a good estimate for the number of points needed to perform the computation to a given accuracy. For a given data window between t1 and t2, the computation time is shown to be proportional to ln(t1/t2).

  18. Thermal stability of magnetron and ion beam sputtered top and bottom spin-valve films

    SciTech Connect

    Mao, Ming; Cerjan, Charlie; Hung, Stephanie; Miloslavsky, Lena; Chien, Chester; Sant, Sudhi

    2001-06-01

    The thermal stability of top and bottom IrMn exchange-biased spin-valve films prepared by ion beam deposition (IBD) and magnetron sputtering physical vapor deposition (PVD) is compared. These films exhibit identical temperature dependence for the exchange bias field H{sub ex}, with a blocking temperature of T{sub B}=250{degree}C, that is independent of preparation technique. Isothermal annealing at temperatures below T{sub B} led to a ln(t) dependent degradation in H{sub ex}, suggesting a thermal activation process. The high crystallographic quality of the IBD films leads to a superior stability compared to PVD films. Top spin-valve films are also found to be more stable than bottom spin-valve films. {copyright} 2001 American Institute of Physics.

  19. Thermal stability of magnetron and ion beam sputtered top and bottom spin-valve films

    NASA Astrophysics Data System (ADS)

    Mao, Ming; Cerjan, Charlie; Hung, Stephanie; Miloslavsky, Lena; Chien, Chester; Sant, Sudhi

    2001-06-01

    The thermal stability of top and bottom IrMn exchange-biased spin-valve films prepared by ion beam deposition (IBD) and magnetron sputtering physical vapor deposition (PVD) is compared. These films exhibit identical temperature dependence for the exchange bias field Hex, with a blocking temperature of TB=250 °C, that is independent of preparation technique. Isothermal annealing at temperatures below TB led to a ln(t) dependent degradation in Hex, suggesting a thermal activation process. The high crystallographic quality of the IBD films leads to a superior stability compared to PVD films. Top spin-valve films are also found to be more stable than bottom spin-valve films.

  20. Power law breakthrough curve tailing in a fracture: The role of advection

    NASA Astrophysics Data System (ADS)

    Fiori, Aldo; Becker, Matthew W.

    2015-06-01

    We offer an explanation of the strongly tailed solute breakthrough curve typically observed when a tracer test is conducted in fractured bedrock. In this example, we limit the model to a single planar fracture of varying aperture. Flow heterogeneity derives from variable fracture aperture, which implies variable transmissivity (T). The analysis employs a physically based model well-suited to strong heterogeneity and relies only upon advective transport. The purely advective model is able to explain a power-law trend of magnitude -2 to -3 in the breakthrough curve tail; a range that has been found in field tracer experiments. The principle cause of this trend is the comparatively slow transport in zones of small transmissivity (tight aperture). Slow advection occurs when either heterogeneity (variance of lnT) is strong or when the assumed heterogeneity distribution is non-Gaussian. Thus, we link breakthrough tailing to the statistical parameters for the transmissivity field.

  1. 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.

  2. 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.

  3. 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. PMID:23906471

  4. Radiation hormesis--a remedy for fear.

    PubMed

    Jaworowski, Zbigniew

    2010-04-01

    Personal reflections on radiation hormesis for the past 50 years are presented. The causes of ignoring and rejections of this phenomenon by international and national bodies and by radiation protection establishment are analyzed. The opposition against nuclear weapons and preparations for nuclear war was probably the main factor in inducing the concern for adverse effects of low doses of ionizing radiation, a byproduct of activism against the nuclear weapon tests. UNSCEAR was deeply involved in preparation of the scientific basis for cessation of nuclear test, and contributed to elaboration of the LNT assumption, which is in contradiction with the hormetic phenomenon. However, this authoritative body recognized also the existence of radiation hormesis, termed as 'adaptive response.' The political and vested interests behind exclusion of hormesis from the current risk assessment methodology are discussed. PMID:20332170

  5. Following fluctuating signs: Anomalous active superdiffusion of swimmers in anisotropic media

    NASA Astrophysics Data System (ADS)

    Toner, John; Löwen, Hartmut; Wensink, Henricus H.

    2016-06-01

    Active (i.e., self-propelled or swimming) particles moving through an isotropic fluid exhibit conventional diffusive behavior. We report anomalous diffusion of an active particle moving in an anisotropic nematic background. While the translational motion parallel to the nematic director shows ballistic behavior, the long-time transverse motion is superdiffusive, with an anomalous scaling proportional to t lnt of the mean-square displacement with time t . This behavior is predicted by an analytical theory that we present here and is corroborated by numerical simulation of active particle diffusion in a simple lattice model for a nematic liquid crystal. It is universal for any collection of self-propelled elements (e.g., bacteria or active rods) moving in a nematic background, provided only that the swimmers are sufficiently dilute that their interactions with each other can be neglected and that they do not perform hairpin turns.

  6. The Neglected Side of the Coin: Quantitative Benefit-risk Analyses in Medical Imaging.

    PubMed

    Zanzonico, Pat B

    2016-03-01

    While it is implicitly recognized that the benefits of diagnostic imaging far outweigh any theoretical radiogenic risks, quantitative estimates of the benefits are rarely, if ever, juxtaposed with quantitative estimates of risk. This alone - expression of benefit in purely qualitative terms versus expression of risk in quantitative, and therefore seemingly more certain, terms - may well contribute to a skewed sense of the relative benefits and risks of diagnostic imaging among healthcare providers as well as patients. The current paper, therefore, briefly compares the benefits of diagnostic imaging in several cases, based on actual mortality or morbidity data if ionizing radiation were not employed, with theoretical estimates of radiogenic cancer mortality based on the "linear no-threshold" (LNT) dose-response model. PMID:26808890

  7. Formation and Relaxation of Two-Dimensional Vortex Crystals in a Magnetized Pure-Electron Plasma

    SciTech Connect

    Kiwamoto, Y.; Hashizume, N.; Soga, Y.; Aoki, J.; Kawai, Y.

    2007-09-14

    Systematic examinations are carried out experimentally about the contribution of background vorticity distributions (BGVD's) to the spontaneous formation and decay of ordered arrays (vortex crystals) composed of strong vortices (clumps) by using a pure-electron plasma. It is found that the BGVD level needs to be higher for an increasing number of clumps to form vortex crystals and that the number of the clumps constituting the crystal decreases in time as {proportional_to}{gamma}lnt in contrast to {proportional_to}t{sup -{xi}} with {xi}{approx_equal}1 as accepted well in turbulence models. The decay rate {gamma} increases with the BGVD level. The observed configurations of the clumps cover the theoretically predicted catalogue of vortex arrays in superfluid helium, suggesting a possible relaxation path of the crystal states.

  8. Non-Fermi-liquid behavior within the ferromagnetic phase in URu2-xRexSi2.

    PubMed

    Bauer, E D; Zapf, V S; Ho, P-C; Butch, N P; Freeman, E J; Sirvent, C; Maple, M B

    2005-02-01

    The URu2-xRexSi2 system exhibits ferromagnetic order for Re concentrations 0.3 < x < or =1.0. Non-Fermi-liquid (NFL) behavior is observed in the specific heat for 0.15< or = x< or =0.6 [C/T proportional to, -lnT (or T(-0.1))], and also in the power-law T dependence of the electrical resistivity [rhoT proportional to, Tn] with n<2 for 0.15< or = x <0.8, at low T, providing strong evidence that the NFL behavior persists within the ferromagnetic phase. Furthermore, the deviation of the physical properties of URu2-xRexSi2 from Fermi-liquid behavior is most pronounced at the ferromagnetic quantum critical point, and the NFL behavior found in the ferromagnetic phase may be consistent with the Griffiths-McCoy phase model. PMID:15783577

  9. 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.

  10. 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.

  11. Rad-by-Rad (Bit-by-Bit): Triumph of Evidence Over Activities Fostering Fear of Radiogenic Cancers at Low Doses

    PubMed Central

    Strzelczyk, J.; Potter, W.; Zdrojewicz, Z.

    2007-01-01

    Large segments of Western populations hold sciences in low esteem. This trend became particularly pervasive in the field of radiation sciences in recent decades. The resulting lack of knowledge, easily filled with fear that feeds on itself, makes people susceptible to prevailing dogmas. Decades-long moratorium on nuclear power in the US, resentment of “anything nuclear”, and delay/refusal to obtain medical radiation procedures are some of the societal consequences. The problem has been exacerbated by promulgation of the linear-no-threshold (LNT) dose response model by advisory bodies such as the ICRP, NCRP and others. This model assumes no safe level of radiation and implies that response is the same per unit dose regardless of the total dose. The most recent (June 2005) report from the National Research Council, BEIR VII (Biological Effects of Ionizing Radiation) continues this approach and quantifies potential cancer risks at low doses by linear extrapolation of risk values obtained from epidemiological observations of populations exposed to high doses, 0.2 Sv to 3 Sv. It minimizes the significance of a lack of evidence for adverse effects in populations exposed to low doses, and discounts documented beneficial effects of low dose exposures on the human immune system. The LNT doctrine is in direct conflict with current findings of radiobiology and important features of modern radiation oncology. Fortunately, these aspects are addressed in-depth in another major report—issued jointly in March 2005 by two French Academies, of Sciences and of Medicine. The latter report is much less publicized, and thus it is a responsibility of radiation professionals, physicists, nuclear engineers, and physicians to become familiar with its content and relevant studies, and to widely disseminate this information. To counteract biased media, we need to be creative in developing means of sharing good news about radiation with co-workers, patients, and the general public. PMID

  12. Nonlinearity of radiation health effects.

    PubMed Central

    Pollycove, M

    1998-01-01

    The prime concern of radiation protection policy since 1959 has been to protect DNA from damage. In 1994 the United Nations Scientific Community on the Effects of Atomic Radiation focused on biosystem response to radiation with its report Adaptive Responses to Radiation of Cells and Organisms. The 1995 National Council on Radiation Protection and Measurements report Principles and Application of Collective Dose in Radiation Protection states that because no human data provides direct support for the linear nonthreshold hypothesis (LNT), confidence in LNT is based on the biophysical concept that the passage of a single charged particle could cause damage to DNA that would result in cancer. Several statistically significant epidemiologic studies contradict the validity of this concept by showing risk decrements, i.e., hormesis, of cancer mortality and mortality from all causes in populations exposed to low-dose radiation. Unrepaired low-dose radiation damage to DNA is negligible compared to metabolic damage. The DNA damage-control biosystem is physiologically operative on both metabolic and radiation damage and effected predominantly by free radicals. The DNA damage-control biosystem is suppressed by high dose and stimulated by low-dose radiation. The hormetic effect of low-dose radiation may be explained by its increase of biosystem efficiency. Improved DNA damage control reduces persistent mis- or unrepaired DNA damage i.e., the number of mutations that accumulate during a lifetime. This progressive accumulation of gene mutations in stem cells is associated with decreasing DNA damage control, aging, and malignancy. Recognition of the positive health effects produced by adaptive responses to low-dose radiation would result in a realistic assessment of the environmental risk of radiation. Images Figure 1 Figure 3 Figure 5 Figure 6 Figure 8 Figure 10 PMID:9539031

  13. Fictive temperature, structural relaxation, and reality of residual entropy.

    PubMed

    Aji, Daisman P B; Johari, G P

    2010-07-29

    By determining the fictive temperature, Tf, in two ways from the same Cp data, we investigate whether the residual entropy, Sres, of a glass could be an artifact of using the Cp d ln(T) integral in the glass-liquid temperature range. Although the integral gives only the upper and lower limits of the real entropy change, it is still useful and is distinguished as Delta(sigma). We determine Tf(sigma) from Delta(sigma) and the usual TfH from the Cp dT integral for two metal alloy glasses, a basalt composition glass and a spray-quenched propylene glycol glass from the available data, and find that Tf9sigma is about the same as TfH within errors. To substantiate it, we report a differential scanning calorimetry study performed during cooling of the Mg65Cu25Tb10 and Pd40Ni10Cu30P20 melts and on heating their glassy states at the same rates. In addition, we simulate Cp-T plots from a known model for nonexponential, nonlinear relaxation and analyze the data. The quantity Delta(sigma) on cooling the liquid and heating the glass differs negligibly; that is, net change in a temperature cycle between glass and its melt is close to zero, a characteristic of a nearly reversible change. We conclude that spontaneous enthalpy release has little effect on the entropy change determined from the Cp d ln(T) integral and, contrary to recent suggestions, Sres is real. PMID:20602534

  14. 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.

  15. 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.

  16. Collective dose: Dogma, tool, or trauma?

    SciTech Connect

    Becker, K.

    1996-12-31

    In Europe as well as in the United States, the argument continues in the radiation protection community between the {open_quotes}fundamentalists,{close_quotes} who firmly believe in the linear no-threshold (LNT) hypothesis and the closely related concept of collective dose, and {open_quotes}pragmatists,{close_quotes} who have serious doubts about these concepts for both radiobiological and socioeconomic reasons. The latter view is reflected in many recent compilations in the scientific literature, in particular in the books by G. Walinder and S. Kondo. The fundamentalist view has been expressed in other recent publications. What has been described as the good old boys` network of the establishment threatens nonbelievers with excommunication: in his 1996 Sievert lecture, D. Beninson described doubts about the LNT hypothesis as {open_quotes}arrogant ignorance{close_quotes}; A. Gonzales, in a 1995 letter to the author, described them as {open_quotes}intellectual laziness{close_quotes}; and R. Clarke, chairman of the International Commission on Radiological Protection (ICRP), during the 1996 IRPA Congress, described them as {open_quotes}seriously misguided.{close_quotes} Threshold or no threshold, that is the question - the most important one for this and the next generation of health physicists. Corrections of the current dogmas are needed soon and should be initiated not only by the nuclear community (which may be blamed by opinion makers for a biased view) but by those members of the radiation protection community, who are not only interested in order to `keep the hazard alive` for reasons of publicity, research funding, and sales of instruments and services. The International Atomic Energy Agency will devote a symposium to these questions next year. The results should be interesting.

  17. On the estimation of radiation-induced cancer risks from very low doses of radiation and how to communicate these risks.

    PubMed

    Mattsson, Sören; Nilsson, Mats

    2015-07-01

    The article is intended to give a short overview of epidemiological data on cancer risks associated with very low absorbed doses of ionising radiation. The linear no-threshold (LNT) approach to estimate cancer risks involves the use of epidemiological data at higher doses (>100 mSv), but is supported by data from lower exposure of more sensitive population groups like fetuses and children and the presence of rare types of cancer. The International Commission on Radiological Protection (ICRP) concludes that the LNT model, combined with a dose and dose-rate effectiveness (reduction) factor (DDREF) of 2 for extrapolation from high doses, should be used. The numerical value of the DDREF is challenged by the findings from some recent epidemiological studies demonstrating risks per unit dose compatible with the risks observed in the higher dose studies. In general there is very limited knowledge about the cancer risk after low absorbed doses (10-100 mSv), as most of epidemiological studies have limitations in detecting small excess risks arising from low doses of radiation against fluctuations in the influence of background risk factors. Even if there may be significant deviations from linearity in the relevant dose range 0-100 mSv, one does not know the magnitude or even the direction of any such deviations. The risks could be lower than those predicted by a linear extrapolation, but they could also be higher. Until more results concerning the effects of low-dose exposure are available, a reasonable radiation protection approach is to consider the risk proportional to the dose. PMID:25802468

  18. 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

  19. 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

  20. 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.

  1. Cancer-Prone Mice Expressing the Ki-rasG12C Gene Show Increased Lung Carcinogenesis after CT Screening Exposures

    PubMed Central

    Munley, Michael T.; Moore, Joseph E.; Walb, Matthew C.; Isom, Scott P.; Olson, John D.; Zora, J. Gregory; Kock, Nancy D.; Wheeler, Kenneth T.; Miller, Mark Steven

    2011-01-01

    A >20-fold increase in X-ray computed tomography (CT) use during the last 30 years has caused considerable concern because of the potential carcinogenic risk from these CT exposures. Estimating the carcinogenic risk from high-energy, single high-dose exposures obtained from atomic bomb survivors and extrapolating these data to multiple low-energy, low-dose CT exposures using the Linear No-Threshold (LNT) model may not give an accurate assessment of actual cancer risk. Recently, the National Lung Cancer Screening Trial (NLST) reported that annual CT scans of current and former heavy smokers reduced lung cancer mortality by 20%, highlighting the need to better define the carcinogenic risk associated with these annual CT screening exposures. In this study, we used the bitransgenic CCSP-rtTA/Ki-ras mouse model that conditionally expresses the human mutant Ki-rasG12C gene in a doxycycline-inducible and lung-specific manner to measure the carcinogenic risk of exposure to multiple whole-body CT doses that approximate the annual NLST screening protocol. Irradiated mice expressing the Ki-rasG12C gene in their lungs had a significant (P = 0.01) 43% increase in the number of tumors/mouse (24.1 ± 1.9) compared to unirradiated mice (16.8 ± 1.3). Irradiated females had significantly (P < 0.005) more excess tumors than irradiated males. No tumor size difference or dose response was observed over the total dose range of 80–160 mGy for either sex. Irradiated bitransgenic mice that did not express the Ki-rasG12C gene had a low tumor incidence (≤0.1/mouse) that was not affected by exposure to CT radiation. These results suggest that (i) estimating the carcinogenic risk of multiple CT exposures from high-dose carcinogenesis data using the LNT model may be inappropriate for current and former smokers and (ii) any increased carcinogenic risk after exposure to fractionated low-dose CT-radiation may be restricted to only those individuals expressing cancer susceptibility genes in

  2. Sulfur and temperature effects on the spatial distribution of reactions inside a lean NOx trap and resulting changes in global performance

    SciTech Connect

    Choi, Jae-Soon; Partridge Jr, William P; Pihl, Josh A; Daw, C Stuart

    2008-01-01

    We experimentally studied the influence of temperature and sulfur loading on the axial distribution of reactions inside a commercial lean NOx trap (LNT) catalyst to better understand the global performance trends. Our measurements were made on a monolith core, bench-flow reactor under cycling conditions (60-s lean/5-s rich) at 200, 325, and 400 C with intra-catalyst and reactor-outlet gas speciation. Postmortem elemental and diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) analyses of the catalyst also supplemented our gas species measurements. For the unsulfated catalyst, the NOx storage/reduction (NSR) reactions were localized in the front (upstream) portion of the monolith, whereas oxygen storage/reduction reactions were distributed more evenly along the entire catalyst length. As a result, two axially distinct reaction zones were developed inside the working catalyst: an upstream 'NSR zone' where both NOx and oxygen storage/reduction took place and a downstream oxygen storage capacity (OSC)-only zone where the NSR reactions did not penetrate. The NSR zone involved less than half the LNT at 325 and 400 C, but it included almost the entire length at 200 C. Sulfation poisoned both the NSR and OSC reactions beginning at the catalyst upstream edge, with the NSR degradation occurring more rapidly and distinctly than the OSC. As sulfation proceeded, a third zone (the sulfated zone) developed and the NSR zone moved downstream, with a concomitant decrease in both the OSC-only zone and global NOx conversion. The sulfation impact on NOx conversion was greatest at 200 C, when the NSR zone was largest. Ammonia selectivity increased with sulfation, which we attributed to a shortened OSC-only zone and resultantly reduced consumption of NH{sub 3}, slipping from the NSR zone, by downstream OSC. Lower temperatures also increased NH{sub 3} selectivity. Nitrous oxide selectivity also increased with decreasing temperature but showed little dependence on

  3. EPR and optical absorption studies of Cu2+ doped lithium maleate dihydrate single crystal

    NASA Astrophysics Data System (ADS)

    Kripal, Ram; Pandey, Shri Devi

    Electron paramagnetic resonance (EPR) study of Cu2+ doped lithium maleate dihydrate single crystal is done at liquid nitrogen temperature (LNT). Four hyperfine lines are observed in all directions, i.e. only a single site is observed. The spin Hamiltonian parameters are determined from EPR spectra: gx=2.100±0.002, gy=2.162±0.002, gz=2.215±0.002, Ax=(55±5)×10-4 cm-1, Ay=(52±5)×10-4 cm-1, Az=(50±5)×10-4 cm-1. The results indicate that the copper ion enters the lattice interstitially. Using the spin Hamiltonian parameters obtained from EPR study the ground state wave function of Cu2+ ion in the lattice is determined. The optical absorption study of Cu2+ doped lithium maleate dihydrate at room temperature is also performed. With the help of optical and EPR data, the nature of bonding in the complex is discussed.

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

    NASA Astrophysics Data System (ADS)

    Kanchana Devi, A.; Ramesh, R.

    2014-01-01

    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 (RuIII-RuIII/RuIII-RuIV; RuIII-RuIV/RuIV-RuIV) within the E1/2 range of 0.61-0.74 V and 0.93-0.98 V respectively, versus Ag/AgCl.

  5. Protective effect of polysaccharides on simulated microgravity-induced functional inhibition of human NK cells.

    PubMed

    Huyan, Ting; Li, Qi; Yang, Hui; Jin, Ming-Liang; Zhang, Ming-Jie; Ye, Lin-Jie; Li, Ji; Huang, Qing-Sheng; Yin, Da-Chuan

    2014-01-30

    Polysaccharides are believed to be strong immunostimulants that can promote the proliferation and activity of T cells, B cells, macrophages and natural killer (NK) cells. This study aimed to investigate the effects of five polysaccharides (Grifola frondosa polysaccharide (GFP), lentinan (LNT), G. lucidum polysaccharide (GLP), Lycium barbarum polysaccharide (LBP) and yeast glucan (YG)) on primary human NK cells under normal or simulated microgravity (SMG) conditions. Our results demonstrated that polysaccharides markedly promoted the cytotoxicity of NK cells by enhancing IFN-γ and perforin secretion and increasing the expression of the activating receptor NKp30 under normal conditions. Meanwhile polysaccharides can enhance NK cell function under SMG conditions by restoring the expression of the activating receptor NKG2D and reducing the early apoptosis and late apoptosis/necrosis. Moreover, the antibody neutralization test showed that CR3 may be the critical receptor involved in polysaccharides induced NK cells activation. These findings indicated that polysaccharides may be used as immune regulators to promote the health of the public and astronauts during space missions. PMID:24299844

  6. 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. PMID:26945284

  7. The cost of a small membrane bioreactor.

    PubMed

    Lo, C H; McAdam, E; Judd, S

    2015-01-01

    The individual cost contributions to the mechanical components of a small membrane bioreactor (MBR) (100-2,500 m3/d flow capacity) are itemised and collated to generate overall capital and operating costs (CAPEX and OPEX) as a function of size. The outcomes are compared to those from previously published detailed cost studies provided for both very small containerised plants (<40 m3/day capacity) and larger municipal plants (2,200-19,000 m3/d). Cost curves, as a function of flow capacity, determined for OPEX, CAPEX and net present value (NPV) based on the heuristic data used indicate a logarithmic function for OPEX and a power-based one for the CAPEX. OPEX correlations were in good quantitative agreement with those reported in the literature. Disparities in the calculated CAPEX trend compared with reported data were attributed to differences in assumptions concerning cost contributions. More reasonable agreement was obtained with the reported membrane separation component CAPEX data from published studies. The heuristic approach taken appears appropriate for small-scale MBRs with minimal costs associated with installation. An overall relationship of net present value=(a tb)Q(-c lnt+d) was determined for the net present value where a=1.265, b=0.44, c=0.00385 and d=0.868 according to the dataset employed for the analysis. PMID:26540534

  8. Description of the mathematical law that defines the relaxation of bovine pericardium subjected to stress.

    PubMed

    Garcia Sestafe, J V; García Paez, J M; Carrera San Martín, A; Jorge-Herrero, E; Navidad, R; Candela, I; Castillo-Olivares, J L

    1994-06-01

    A material subjected to traction stress increases in length; if we maintain the elongation constant, the stress varies over a period of time. This phenomenon has been referred to as relaxation. The purpose of this study was to define a mathematical law that relates the variation in stress to time when elongation remains constant in bovine pericardium. The mathematical function obtained after assaying 34 samples to the point of relaxation, subjected to initial stresses ranging from 0.17-10.07 MPa, responds to the following equation: y = -0.0252 + 0.953 alpha - (0.0165 + 0.015 alpha)lnt, where y is the stress withstood at an instant in time, t, after initial stress alpha. A normogram, validated by assays of up to 6,340 min duration (4.40 days), is presented for graphic calculation, permitting the computation of the loss of stress due to relaxation of this biomaterial, with initial stresses ranging from 1-10 MPa. PMID:8071387

  9. 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.

  10. Radio-Adaptive Response to Environmental Exposures at Chernobyl

    PubMed Central

    Rodgers, Brenda E.; Holmes, Kristen M.

    2008-01-01

    The genetic consequences resulting from environmental exposure to ionizing radiation have a significant impact on both radiation regulatory policies and the comprehension of the human health risks associated with radiation exposure. The primary objectives of the study were to assess 1) genotoxicity of exposure to radiation as a function of absorbed dose and dose rate, and 2) induction of a radio-adaptive response following a priming dose at varying dose rates. Results demonstrated that sub-acute environmental exposures of 10cGy gamma radiation resulted in indistinguishable levels of chromosomal damage as compared to controls. A radio-adaptive response was observed in all experimental groups, exposed to a subsequent acute challenge dose of 1.5 Gy, demonstrating that low dose rates of low energy transfer (LET) radiation are effective in reducing genetic damage from a subsequent acute low-LET radiation exposure. Furthermore, the data presented herein demonstrate a potential beneficial effect of sub-chronic exposure to low levels of low-LET radiation in an environmental setting and do not support the Linear No Threshold (LNT) hypothesis. PMID:18648577

  11. Quantum critical response function in quasi-two-dimensional itinerant antiferromagnets

    NASA Astrophysics Data System (ADS)

    Varma, C. M.; Zhu, Lijun; Schröder, Almut

    2015-10-01

    We reexamine the experimental results for the magnetic response function χ''(q ,E ,T ) for q around the antiferromagnetic vectors Q , in the quantum-critical region, obtained by inelastic neutron scattering, on an Fe-based superconductor and on a heavy-fermion compound. The motivation is to compare the results with a recent theory, which shows that the fluctuations in a generic antiferromagnetic model for itinerant fermions map to those in the universality class of the dissipative quantum-XY model. The quantum-critical fluctuations in this model, in a range of parameters, are given by the correlations of spatial and temporal topological defects. The theory predicts a χ''(q ,E ,T ) (i) which is a separable function of (q -Q ) and of (E ,T ) , (ii) at criticality, the energy-dependent part is ∝tanh(E /2 T ) below a cutoff energy, (iii) the correlation time departs from its infinite value at criticality on the disordered side by an essential singularity, and (iv) the correlation length depends logarithmically on the correlation time, so that the dynamical critical exponent z is ∞ . The limited existing experimental results are found to be consistent with the first two unusual predictions from which the linear dependence of the resistivity on T and the T lnT dependence of the entropy also follow. More experiments are suggested, especially to test the theory of variations on the correlation time and length on the departure from criticality.

  12. 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.

  13. Critical phenomena of a single defect

    NASA Astrophysics Data System (ADS)

    Wu, Xintian; Zhang, Yangyang

    2015-09-01

    We consider the critical system with a point defect and study the variation of thermodynamic quantities, which are the differences between those with and without the defect. Within renormalization group theory, we show generally that the critical exponent of the internal energy variation is the specific heat exponent of a pure system, and the critical exponent of the heat capacity variation is that for the temperature derivative of specific heat of a pure system. This conclusion is valid for the isotropic systems with a short-range interaction. As an example we solve the two-dimensional Ising model with a point defect numerically. The variations of the free energy, internal energy, and specific heat are calculated with the bond propagation algorithm. At the critical point, the internal energy variation diverges with the lattice size logarithmically and the heat capacity variation diverges with size linearly. Near the critical point, the internal energy variation behaves as ln|t | and the heat capacity variation behaves as |t| -1, where t is the reduced temperature.

  14. 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.

  15. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers.

    PubMed

    Chen, Feng; Zhu, Ying-Jie; Zhang, Kui-Hua; Wu, Jin; Wang, Ke-Wei; Tang, Qi-Li; Mo, Xiu-Mei

    2011-01-01

    Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated. PMID:21711603

  16. 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. PMID:25600993

  17. 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.

  18. Water-induced two-dimensional Kondo-like scattering in Na0.23CoO2 single crystals

    NASA Astrophysics Data System (ADS)

    Cao, Guixin; Gao, Yuze; Zhang, Jincang; Lin, Chengtian

    2013-01-01

    An in-plane Kondo-like resistivity minimum is found with a corresponding temperature Tmin, around 7 K for hydrated Na0.23CoO2 single crystals. Below 7 K, the resistivity exhibits logarithmic temperature dependence of α lnT, where α is independent of the external magnetic field up to 8 T. The feature is resulted in terms of the Kondo-like effect arising from the presence of spin disorder induced by water intercalation in the a-b plane. Our results indicate that the water intercalation weakens the coupling between the CoO2 layers and increases the two-dimensional characteristic of transport properties. The dependence of resistivity minimum on applied field proved also the suppression of localized Co(1) site on paramagnetic triangular superlattice. Further, the present experiments give the evidence of a more complex cooperative phenomena involving charge or spin ordering in the CoO2 layers as a dominating factor for the understanding of hydrated NaxCoO2 compounds.

  19. 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

  20. Local diffusion induced roughening in cobalt phthalocyanine thin film growth.

    PubMed

    Gedda, Murali; Subbarao, Nimmakayala V V; Goswami, Dipak K

    2014-07-29

    We have studied the kinetic roughening in the growth of cobalt phthalocyanine (CoPc) thin films grown on SiO2/Si(001) surfaces as a function of the deposition time and the growth temperature using atomic force microscopy (AFM). We have observed that the growth exhibits the formation of irregular islands, which grow laterally as well as vertically with coverage of CoPc molecules, resulting rough film formation. Our analysis further disclosed that such formation is due to an instability in the growth induced by local diffusion of the molecules following an anomalous scaling behavior. The instability relates the (ln(t))(1/2), with t as deposition time, dependence of the local surface slope as described in nonequilibrium film growth. The roughening has been characterized by calculating different scaling exponents α, β, and 1/z determined from the height fluctuations obtained from AFM images. We obtained an average roughness exponent α = 0.78 ± 0.04. The interface width (W) increases following a power law as W ∼ t(β), with growth exponent β = 0.37 ± 0.05 and lateral correlation length (ξ) grows as ξ ∼ t(1/z) with dynamic exponent 1/z = 0.23 ± 0.06. The exponents revealed that the growth belongs to a different class of universality. PMID:24992503

  1. Distribution and migration of nitrobenzene in water following a simulated spill.

    PubMed

    Li, Peijun; Yin, Wei; Li, Peng; Li, Xiaojun; Zhang, Chungui; Stagnitti, Frank; Xiong, Xianzhe

    2010-10-15

    Releases of nitrobenzene into the aquatic environment pose a threat to human health and aquatic resources, and have attracted much attention world-wide. In order to find out the distribution and migration patterns of pooled nitrobenzene underwater in different conditions, laboratory column experiments were designed to simulate stagnant water, flowing water and rainfall disturbance events. The results showed that in stagnant water there was a slow diffusion of the nitrobenzene from the pool leading to higher concentrations of the chemical deeper in the water column. In flowing water, the removal of the substance was rapid and water concentrations were much lower and more uniform throughout the column. The disturbance event brought a substantial quantity of nitrobenzene into the water column which then dissipated according to the flow regime. Analysis of the data showed that distribution pattern of nitrobenzene in the stagnant water column followed a logarithmic equation C(NB) = a ln(t) + b, and in disturbed flowing water, the distribution pattern of nitrobenzene followed a negative exponential regression equation C(NB) = Ne(-Mt). These conclusions have practical significance in developing remediation technologies for water polluted by nitrobenzene. PMID:20667658

  2. 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.

  3. Hypoxia enhances the antiglioma cytotoxicity of B10, a glycosylated derivative of betulinic acid.

    PubMed

    Fischer, Sebastian; Ronellenfitsch, Michael W; Thiepold, Anna-Luisa; Harter, Patrick N; Reichert, Sebastian; Kögel, Donat; Paschke, Reinhard; Mittelbronn, Michel; Weller, Michael; Steinbach, Joachim P; Fulda, Simone; Bähr, Oliver

    2014-01-01

    B10 is a glycosylated derivative of betulinic acid with promising activity against glioma cells. Lysosomal cell death pathways appear to be essential for its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation and current standard therapies on B10 cytotoxicity. The human glioma cell lines LN-308 and LNT-229 were exposed to B10 alone or together with irradiation, temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were evaluated by crystal violet staining, clonogenicity assays, propidium iodide uptake and LDH release assays. Cell death was examined using an inhibitor of lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10-induced cell death. This effect was sensitive to bafilomycin A1 and thus dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to mediate cell death because either the inhibitor CA074-Me or cathepsin B gene silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred by increased lysosomal cell death pathway activation. Given the importance of hypoxia for therapy resistance, malignant progression, and as a result of antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors like malignant glioma. PMID:24743710

  4. Hypoxia Enhances the Antiglioma Cytotoxicity of B10, a Glycosylated Derivative of Betulinic Acid

    PubMed Central

    Thiepold, Anna-Luisa; Harter, Patrick N.; Reichert, Sebastian; Kögel, Donat; Paschke, Reinhard; Mittelbronn, Michel; Weller, Michael; Steinbach, Joachim P.; Fulda, Simone; Bähr, Oliver

    2014-01-01

    B10 is a glycosylated derivative of betulinic acid with promising activity against glioma cells. Lysosomal cell death pathways appear to be essential for its cytotoxicity. We investigated the influence of hypoxia, nutrient deprivation and current standard therapies on B10 cytotoxicity. The human glioma cell lines LN-308 and LNT-229 were exposed to B10 alone or together with irradiation, temozolomide, nutrient deprivation or hypoxia. Cell growth and viability were evaluated by crystal violet staining, clonogenicity assays, propidium iodide uptake and LDH release assays. Cell death was examined using an inhibitor of lysosomal acidification (bafilomycin A1), a cathepsin inhibitor (CA074-Me) and a short-hairpin RNA targeting cathepsin B. Hypoxia substantially enhanced B10-induced cell death. This effect was sensitive to bafilomycin A1 and thus dependent on hypoxia-induced lysosomal acidification. Cathepsin B appeared to mediate cell death because either the inhibitor CA074-Me or cathepsin B gene silencing rescued glioma cells from B10 toxicity under hypoxia. B10 is a novel antitumor agent with substantially enhanced cytotoxicity under hypoxia conferred by increased lysosomal cell death pathway activation. Given the importance of hypoxia for therapy resistance, malignant progression, and as a result of antiangiogenic therapies, B10 might be a promising strategy for hypoxic tumors like malignant glioma. PMID:24743710

  5. Dosimeter-type NOx sensing properties of KMnO4 and its electrical conductivity during temperature programmed desorption.

    PubMed

    Groß, 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

  6. Europium-doped amorphous calcium phosphate porous nanospheres: preparation and application as luminescent drug carriers

    PubMed Central

    2011-01-01

    Calcium phosphate is the most important inorganic constituent of biological tissues, and synthetic calcium phosphate has been widely used as biomaterials. In this study, a facile method has been developed for the fabrication of amorphous calcium phosphate (ACP)/polylactide-block-monomethoxy(polyethyleneglycol) hybrid nanoparticles and ACP porous nanospheres. Europium-doping is performed to enable photoluminescence (PL) function of ACP porous nanospheres. A high specific surface area of the europium-doped ACP (Eu3+:ACP) porous nanospheres is achieved (126.7 m2/g). PL properties of Eu3+:ACP porous nanospheres are investigated, and the most intense peak at 612 nm is observed at 5 mol% Eu3+ doping. In vitro cytotoxicity experiments indicate that the as-prepared Eu3+:ACP porous nanospheres are biocompatible. In vitro drug release experiments indicate that the ibuprofen-loaded Eu3+:ACP porous nanospheres show a slow and sustained drug release in simulated body fluid. We have found that the cumulative amount of released drug has a linear relationship with the natural logarithm of release time (ln(t)). The Eu3+:ACP porous nanospheres are bioactive, and can transform to hydroxyapatite during drug release. The PL properties of drug-loaded nanocarriers before and after drug release are also investigated. PMID:21711603

  7. Ultrasonic disruption of fungal mycelia for efficient recovery of polysaccharide-protein complexes from viscous fermentation broth of a medicinal fungus.

    PubMed

    Cheung, Yi-Ching; Liu, Xing-Xun; Wang, Wing-Qiang; Wu, Jian-Yong

    2015-01-01

    High-intensity ultrasound (US) was applied to facilitate the extraction of intracellular and extracellular polysaccharide-protein complexes (PSPs) from the viscous mycelial fermentation broth of a medicinal fungus Cordyceps sinensis Cs-HK1. The US treatment caused the disruption of fungal mycelia, a dramatic reduction of the apparent broth viscosity, and the release of intracellular products into the liquid medium. The degree of mycelium disruption and the rate of intracellular product release were dependent on US power intensity, treatment period and biomass concentration of broth. The extraction or release kinetics of total water-soluble products and PSPs (yield Y versus time t) under the effect of US was fitted closely to the Elovich model Y=Yo+Y1 lnt and parabolic model Y=Yo+Y1t(½), respectively. Another interesting effect of the US treatment was a notable increase in the antioxidant cytoprotective activity of PSP against H2O2 induced cell death. PMID:24889549

  8. 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.

  9. Bulk and shear viscosities of the two-dimensional electron liquid in a doped graphene sheet

    NASA Astrophysics Data System (ADS)

    Principi, Alessandro; Vignale, Giovanni; Carrega, Matteo; Polini, Marco

    2016-03-01

    Hydrodynamic flow occurs in an electron liquid when the mean free path for electron-electron collisions is the shortest length scale in the problem. In this regime, transport is described by the Navier-Stokes equation, which contains two fundamental parameters, the bulk and shear viscosities. In this paper, we present extensive results for these transport coefficients in the case of the two-dimensional massless Dirac fermion liquid in a doped graphene sheet. Our approach relies on microscopic calculations of the viscosities up to second order in the strength of electron-electron interactions and in the high-frequency limit, where perturbation theory is applicable. We then use simple interpolation formulas that allow to reach the low-frequency hydrodynamic regime where perturbation theory is no longer directly applicable. The key ingredient for the interpolation formulas is the "viscosity transport time" τv, which we calculate in this paper. The transverse nature of the excitations contributing to τv leads to the suppression of scattering events with small momentum transfer, which are inherently longitudinal. Therefore, contrary to the quasiparticle lifetime, which goes as -1 /[T2ln(T /TF) ] , in the low-temperature limit we find τv˜1 /T2 .

  10. Clusterin over-expression modulates proapoptotic and antiproliferative effects of 1,25(OH)2D3 in prostate cancer cells in vitro.

    PubMed

    Shannan, B; Seifert, M; Boothman, D A; Tilgen, W; Reichrath, J

    2007-03-01

    Prostate cancer is the most commonly diagnosed cancer in the majority of western countries. Due to their antiproliferative and proapoptotic activity, vitamin D analogues have been introduced recently as an experimental therapy for prostate cancer. Clusterin (CLU) is a glycoprotein that has two known isoforms generated in human cells. A nuclear form of CLU protein (nCLU) is pro-apoptotic, and a secretory form (sCLU) is pro-survival. In this study, we analyzed whether proapoptotic and antiproliferative effects of 1,25(OH)(2)D(3) on LNCaP prostate cancer cells are modulated by expression of sCLU. Using colony forming assay, we studied the effect of treatment with different doses of 1,25(OH)(2)D(3) (10(-6), 10(-7), 10(-10)M) on proliferation of LNCaP cells that were stable transfected and over-express sCLU (LNT-1) as compared to empty vector-transfected cells (LN/C). We also measured apoptosis using TUNEL assay. sCLU over-expression protected against both antiproliferative (30%) and proapoptotic (15%) effects of 1,25(OH)(2)D(3), although this effect was statistically not significant. In conclusion, our findings demonstrate that expression of sCLU modulates growth regulatory effects of 1,25(OH)(2)D(3) in prostate cancer indicating that CLU interferes with vitamin D signalling pathways. PMID:17224269

  11. 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.

  12. 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.

  13. Entanglement entropy of disordered quantum chains following a global quench

    NASA Astrophysics Data System (ADS)

    Zhao, Y.; Andraschko, F.; Sirker, J.

    2016-05-01

    We numerically investigate the growth of the entanglement entropy Sent(t ) in time t , after a global quench from a product state, in quantum chains with various kinds of disorder. The main focus is, in particular, on fermionic chains with bond disorder. In the noninteracting case at criticality we numerically test recent predictions by the real-space renormalization group for the entanglement growth in time, the maximal entanglement as a function of block size, and the decay of a density-wave order parameter. We show that multiprecision calculations are required to reach the scaling regime and perform such calculations for specific cases. For interacting models with binary bond disorder we present data based on infinite-size density matrix renormalization group calculations and exact diagonalizations. We obtain numerical evidence of a many-body localized phase in bond-disordered systems where Sent(t ) ˜lnt seems to hold. Our results for bond disorder are contrasted with the well-studied case of potential disorder.

  14. Coarsening of sand ripples in mass transfer models.

    PubMed

    Hellén, E K O; Krug, J

    2002-07-01

    Coarsening of sand ripples is studied in a one-dimensional stochastic model, where neighboring ripples exchange mass with algebraic rates, Gamma(m) approximately m(gamma), and ripples of zero mass are removed from the system. For gamma<0, ripples vanish through rare fluctuations and the average ripple mass grows as (t) approximately -gamma(-1)ln(t). Temporal correlations decay as t(-1/2) or t(-2/3) depending on the symmetry of the mass transfer, and asymptotically the system is characterized by a product measure. The stationary ripple mass distribution is obtained exactly. For gamma>0, ripple evolution is linearly unstable, and the noise in the dynamics is irrelevant. For gamma=1, the problem is solved on the mean-field level, but the mean-field theory does not adequately describe the full behavior of the coarsening. In particular, it fails to account for the numerically observed universality with respect to the initial ripple size distribution. The results are not restricted to sand ripple evolution since the model can be mapped to zero range processes, urn models, exclusion processes, and cluster-cluster aggregation. PMID:12241351

  15. 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

  16. Influences of solar wind parameters and geomagnetic activity on the tail lobe magnetic field: A statistical study

    SciTech Connect

    Nakai, H. ); Kamide, Y. ); Russell, C.T. )

    1991-04-01

    The size and magnetic field strength of the tail lobe at the downstream distance of 10 to 22.6 R{sub E} are examined statistically by utilizing data from the magnetometer on board the ISEE 1 satellite. The probability that the satellite encounters the lobe region is mapped on the tail cross sections, the Y-Z plane. It is found that the magnetotail lobe expands in association with increasing auroral electrojet activity. This expansion is particularly evident at the dawn and dusk flanks of the magnetotail, while the lobe region seems not to expand appreciably near the aberrated X axis. The lobe field strength, B{sub L}, is found to be represented as B{sub L}(nT) = 1.03 {times} 10{sup 3} R{sup {minus}1.20}, where R denotes the geocentric distance in Earth radii. Multiple regression analyses reveal that the lobe field strength principally depends on the dynamic pressure (P{sub D}) and static pressure (P{sub S}) of the solar wind as well as on the IMF B{sub Z}. It is also shown that the flaring angle of the tail lobe, {theta}, is represented as sin{sup 2}{theta} = 1.97 {times} 10{sup {minus}5} P{sub D}{sup {minus}0.47}{vert bar} AL {vert bar}{sup 0.11}, where AL denotes the auroral electrojet AL index.

  17. Mononuclear ruthenium(III) complexes containing chelating thiosemicarbazones: Synthesis, characterization and catalytic property

    NASA Astrophysics Data System (ADS)

    Raja, N.; Ramesh, R.

    2010-02-01

    Mononuclear ruthenium(III) complexes of the type [RuX(EPh 3) 2(L)] (E = P or As; X = Cl or Br; L = dibasic terdentate dehydroacetic acid thiosemicarbazones) have been synthesized from the reaction of thiosemicarbazone ligands with ruthenium(III) precursors, [RuX 3(EPh 3) 3] (where E = P, X = Cl; E = As, X = Cl or Br) and [RuBr 3(PPh 3) 2(CH 3OH)] in benzene. The compositions of the complexes have been established by elemental analysis, magnetic susceptibility measurement, FT-IR, UV-vis and EPR spectral data. These complexes are paramagnetic and show intense d-d and charge transfer transitions in dichloromethane. The complexes show rhombic EPR spectra at LNT which are typical of low-spin distorted octahedral ruthenium(III) species. All the complexes are redox active and display an irreversible metal centered redox processes. Complex [RuCl(PPh 3) 2(DHA-PTSC)] ( 5) was used as catalyst for transfer hydrogenation of ketones in the presence of isopropanol/KOH and was found to be the active species.

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

    PubMed

    Kanchana Devi, A; Ramesh, R

    2014-01-01

    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. PMID:23988528

  19. Mesoscopic structure of neuronal tracts from time-dependent diffusion

    PubMed Central

    Burcaw, Lauren M.; Fieremans, Els; Novikov, Dmitry S.

    2015-01-01

    Interpreting brain diffusion MRI measurements in terms of neuronal structure at a micrometer level is an exciting unresolved problem. Here we consider diffusion transverse to a bundle of fibers, and show theoretically, as well as using Monte Carlo simulations and measurements in a phantom made of parallel fibers mimicking axons, that the time dependent diffusion coefficient approaches its macroscopic limit slowly, in a (lnt)/t fashion. The logarithmic singularity arises due to short range disorder in the fiber packing. We identify short range disorder in axonal fibers based on histological data from the splenium, and argue that the time dependent contribution to the overall diffusion coefficient from the extra-axonal water dominates that of the intra-axonal water. This dominance may explain the bias in measuring axon diameters in clinical settings. The short range disorder is also reflected in the linear frequency dependence of the diffusion coefficient measured with oscillating gradients, in agreement with recent experiments. Our results relate the measured diffusion to the mesoscopic structure of neuronal tissue, uncovering the sensitivity of diffusion metrics to axonal arrangement within a fiber tract, and providing an alternative interpretation of axonal diameter mapping techniques. PMID:25837598

  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. 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.

  2. 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…

  3. 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 ...

  4. The Search for Non-Linear Exposure-Response Relationships at Ambient Levels in Environmental Epidemiology

    PubMed Central

    Lippmann, Morton

    2005-01-01

    Environmental exposures to ambient air particulate matter (PM), ozone (O3), environmental tobacco smoke (ETS), and to dioxin and related compounds are of considerable public health concern, and risk assessments for them have generally been based on linear, non-threshold models derived from epidemiological study data. While the epidemiological databases for PM, O3, and ETS have been sufficient to show that adverse health effects are occurring, the relative risks have been quite low, and it has not been possible, to date, to identify thresholds or non-linear relationships for them. For dioxin and related compounds, the evidence for excess cancer risks has been inadequate to establish causality, and there is suggestive evidence that hormesis may have occurred. PMID:19330159

  5. Defect states and exceptional point splitting in the band gaps of one-dimensional parity-time lattices.

    PubMed

    Zhu, Xue-Feng

    2015-08-24

    We investigated defect states in band gaps of one-dimensional photonic lattices with delicate modulations of gain and loss that respect parity-time-symmetry (PT-symmetry), viz. n(z) = n*(-z). For the sake of generality, we employ not only periodic structures but also quasiperiodic structures, e.g. Fibonacci sequences, to construct aperiodic PT lattices. Differed from lossless systems for which the defect state is related to only one exceptional point (EP) of the S-matrix, we observed the splitting of one EP into a pair after the introduction of judiciously designed gain and loss in those PT systems, where the defect state enters a non-threshold broken symmetry phase bounded by the EP pair. Some interesting properties associated with defect states and EP splitting are demonstrated, such as enhanced spectral localization, double optical phase abrupt change, and wavelength sensitive reversion of unidirectional transparency. PMID:26368199

  6. 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. PMID:20073123

  7. A conceptual ozone dose-response model to develop a standard to protect vegetation

    NASA Astrophysics Data System (ADS)

    Massman, William J.; Musselman, Robert C.; Lefohn, Allen S.

    The present air quality standard to protect vegetation from ozone is based on a measured concentration (i.e., exposure) rather than on plant uptake rates (or dose). Proposed exposure-based standards have led to concerns about the appropriateness of chamber studies. There has also been some debate about the importance of the diel phase difference between plant conductance and ozone concentration in assessing the potential for plant damage. In this paper, we use physical reasoning based on (i) plant defenses and (ii) general resistance concepts of dry deposition to derive a suggested general form of a dose-based standard. The dose-based standard is then related to the more traditional exposure-based standard. Although we develop the model in terms of plant injury, we also discuss how the model can be extended to include damage, which historically has been the focus of air quality standards. With this new dose-based approach, we clarify some of the issues concerning chambers and the interaction of the daily cycles of ozone concentration and plant stomatal conductance. We further demonstrate that (i) weighted fluxes can be used as a surrogate for plant defenses, (ii) injury or damage to vegetation is more likely to be correlated with a dose-based index that differentially weights ambient ozone concentration or plant uptake rates than one which does not, (iii) the potential for ozone injury or damage to plants can occur throughout the day, and (iv) when assessing the potential for plant damage, a differentially weighted flux-based standard is likely to be more precise and more discriminating than a cumulative ozone-based exposure index. Finally, because our basic premise relies on plant defensive mechanisms, we outline areas of research that are necessary before a dose-based standard can be implemented.

  8. 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.

  9. 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

  10. 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

  11. Preparation, pharmacokinetics and biodistribution of baicalin-loaded liposomes

    PubMed Central

    Wei, Yumeng; Guo, Jianmin; Zheng, Xiaoli; Wu, Jun; Zhou, Yang; Yu, Yu; Ye, Yun; Zhang, Liangke; Zhao, Ling

    2014-01-01

    Baicalin (BA) is a major constituent of Scutellaria baicalensis Georgi, a medicinal herb. Previous pharmacokinetic studies of BA showed its low oral bioavailability. The aim of the present study was to develop a novel BA-loaded liposome (BA-LP) to enhance oral bioavailability. BA-LP, composed of BA, Tween® 80, Phospholipon® 90H, and citric acid at weight ratio of 96/50/96/50, respectively, was prepared by the effervescent dispersion technique and characterized in terms of morphology, size, zeta potential, encapsulation efficiency, and the in vitro release. Pharmacokinetics and biodistribution studies were carried out in rats after oral administration of BA-LP and a carboxymethyl cellulose suspension containing BA (BA-CMC) as a control. BA-LP exhibited a spherical shape by transmission electron microscopy observation. BA-LP had a mean particle size of 373±15.5 nm, zeta potential of −20.1±0.22 mV, and encapsulation efficiency of 82.7%±0.59%. The BA-LP showed a sustained-release behavior, and the in vitro drug-release kinetic model fit well with the Weibull distribution equation: lnln (1/(1−Q)) =0.609 lnt −1.230 (r=0.995). The oral bioavailability and the peak concentration of the BA-LP was threefold and 2.82-fold that of BA-CMC, respectively. The in vivo distribution results indicated that drug concentrations were significantly increased in the liver, kidney, and lung in the case of BA-LP, which were 5.59-fold, 2.33-fold, and 1.25-fold higher than those of BA-CMC, respectively. In conclusion, the study suggested that BA-LP might be a potential oral drug delivery system to improve bioavailability of BA. PMID:25120360

  12. 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

  13. 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. PMID:26443779

  14. Development of 3He insert for Magnetization Measurements down to T = 0.4 K with SQUID magnetometer

    NASA Astrophysics Data System (ADS)

    Sato, Yoshiaki; Hasuo, Tadahiko; Inagaki, Yuji; Kawae, Tatsuya

    2015-03-01

    We have developed a 9-mm-diameter 3He insert for precise magnetization measurements down to T = 0.4 K that is attachable to a commercial superconducting quantum interference device magnetometer. The insert is made from a thin-walled stainless steel pipe with an inner diameter of 6.2 mm, which determines the maximum sample size. 3He gas is condensed in the pipe, which is liquefied by 4He gas at T = 1.8 K generated by the magnetometer via the heat exchanger of a Cu vacuum jacket with an outer diameter of 8.6mm soldered to the stainless steel pipe. The temperature of the insert is decreased to T = 0.5 K by evacuating liquid 3He using a rotary pump and then to T = 0.36 K with a sorption pump. From the diamagnetization signal of a superconducting Al chip with a mass below 0.1 mg, the magnetization resolution with the insert is confirmed to be less than 10-7 emu. We measure the temperature dependence of magnetization down to T = 0.5 K in PrxLa1-xPb3, which is a good candidate for the reality of the quadrupolar Kondo effect, using the 3He insert. Non-Fermi liquid behavior of the nonlinear susceptibility in χ3 with a -lnT dependence is detected in the [100] and [110] directions below T = 2.5 K, suggesting the screening of quadrupolar moments. In contrast, χ3 in the [111] direction becomes constant below T = 3 K. The observed features indicate that a low-lying Γ3 doublet plays a crucial role in the anomalous properties of PrxLa1-xPb3.

  15. 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. PMID:26011495

  16. Resonant spin Hall effect in two dimensional electron gas

    NASA Astrophysics Data System (ADS)

    Shen, Shun-Qing

    2005-03-01

    Remarkable phenomena have been observed in 2DEG over last two decades, most notably, the discovery of integer and fractional quantum Hall effect. The study of spin transport provides a good opportunity to explore spin physics in two-dimensional electron gas (2DEG) with spin-orbit coupling and other interaction. It is already known that the spin-orbit coupling leads to a zero-field spin splitting, and competes with the Zeeman spin splitting if the system is subjected to a magnetic field perpendicular to the plane of 2DEG. The result can be detected as beating of the Shubnikov-de Haas oscillation. Very recently the speaker and his collaborators studied transport properties of a two-dimensional electron system with Rashba spin-orbit coupling in a perpendicular magnetic field. The spin-orbit coupling competes with the Zeeman splitting to generate additional degeneracies between different Landau levels at certain magnetic fields. It is predicted theoretically that this degeneracy, if occurring at the Fermi level, gives rise to a resonant spin Hall conductance, whose height is divergent as 1/T and whose weight is divergent as -lnT at low temperatures. The charge Hall conductance changes by 2e^2/h instead of e^2/h as the magnetic field changes through the resonant point. The speaker will address the resonance condition, symmetries in the spin-orbit coupling, the singularity of magnetic susceptibility, nonlinear electric field effect, the edge effect and the disorder effect due to impurities. This work was supported by the Research Grants Council of Hong Kong under Grant No.: HKU 7088/01P. *S. Q. Shen, M. Ma, X. C. Xie, and F. C. Zhang, Phys. Rev. Lett. 92, 256603 (2004) *S. Q. Shen, Y. J. Bao, M. Ma, X. C. Xie, and F. C. Zhang, cond-mat/0410169

  17. Lignin nanotubes as vehicles for gene delivery into human cells.

    PubMed

    Ten, Elena; Ling, Chen; Wang, Yuan; Srivastava, Arun; Dempere, Luisa Amelia; Vermerris, Wilfred

    2014-01-13

    Lignin nanotubes (LNTs) synthesized from the aromatic plant cell wall polymer lignin in a sacrificial alumina membrane template have as useful features their flexibility, ease of functionalization due to the availability of many functional groups, label-free detection by autofluorescence, and customizable optical properties. In this report we show that the physicochemical properties of LNTs can be varied over a wide range to match requirements for specific applications by using lignin with different subunit composition, a function of plant species and genotype, and by choosing the lignin isolation method (thioglycolic acid, phosphoric acid, sulfuric acid (Klason), sodium hydroxide lignin), which influences the size and reactivity of the lignin fragments. Cytotoxicity studies with human HeLa cells showed that concentrations of up to 90 mg/mL are tolerated, which is a 10-fold higher concentration than observed for single- or multiwalled carbon nanotubes (CNTs). Confocal microscopy imaging revealed that all LNT formulations enter HeLa cells without auxiliary agents and that LNTs made from NaOH-lignin penetrate the cell nucleus. We further show that DNA can adsorb to LNTs. Consequently, exposure of HeLa cells to LNTs coated with DNA encoding the green fluorescent protein (GFP) leads to transfection and expression of GFP. The highest transfection efficiency was obtained with LNTs made from NaOH-lignin due to a combination of high DNA binding capacity and DNA delivery directly into the nucleus. These combined features of LNTs make LNTs attractive as smart delivery vehicles of DNA without the cytotoxicity associated with CNTs or the immunogenicity of viral vectors. PMID:24308459

  18. Identification of heterogeneous aquifer transmissivity using an AE-based method.

    PubMed

    Janković, Igor; Fiori, Aldo; Suribhatla, Raghavendra; Dagan, Gedeon

    2006-01-01

    Determination of hydraulic head, H, as a function of spatial coordinates and time, in ground water flow is the basis for aquifer management and for prediction of contaminant transport. Several computer codes are available for this purpose. Spatial distribution of the transmissivity, T(x,y), is a required input to these codes. In most aquifers, T varies in an erratic manner, and it can be characterized statistically in terms of a few moments: the expected value, the variance, and the variogram. Knowledge of these moments, combined with a few measurements, permits one to estimate T at any point using geostatistical methods. In a review of transmissivity data from 19 unconsolidated aquifers, Hoeksema and Kitanidis (1985) identified two types of the logtransmissivity Y= ln(T) variations: correlated variations with variance sigma2Yc and correlation scale, I(Y), on the order of kilometers, and uncorrelated variations with variance sigma2Yn. Direct identification of the logtransmissivity variogram, Gamma(Y), from measurements is difficult because T data are generally scarce. However, many head measurements are commonly available. The aim of the paper is to introduce a methodology to identify the transmissivity variogram parameters (sigma2Yc, I(Y), and sigma2Yn) using head data in formations characterized by large logtransmissivity variance. The identification methodology uses a combination of precise numerical simulations (carried out using analytic element method) and a theoretical model. The main objective is to demonstrate the application of the methodology to a regional ground water flow in Eagle Valley basin in west-central Nevada for which abundant transmissivity and head measurements are available. PMID:16405467

  19. 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. PMID:25843303

  20. 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.

  1. Ferromagnetism and magnetoresistance of nanocomposite ZnO-Co thin films

    NASA Astrophysics Data System (ADS)

    Hamieh, M.; Jedrecy, N.; Hebert, C.; Demaille, D.; Perriere, J.

    2015-10-01

    We give evidence of nanocomposite ZnO-Co thin films displaying room temperature ferromagnetism as well as semiconducting-type behavior. The remanent magnetization may reach up to 70 kA m-1 and the resistivity at 300 K is ranging from 0.1 to 2 Ω cm . The size (from 2 to 30 nm) and shape of the metallic Co clusters in the ZnO host matrix are determined by the temperature and the pressure conditions used during the pulsed laser deposition process. While the ferromagnetic response is entirely based on the Co clusters, the electrical transport essentially takes place in the oxide matrix. At low temperature (<100 K ) , the resistivity varies according to the variable range hopping model while at high temperature (>100 K ) a Kondo-type ln(T ) dependence is observed. The magnetoresistance (MR) at high magnetic fields (>1 T ) is shown to result from the oxide matrix. Large positive MR values (+20 %) are obtained at low temperature (10 K), originating from the C o2 + paramagnetic ions in the ZnO host, while low negative values (-1 %) are systematically found in the high-temperature range (>80 K ) due to spin scattering at defects. Distinctly, at low magnetic fields (<1 T ) , MR hysteresis curves are measured, in perfect correspondence with the magnetization curves due to the Co clusters. This proves that the ZnO-Co boundaries act as efficient spin filters for the electrons which cross them, making the nanocomposite films interesting for spintronic applications.

  2. The Predominance of Type I Oligosaccharides Is a Feature Specific to Human Breast Milk123

    PubMed Central

    Urashima, Tadasu; Asakuma, Sadaki; Leo, Fiame; Fukuda, Kenji; Messer, Michael; Oftedal, Olav T.

    2012-01-01

    Human milk and colostrum contain ∼12–13 g/L and ∼22–24 g/L of oligosaccharides, respectively. The chemical structures of >100 human milk oligosaccharides (HMO) have been characterized to date. We determined the concentrations of 10 neutral and 9 acidic colostrum HMO collected during the first 3 d of lactation by using reverse phase HPLC after derivatization with 2-aminopyridine or 1-methyl-3-phenyl-5-pyrazolon. The predominant oligosaccharides were Fuc(α1-2)Gal(β1-4Glc (2′-FL), Fuc(α1-2)Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNFP I), Fuc(α1-2)Gal(β1-3)[Fuc(α1-4)]GlcNAc(β1-3)Gal(β1-4)Glc (LNDFH I), and Gal(β1-3)GlcNAc(β1-3)Gal(β1-4)Glc (LNT), the concentration of each of which was ∼1–3 g/L. Because these HMO, other than 2′-FL, all contain the Lacto-N-biose type I structure [Gal(β1-3)GlcNAc], we conclude that HMO containing the type I structure predominate over those containing the N-acetyllactosamine type II structure [Gal(β1-4)GlcNAc]. This appears to be a feature that is specific to humans, because the milk and colostrum of other species, including apes and monkeys, either contain only type II oligosaccharides or type II predominate over type I. It is possible that type I HMO may have importance as substrates for beneficial bifidobacteria in breast-fed infants. The biological importance of type I HMO predominance warrants further study, both in relation to human health and to human evolution. PMID:22585927

  3. Manifestations of one-dimensional electronic correlations in higher-dimensional systems

    NASA Astrophysics Data System (ADS)

    Saha, Ronojoy

    In this work we have studied the fundamental aspects of transport and thermodynamic properties of a one-dimensional (1D) electron system, and have shown that these 1D correlations play an important role in understanding the physics of higher-dimensional systems. The first system we studied is a three-dimensional (3D) metal subjected to a strong magnetic field that confines the electrons to the lowest Landau level. We investigated the effect of dilute impurities in the transport properties of this system. We showed that the nature of electron transport is one dimensional due to the reduced effective dimensionality induced by the magnetic field. The localization behavior in this system was shown to be intermediate, between a 1D and a 3D system. The interaction corrections to the conductivity exhibit power law scaling, sigma ∝ Talpha with a field dependent exponent. Next we studied the thermodynamic properties of a one-dimensional interacting system, where we showed that the next-to-leading terms in the specific heat and spin susceptibility are nonanalytic, in the same way as they are for higher-dimensional (D = 2,3) systems. We obtained the nonanalytic, T lnT term in the specific heat in 1D and showed that although the nonanalytic corrections in all dimensions arise from the same source, there are subtle differences in the magnitude of the effect in different dimensions. In the final part of this work we analyzed the nonanalytic corrections to the spin susceptibility (chis(H)) in higher dimensional systems. We showed that, although there were contributions from non-1D scattering in these nonanalytic terms, the dominant contribution came from 1D scattering. We also showed that the second order ferromagnetic quantum phase transition is unstable both in 2D and 3D, with a tendency towards a first order transition.

  4. A hot-wire method based thermal conductivity measurement apparatus for teaching purposes

    NASA Astrophysics Data System (ADS)

    Alvarado, S.; Marín, E.; Juárez, A. G.; Calderón, A.; Ivanov, R.

    2012-07-01

    The implementation of an automated system based on the hot-wire technique is described for the measurement of the thermal conductivity of liquids using equipment easily available in modern physics laboratories at high schools and universities (basically a precision current source and a voltage meter, a data acquisition card, a personal computer and a high purity platinum wire). The wire, which is immersed in the investigated sample, is heated by passing a constant electrical current through it, and its temperature evolution, ΔT, is measured as a function of time, t, for several values of the current. A straightforward methodology is then used for data processing in order to obtain the liquid thermal conductivity. The start point is the well known linear relationship between ΔT and ln(t) predicted for long heating times by a model based on a solution of the heat conduction equation for an infinite lineal heat source embedded in an infinite medium into which heat is conducted without convective and radiative heat losses. A criterion is used to verify that the selected linear region is the one that matches the conditions imposed by the theoretical model. As a consequence the method involves least-squares fits in linear, semi-logarithmic (semi-log) and log-log graphs, so that it becomes attractive not only to teach about heat transfer and thermal properties measurement techniques, but also as a good exercise for students of undergraduate courses of physics and engineering learning about these kinds of mathematical functional relationships between variables. The functionality of the experiment was demonstrated by measuring the thermal conductivity in samples of liquids with well known thermal properties.

  5. 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.

  6. Temporal stability of chemical hormesis (CH): Is CH just a temporary stop on the road to thresholds and toxic responses?

    PubMed

    Mushak, Paul

    2016-11-01

    Chemical hormesis (CH) is currently described as a nonmonotonic, bidirectional dose-response relationship for chemicals, where a stimulatory, (beneficial?) response at low dose or exposure is followed by an inhibitory response at higher doses/exposures (or vice-versa). CH is depicted as U(J)-shaped or inverse U(J)-shaped curves, i.e., curve slopes change sign. Some describe CH as a homeostasis-preserving response; others view CH as adaptive or (pre)conditioning responses to chemical stress. One aspect of CH and stress hormesis in general that has not been researched is its temporal stability, i.e., persistence, particularly in experimental animals and humans having long-term chemical stressing. Once maximized, does the CH response remain operative over the entire time of chemical exposure? One possible reason for the question's neglect is that temporal stability, e.g., 'steady-state hormesis,' has been assumed. Another is that CH temporality is not well understood or has been under-appreciated as to its importance. Available data, mainly for simpler biological systems, describe cases of transitory CH. Other examples, in human and experimental animal studies, show transitory existence of CH and, in some specialized cases, persisting CH. Also, certain disease state-induced hormetic responses are transitory over time in humans. The question requires resolution if CH is to be considered (i) a stable and beneficial or adverse response, (ii) a stable dose-response model competitive with stable threshold and linear, nonthreshold (LNT) dose-response models, and (iii) a model having any impact on, or role in, regulatory and public health policies. PMID:27396315

  7. 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

  8. Secretion of Bacterial Lipoproteins: Through the Cytoplasmic Membrane, the Periplasm and Beyond

    PubMed Central

    Zückert, Wolfram R.

    2014-01-01

    Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., grampositive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporterlike LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the “+2 rule”. Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

  9. A tool for the prediction of structures of complex sugars.

    PubMed

    Xia, Junchao; Margulis, Claudio

    2008-12-01

    In two recent back to back articles(Xia et al., J Chem Theory Comput 3:1620-1628 and 1629-1643, 2007a, b) we have started to address the problem of complex oligosaccharide conformation and folding. The scheme previously presented was based on exhaustive searches in configuration space in conjunction with Nuclear Overhauser Effect (NOE) calculations and the use of a complex rotameric library that takes branching into account. NOEs are extremely useful for structural determination but only provide information about short range interactions and ordering. Instead, the measurement of residual dipolar couplings (RDC), yields information about molecular ordering or folding that is long range in nature. In this article we show the results obtained by incorporation RDC calculations into our prediction scheme. Using this new approach we are able to accurately predict the structure of six human milk sugars: LNF-1, LND-1, LNF-2, LNF-3, LNnT and LNT. Our exhaustive search in dihedral configuration space combined with RDC and NOE calculations allows for highly accurate structural predictions that, because of the non-ergodic nature of these molecules on a time scale compatible with molecular dynamics simulations, are extremely hard to obtain otherwise (Almond et al., Biochemistry 43:5853-5863, 2004). Molecular dynamics simulations in explicit solvent using as initial configurations the structures predicted by our algorithm show that the histo-blood group epitopes in these sugars are relatively rigid and that the whole family of oligosaccharides derives its conformational variability almost exclusively from their common linkage (beta-D: -GlcNAc-(1-->3)-beta-D: -Gal) which can exist in two distinct conformational states. A population analysis based on the conformational variability of this flexible glycosidic link indicates that the relative population of the two distinct states varies for different human milk oligosaccharides. PMID:18953494

  10. Metallic Spin Liquid Behavior and Unconventional Anomalous Hall Transport of the Geometrically Frustrated Kondo Lattice Pr2Ir2O7

    NASA Astrophysics Data System (ADS)

    Nakatsuji, Satoru

    2008-03-01

    Among metallic magnets on geometrical frustrated lattices, the pyrochlore oxide Pr2Ir2O7 is unique for its metallic spin liquid behavior ootnotetextS. Nakatsuji, Y. Machida, Y. Maeno, T. Tayama, T. Sakakibara, J. v. Duijn, L. Balicas, J. N. Millican, R. T. Macaluso, and Julia Y. Chan, Phys. Rev. Lett. 96, 087204 (2006)., and unconventional Hall transport phenomena ootnotetextY. Machida, S. Nakatsuji, Y. Maeno, T. Tayama, T. Sakakibara, and S. Onoda, Phys. Rev. Lett. 98, 057203 (2007).. Despite the Weiss temperature T^* = 20 K deu to the RKKY interaction, Pr2Ir2O7 exhibits no magnetic long range order, but spin freezing at a very low temperature ˜120 mK. Instead, the Kondo effect, including lnT dependence in the resistivity, emerges and leads to partial screening of the 4f-moments below T^*. Moreover, the underscreened 4f- moments show spin-liquid behavior below a renormalized energy scale of θw˜1.7 K. Interestingly, in this spin-liquidlike paramagnetic regime, the Hall resistivity ρxy becomes largely enhanced, and shows behavior far different from anomalous Hall effects (AHE) due to the spin- orbit coupling observed in ordinary magnetic conductors. We discuss the origin of the metallic spin liquid behavior and unconventional AHE in terms of the spin chirality due to the non-coplanar texture of the <111> Ising-like Pr moments. This work is based on the collaboration with Y. Machida, T. Tayama, T. Sakakibara (ISSP, Univ.of Tokyo), Y. Maeno (Kyoto Univ.), S. Onoda (RIKEN, Tokyo), C. Broholm (Johns Hopkins Univ.), C. Stock and J. van Duijn (ISIS), L. Balicas (NHMFL), Jung Young Cho, and Julia Y. Chan (Louisiana State Univ.).

  11. Electro-optic properties of organic nanotubes.

    PubMed

    Stoylov, Stoyl P; Stoilova-McPhie, Svetla

    2011-08-10

    In this review article the theoretical and experimental possibilities of applying EO-methods for estimation of the physico-chemical properties of the organic nanotubes (ONTs) are studied. The ONTs are highly organized nanostructures of strongly elongated, anysometric, and hollow cylinders with a size range of 1 nm to 10,000 nm, e.g. in aqueous solutions they could behave as colloid (disperse) particles. They have high interaction ability due to their extremely large curved, rolled-up external surfaces (bilayers of membrane walls) and unique properties because of their specific electric charge distribution and dynamics that make possible the functionalization of their surfaces. Thus they could template guestsubstances such as membrane proteins and protein complexes on the exterior surfaces and in the membrane. We performed our investigations for the case of ONT aqueous colloid suspension. Following our earlier proposition of the general expression for the electro-optic (EO) effect we derived equations for the evaluation of the electric properties of ONT particles such as mechanism of electric polarization and identification of their most important electric Dipole Moments (DM), permanent (pDM) and induced (iDMs). Further we recommend ways for the calculation of their magnitude and direction. Also we evaluated some geometrical properties such as length of the ONT particles and their polydispersity. The knowledge that we provided about the ONT properties may enable us to elucidate and predict their biological activity. Templating biological active ligands (such as membrane proteins and protein complexes) on the inner and outer surfaces as well as in the surface membrane creates their potential usefulness as carrier and deliverer of biopharmaceuticals in bio-nanodevices. The theoretical equations were compared with the experimental data for ONTs such as (lipid) LNT, Tobacco Mosaic Virus (TMV) and microtubules (MT). Comparison of EO methods with other methods used till

  12. 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

  13. 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.

  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. Critical Masses for Unreflected Metal Spheres

    SciTech Connect

    Westfall, Robert Michael; Wright, Richard Q

    2009-01-01

    Calculated critical masses of bare metal spheres for 28 actinide isotopes, using the SCALE/XSDRNPM one-dimensional, discrete-ordinates system, are presented. ENDF/B-VI, ENDF/B-VII, and JENDL-3.3 cross sections were used in the calculations. Results are given for isotopes of uranium, neptunium, plutonium, americium, curium, californium, and for one isotope of einsteinium. Calculated k values for these same nuclides are also given. We show that, for non-threshold or low-threshold fission nuclides, a good approximation for the nuclide k is the value of nubar at 1 MeV. A plot of the critical mass versus k values is given for 19 nuclides with A-numbers between 232 and 250. The peaks in the critical mass curve (for seven nuclides) correspond to dips in the k curve. For the seven cases with the largest critical mass, six are even-even nuclides. Neptunium-237, with a critical mass of about 62.7 kg (ENDF/B-VI calculation), has an odd number of protons and an even number of neutrons. However, two cases with quite small critical masses, 232U and 236Pu, are also even-even. These two nuclides do not exhibit threshold fission behavior like most other even-even nuclides. The largest critical mass is 208.8 kg for 243Am and the smallest is 2.44 kg for 251Cf. The calculated k values vary from 1.5022 for 234U to 4.4767 for 251Cf. A correlation between the calculated critical mass (kg) and the fission spectrum averaged value of is given for the elements U, Np, Pu, Am, Cm, and Cf. For each of the five elements, a fit to the data for that element is provided. In each case the fit employs a negative exponential of the form mass = exp(A + B ~ ln( ) The values of A and B are element dependent and vary slightly for each of the five elements. The method described here is mainly applicable for non-threshold fission nuclides (15 of the 28 nuclides considered in this paper). There are three exceptions, 238Pu, 244Cm, and 250Cf, which all exhibit threshold fission behavior.

  16. 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)

  17. The effects of lead sources on oral bioaccessibility in soil and implications for contaminated land risk management.

    PubMed

    Palmer, Sherry; McIlwaine, Rebekka; Ofterdinger, Ulrich; Cox, Siobhan F; McKinley, Jennifer M; Doherty, Rory; Wragg, Joanna; Cave, Mark

    2015-03-01

    Lead (Pb) is a non-threshold toxin capable of inducing toxic effects at any blood level but availability of soil screening criteria for assessing potential health risks is limited. The oral bioaccessibility of Pb in 163 soil samples was attributed to sources through solubility estimation and domain identification. Samples were extracted following the Unified BARGE Method. Urban, mineralisation, peat and granite domains accounted for elevated Pb concentrations compared to rural samples. High Pb solubility explained moderate-high gastric (G) bioaccessible fractions throughout the study area. Higher maximum G concentrations were measured in urban (97.6 mg kg(-1)) and mineralisation (199.8 mg kg(-1)) domains. Higher average G concentrations occurred in mineralisation (36.4 mg kg(-1)) and granite (36.0 mg kg(-1)) domains. Findings suggest diffuse anthropogenic and widespread geogenic contamination could be capable of presenting health risks, having implications for land management decisions in jurisdictions where guidance advises these forms of pollution should not be regarded as contaminated land. PMID:25603155

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

    PubMed Central

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

    2013-01-01

    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 3 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. PMID:23051714

  19. 1989 Alice Hamilton lecture. Lead and human health: background and recent findings.

    PubMed

    Lippmann, M

    1990-02-01

    This paper, prepared in tribute to Dr. Alice Hamilton on her 120th birthday, reviews her pioneering studies of occupational lead poisoning and its control, her largely unheeded warnings about the possible consequences of widespread lead exposure to the general public through the use of leaded fuel, and the results of recent studies of human exposure to and health effects of lead in the general environment. Evidence is presented for dose-related non-threshold effects for children with blood lead concentrations below 25 micrograms/dl for a variety of effects including verbal IQ; mental development; physical size; and age at physical milestones such as first steps, hearing thresholds, and postural sway. For adults, various studies have produced associations between blood pressure and blood lead concentrations below 35 micrograms/dl, suggesting possible effects on cardiovascular health. While the biological mechanisms responsible for these effects remain poorly understood, recent and current efforts to reduce exposure to lead by the virtual elimination of lead in gasoline and food packaging show that we have learned one of Dr. Hamilton's important lessons, i.e., that the most effective means of reducing excessive exposures are through control of the environmental sources. PMID:2404752

  20. 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)). PMID:24742547

  1. 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). PMID:27263113

  2. 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. PMID:24747397

  3. Intelligent sensor management to minimize detection error

    NASA Astrophysics Data System (ADS)

    Wegrzyn, John W.; Kastella, Keith D.

    2003-08-01

    This paper analyzes the impact on target detection of several alternative sensor management schemes. Past work in this area has shown that myopic discrimination optimization can be a useful heuristic. In this paper we compare the performance obtained using discrimination with direct optimization of the detection error rate using both myopic and non-myopic optimization techniques. Our model consists of a gridded region containing a set of targets with known priors. Each grid location contains at most one target. At each time step, the sensor can sample a grid location, returning sample values that may or may not be thresholded. The sensor output distribution conditioned on the content of the location is known. Bayesian methods are used to recursively update the posterior probability that each location contains a target. These probabilities can then in turn be used to classify each location as either containing a target or not. At each time step, sensor management is used to determine which location to test next. For non-myopic optimization, graph search techniques are used. When the sensor output is thresholded, the performance obtained using myopic optimization of the expected error rate is worse then that obtained using our other three approaches. Interestingly, we find that for non-thresholded measurements on symmetric distributions, the performance is the same for the four cases tested (myopic/non-myopic discrimination gain/expected error rate). This supports that discrimination is a useful heuristic that provides near-optimal performance under the given assumptions.

  4. Growth, bioluminescence and shoal behavior hormetic responses to inorganic and/or organic chemicals: a review.

    PubMed

    Hashmi, Muhammad Zaffar; Naveedullah; Shen, Hui; Zhu, Shenhai; Yu, Chunna; Shen, Chaofeng

    2014-03-01

    A biphasic dose response, termed hormesis, is characterized by beneficial effects of a chemical at a low dose and harmful effects at a high dose. This biphasic dose response phenomenon has the potential to strongly alter toxicology in a broad range. The present review focuses on the progress of research into hormetic responses in terms of growth (in plants, birds, algae and humans), bioluminescence, and shoal behavior as end points. The paper describes how both inorganic and organic chemicals at a low dose show stimulatory responses while at higher doses are inhibitory. The article highlights how factors such as symbiosis, density-dependent factors, time, and contrasting environmental factors (availability of nutrients, temperature, light, etc.) affect both the range and amplitude of hormetic responses. Furthermore, the possible underlying mechanisms are also discussed and we suggest that, for every end point, different hormetic mechanisms may exist. The occurrences of varying interacting receptor systems or receptor systems affecting the assessment of hormesis for each endpoint are discussed. The present review suggests that a hormetic model should be adopted for toxicological evaluations instead of the older threshold and linear non-threshold models. PMID:24361513

  5. ICRP Publication 131: Stem cell biology with respect to carcinogenesis aspects of radiological protection.

    PubMed

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

    2016-06-01

    Current knowledge of stem cell characteristics, maintenance and renewal, evolution with age, location in 'niches', and radiosensitivity to acute and protracted exposures is reviewed regarding haematopoietic tissue, mammary gland, thyroid, digestive tract, lung, skin, and bone. The identity of the target cells for carcinogenesis continues to point to the more primitive and mostly quiescent stem cell population (able to accumulate the protracted sequence of mutations necessary to result in malignancy), and, in a few tissues, to daughter progenitor cells. Several biological processes could contribute to the protection of stem cells from mutation accumulation: (1) accurate DNA repair; (2) rapid induced death of injured stem cells; (3) retention of the intact parental strand during divisions in some tissues so that mutations are passed to the daughter differentiating cells; and (4) stem cell competition, whereby undamaged stem cells outcompete damaged stem cells for residence in the vital niche. DNA repair mainly operates within a few days of irradiation, while stem cell replications and competition require weeks or many months depending on the tissue type. This foundation is used to provide a biological insight to protection issues including the linear-non-threshold and relative risk models, differences in cancer risk between tissues, dose-rate effects, and changes in the risk of radiation carcinogenesis by age at exposure and attained age. PMID:26956677

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

    PubMed

    Yang, J Y; Kwak, H S; Han, J Y; 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

  7. Massive S-matrix of AdS3×S3×T4 superstring theory with mixed 3-form flux

    NASA Astrophysics Data System (ADS)

    Hoare, B.; Tseytlin, A. A.

    2013-08-01

    The type IIB supergravity AdS3×S3×T4 background with mixed RR and NSNS 3-form fluxes is a near-horizon limit of a non-threshold bound state of D5-D1 and NS5-NS1 branes. The corresponding superstring world-sheet theory is expected to be integrable, opening the possibility of computing its exact spectrum for any values of the coefficient q of the NSNS flux and the string tension. In arXiv:1303.1447 we have found the tree-level S-matrix for the massive BMN excitations in this theory, which turned out to have a simple dependence on q. Here, by analyzing the constraints of symmetry and integrability, we propose an exact massive-sector dispersion relation and the exact S-matrix for this world-sheet theory. The S-matrix generalizes its recent construction in the q=0 case in arXiv:1303.5995. This is a consequence of the fact that parity symmetry is broken with the introduction of the NSNS flux. However, charge conjugation composed with parity is still a symmetry.

  8. 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

  9. Secretion of bacterial lipoproteins: through the cytoplasmic membrane, the periplasm and beyond.

    PubMed

    Zückert, Wolfram R

    2014-08-01

    Bacterial lipoproteins are peripherally anchored membrane proteins that play a variety of roles in bacterial physiology and virulence in monoderm (single membrane-enveloped, e.g., gram-positive) and diderm (double membrane-enveloped, e.g., gram-negative) bacteria. After export of prolipoproteins through the cytoplasmic membrane, which occurs predominantly but not exclusively via the general secretory or Sec pathway, the proteins are lipid-modified at the cytoplasmic membrane in a multistep process that involves sequential modification of a cysteine residue and cleavage of the signal peptide by the signal II peptidase Lsp. In both monoderms and diderms, signal peptide processing is preceded by acylation with a diacylglycerol through preprolipoprotein diacylglycerol transferase (Lgt). In diderms but also some monoderms, lipoproteins are further modified with a third acyl chain through lipoprotein N-acyl transferase (Lnt). Fully modified lipoproteins that are destined to be anchored in the inner leaflet of the outer membrane (OM) are selected, transported and inserted by the Lol (lipoprotein outer membrane localization) pathway machinery, which consists of the inner-membrane (IM) ABC transporter-like LolCDE complex, the periplasmic LolA chaperone and the OM LolB lipoprotein receptor. Retention of lipoproteins in the cytoplasmic membrane results from Lol avoidance signals that were originally described as the "+2 rule". Surface localization of lipoproteins in diderms is rare in most bacteria, with the exception of several spirochetal species. Type 2 (T2SS) and type 5 (T5SS) secretion systems are involved in secretion of specific surface lipoproteins of γ-proteobacteria. In the model spirochete Borrelia burgdorferi, surface lipoprotein secretion does not follow established sorting rules, but remains dependent on N-terminal peptide sequences. Secretion through the outer membrane requires maintenance of lipoproteins in a translocation-competent unfolded conformation

  10. Smectic-A-C transition in three dimensions

    NASA Astrophysics Data System (ADS)

    Grinstein, G.; Pelcovits, R. A.

    1982-10-01

    A theory of the smectic-A-C transition in which fluctuations in both the elastic and director degrees of freedom are treated is developed. It is argued that in zero magnetic field the asymptotic critical behavior belongs in the universality class of the threedimensional XY model, in agreement with earlier studies which did not treat fully both elastic and director fluctuations. For most experimental situations the true critical region is unobservably narrow whereupon a simple-harmonic approximation adequately describes the transition; in this approximation the static structure factor exhibits a crossover from algebraic decay characterized by a nonuniversal exponent ηA in the A phase to algebraic decay characterized by a different nonuniversal exponent ηAC at the critical temperature Tc. The splay elastic constant K1 is <∞ and =∞ in the A and C phases, respectively, but does not exhibit diverging pretransitional fluctuations in the A phase even arbitrarily near Tc; it jumps discontinuously at Tc. A strong magnetic field stabilizes long-range positional order in both the A and C phases. There is, nevertheless, no long-range order at Tc, where the density correlation function )m(o-->)> decays algebraically; schematically, )m(o-->)>~x-(2+η) at Tc in the harmonic theory, while m(x-->) vanishes like tβ, where t is the reduced temperature. The exponents β and η, though nonuniversal, satisfy the scaling law 4β=2+η. These finite-field results are modified at large distances (say x>~105 Å) by the inclusion of anharmonic terms. We find )m(o-->)>~x exp[-(2+η~)|lnx|137] at Tc, while )>~tβ~|lnt|137 as t-->0. Here β~ and η~ are nonuniversal but satisfy 4β~=2+η~. At Tc, K1 and B (the compressional elastic constant), respectively, diverge and vanish like (lnk)237 and (lnk)-437 as the momentum k-->0. The exponents 137, 237, and 437 are universal.

  11. 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

  12. 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

  13. Risk estimates for radiation-induced cancer--the epidemiological evidence.

    PubMed

    Kellerer, A M

    2000-03-01

    The risk of low-dose radiation exposures has--for a variety of reasons--been highly politicised. This has led to a frequently exaggerated perception of the potential health effects, and to lasting public controversies. A balanced view requires a critical reassessment of the epidemiological basis of current assumptions. There is reliable quantitative information available on the increase of cancer rates due to moderate and high doses. This provides a firm basis for the derivation of probabilities of causation, e.g. after high radiation exposures. For small doses or dose rates, the situation is entirely different: potential increases of cancer rates remain hidden below the statistical fluctuations of normal rates, and the molecular mechanisms of cancerogenesis are not sufficiently well known to allow numerical predictions. Risk coefficients for radiation protection must, therefore, be based on the uncertain extrapolation of observations obtained at moderate or high doses. While extrapolation is arbitrary, it is, nevertheless, used and mostly with the conservative assumption of a linear dose dependence with no threshold (LNT model). All risk estimates are based on this hypothesis. They are, thus, virtual guidelines, rather than firm numbers. The observations on the A-bomb survivors are still the major source of information on the health effects of comparatively small radiation doses. A fairly direct inspection of the data shows that the solid cancer mortality data of the A-bomb survivors are equally consistent with linearity in dose and with reduced effectiveness at low doses. In the leukemia data a reduction is strongly indicated. With one notable exception -- leukemia after prenatal exposure--these observations are in line with a multitude of observations in groups of persons exposed for medical reasons. The low-dose effects of densely ionizing radiations--such as alpha-particles from radon decay products or high-energy neutrons--are a separate important issue. For

  14. 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. PMID:19454801

  15. 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

  16. Monte Carlo simulation of a film growth with reactive hydrophobic, polar, and aqueous components by a covalent bond fluctuating model

    NASA Astrophysics Data System (ADS)

    Yang, Shihai; Pandey, Ras B.

    2007-04-01

    polyurethane film. The steady-state film thickness increases monotonically with the temperature possibly with two logarithmic dependences. The equilibrium interface width shows a nonmonotonic dependence: on increasing the temperature, Ws seems to increase slowly before it begins to decay Ws=4.12-1.39ln(T).

  17. 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

  18. Environmental transcriptome analysis reveals physiological differences between biofilm and planktonic modes of life of the iron oxidizing bacteria Leptospirillum spp. in their natural microbial community

    PubMed Central

    2010-01-01

    Background Extreme acidic environments are characterized by their high metal content and lack of nutrients (oligotrophy). Macroscopic biofilms and filaments usually grow on the water-air interface or under the stream attached to solid substrates (streamers). In the Río Tinto (Spain), brown filaments develop under the water stream where the Gram-negative iron-oxidizing bacteria Leptospirillum spp. (L. ferrooxidans and L. ferriphilum) and Acidithiobacillus ferrooxidans are abundant. These microorganisms play a critical role in bioleaching processes for industrial (biominery) and environmental applications (acid mine drainage, bioremediation). The aim of this study was to investigate the physiological differences between the free living (planktonic) and the sessile (biofilm associated) lifestyles of Leptospirillum spp. as part of its natural extremely acidophilic community. Results Total RNA extracted from environmental samples was used to determine the composition of the metabolically active members of the microbial community and then to compare the biofilm and planktonic environmental transcriptomes by hybridizing to a genomic microarray of L. ferrooxidans. Genes up-regulated in the filamentous biofilm are involved in cellular functions related to biofilm formation and maintenance, such as: motility and quorum sensing (mqsR, cheAY, fliA, motAB), synthesis of cell wall structures (lnt, murA, murB), specific proteases (clpX/clpP), stress response chaperons (clpB, clpC, grpE-dnaKJ, groESL), etc. Additionally, genes involved in mixed acid fermentation (poxB, ackA) were up-regulated in the biofilm. This result, together with the presence of small organic acids like acetate and formate (1.36 mM and 0.06 mM respectively) in the acidic (pH 1.8) water stream, suggests that either L. ferrooxidans or other member of the microbial community are producing acetate in the acidophilic biofilm under microaerophilic conditions. Conclusions Our results indicate that the acidophilic

  19. The bioaccumulation and fate of a branched 14C-p-nonylphenol isomer in Lymnaea stagnalis L.

    PubMed

    Lalah, Joseph O; Behechti, Akbar; Severin, Gabriele F; Lenoir, Dieter; Günther, Klaus; Kettrup, Antonius; Schramm, Karl-Werner

    2003-07-01

    A single branched isomer of p-nonylphenol, 4(3',6'-dimethyl-3'-heptyl)-phenol, previously identified by gas chromatography-mass spectrometry as one of the major constituent isomers in p-nonylphenol (constituting approximately 10% of all its isomers), was synthesized and used in studies of its bioaccumulation and excretion in the hermophroditic pond snail Lymnaea stagnalis L. Branched isomers of nonylphenol are perceived to have more estrogenlike toxicity than the straight-chain isomers in addition to being more resistant to biodegradation in the environment. With an average static exposure concentration of 104 microg/L (range: 92-116 microg/L) in water at 19 degrees C for 8 d, the uptake of the compound was found to be fairly rapid, reaching a peak concentration of 23,548 microg/kg of whole tissue wet weight after 5 d and a peak bioaccumulation factor (BAFw) of 242 (5,562, based on lipid weight) after 3 d. The uptake data fitted into a logarithmic expression C(t) = 5,231 ln(t) + 11,956, where C(t) is the amount of residues accumulated in whole tissue in micrograms per kilogram tissue wet weight after a period of time, t, and t is the period of exposure in days. By determination of the excretion of 14C-residues released in water and in feces, an average loss of 96% of the accumulated residues was achieved after 22 d of continuous exposure to clean water. By first-order kinetics analysis of the excretion data, an average half-life of excretion of 4.9 d was obtained. By high-performance liquid chromatography and gas-liquid chromatography-mass spectrometry, a catechol metabolite, 4(3',6'-dimethyl-3'-heptyl)-catechol, was detected in tissue extracts (after hydrolysis with beta-glucuronidase) and in feces, in addition to the parent isomer, suggesting that the isomer may have been metabolized by glucuronic acid conjugation and hydroxylation at the ortho position of its phenolic ring. PMID:12836966

  20. 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

  1. 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

  2. Spectroscopic measurements of the pH in NaCl brines

    NASA Astrophysics Data System (ADS)

    Millero, Frank J.; DiTrolio, Benjamin; Suarez, Andres F.; Lando, Gabriele

    2009-06-01

    Spectrophotometric measurements of the pH in natural waters such as seawater have been shown to yield precise results. In this paper, the sulfonephthalein indicator m-cresol purple ( mCP, H 2I) has been used to determine the pH of NaCl brines. The indicator has been calibrated in NaCl solutions from 5 to 45 °C and ionic strengths from 0.03 to 5.5 m. The calibrations were made using TRIS buffers (0.03 m, TRIS/TRIS-HCl) with known dissociation constants pK TRIS in NaCl solutions [Foti C., Rigano C. and Sammartano S. (1999) Analysis of thermodynamic data for complex formation: protonation of THAM and fluoride ion at different temperatures and ionic strength. Ann. Chim. 89, 1-12]. The values of pH were determined from pH=pK+log{(R-e1)/(e2-Re3)} where R = 578A/ 434A, the ratios of the indicator absorbance maximum at 578 and 434 nm, e1 = 0.00691, e2 = 2.222 and e3 = 0.1331 [Clayton T. and Byrne R. H. (1993) Spectrophotometric seawater pH measurements: total hydrogen ion concentration scale calibration of m-cresol purple and at-sea results. Deep-Sea Res. 40, 2115-2129]. Measurements were also made in NaCl solutions with different levels of TRIS (0.01-0.11 m). At low levels of TRIS buffer (<0.03 m), the values of pK mCP increased significantly. This effect can lead to erroneous values of pK mCP at low ionic strengths in estuaries and lakes. The measured values of pK mCP in NaCl as a function of ionic strength ( I/m) and temperature ( T/K) were fitted to the equation ( σ = 0.0072) pK=-29.095+2639.2/T+5.0417lnT-0.3307I0.5-186.80I0.5/T-0.28346I+296.44I/T+0.12841I1.5-68.23I1.5/T These results should be useful in determining the pH of NaCl brines in natural waters from 0 to 50 °C.

  3. 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.

  4. Mixed integer programming improves comprehensibility and plan quality in inverse optimization of prostate HDR brachytherapy.

    PubMed

    Gorissen, Bram L; den Hertog, Dick; Hoffmann, Aswin L

    2013-02-21

    Current inverse treatment planning methods that optimize both catheter positions and dwell times in prostate HDR brachytherapy use surrogate linear or quadratic objective functions that have no direct interpretation in terms of dose-volume histogram (DVH) criteria, do not result in an optimum or have long solution times. We decrease the solution time of the existing linear and quadratic dose-based programming models (LP and QP, respectively) to allow optimizing over potential catheter positions using mixed integer programming. An additional average speed-up of 75% can be obtained by stopping the solver at an early stage, without deterioration of the plan quality. For a fixed catheter configuration, the dwell time optimization model LP solves to optimality in less than 15 s, which confirms earlier results. We propose an iterative procedure for QP that allows us to prescribe the target dose as an interval, while retaining independence between the solution time and the number of dose calculation points. This iterative procedure is comparable in speed to the LP model and produces better plans than the non-iterative QP. We formulate a new dose-volume-based model that maximizes V(100%) while satisfying pre-set DVH criteria. This model optimizes both catheter positions and dwell times within a few minutes depending on prostate volume and number of catheters, optimizes dwell times within 35 s and gives better DVH statistics than dose-based models. The solutions suggest that the correlation between the objective value and the clinical plan quality is weak in the existing dose-based models. PMID:23363622

  5. Novel lung IMRT planning algorithms with nonuniform dose delivery strategy to account for respiratory motion.

    PubMed

    Li, Xiang; Zhang, Pengpeng; Mah, Dennis; Gewanter, Richard; Kutcher, Gerald

    2006-09-01

    To effectively deliver radiation dose to lung tumors, respiratory motion has to be considered in treatment planning. In this paper we first present a new lung IMRT planning algorithm, referred as the dose shaping (DS) method, that shapes the dose distribution according to the probability distribution of the tumor over the breathing cycle to account for respiratory motion. In IMRT planning a dose-based convolution method was generally adopted to compensate for random organ motion by performing 4-D dose calculations using a tumor motion probability density function. We modified the CON-DOSE method to a dose volume histogram based convolution method (CON-DVH) that allows nonuniform dose distribution to account for respiratory motion. We implemented the two new planning algorithms on an in-house IMRT planning system that uses the Eclipse (Varian, Palo Alto, CA) planning workstation as the dose calculation engine. The new algorithms were compared with (1) the conventional margin extension approach in which margin is generated based on the extreme positions of the tumor, (2) the dose-based convolution method, and (3) gating with 3 mm residual motion. Dose volume histogram, tumor control probability, normal tissue complication probability, and mean lung dose were calculated and used to evaluate the relative performance of these approaches at the end-exhale phase of the respiratory cycle. We recruited six patients in our treatment planning study. The study demonstrated that the two new methods could significantly reduce the ipsilateral normal lung dose and outperformed the margin extension method and the dose-based convolution method. Compared with the gated approach that has the best performance in the low dose region, the two methods we proposed have similar potential to escalate tumor dose, but could be more efficient because dose is delivered continuously. PMID:17022235

  6. Balanced anesthesia and constant-rate infusions in horses.

    PubMed

    Valverde, Alexander

    2013-04-01

    Balanced anesthetic techniques are commonly used in equine patients, and include the combination of a volatile anesthetic with at least one injectable anesthetic throughout the maintenance period. Injectable anesthetics used in balanced anesthesia include the α2-agonists, lidocaine, ketamine, and opioids, and those with muscle-relaxant properties such as benzodiazepines and guaifenesin. Administration of these injectable anesthetics is best using constant-rate infusions based on the pharmacokinetics of the drug, which allows steady-state concentrations and predictable pharmacodynamic actions. This review summarizes the different drug combinations used in horses, and provides calculated recommended doses based on the pharmacokinetics of individual drugs. PMID:23498047

  7. Control-relevant erythropoiesis modeling in end-stage renal disease.

    PubMed

    Chait, Yossi; Horowitz, Joseph; Nichols, Brendan; Shrestha, Rajiv P; Hollot, C V; Germain, Michael J

    2014-03-01

    Anemia is prevalent in end-stage renal disease (ESRD). The discovery of recombinant human erythropoietin (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hb) measurements. In order to facilitate the design of an AMP using model-based feedback control theory, we present a physiologically relevant erythropoiesis model and demonstrate its applicability using clinical data. PMID:24235247

  8. A Framework for Treating Uncertainty to Facilitate Waste Disposal Decision Making - Application of the Approach to GCD Performance Assessment

    SciTech Connect

    Brown, T.J.; Cochran, J.R.; Gallegos, D.P.

    1999-03-09

    This paper presents an approach for treating uncertainty in the performance assessment process to efficiently address regulatory performance objectives for radioactive waste disposal and discusses the application of the approach at the Greater Confinement Disposal site. In this approach, the performance assessment methodology uses probabilistic risk assessment concepts to guide effective decisions about site characterization activities and provides a path toward reasonable assurance regarding regulatory compliance decisions. Although the approach is particularly amenable to requirements that are probabilistic in nature, the approach is also applicable to deterministic standards such as the dose-based and concentration-based requirements.

  9. Magnetic nanoemulsions as drug delivery system for Foscan ®: Skin permeation and retention in vitro assays for topical application in photodynamic therapy (PDT) of skin cancer

    NASA Astrophysics Data System (ADS)

    Primo, Fernando L.; Michieleto, Leandro; Rodrigues, Marcilene A. M.; Macaroff, Patrícia P.; Morais, Paulo C.; Lacava, Zulmira G. M.; Bentley, Maria Vitória L. B.; Tedesco, Antonio C.

    2007-04-01

    In this work, we performed the synthesis and in vitro characterization of a new class of drug delivery system (DDS) denominated magnetic nanoemulsion (MNE). The association of colloidal nanoparticles with biocompatible magnetic fluids results in a new DDS for application in photodynamic therapy (PDT) and magnetic hyperthermia treatment. It works in a synergic manner with an expected enhancement in tumor damage after minimum drug doses, based on heat dissipation and/or light photosensitization. For this purpose, we investigated the permeation and retention in vitro model using Foscan ® as a photosensitizer incorporated in MNE using a Franz diffusion cell and a biological skin model in biomimetic conditions.

  10. Verification of nuclear data for the Tsukuba plan, a newly developed treatment planning system for boron neutron capture therapy.

    PubMed

    Kumada, Hiroaki; Takada, Kenta; Yamanashi, Koichi; Sakae, Takeji; Matsumura, Akira; Sakurai, Hideyuki

    2015-12-01

    Various verifications were performed to apply JENDL-4.0 as nuclear data for a newly developed treatment planning system with a homogeneous or precise human-like phantom. The nitrogen dose calculated by JENDL-4.0 differed slightly from that calculated by ENDF/B-VII.0. However, the total weighted dose-based dose volume histogram in the boron neutron capture therapy (BNCT) treatment for brain tumors calculated by JENDL-4.0 was in good agreement with the results of the ENDF/B-VII.0 calculation. Therefore, calculation with JENDL-4.0 can be applied to the BNCT dose calculation. PMID:26361835

  11. 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.

  12. Downstream Transport System for the Second Axis of the Dual-Axis Radiographic Hydrodynamic Test Facility

    NASA Astrophysics Data System (ADS)

    Chen, Yu-Jiuan; Bertolini, Lou; Caporaso, George J.; Ho, Darwin D.-M.; McCarrick, James F.; Paul, Arthur C.; Pincosy, Philip A.; Poole, Brian R.; Wang, Li-Fang; Westenskow, Glen A.

    2002-12-01

    This paper presents physics design of the DARHT-II downstream system, which consists of a diagnostic beam stop, a novel, fast, high-precision kicker system and the x-ray converter target assembly. The beamline configuration and its beam parameter acceptance, the transverse resistive wall instability modeling, the ion hose instability in the presence of the background gas, and the simulations of beam spill are discussed. We also present the target converter assembly's configuration, and the simulated x-ray spot sizes and doses based on the radiation hydrodynamics code LASNEX and the Monte Carlo radiation transport code MCNP.

  13. 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.

  14. 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.; Osovets, Sergey, V.; Syrchikov, Victor, A.; Pesternikova, Valentina, S.; Belyaeva, Zinaida, D.; Khokhryakov, Valentin, F; Vasilenko, Evgeny, K.; Okladnikova, Nadezhda D.

    2004-12-10

    for the relative risk (RR) for lung cancer induction in humans [Mayak Plutonium Facility Production Association (PA) workers in Russia] after combined exposure to alpha and gamma radiations. This is based on the published observation that RR for neoplastic transformation has a similar dependence on dose as for the RR of cancer induction. Based on our mechanistic model, low dose-rate exposure to low or moderate doses of gamma radiation is predicted to possibly protect adult humans from cancer occurrence, including cancer induction by low dose alpha-radiation and cigarette smoke. The gamma irradiation associated protection arises through gamma rays hitting many of the millions of normal cells in the irradiated tissue, which turns on intra- and intercellular signaling that leads to cleansing of tissue of neoplastically transformed and other genomically compromised cells (e.g., mutants, micronucleated cells, etc.) via a selective apoptosis mechanism. Using available cohort study data for Mayak PA workers chronically exposed to gamma rays in combination with alpha radiation from inhaled Pu-239, we can explain the hormetic-type, dose-response relationship for the RR for radiation-induced lung cancer seen in the workers as well as in tuberculosis patients receiving chronic X-ray irradiation. Based on currently available information, the linear nonthreshold (LNT) model appears to apply to chronic exposure to alpha radiation alone but, in adults, not to exposure to gamma radiation or combinations of gamma and alpha radiations. We found that linear extrapolation from high-dose data to low doses can introduce phantom (nonexistent) excess cancer risk in the case of combined exposure of adults to gamma and alpha radiations or exposure only to gamma rays. Because remediation of radionuclide-contaminated U. S. Department of Energy (DOE) sites is driven by risk-based considerations, and risks are assumed to increase according to the LNT model, it is important to understand under what

  15. 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.

  16. Radiation biodosimetry: applications for spaceflight

    NASA Astrophysics Data System (ADS)

    Blakely, W.; Miller, A.; Grace, M.; Prasanna, P.; Muderhwa, J.

    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 cytogenetic analysis of chromosome aberrations, considered the best means of documenting radiation doses for health records. Our system consists of a dose assessment software application, a portable blood cell counter, and molecular biodosimetry using miniaturized equipment. The Biodosimetry Assessment Tool (BAT) software application calculates radiation dose based on a patient's physical signs and symptoms and blood analysis, annotates location of personnel dosimeters, displays a summary of a patient's dosimetric information to healthcare professionals, and archives the data for further use. The dry reagent centrifuge-based 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), once dose-dependent targets are identified, optimized, and validated, will make use of miniaturized diagnostic equipment for nucleic acid sequence and antigen-based biosensor detection technologies. These radiation assessment diagnostic technologies can have dual use for other medical related applications. [The Armed Forces Radiobiology Research Institute, under work unit AFRRI-01-3, and the Defense Threat Reduction Agency, under contract GG4661, supported this research.

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

    PubMed Central

    Hamada, Nobuyuki; Fujimichi, Yuki

    2014-01-01

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

  18. 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. PMID:21713498

  19. 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. PMID:24729053

  20. Population dynamics and management of diamondback moth (Plutella xylostella) in China: the relative contributions of climate, natural enemies and cropping patterns.

    PubMed

    Li, Z; Zalucki, M P; Yonow, T; Kriticos, D J; Bao, H; Chen, H; Hu, Z; Feng, X; Furlong, M J

    2016-04-01

    Diamondback moth or DBM is the major pest of Brassica vegetable production worldwide. Control has relied on insecticides, and DBM resistance to these compounds has evolved rapidly. We review and summarize data on DBM population dynamics across a large latitudinal gradient from southwest to northeast China: DBM is, on average, more common in southern locations than in northern locations. The species' phenology is consistent: in southern and central locations there is a decline during hot summer months, while in the north, the species can only exist in the summer following migrations from the south. A cohort-based discrete-time model, driven by daily maximum and minimum temperatures and rainfall, which was built using the DYMEX modelling software, captures the age-structured population dynamics of DBM at representative locations, with year round cropping and threshold-based insecticide applications. The scale of the simulated pest problem varies with cropping practices. Local production breaks and strict post-harvest crop hygiene are associated with lower DBM populations. Biological control appears to improve the management of DBM. Of the management strategies explored, non-threshold based applications of insecticides with reduced spray efficacy (due to poor application or resistance) appear the least effective. The model simulates the phenology and abundance patterns in the population dynamics across the climatic gradient in China reasonably well. With planned improvements, and backed by a system of field sampling and weather inputs, it should serve well as a platform for a local pest forecast system, spanning the range of DBM in China, and perhaps elsewhere. PMID:26693884

  1. Investigation of Non-Magnetic Iron in LUTETIUM(2)IRON(3)SILICON(5) - Superconductors.

    NASA Astrophysics Data System (ADS)

    Xu, Youwen

    1987-03-01

    A focussed study on the effect of transition metal substitution for Fe in the compounds {rm Lu_2(Fe_{1-x}T_{x}) _3Si}_5 (Where T = Cr, Mn, Co, Ni Cu, and Ru) is reported. The effect of these transition metals on the superconducting transition temperature shows that Cr, Co, Ni and Ru all act as non-magnetic impurities. By fitting the experimental data {rm T _{c}/T_{co}} to Kaiser's equation, a good agreement with Kaiser's theory is obtained. The rate of suppression due to Co substitution is similar to that of Ru. Superconductivity persists ({rm T_{c}} = 0.49K) even when 10 at.% Co is substituted for Fe. In contrast, Mn and Cu act as magnetic impurities and suppress {rm T_{c}} in a way described by the theory of Abrikosov and Gor'kov. The molar magnetic susceptibility of {rm Lu_2Fe_3Si}_5 does not follow a Curie-Weiss law, but rather increases slightly as temperature increases. The addition of Ru lowers the value of chi{rm (T) }, but the overall shape of chi {rm (T)} is unchanged. In contrast, the substitution of the nominally magnetic transition metals Cr, Mn, Co and Ni for Fe causes chi{ rm (T)} to become more Curie-Weiss like. The magnetic susceptibility of the compound { rm Lu_2Co_3Si}_5 follows the Curie-Weiss law, while that of the compound {rm Lu_2Ru_3Si}_5 is diamagnetic. The electrical resistivity rho{ rm (T)} of the compound { rm Lu_2Fe_3Si}_5 is approximately quadratic in T at temperatures below 50 K and proportional to lnT at temperature above 100 K. The low temperature heat capacity data of the Co- and Ru-containing samples are similar and both fit to equations gamma{_ {s}T+beta_{s}T}^3 below {rm T_{c} } and gamma{_ {n}T+beta_{n}T^3+ alpha_{n}T}^5 above {rm T_{c}} in agreement with the heat capacity measurement by C. B. Vining for the compound {rm Lu_2Fe_3Si}_5. Increasing the concentration of Co or Ru lowers the Debye temperature and the electronic density of states at the Fermi level of the compounds and enhances the linear term in the superconducting

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. Simplification of an erythropoiesis model for design of anemia management protocols in end stage renal disease.

    PubMed

    Nichols, B; Shrestha, R P; Horowitz, J; Hollot, C V; Germain, M J; Gaweda, A E; Chait, Y

    2011-01-01

    Many end stage renal disease (ESRD) patients suffer from anemia due to insufficient endogenous production of erythropoietin (EPO). The discovery of recombinant human EPO (rHuEPO) over 30 years ago has shifted the treatment of anemia for patients on dialysis from blood transfusions to rHuEPO therapy. Many anemia management protocols (AMPs) used by clinicians comprise a set of experience-based rules for weekly-to-monthly titration of rHuEPO doses based on hemoglobin (Hgb) measurements. In order to facilitate the design of an AMP based on formal control design methods, we present a physiologically-relevant erythropoiesis model, and show that its nonlinear dynamics can be approximated using a static nonlinearity, a step that greatly simplifies AMP design. We demonstrate applicability of our results using clinical data. PMID:22254256

  9. 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.

  10. Active radiation hardening of Tm-doped silica fiber based on pump bleaching.

    PubMed

    Xing, Ying-bin; Zhao, Nan; Liao, Lei; Wang, Yi-bo; Li, Hai-qing; Peng, Jing-gang; Yang, Lv-yun; Dai, Neng-li; Li, Jin-yan

    2015-09-21

    Tm-doped fiber laser or amplifier can be applied in varied adverse environments. In this work, we demonstrate the pump bleaching of Tm-doped silica fiber with 793nm pump source under gamma-ray irradiation in the range 50Gy-675Gy. The recovery time, the fiber slope efficiency and the fiber cladding absorption spectra after irradiation and bleaching have been measured. It is found that the recovery time and radiation induce absorption are positively associated with doses, however, the fiber slope efficiency of irradiated TDF and bleached TDF are both negatively correlated with doses. Based on the simulation of the fiber core temperature, the probable mechanism of pump bleaching is also discussed. PMID:26406629

  11. Haze defect control and containment in a high volume DRAM manufacturing environment

    NASA Astrophysics Data System (ADS)

    Chen, Jerry X.; Nguyen, Maihan; Arasaki, Osamu; Maraquin, Tammy; Sawyer, Daniel; Morrison, Pedro

    2005-11-01

    Haze and other progressive reticle defects have been known in the semiconductor industry for more than a decade [1]. Extensive research and experiments have been carried out to determine the sources and origins of the progressive haze growth, but the true mechanisms of its cause are still under speculation. To minimize the wafer yield loss at Samsung Austin Semiconductor (SAS), we introduced a practical method to control the haze defects in a DRAM manufacturing environment that integrates reticle and wafer inspections, reticle cleaning, and a dose-based and time-based control forecast software system. This development has been proven to be very effective in controlling the haze defects and reducing the related yield loss while still supporting high volume wafer production.

  12. 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

    2016-02-01

    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. PMID:26772631

  13. 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. PMID:25349458

  14. 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.

  15. [Guideline for the additional test positions according to the EPQC 4th Edition for Digital Mammography Systems].

    PubMed

    Sommer, A; Lenzen, H; Blaser, D; Ehlers, S-E; Schopphoven, S; John, C

    2009-09-01

    Within the physical-technical quality assurance of the German breast cancer screening program all digital mammography systems have to perform the contrast resolution test and the determination of the average glandular dose based on the European guidelines for quality assurance in breast cancer screening and diagnosis (4th Edition). Since 1.1.2009 this applies to digital systems outside the screening program too. To accomplish uniform measurements in all federal states of Germany, the physical board of the reference centers developed together a special guideline for these test position. This Guideline describes the determination of the average glandular dose for different types of mammography systems, the CDMAM image acquisition and the CDMAM image evaluation as well. This guideline was verified by the German task group "Röntgenverordnung". PMID:19676011

  16. 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.

  17. 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.

  18. The use of novel agents in multiple myeloma patients with hepatic impairment.

    PubMed

    Stansfield, Lindsay C; Gonsalves, Wilson I; Buadi, Francis K

    2015-01-01

    Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate dosing based on metabolism and clearance is important to maintain efficacy while avoiding toxicity. Hepatic impairment (HI) in multiple myeloma patients is rare but well described either due to disease or therapy-related factors. However, limited data are available on the appropriate use and dosing of the novel agent therapeutics in myeloma patients with HI. Furthermore, data on HI secondary to the novel agent toxicity are also sparse. This systematic review highlights the evidence on the use of novel agents like thalidomide, lenalidomide, pomalidomide, bortezomib and carfilzomib in patients with HI as well as their associated hepatic toxicities. PMID:25675129

  19. The use of novel agents in multiple myeloma patients with hepatic impairment

    PubMed Central

    Stansfield, Lindsay C; Gonsalves, Wilson I; Buadi, Francis K

    2015-01-01

    Novel drugs such as immunomodulators and proteasome inhibitors have improved the survival of patients with multiple myeloma. Like all therapeutic agents, appropriate dosing based on metabolism and clearance is important to maintain efficacy while avoiding toxicity. Hepatic impairment (HI) in multiple myeloma patients is rare but well described either due to disease or therapy-related factors. However, limited data are available on the appropriate use and dosing of the novel agent therapeutics in myeloma patients with HI. Furthermore, data on HI secondary to the novel agent toxicity are also sparse. This systematic review highlights the evidence on the use of novel agents like thalidomide, lenalidomide, pomalidomide, bortezomib and carfilzomib in patients with HI as well as their associated hepatic toxicities. PMID:25675129

  20. 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.

  1. 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. PMID:26303151

  2. Effect of Relative Humidity on Dynamic Aerosols of Adenovirus 12

    PubMed Central

    Davis, Gary W.; Griesemer, Richard A.; Shadduck, John A.; Farrell, Robert L.

    1971-01-01

    Dynamic aerosols of adenovirus 12 were generated in the same Henderson apparatus under conditions of high, medium, and low relative humidity. High relative humidities resulted in more recovery of adenovirus 12 from aerosols and lungs of newborn Syrian hamsters. At 89, 51, and 32% relative humidity, the total infectious virus recovered from a 20-min aerosol was 106.7, 106.0, and 104.3 TCD50, respectively. Hamsters exposed to these 20-min aerosols retained measured lung doses of 103.0, 102.4, and 101.0 TCD50, respectively. The measured retained lung doses were compared to calculated inhaled lung doses based on both total virus aerosolized and total virus recovery from the aerosols. PMID:4930277

  3. 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%). PMID:25771362

  4. Population Pharmacokinetics of Busulfan in Pediatric and Young Adult Patients Undergoing Hematopoietic Cell Transplant: A Model-Based Dosing Algorithm for Personalized Therapy and Implementation into Routine Clinical Use

    PubMed Central

    Long-Boyle, Janel; Savic, Rada; Yan, Shirley; Bartelink, Imke; Musick, Lisa; French, Deborah; Law, Jason; Horn, Biljana; Cowan, Morton J.; Dvorak, Christopher C.

    2014-01-01

    Background Population pharmacokinetic (PK) studies of busulfan in children have shown that individualized model-based algorithms provide improved targeted busulfan therapy when compared to conventional dosing. The adoption of population PK models into routine clinical practice has been hampered by the tendency of pharmacologists to develop complex models too impractical for clinicians to use. The authors aimed to develop a population PK model for busulfan in children that can reliably achieve therapeutic exposure (concentration-at-steady-state, Css) and implement a simple, model-based tool for the initial dosing of busulfan in children undergoing HCT. Patients and Methods Model development was conducted using retrospective data available in 90 pediatric and young adult patients who had undergone HCT with busulfan conditioning. Busulfan drug levels and potential covariates influencing drug exposure were analyzed using the non-linear mixed effects modeling software, NONMEM. The final population PK model was implemented into a clinician-friendly, Microsoft Excel-based tool and used to recommend initial doses of busulfan in a group of 21 pediatric patients prospectively dosed based on the population PK model. Results Modeling of busulfan time-concentration data indicates busulfan CL displays non-linearity in children, decreasing up to approximately 20% between the concentrations of 250–2000 ng/mL. Important patient-specific covariates found to significantly impact busulfan CL were actual body weight and age. The percentage of individuals achieving a therapeutic Css was significantly higher in subjects receiving initial doses based on the population PK model (81%) versus historical controls dosed on conventional guidelines (52%) (p = 0.02). Conclusion When compared to the conventional dosing guidelines, the model-based algorithm demonstrates significant improvement for providing targeted busulfan therapy in children and young adults. PMID:25162216

  5. 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.

  6. Morbid Obesity Alters Both Pharmacokinetics and Pharmacodynamics of Propofol: Dosing Recommendation for Anesthesia Induction.

    PubMed

    Dong, Dong; Peng, Xuemei; Liu, Jie; Qian, Hao; Li, Jiayang; Wu, Baojian

    2016-10-01

    The prevalence of obesity has markedly increased worldwide. Obese patients pose significant challenges to anesthesiologists with regard to accurate dosing of anesthetics due to potentially altered pharmacokinetics (PK). Here we determined the PK and pharmacodynamics (PD) of propofol for anesthesia induction in morbidly obese (MO) subjects (body mass index >35 kg/m(2)) at two dosing regimens: dosing based on total body weight and lean body weight (LBW), respectively. The propofol pharmacokinetic profile was well fitted with a two-compartment model. Both elimination clearance (223%-243% of controls, who had a body mass index <25 kg/m(2); P < 0.01) and peripheral compartment volume (156%-180% of controls; P < 0.01) were significantly increased in MO subjects, resulting in an equal or decreased propofol level in plasma (total body weight-based dosing). Furthermore, propofol PD (measured by the bispectral index) was adequately described by a PK/PD model that linked an effect compartment to the two-compartment PK model through a sigmoidal Emax model. All PD parameters except EC50 values (the half maximal effect concentration) were similar (P > 0.05) between MO subjects and controls. Morbid obesity led to a significant decrease (37.9%-38.6%; P < 0.01) in EC50 values, which suggests increased brain sensitivity to propofol in the MO population. Moreover, dose reduction (i.e., dosing based on LBW) generated identical anesthetic effects in MO subjects compared with controls. In conclusion, morbid obesity significantly altered both PK and PD of propofol. LBW was a better weight-based dosing scalar for anesthesia induction with propofol in MO subjects. PMID:27481855

  7. 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

  8. The Short-Term Effect of Ambient Temperature on Mortality in Wuhan, China: A Time-Series Study Using a Distributed Lag Non-Linear Model

    PubMed Central

    Zhang, Yunquan; Li, Cunlu; Feng, Renjie; Zhu, Yaohui; Wu, Kai; Tan, Xiaodong; Ma, Lu

    2016-01-01

    Less evidence concerning the association between ambient temperature and mortality is available in developing countries/regions, especially inland areas of China, and few previous studies have compared the predictive ability of different temperature indictors (minimum, mean, and maximum temperature) on mortality. We assessed the effects of temperature on daily mortality from 2003 to 2010 in Jiang’an District of Wuhan, the largest city in central China. Quasi-Poisson generalized linear models combined with both non-threshold and double-threshold distributed lag non-linear models (DLNM) were used to examine the associations between different temperature indictors and cause-specific mortality. We found a U-shaped relationship between temperature and mortality in Wuhan. Double-threshold DLNM with mean temperature performed best in predicting temperature-mortality relationship. Cold effect was delayed, whereas hot effect was acute, both of which lasted for several days. For cold effects over lag 0–21 days, a 1 °C decrease in mean temperature below the cold thresholds was associated with a 2.39% (95% CI: 1.71, 3.08) increase in non-accidental mortality, 3.65% (95% CI: 2.62, 4.69) increase in cardiovascular mortality, 3.87% (95% CI: 1.57, 6.22) increase in respiratory mortality, 3.13% (95% CI: 1.88, 4.38) increase in stroke mortality, and 21.57% (95% CI: 12.59, 31.26) increase in ischemic heart disease (IHD) mortality. For hot effects over lag 0–7 days, a 1 °C increase in mean temperature above the hot thresholds was associated with a 25.18% (95% CI: 18.74, 31.96) increase in non-accidental mortality, 34.10% (95% CI: 25.63, 43.16) increase in cardiovascular mortality, 24.27% (95% CI: 7.55, 43.59) increase in respiratory mortality, 59.1% (95% CI: 41.81, 78.5) increase in stroke mortality, and 17.00% (95% CI: 7.91, 26.87) increase in IHD mortality. This study suggested that both low and high temperature were associated with increased mortality in Wuhan, and that

  9. The Short-Term Effect of Ambient Temperature on Mortality in Wuhan, China: A Time-Series Study Using a Distributed Lag Non-Linear Model.

    PubMed

    Zhang, Yunquan; Li, Cunlu; Feng, Renjie; Zhu, Yaohui; Wu, Kai; Tan, Xiaodong; Ma, Lu

    2016-01-01

    Less evidence concerning the association between ambient temperature and mortality is available in developing countries/regions, especially inland areas of China, and few previous studies have compared the predictive ability of different temperature indictors (minimum, mean, and maximum temperature) on mortality. We assessed the effects of temperature on daily mortality from 2003 to 2010 in Jiang'an District of Wuhan, the largest city in central China. Quasi-Poisson generalized linear models combined with both non-threshold and double-threshold distributed lag non-linear models (DLNM) were used to examine the associations between different temperature indictors and cause-specific mortality. We found a U-shaped relationship between temperature and mortality in Wuhan. Double-threshold DLNM with mean temperature performed best in predicting temperature-mortality relationship. Cold effect was delayed, whereas hot effect was acute, both of which lasted for several days. For cold effects over lag 0-21 days, a 1 °C decrease in mean temperature below the cold thresholds was associated with a 2.39% (95% CI: 1.71, 3.08) increase in non-accidental mortality, 3.65% (95% CI: 2.62, 4.69) increase in cardiovascular mortality, 3.87% (95% CI: 1.57, 6.22) increase in respiratory mortality, 3.13% (95% CI: 1.88, 4.38) increase in stroke mortality, and 21.57% (95% CI: 12.59, 31.26) increase in ischemic heart disease (IHD) mortality. For hot effects over lag 0-7 days, a 1 °C increase in mean temperature above the hot thresholds was associated with a 25.18% (95% CI: 18.74, 31.96) increase in non-accidental mortality, 34.10% (95% CI: 25.63, 43.16) increase in cardiovascular mortality, 24.27% (95% CI: 7.55, 43.59) increase in respiratory mortality, 59.1% (95% CI: 41.81, 78.5) increase in stroke mortality, and 17.00% (95% CI: 7.91, 26.87) increase in IHD mortality. This study suggested that both low and high temperature were associated with increased mortality in Wuhan, and that mean

  10. 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. PMID:15688986

  11. Web-based training related to NRC staff review of dose modeling aspects of license termination and decommissioning plans.

    SciTech Connect

    LePoire, D.; Arnish, J.; Cheng, J. J.; Kamboj, S.; Richmond, P.; Chen, S. Y.; Barr, C.; McKenney, C.; Environmental Science Division; NRC

    2007-01-01

    NRC licensees at decommissioning nuclear facilities submit License Termination Plans (LTP) or Decommissioning Plans (DP) to NRC for review and approval. To facilitate a uniform and consistent review of these plans, the NRC developed training for its staff. A live classroom course was first developed in 2005, which targeted specific aspects of the LTP and DP review process related to dose-based compliance demonstrations or modeling. A web-based training (WBT) course is being developed in 2006 to replace the classroom-based course. The advantage of the WBT is that it will allow for staff training or refreshers at any time, while the advantage of a classroom-based course is that it provides a forum for lively discussion and the sharing of experience of classroom participants. The training course consists of the core and advanced modules tailored to specific NRC job functions. Topics for individual modules include identifying the characteristics of simple and complex sites, identifying when outside expertise or consultation is needed, demonstrating how to conduct acceptance and technical reviews of dose modeling, and providing details regarding the level of justification needed for realistic scenarios for both dose modeling and derivation of DCGLs. Various methods of applying probabilistic uncertainty analysis to demonstrate compliance with dose-based requirements are presented. These approaches include: (1) modeling the pathways of radiological exposure and estimating doses to receptors from a combination of contaminated media and radionuclides, and (2) using probabilistic analysis to determine an appropriate set of input parameters to develop derived concentration guideline limits or DCGLs (DCGLs are media- and nuclide-specific concentration limits that will meet dose-based, license termination rule criteria found in 10 CFR Part 20, Subpart E). Calculation of operational (field) DCGL's from media- and nuclide-specific DCGLs and use of operational DCGLs in conducting

  12. 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

  13. Web-based training related to NRC staff review of dose modeling aspects of license termination and decommissioning plans

    SciTech Connect

    LePoire, D.; Arnish, J.; Cheng, J.J.; Kamboj, S.; Richmond, P.; Chen, S.Y.; Barr, C.; McKenney, C.

    2007-07-01

    NRC licensees at decommissioning nuclear facilities submit License Termination Plans (LTP) or Decommissioning Plans (DP) to NRC for review and approval. To facilitate a uniform and consistent review of these plans, the NRC developed training for its staff. A live classroom course was first developed in 2005, which targeted specific aspects of the LTP and DP review process related to dose-based compliance demonstrations or modeling. A web-based training (WBT) course is being developed in 2006 to replace the classroom-based course. The advantage of the WBT is that it will allow for staff training or refreshers at any time, while the advantage of a classroom-based course is that it provides a forum for lively discussion and the sharing of experience of classroom participants. The training course consists of the core and advanced modules tailored to specific NRC job functions. Topics for individual modules include identifying the characteristics of simple and complex sites, identifying when outside expertise or consultation is needed, demonstrating how to conduct acceptance and technical reviews of dose modeling, and providing details regarding the level of justification needed for realistic scenarios for both dose modeling and derivation of DCGLs. Various methods of applying probabilistic uncertainty analysis to demonstrate compliance with dose-based requirements are presented. These approaches include 1) modeling the pathways of radiological exposure and estimating doses to receptors from a combination of contaminated media and radionuclides, and 2) using probabilistic analysis to determine an appropriate set of input parameters to develop derived concentration guideline limits or DCGLs (DCGLs are media- and nuclide-specific concentration limits that will meet dose-based, license termination rule criteria found in 10 CFR Part 20, Subpart E). Calculation of operational (field) DCGL's from media- and nuclide-specific DCGLs and use of operational DCGLs in conducting

  14. 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

  15. Transport of Low-Level NORM - A Case for Consistency and Practicality

    SciTech Connect

    Rawl, Richard R; Cook, John; Leggett, Richard Wayne

    2007-01-01

    In 1996 the IAEA adopted a system for exemption of low-level radioactive material from transport regulations based on the principle that exemption values should be commensurate with the radiological risk posed by the material as estimated in terms of radiation dose (TS-R-1, 1996, Rev. 2005). For many naturally occurring radionuclides the dose-based, radionuclide-specific exemption concentrations tabulated in TS-R-1 were substantially lower than the previous radionuclide-independent definition of radioactive material (70 Bq g-1) due to the stringent dose criterion applied. It was recognized that this would bring huge quantities of previously unregulated natural materials handled in industry into the scope of the transport regulations. To minimize the economic impact of the dose-based values, a special provision in TS-R-1 provides for a 10-fold increase in exemption values for radionuclides in natural material provided the material is not intended to be processed for recovery of its radionuclides (Paragraph 107(e)). This provision reflects the IAEA concept that a dose criterion may be relaxed within cautious bounds to achieve a balance between practical issues and radiological concerns. For example, in a recent extension of the concepts underlying the IAEA Basic Safety Standards to bulk material (RS-G-1.7, 2004), the dose criterion for exposure to naturally occurring radionuclides is, in effect, 100-fold greater than that for artificial radionuclides on the basis of practical considerations. However, the intended use aspect of Paragraph 107(e) is inconsistent with the basic principle underlying the Transport Regulations in that there is no dose basis for assigning different exemption values to identical materials on the basis of their anticipated use. In fact, under this provision the same material can move in and out of the scope of regulatory control as its anticipated use changes. The technical justification for safety requirements, or exemption from those

  16. 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.

  17. 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.

  18. Glucagon sensitivity and clearance in type 1 diabetes: insights from in vivo and in silico experiments.

    PubMed

    Hinshaw, Ling; Mallad, Ashwini; Dalla Man, Chiara; Basu, Rita; Cobelli, Claudio; Carter, Rickey E; Kudva, Yogish C; Basu, Ananda

    2015-09-01

    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

  19. Efficacy of prothrombin complex concentrates for the emergency reversal of dabigatran-induced anticoagulation.

    PubMed

    Grottke, Oliver; Aisenberg, James; Bernstein, Richard; Goldstein, Patrick; Huisman, Menno V; Jamieson, Dara G; Levy, Jerrold H; Pollack, Charles V; Spyropoulos, Alex C; Steiner, Thorsten; Del Zoppo, Gregory J; Eikelboom, John

    2016-01-01

    Dabigatran is effective in decreasing the risk of ischaemic stroke in patients with atrial fibrillation. However, like all anticoagulants, it is associated with a risk of bleeding. In cases of trauma or emergency surgery, emergency reversal of dabigatran-induced anticoagulation may be required. A specific reversal agent for dabigatran, idarucizumab, has been approved by the US Food and Drug Administration. Alternative reversal agents are available, such as prothrombin complex concentrates (PCCs) and activated PCCs (aPCCs). In this review we evaluate the role of PCCs and aPCCs in the reversal of dabigatran anticoagulation and consider which tests are appropriate for monitoring coagulation in this setting. Pre-clinical studies, small clinical studies and case reports indicate that PCCs and aPCCs may be able to reverse dabigatran-induced anticoagulation in a dose-dependent manner. However, dosing based on coagulation parameters can be difficult because available assays may not provide adequate sensitivity and specificity for measuring anticoagulation induced by dabigatran or the countering effects of PCCs/aPCCs. In addition, PCCs or aPCCs can potentially provoke thromboembolic complications. Despite these limitations and the fact that PCCs and aPCCs are not yet licensed for dabigatran reversal, their use appears to be warranted in patients with life-threatening haemorrhage if idarucizumab is not available. PMID:27125504

  20. A study to investigate dose escalation of doxorubicin in ABVD chemotherapy for Hodgkin lymphoma incorporating biomarkers of response and toxicity

    PubMed Central

    Gibb, A; Greystoke, A; Ranson, M; Linton, K; Neeson, S; Hampson, G; Illidge, T; Smith, E; Dive, C; Pettitt, A; Lister, A; Johnson, P; Radford, J

    2013-01-01

    Background: Myelotoxicity during initial cycles of chemotherapy for Hodgkin lymphoma is associated with better outcome, supporting the concept of individualised dosing based on pharmacodynamic end points to optimise results. This study was performed to identify the maximum tolerated dose (MTD) of doxorubicin within cycles 1–3 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine). Circulating biomarkers of response (nucleosomal DNA, nDNA) and epithelial toxicity (Cytokeratin 18, CK18) were also measured. Methods: Dose escalation of doxorubicin in cycles 1–3 ABVD supported by pegfilgrastim was performed on a six-patient cohort basis (35, 45 and 55 mg m–2) with doxorubicin reduced to 25 mg m–2 or omitted in cycles 4–6 to maintain cumulative exposure of 103–130% standard ABVD. BVD was given at standard doses throughout. Six additional subjects were recruited at the MTD. Results: Twenty-four subjects were recruited. Dose-limiting toxicities (DLTs) of grade 3 neuropathy, pneumonitis, palmar-plantar erythema and neutropenic infection were observed at 55 mg m–2, so 45 mg m–2 was declared the MTD. In patients who subsequently experienced DLT at any time, large increases in CK18 were seen on day 3 of cycle 1 ABVD. Conclusion: Escalated ABVD incorporating doxorubicin at 45 mg m–2 in cycles 1–3 can be delivered safely with pegfilgrastim support. Circulating cell death biomarkers may assist in the development of future individualised dosing strategies. PMID:24136151

  1. 32P measurement and dose conversion factor evaluation of activated human hair by criticality accident.

    PubMed

    Yoon, Seokwon; Ha, Wi-Ho; Park, Seyoung; Shin, Seongwook; Yoo, Jaeryong; Park, Sunhoo; Lee, Seung-Sook

    2014-10-01

    In order to conduct dose assessment of victims in criticality accidents, a method of fast neutron capture-activated (32)P measurement of hair in which samples are treated by a chemical and analytical procedure that takes 9 h and measurement is conducted by liquid scintillation counting is presented. To validate this measurement method, hair samples spiked with a (32)P reference source were measured and the results analysed and the optimal sample mass and detection efficiency were determined. To verify the correlation between (32)P-specific activity and absorbed dose for spectra with two neutron mean energies, samples collected from three normal individuals were irradiated at various neutron energies and irradiation times using the MC50 Cyclotron of the Korea Institute of Radiological and Medical Sciences. The (32)P-specific activity trend of the irradiated hair agreed well with the absorbed doses. Based on the results, dose conversion factors, which were 0.67 ± 0.15 and 0.59 ± 0.06 Gy (Bq g(-1))(-1) at neutron mean energies of 2.33 and 5.36 MeV, respectively, were calculated as a guide for medical treatment of criticality accident victims. PMID:24516187

  2. Optimisation of Radiation Exposure to Gastroenterologists and Patients during Therapeutic ERCP

    PubMed Central

    Alzimami, Khalid; Sulieman, Abdelmoneim; Paroutoglou, Georgios; Potamianos, Spiros; Vlychou, Marianna; Theodorou, Kiki

    2013-01-01

    This study intended to optimize the radiation doses for gastroenterologists and patients during therapeutic endoscopic retrograde cholangiopancreatography (ERCP) and to compare the doses based on available data obtained by other researchers. A total of 153 patients were studied in two Gastroenterology Departments, (group A, 111; group B, 42). Thermoluminescent dosimeters (TLD) were used to measure the staff and patients entrance surface air kerma (ESAK) at different body sites. The mean ESAK and effective doses per procedure were estimated to be 68.75 mGy and 2.74 mSv, respectively. Staff was exposed to a heterogonous doses. The third examiner (trainee) was exposed to a high dose compared with other examiners because no shield was located to protect him from stray radiation. Patients and examiners doses were lower compared to the lowest values found in previous studies taking into consideration the heterogeneity of patients and equipment. Staff doses during ERCP are within the safety limit in the light of the current practice. PMID:23589714

  3. 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. PMID:26562768

  4. 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. PMID:21106242

  5. Radiocesium concentrations in wild mushrooms collected in Kawauchi Village after the accident at the Fukushima Daiichi Nuclear Power Plant.

    PubMed

    Nakashima, Kanami; Orita, Makiko; Fukuda, Naoko; Taira, Yasuyuki; Hayashida, Naomi; Matsuda, Naoki; Takamura, Noboru

    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

  6. 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. PMID:27120656

  7. 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. PMID:23491027

  8. 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

  9. 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.

  10. Obesity and asthma.

    PubMed

    Gibson, Peter G

    2013-12-01

    There is a global epidemic of asthma and obesity that is concentrated in Westernized and developed countries. A causal association in some people with asthma is suggested by observations that obesity precedes the onset of asthma and that bariatric surgery for morbid obesity can resolve asthma. The obese asthma phenotype features poor asthma control, limited response to corticosteroids, and an exaggeration of the physiological effects of obesity on lung function, which includes a reduction in expiratory reserve volume and airway closure occurring during tidal breathing. Obesity has important implications for asthma treatment. Increasing corticosteroid doses based on poor asthma control, as currently recommended in guidelines, may lead to overtreatment with corticosteroids in obese asthma. Enhanced bronchodilation, particularly of the small airways, may reduce the component of airway closure due to increased bronchomotor tone and suggests that greater emphasis should be placed on long-acting bronchodilators in obese asthma. The societal implications of this are important: with increasing obesity there will be increasing asthma from obesity, and the need to identify successful individual and societal weight-control strategies becomes a key goal. PMID:24313764

  11. Stereotactic ablative body radiotherapy (SABR): an alternative to surgery in stage I-II non-small-cell cancer of the lung?

    PubMed

    Mirimanoff, René-Olivier

    2015-12-01

    For decades, surgery was considered to be the only standard therapy for early-stage non-small cell lung cancer (NSCLC). However stereotactic ablative body radiotherapy (SABR) has been used in a growing number of patients and institutions since the early 2000's. Initially this technique was intended mainly for patients who were deemed to be medically inoperable due to co-morbidities or who refused surgery, but more recently it has been applied to operable patients as well. Strict criteria for treatment planning, the use of high-technology equipment and the appropriate selection of dose based on tumor size and location are of paramount importance for a proper application of SABR. Under these conditions, SABR offers high control rates with a moderate risk of severe toxicity, quite comparable to those of modern surgery. This article reviews the basic principles of SABR, its practical aspects, the definition of biologically equivalent doses, the results in terms of tumor control, survival and toxicity and an attempt will be made to compare the results of SABR with those of surgery. PMID:26730754

  12. 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.

  13. 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.

  14. 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. PMID:26886806

  15. Paraplegia following intrathecal methotrexate: report of a case and review of the literature.

    PubMed

    Gagliano, R G; Costanzi, J J

    1976-04-01

    A patient who developed paraplegia following the intrathecal instillation of methotrexate is discribed. The ten previously reported cases of this unusual complication are reviewed. The following factors appear to predispose to the development of this complication: abnormal cerebrospinal dynamics related to the presence of central nervous system leukemia, and epidural cerebrospinal leakage; elevated cerebrospinal fluid methothexate concentration related to abnormal cerebrospinal fluid dynamics and to inappropriately high methotrexate doses based on body surface area calculations in older children and adults; the presence of neurotoxic preservatives in commercially available methotrexate preparations and diluents; and the use of methotrexate diluents of unphysiologic pH, ionic content and osmolarity. The role of methotrexate contaminants, local folate deficiency, and cranial irradiation in the pathogenesis of intrathecal methotrexate toxicity is unclear. The incidence of neurotoxicity may be reduced by employing lower doses of methotrexate in the presence of central nervous system leukemia, in older children and adults, and in the presence of epidural leakage. Only preservative-free methotrexate in Elliott's B Solution at a concentration of not more than 1 mg/ml should be used for intrathecal administration. Periodic monitoring of cerebruspinal fluid methotrexate levels may be predictive of the development of serious neurotoxicity. PMID:946593

  16. Estimating Annual Individual Doses for Evacuees Returning Home to Areas Affected by the Fukushima Nuclear Accident.

    PubMed

    Yajima, Kazuaki; Kurihara, Osamu; Ohmachi, Yasushi; Takada, Masashi; Omori, Yasutaka; Akahane, Keiichi; Kim, Eunjoo; Torikoshi, Masami; Yonehara, Hidenori; Yoshida, Satoshi; Sakai, Kazuo; Akashi, Makoto

    2015-08-01

    To contribute to the reconstruction and revitalization of Fukushima Prefecture following the 2011 nuclear power disaster, annual individual doses were estimated for evacuees who will return home to Tamura City, Kawauchi Village, and Iitate Village in Fukushima. Ambient external dose rates and individual doses obtained with personal dosimeters were measured at many residential and occupational sites throughout the study areas to obtain fundamental data needed for the estimation. The measurement results indicated that the ratio of individual dose based on a personal dosimeter to the ambient external dose measurement was 0.7 with 10% uncertainty. Multiplying the ambient external dose by 0.7 may be an appropriate measure of the effective dose to an individual in the investigated area. Annual individual doses were estimated for representative lifestyles and occupations based on the ambient external dose rates at the measurement sites, taking into account the relationship between the ambient external dose and individual dose. The results were as follows: 0.6-2.3 mSv y in Tamura, 1.1-5.5 mSv y in Kawauchi, and 3.8-17 mSv y in Iitate. For all areas investigated, the estimated dose to outdoor workers was higher than that to indoor workers. Identifying ways to reduce the amount of time that an outdoor worker spends outdoors would provide an effective measure to reduce dose. PMID:26107433

  17. 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.

  18. Appropriate Use of Antithrombotic Medication in Canadian Patients With Nonvalvular Atrial Fibrillation.

    PubMed

    Bell, Alan D; Gross, Peter; Heffernan, Michael; Deschaintre, Yan; Roux, Jean-Francois; Purdham, Daniel M; Shuaib, Ashfaq

    2016-04-01

    This national chart audit of 7,019 patients with nonvalvular atrial fibrillation (AF) from 735 primary care physician practices sought to examine the management of Canadian patients with AF through an evidence-based, guideline-recommended approach. The appropriate use of oral anticoagulants (OACs) in this patient population and the potential factors guiding OAC choice were examined. Suboptimal dosing was seen. In patients on warfarin, 30.9% had not achieved a time in therapeutic range (TTR) in excess of 65% and, despite current Canadian guideline recommendations, were continued on warfarin rather than one of the novel OACs. In patients who received no antithrombotic therapy, 65.5% met criteria for treatment with an OAC. In addition, 62.8% of patients who were treated with acetylsalicylic acid monotherapy met guideline criteria for the use of an OAC. In those patients treated with an OAC, 24.8% were not on the recommended dose based on the product monograph or, if on warfarin, had a TTR <65%. Of the patients on novel OACs (NOACs), 7.4% of patients were underdosed, whereas overdosing was seen in 4.3%. Factors that may have contributed to dosing outside recommendations included underestimation of stroke risk, overestimation of bleed risk, compliance concerns, and lack of provincial reimbursement. In conclusion, significant correctable gaps remain in optimal treatment for stroke prevention in AF. PMID:26879070

  19. Restructuring nuclear regulations.

    PubMed Central

    Mossman, Kenneth L

    2003-01-01

    Nuclear regulations are a subset of social regulations (laws to control activities that may negatively impact the environment, health, and safety) that concern control of ionizing radiation from radiation-producing equipment and from radioactive materials. The impressive safety record among nuclear technologies is due, in no small part, to the work of radiation safety professionals and to a protection system that has kept pace with the rapid technologic advancements in electric power generation, engineering, and medicine. The price of success, however, has led to a regulatory organization and philosophy characterized by complexity, confusion, public fear, and increasing economic costs. Over the past 20 years, regulatory costs in the nuclear sector have increased more than 250% in constant 1995 U.S. dollars. Costs of regulatory compliance can be reduced sharply, particularly when health and environmental benefits of risk reduction are questionable. Three key regulatory areas should be closely examined and modified to improve regulatory effectiveness and efficiency: a) radiation protection should be changed from a risk-based to dose-based system; b) the U.S. government should adopt the modern metric system (International System of Units), and radiation quantities and units should be simplified to facilitate international communication and public understanding; and c) a single, independent office is needed to coordinate nuclear regulations established by U.S. federal agencies and departments. PMID:12515683

  20. Assessing the non-cancer risk for RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) using physiologically based pharmacokinetic (PBPK) modeling.

    PubMed

    Sweeney, Lisa M; Gut, Chester P; Gargas, Michael L; Reddy, Gunda; Williams, Larry R; Johnson, Mark S

    2012-02-01

    RDX (hexahydro-1,3,5-trinitro-1,3,5-triazine) is an explosive used in military applications. It has been detected in ground water surrounding US military installations and at manufacturing facilities. RDX has been shown to produce hepatotoxicity, testicular, and neurological effects in animals, the latter also in humans. The current chronic oral reference dose (RfD) of 0.003 mg/kg/day was derived based on prostate effects in rats. Here, we provide a reevaluation of the risk associated with RDX exposure by examining old and new data and using physiologically based pharmacokinetic (PBPK) modeling approaches. Candidate non-cancer endpoints in rodents were evaluated and the most plausible mode(s) of action were determined. A PBPK model was used to derive appropriate internal doses based on the mode of action, and then a benchmark dose (BMD) and the lower confidence limit on the BMD (BMDL) were determined using these internal doses in animals. Uncertainty factors (UF) were applied to the animal BMDL or no-observed effect level and a human PBPK model was used to determine a human equivalent dose resulting in the candidate RfDs (cRfDs). A proposed chronic RfD of 0.07 mg/kg/day, based on multiple effects observed in rats, was selected from among the cRfDs. PMID:22197625

  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. MARSSIM vs. DOE Order 5400.5: the Final Status Survey plan at the Rocky Flats Environmental Technology Site.

    PubMed

    Roberts, Sarah J; Stevens, Jeff

    2003-06-01

    A challenge unique to the decommissioning of Department of Energy (DOE) facilities involves the compromise between the existing and newly recommended standards for the unrestricted release of property and materials. The Rocky Flats Environmental Technology Site (RFETS) is currently decommissioning numerous plutonium contaminated facilities. The default DOE standard for unrestricted release, Order 5400.5, defines surface activity guidelines as averaged over a 1-square-meter area with a maximum value defined for any given 100-square-centimeter area. While the Order was initially developed to release property and materials from an operating site, it is restrictive in its use when performing Final Status Survey and, to date, no new complex wide standard has been developed. However, the RFETS stakeholders selected the MARSSIM, which provides a progressive method to demonstrate compliance with the defined "dose-based" limits for a specific site, as the governing document in developing a final survey method. The end result is a hybrid final status survey plan that incorporates the requirements of both documents. This plan represents several years of development and negotiation between the contractor, the DOE, the Colorado Department of Public Health and Environment, the Rocky Flats stakeholders, and other interested parties. PMID:12792399

  3. Radiation inactivation target size of rat adipocyte glucose transporters in the plasma membrane and intracellular pools

    SciTech Connect

    Jacobs, D.B.; Berenski, C.J.; Spangler, R.A.; Jung, C.Y.

    1987-06-15

    The in situ assembly states of the glucose transport carrier protein in the plasma membrane and in the intracellular (microsomal) storage pool of rat adipocytes were assessed by studying radiation-induced inactivation of the D-glucose-sensitive cytochalasin B binding activities. High energy radiation inactivated the glucose-sensitive cytochalasin B binding of each of these membrane preparations by reducing the total number of the binding sites without affecting the dissociation constant. The reduction in total number of binding sites was analyzed as a function of radiation dose based on target theory, from which a radiation-sensitive mass (target size) was calculated. When the plasma membranes of insulin-treated adipocytes were used, a target size of approximately 58,000 daltons was obtained. For adipocyte microsomal membranes, we obtained target sizes of approximately 112,000 and 109,000 daltons prior to and after insulin treatment, respectively. In the case of microsomal membranes, however, inactivation data showed anomalously low radiation sensitivities at low radiation doses, which may be interpreted as indicating the presence of a radiation-sensitive inhibitor. These results suggest that the adipocyte glucose transporter occurs as a monomer in the plasma membrane while existing in the intracellular reserve pool either as a homodimer or as a stoichiometric complex with a protein of an approximately equal size.

  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. 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.

  6. Production, PET performance and dosimetric considerations of 134Ce/134La, an Auger electron and positron-emitting generator for radionuclide therapy

    NASA Astrophysics Data System (ADS)

    Lubberink, Mark; Lundqvist, Hans; Tolmachev, Vladimir

    2002-02-01

    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.

  7. 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.

  8. 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.

  9. 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. PMID:26205160

  10. A Bayesian population PBPK model for multiroute chloroform exposure

    PubMed Central

    Yang, Yuching; Xu, Xu; Georgopoulos, Panos G.

    2011-01-01

    A Bayesian hierarchical model was developed to estimate the parameters in a physiologically based pharmacokinetic (PBPK) model for chloroform using prior information and biomarker data from different exposure pathways. In particular, the model provides a quantitative description of the changes in physiological parameters associated with hot-water bath and showering scenarios. Through Bayesian inference, uncertainties in the PBPK parameters were reduced from the prior distributions. Prediction of biomarker data with the calibrated PBPK model was improved by the calibration. The posterior results indicate that blood flow rates varied under two different exposure scenarios, with a two-fold increase of the skin's blood flow rate predicted in the hot-bath scenario. This result highlights the importance of considering scenario-specific parameters in PBPK modeling. To demonstrate the application of a probability approach in toxicological assessment, results from the posterior distributions from this calibrated model were used to predict target tissue dose based on the rate of chloroform metabolized in liver. This study demonstrates the use of the Bayesian approach to optimize PBPK model parameters for typical household exposure scenarios. PMID:19471319

  11. The Average Body Surface Area of Adult Cancer Patients in the UK: A Multicentre Retrospective Study

    PubMed Central

    Sacco, Joseph J.; Botten, Joanne; Macbeth, Fergus; Bagust, Adrian; Clark, Peter

    2010-01-01

    The majority of chemotherapy drugs are dosed based on body surface area (BSA). No standard BSA values for patients being treated in the United Kingdom are available on which to base dose and cost calculations. We therefore retrospectively assessed the BSA of patients receiving chemotherapy treatment at three oncology centres in the UK between 1st January 2005 and 31st December 2005. A total of 3613 patients receiving chemotherapy for head and neck, ovarian, lung, upper GI/pancreas, breast or colorectal cancers were included. The overall mean BSA was 1.79 m2 (95% CI 1.78–1.80) with a mean BSA for men of 1.91 m2 (1.90–1.92) and 1.71 m2 (1.70–1.72) for women. Results were consistent across the three centres. No significant differences were noted between treatment in the adjuvant or palliative setting in patients with breast or colorectal cancer. However, statistically significant, albeit small, differences were detected between some tumour groups. In view of the consistency of results between three geographically distinct UK cancer centres, we believe the results of this study may be generalised and used in future costings and budgeting for new chemotherapy agents in the UK. PMID:20126669

  12. 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

  13. 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). PMID:27187161

  14. 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

  15. 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.

  16. Acrocomia aculeata prevents toxicogenetic damage caused by the antitumor agent cyclophosphamide.

    PubMed

    Magosso, M F; Carvalho, P C; Shneider, B U C; Pessatto, L R; Pesarini, J R; Silva, P V B; Correa, W A; Kassuya, C A L; Muzzi, R M; Oliveira, R J

    2016-01-01

    Acrocomia aculeata is a plant rich in antioxidant compounds. Studies suggest that this plant has anti-inflammatory, antidiabetic, and diuretic potential. We assessed the antigenotoxic, antimutagenic, immunomodulation, and apoptotic potentials of A. aculeata alone and in combination with an antitumor agent, cyclophosphamide. Swiss male mice (N = 140) were used. The animals were divided into 14 experimental groups as follows: a negative group, a positive group (100 mg/kg cyclophosphamide), groups that only received the oil extracted from the almond (AO) and from the pulp (PO) of A. aculeata at doses of 3, 15, and 30 mg/kg, and the associated treatment groups (oils combined with cyclophosphamide) involving pretreatment, simultaneous, and post-treatment protocols. Data suggest that both oils were chemopreventive at all doses, based on the tested protocols. The highest damage reduction percentages, observed for AO and PO were 88.19 and 90.03%, respectively, for the comet assay and 69.73 and 70.93%, respectively, for the micronucleus assay. Both AO and PO demonstrated immunomodulatory activity. The oils reduced the capacity of cyclophosphamide to trigger apoptosis in the liver, spleen, and kidney cells. These results suggest that A. aculeate AO and PO can be classified as a functional food and also enrich other functional foods and nutraceuticals with chemopreventive features. However, they are not appropriate sources for chemotherapeutic adjuvants, in particular for those used in combination with cyclophosphamide. PMID:27173316

  17. 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.

  18. Evaluation of phosphate fertilizers for the stabilization of cadmium in highly contaminated soils.

    PubMed

    Thawornchaisit, Usarat; Polprasert, Chongrak

    2009-06-15

    The efficiency of three phosphate fertilizers including triple superphosphate (TSP), diammonium phosphate (DAP), and phosphate rock (PR) as stabilizing agents of cadmium-contaminated soils has been assessed in this study. Two types of assessment criteria, (a) the reduction of leachable cadmium concentration; and (b) the changes in Cd association with specific operational soil fraction based on the sequential extraction data, are used in the evaluation of stabilization performance of each fertilizer. Results of the study showed that after the 60-day stabilization, the leachable concentrations of Cd in PR-, DAP- and TSP- treated soils reduced from 306 mg/kg (the control) to 140, 34, and 12 mg/kg with the stabilization efficiency as TSP>DAP>PR. Results from the assessment of Cd speciation via sequential extraction procedure revealed that the soluble-exchangeable fraction and the surface adsorption fraction of Cd in the soils treated with PO(4) fertilizers, especially with TSP, have been reduced considerably. In addition, it is found that the reduction was correspondingly related with the increase of more stable forms of cadmium: the metal bound to manganese oxides and the metal bound to crystalline iron oxides. Treatment efficiency increased as the phosphate dose (based on the molar ratio of PO(4)/Cd) increased. In addition, it was observed that stabilization was most effective when using the molar ratio of PO(4)/Cd at 2:1 and at least 21-day and 28-day stabilization time for TSP and DAP, respectively. PMID:19118949

  19. Imaging of dose distributions using polymer gels based on radiation induced changes in stiffness

    NASA Astrophysics Data System (ADS)

    Crescenti, Remo A.; Bamber, Jeffrey C.; Oberai, Assad A.; Barbone, Paul E.; Richter, Joseph P.; Rivas, Carlos; Bush, Nigel L.; Webb, Steve

    2009-05-01

    Previously, dose determination based on radiation induced stiffness difference measurements has received no or very little attention. Here, a preliminary evaluation of a combined system for dosimetry based on radiation sensitive gels, ultrasonic elastography and a plane strain inverse algorithm is presented. A block of gel was irradiated along one of its axes producing stiff rod-like regions. The dose distribution found with quantitative ultrasound elastography was compared with a reference dose distribution measured with magnetic resonance imaging. In these early results, the high dose areas were clearly detected, while noise in the ultrasound measurement and strong regularisation in the inverse computing introduced shape distortions, noise in the dose estimates and problems estimating the correct dose contrast. Improvements in the experimental setup and inverse computing are possible, for example by acquisition of transversal ultrasound data, which could essentially reduce the noise and restrict direct influence of the experimental boundary condition on the dose estimation by providing additional information for inverse computing. Based on the preliminary results and the potential for improvement it is concluded that further investigations should follow to establish the potential of the rapidly developing field of elastography for measuring radiation dose based on radiation induced changes in stiffness.

  20. 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. PMID:27356056

  1. HEMODOSE: A Biodosimetry Tool Based on Multi-type Blood Cell Counts.

    PubMed

    Hu, Shaowen; Blakely, William F; Cucinotta, Francis A

    2015-07-01

    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

  2. An Approach to Mitigate Particle Formation on the Dilution of a Monoclonal Antibody Drug Product in an IV Administration Fluid.

    PubMed

    Zheng, Songyan; Adams, Monica; Mantri, Rao V

    2016-03-01

    To support dose reduction, low dose of a monoclonal antibody (mAb) was required to be administered via IV infusion at a concentration of 0.1 mg/mL. To achieve the target protein concentration, the infusion solution was prepared by diluting the drug product containing 10-mg/mL mAb with normal saline, a 0.9% sodium chloride injection solution. However, particles were observed in the diluted solution. Particle formation must be avoided to administer the low dose using the existing drug product. To mitigate the particle formation, an unconventional compounding approach was used. With this approach, a stabilizing vehicle containing polysorbate-80 was added to saline before drug-product dilution to maintain suitable surfactant level to prevent precipitation of the mAb. In this way, use of the stabilizing vehicle to support low doses ensured suitable quality across a wider range of mAb concentrations, thereby allowing additional flexibility to the clinical trial. Such an approach may be useful for broader application in early-stage clinical trials where there is an uncertainty regarding doses or the need to revise to lower doses based on clinical observations or other drivers. PMID:26886343

  3. 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.

  4. Application of optical methods for dose evaluation in normoxic polyacrylamide gels irradiated at two different geometries

    NASA Astrophysics Data System (ADS)

    Adliene, D.; Jakstas, K.; Vaiciunaite, N.

    2014-03-01

    Normoxic gels are frequently used in clinical praxis for dose assessment or 3-D dose imaging in radiotherapy due to their relative simple manufacturing process under normal atmospheric conditions, spatial stability and well expressed modification feature of physical properties which is related to radiation induced polymerization of gels. In this work we have investigated radiation induced modification of the optical properties of home prepared normoxic polyacrylamide gels (nPAG) in relation to polymerization processes that occur in irradiated gels. Two irradiation geometries were used for irradiation of gel samples: broad beam irradiation geometry of teletherapy unit ROKUS-M with a 60Co source and point source irradiation geometry using 192Ir source of high dose rate afterloading brachytherapy unit MicroSelectron v2 which was inserted into gel via 6 Fr (2 mm thick) catheter. Verification of optical methods: UV-VIS spectrometry, spectrophotometry, Raman spectroscopy for dose assessment in irradiated gels has been performed. Aspects of their application for dose evaluation in gels irradiated using different geometries are discussed. Simple pixel-dose based photometry method also has been proposed and evaluated as a potential method for dose evaluation in catheter based interstitial high dose rate brachytherapy.

  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. TOXICITY OF SEVERAL FUNGICIDES FOR ORANGE WHEAT BLOSSOM MIDGE, SITODIPLOSIS MOSELLANA (GÉHIN) (DIPTERA: CECIDOMYIIDAE).

    PubMed

    Chavalle, S; Jansen, J-P; San Martin y Gomez, G; De Proft, M

    2015-01-01

    The orange wheat blossom midge, Sitadiplosis mosellano (Géhin) (Diptera: Cecidomyiidae), can cause severe losses in wheat grain yield and quality. This pest is known to be susceptible to many insecticides, but various field observations have suggested that some fungicides could also significantly affect S. mosellana. In order to confirm these field observations, the effect on adult midges of several fungicides commonly applied to wheat crops was investigated in the laboratory and in small plots in the field. In each experiment, the fungicides were compared with a positive (insecticide) and a negative control (water). Four fungicides were assessed in the laboratory, each with five doses based on basis of a tenfold dilution starting at the field-recommended dose. The mortality rate was evaluated after 24 hours and the lethal dose 50% (LD50) was determined for each product. In the field, six fungicides were tested at the recommended dose. The effect of each product was compared on the basis of the number of S. mosellana adults caught alive with an insect vacuum sampler (Vortis®) on the morning after the treatments. Both experiments showed a significant effect of several fungicides tested on S. mosellana adults. Chlorothalonil was not toxic for S. mosellana, but tebuconazole, fluxapyroxad and azoxystrobin all induced significant mortality rates. PMID:27145574

  7. 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.

  8. 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

    2014-01-01

    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. PMID:25207566

  9. 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. PMID:27027971

  10. 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.

  11. Mathematical modeling of herpes simplex virus-2 suppression with pritelivir predicts trial outcomes.

    PubMed

    Schiffer, Joshua T; Swan, David A; Magaret, Amalia; Corey, Lawrence; Wald, Anna; Ossig, Joachim; Ruebsamen-Schaeff, Helga; Stoelben, Susanne; Timmler, Burkhard; Zimmermann, Holger; Melhem, Murad R; Van Wart, Scott A; Rubino, Christopher M; Birkmann, Alexander

    2016-02-01

    Pharmacokinetic and pharmacodynamic models estimate the potency of antiviral agents but do not capture viral and immunologic factors that drive the natural dynamics of infection. We designed a mathematical model that synthesizes pharmacokinetics, pharmacodynamics, and viral pathogenesis concepts to simulate the activity of pritelivir, a DNA helicase-primase inhibitor that targets herpes simplex virus. Our simulations recapitulate detailed viral kinetic shedding features in five dosage arms of a phase 2 clinical trial. We identify that in vitro estimates of median effective concentration (EC50) are lower than in vivo values for the drug. Nevertheless, pritelivir potently decreases shedding at appropriate doses based on its mode of action and long half-life. Although pritelivir directly inhibits replication in epithelial cells, our model indicates that pritelivir also indirectly limits downstream viral spread from neurons to genital keratinocytes, within genital ulcers, and from ulcer to new mucosal sites of infection. We validate our model based on its ability to predict outcomes in a subsequent trial with a higher dose. The model can therefore be used to optimize dose selection in clinical practice. PMID:26843190

  12. The role of myofibroblasts in the development of osteoradionecrosis in a newly established rabbit model.

    PubMed

    Zong, Chunlin; Cai, Bolei; Wen, Xinxin; Alam, Syed; Chen, Yuanli; Guo, Yuxuan; Liu, Yanpu; Tian, Lei

    2016-06-01

    This study aimed to establish a proper animal model of osteoradionecrosis of jaws (ORNJ) and to observe preliminarily the characteristics of myofibroblasts, the key effector cell of fibrosis, in ORNJ. Rabbit mandibles were irradiated at three different doses based on a human equivalent radiation schedule, and examined by gross manifestation, single-photon emission computed tomography (SPECT), micro-computed tomography, sequential fluorochrome labeling, and histology. Immunohistochemistry staining of α-SMA was applied to detect the existence of myofibroblasts. The exposed necrotic bone, which is the main indication of ORNJ, started to be observed at all rabbits at 9 Gy. With the radiation dose increasing, the microarchitecture of the irradiated mandibles was more destroyed, the metabolism and mineralization of the irradiated mandibles diminished, the osteocytes number decreased, and more mature bones were substituted by fibrosis in the irradiated mandibles. In addition, as the radiation dose increased, the myofibroblast number increased and collected around the separated sequestrum, which indicated that myofibroblasts might relate to the pathogenesis of ORNJ. In summary, a clinically translational ORNJ model was successfully established in our study, and the role of myofibroblasts in the pathogenesis of ORNJ is described for the first time. PMID:27150352

  13. Intensity-modulated x-ray (IMXT) versus proton (IMPT) therapy for theragnostic hypoxia-based dose painting

    NASA Astrophysics Data System (ADS)

    Flynn, Ryan T.; Bowen, Stephen R.; Bentzen, Søren M.; Rockwell Mackie, T.; Jeraj, Robert

    2008-08-01

    In this work the abilities of intensity-modulated x-ray therapy (IMXT) and intensity-modulated proton therapy (IMPT) to deliver boosts based on theragnostic imaging were assessed. Theragnostic imaging is the use of functional or molecular imaging data for prescribing radiation dose distributions. Distal gradient tracking, an IMPT method designed for the delivery of non-uniform dose distributions, was assessed. Dose prescriptions for a hypoxic region in a head and neck squamous cell carcinoma patient were designed to either uniformly boost the region or redistribute the dose based on positron emission tomography (PET) images of the 61Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone) (61Cu-ATSM) hypoxia surrogate. Treatment plans for the prescriptions were created for four different delivery methods: IMXT delivered with step-and-shoot and with helical tomotherapy, and IMPT delivered with spot scanning and distal gradient tracking. IMXT and IMPT delivered comparable dose distributions within the boost region for both uniform and redistributed theragnostic boosts. Normal tissue integral dose was lower by a factor of up to 3 for IMPT relative to the IMXT. For all delivery methods, the mean dose to the nearby organs at risk changed by less than 2 Gy for redistributed versus uniform boosts. The distal gradient tracking method resulted in comparable plans to the spot scanning method while reducing the number of proton beam spots by a factor of over 3.

  14. 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. PMID:12430961

  15. Intra-voxel heterogeneity influences the dose prescription for dose-painting with radiotherapy: a modelling study

    NASA Astrophysics Data System (ADS)

    F Petit, Steven; Dekker, André L. A. J.; Seigneuric, Renaud; Murrer, Lars; van Riel, Natal A. W.; Nordsmark, Marianne; Overgaard, Jens; Lambin, Philippe; Wouters, Bradly G.

    2009-04-01

    The purpose of this study was to increase the potential of dose redistribution by incorporating estimates of oxygen heterogeneity within imaging voxels for optimal dose determination. Cellular oxygen tension (pO2) distributions were estimated for imaging-size-based voxels by solving oxygen diffusion-consumption equations around capillaries placed at random locations. The linear-quadratic model was used to determine cell survival in the voxels as a function of pO2 and dose. The dose distribution across the tumour was optimized to yield minimal survival after 30 × 2 Gy fractions by redistributing the dose based on differences in oxygen levels. Eppendorf data of a series of 69 tumours were used as a surrogate of what might be expected from oxygen imaging datasets. Dose optimizations were performed both taking into account cellular heterogeneity in oxygenation within voxels and assuming a homogeneous cellular distribution of oxygen. Our simulations show that dose redistribution based on derived cellular oxygen distributions within voxels result in dose distributions that require less total dose to obtain the same degree of cell kill as dose distributions that were optimized with a model that considered voxels as homogeneous with respect to oxygen. Moderately hypoxic tumours are expected to gain most from dose redistribution. Incorporating cellular-based distributions of radiosensitivity into dose-planning algorithms theoretically improves the potential gains from dose redistribution algorithms.

  16. A radiation dose study based on analysis of primary color chrominance

    NASA Astrophysics Data System (ADS)

    Huang, Jianyue; Li, Jianhong; Li, Jianwei; Jin, Jian; Li, Yu; Bao, Xiaolu; Chen, Zhilong

    2015-10-01

    Purpose: The purpose of this study was to assess the possibility of measuring radiation dose based on primary color chrominance in chemical solutions. Methods: We used an aqueous solution with different concentrations of Alphaurine A and Tracid Brilliant Red B. This was irradiated by 1.5-13.5 kGy 60Co γ radiation. Data were collected by an instrument that can detect information on the three primary colors. Data were analyzed and manipulated for each experiment. Results and conclusions: The result shows that three primary colors chrominance in the aqueous solutions change with different doses of 60Co γ-rays and different concentrations of Alphaurine A and Tracid Brilliant Red B. For Alphaurine A, the red chrominance is gradually reduced as a function of radiation dose. The blue chrominance gradually increases concurrently. The red and green chrominance changes obviously and inversely, but the green chrominance changes little. In Tracid Brilliant Red B solution, the red chrominance gradually decreases as the radiation dose increases. The green chrominance gradually increases concurrently. The red and green chrominance changes are obvious and inverted. The blue chrominance changes little. Our experiments demonstrate that radiation dose can be studied based on three primary colors chrominance. This may be a new tool to measure the radiation dose.

  17. 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. PMID:21500074

  18. Estimation of radiation doses for atomic-bomb survivors in the Hiroshima University Registry

    SciTech Connect

    Hoshi, M.; Matsuura, M.; Hayakawa, N.; Kamada, N.; Ito, C.

    1996-05-01

    The present study presents the Hiroshima University Registry of atomic bomb survivors, of which the total number is about 270,000, and application of absorbed doses. From this registry, we picked up 49,102 survivors and applied organ doses based on the dosimetry system 1986 (DS86), which is named the Atomic Bomb Survivor 1993 Dose (ABS93D). The applied dose data are based on the tables listed in the DS86 final report such as the free-in-air kermas, the house shielding factors, and organ dose factors for the active bone marrow and the breast. Calculations for the 13 other organs provided in DS86 are possible. To obtained the organ doses for each survivor, it is necessary to obtain information concerning (1) place exposed, (2) whether they were shielded or not, and (3) age. ABS93D body transmission factors for active bone marrow for neutrons and gamma rays agreed with DS 86 to within a few percent. Of the survivors studied, 35, 123 of them were used for the relative risk estimation of leukemia mortality, adopting the same method as the Radiation Effects Research Foundation (RERF) for comparison. For the observation period from 1968 to 1989, the analyzed relative risks for leukemia mortality at 1 Gy by shielded kerm and by active bone marrow dose are 2.01 and 2.37, respectively, which are consistent with the RERF results. 11 refs., 1 fig., 3 tabs.

  19. Unsaturated flow modeling for performance assessment of a radioactive waste disposal facility in Andrews County, Texas

    NASA Astrophysics Data System (ADS)

    Martinez Baquero, G. F.; Singh, A.; Holt, R. M.; grisak, G. E.

    2011-12-01

    Quantitifying infiltration rates is a key component of the performance assessment for radioactive waste disposal facilities. In arid regions with scarce infiltration data, this is a challenging problem because of the computational limitations of available numerical implementations to solve water flow and transport equations. This work summarizes methodology and analysis performed to overcome some of these challenges and to generate infiltration scenarios for a low level waste disposal site in Andrews County, Texas. The work presented here includes preparation of a two dimensional finite element model in HYDRUS that includes the cover system and adjacent geologic units, calibration of hydraulic properties and root water uptake parameters based on soft information, preparation of atmospheric forcings based on current and hypothesized future climatic conditions, evaluation of impacts related to temporal and spatial discretization of forcings and model domain, and definition of scenarios for cover degradation and wetter climate conditions. Results of this work include a sensitivity analysis of infiltration rates to changes in boundary conditions under quasi-steady state, evaluation of the impact of temporal discretization of the atmospheric forcings in terms of water balance error and computational efficiency, and the estimation of infiltration rates under different scenarios. Infiltration rates from this work are being incorporated into a transport model to estimate potential radiological doses based on performance assessment modeling analyses. Findings from this work seek to contribute towards robust approaches to estimate infiltration in arid regions.

  20. 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. PMID:11144238

  1. 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.

  2. Annexin V FITC conjugated as a radiation toxicity indicator in lymphocytes following radiation overexposure in radiotherapy programs

    PubMed Central

    Tavakoli, Mohammad Bagher; Kheirollahi, Majid; Kiani, Ali; Kazemi, Mohammad; Javanmard, Shaghayegh Haghjooy; Mohebat, Leili

    2015-01-01

    Background: Following human radiation exposure in hospital or accidents, dose assessments are of prime importance in radiation accidents. These issues are of continuing importance with respect to socioeconomic policy relating to the industrial and medical uses of ionizing radiation, and also for risk assessment among people who are occupationally exposed to low and/or high linear energy transfer (LET) radiation, such as astronauts, pilots, stewardesses, nuclear power plant workers, and victims of radiation accidents. Materials and Methods: In this study, an assay for assessing radiation dose based on the induction of apoptosis in human T-lymphocytes was done to examine T-lymphocyte cells isolated from the fresh blood of 16volunteers, cultured and exposed to gamma rays. Radiation-induced apoptosis (RIA) was assessed by flow cytometric identification of cells displaying apoptosis-associated DNA condensation. Results: Dose-response experiments showed that at 2Gy dose level of radiotherapy programs, the RIA frequency was significantly above control. Apoptotic levels significantly depend on the dose of radiation rather than the donor. Conclusion: The results demonstrate the potential use of this assay as a biological indicator of radiation toxicity, optimizing patient dose in radiotherapy and biological dosimetry process. PMID:26261821

  3. Effects of meal type on the oral bioavailability of the ALK inhibitor ceritinib in healthy adult subjects.

    PubMed

    Lau, Yvonne Y; Gu, Wen; Lin, Tiffany; Song, Dongweon; Yu, Richard; Scott, Jeffrey W

    2016-05-01

    Ceritinib is a potent inhibitor of anaplastic lymphoma kinase (ALK), which has shown acceptable safety and substantial antitumor activity in ALK-positive non-small cell lung cancer (NSCLC) patients. Two food-effect studies were conducted in healthy adults to investigate the influence of food on the oral bioavailability of ceritinib: a study with low- or high-fat meals at 500 mg and a study with a light snack at 750 mg. Compared with the fasted state, AUC0-∞ (90%CI) of ceritinib was increased by 58% (34%, 86%) after the intake of a low-fat meal, by 73% (46%, 105%) after the intake of a high-fat meal, and by 54% (19%, 99%) after the intake of a light snack. Safety assessments also suggested that food may improve gastrointestinal (GI) tolerability after a single ceritinib dose. Based on the pharmacokinetic results, it is essential to avoid any type of meal during dosing of ceritinib because the intake of food may increase the occurrence of exposure-dependent, non-GI toxicities at the labeled dose of 750 mg daily during fasting. A randomized trial is ongoing to determine an alternative way to give ceritinib (450 mg or 600 mg with food) that may enhance GI tolerability in ALK-positive NSCLC patients. PMID:26272586

  4. [Appropriate use of antibiotics--practices we should employ now: appropriate use of antibiotics for pharmacists in general hospitals].

    PubMed

    Yamada, Kazunori

    2010-07-01

    An authorization system regarding infection has been devised for various occupations in the field of infection control. An infection control team (ICT) consists of authorized, specialized staff, and plays an important role in clinical practice, considering the appropriate use of antibiotics. Board-certified infection control pharmacy specialists also belong to this team. The appropriate use of antibiotics, which I emphasize, indicates the absence of the inappropriate selection of broad-spectrum agents and chronic administration, considering the following 3 points: the selection of antibiotics whose spectra involve causative bacteria (drug sensitivity), prescription of antibiotics using an appropriate administration method/dose based on their transfer to the infected site (pharmacokinetics), and relief of symptoms of infectious diseases (therapeutic effects). In this study, we introduce cases of pharmacists' intervention in Nakamura Memorial South Hospital with respect to the appropriate use of antibiotics by general hospital pharmacists. The contents of pharmacists' intervention included accompanying physicians on their rounds/support regarding prescription, therapeutic drug monitoring, the preparation of guidelines for the hospital use of antibiotics, culture data collection/preparation of antibiograms, ICT/Infection Control Committee (ICC) activities, hospital rounds, preparation of antibiotic injections, and gram staining of sputum. In the future, health care professionals should always consider the appropriate use of antibiotics, contributing to a medical environment in which current options can be maintained for future infectious disease treatment. PMID:20715514

  5. 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.

  6. 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.

  7. [Study of reparative DNA synthesis in lymphocytes of persons occupationally exposed to radiation].

    PubMed

    Nikanorova, E A; Ivanov, K Iu; Khaĭmovich, T I; Ptitsina, S N; Shevchenko, V A

    2002-01-01

    The UDS efficiency in lymphocytes of professionals chronically exposed to gamma/neutron radiation, as well as for a control cohort was estimated. A credible reduction of UV-induced UDS (KUV) index as compared to the control was demonstrated. This shows an invalid repair state of blood cells in professionals. As for the control cohort, the decreasing tendency of UDS index with age was found. The correlative analysis of UDS index dependence upon an absorbed dose (based on physical dosimetry data) revealed the trend towards repair index reduction along with a higher total absorbed doze, that is followed by UDS index coming onto a plateau. It was also demonstrated that after a sharp and/or accidental irradiation UDS index reduces as compared to permanent portioned irradiation. It was not observed the influence of smoking upon UDS efficiency in blood lymphocytes neither for control, nor for experimental group. The analysis of vitamin therapy of the both cohorts showed that such therapy raises UDS index of the control (i.e., non-professional) group. Besides, it was found out an additional positive effect of vitamin therapy, i.e. doze leveling in long-term perspective after irradiation. The most expressed KUV/doze correlation was characteristic for professionals, who do not take vitamins and do not smoke. This proves that in blood cells of professionals it is preserved a dependence of repair system invalidity upon the absorbed doze without similar external factors. PMID:12530166

  8. Allometric scaling of dietary linoleic acid on changes in tissue arachidonic acid using human equivalent diets in mice

    PubMed Central

    2011-01-01

    Background It is hypothesized that dietary linoleic acid (LA) promotes chronic and acute diseases in humans by enriching tissues with arachidonic acid (AA), its downstream metabolite, and dietary studies with rodents have been useful for validation. However, levels of LA in research diets of rodents, as published in the literature, are notoriously erratic making interspecies comparisons unreliable. Therefore, the ability to extrapolate the biological effects of dietary LA from experimental rodents to humans necessitates an allometric scaling model that is rooted within a human equivalent context. Methods To determine the physiological response of dietary LA on tissue AA, a mathematical model for extrapolating nutrients based on energy was used, as opposed to differences in body weight. C57BL/6J mice were divided into 9 groups fed a background diet equivalent to that of the US diet (% energy) with supplemental doses of LA or AA. Changes in the phospholipid fatty acid compositions were monitored in plasma and erythrocytes and compared to data from humans supplemented with equivalent doses of LA or AA. Results Increasing dietary LA had little effect on tissue AA, while supplementing diets with AA significantly increased tissue AA levels, importantly recapitulating results from human trials. Conclusions Thus, interspecies comparisons for dietary LA between rodents and humans can be achieved when rodents are provided human equivalent doses based on differences in metabolic activity as defined by energy consumption. PMID:21702942

  9. 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.

  10. 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

  11. Sensitivity of human granulosa cell tumor cells to epidermal growth factor receptor inhibition.

    PubMed

    Andersson, Noora; Anttonen, Mikko; Färkkilä, Anniina; Pihlajoki, Marjut; Bützow, Ralf; Unkila-Kallio, Leila; Heikinheimo, Markku

    2014-04-01

    Epidermal growth factor receptor (EGFR) is implicated in the progression of many human cancers, but its significance in ovarian granulosa cell tumor (GCT) pathobiology remains poorly understood. We assessed the EGFR gene copy number, surveyed the mRNA and protein expression patterns of EGFR in 90 adult GCTs, and assessed the in vitro sensitivity of GCT cells to EGFR inhibition. Low-level amplification of EGFR gene was observed in five GCTs and high-level amplification in one sample. EGFR mRNA was robustly expressed in GCTs. Most tumors expressed both unphosphorylated and phosphorylated EGFR protein, but the protein expression did not correlate with clinical parameters, including the risk of recurrence. Small-molecule EGFR inhibitors reduced the EGF-induced activation of EGFR and its downstream signaling molecules at nanomolar doses, but cell viability was reduced, and caspase-3/7 was activated in GCT cells only at micromolar doses. Based on the present results, EGFR is active and abundantly expressed in the majority of GCTs, but probably has only minor contribution to GCT cell growth. Given the high doses of EGFR inhibitors required to reduce GCT cell viability in vitro, they are not likely to be effective for GCT treatment as single agents; they should rather be tested as part of combination therapies for these malignancies. PMID:24463098

  12. 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.

  13. A proposed dosing algorithm for the individualized dosing of human immunoglobulin in chronic inflammatory neuropathies.

    PubMed

    Lunn, Michael P; Ellis, Lauren; Hadden, Robert D; Rajabally, Yusuf A; Winer, John B; Reilly, Mary M

    2016-03-01

    Dosing guidelines for immunoglobulin (Ig) treatment in neurological disorders do not consider variations in Ig half-life or between patients. Individualization of therapy could optimize clinical outcomes and help control costs. We developed an algorithm to optimize Ig dose based on patient's response and present this here as an example of how dosing might be individualized in a pharmacokinetically rational way and how this achieves potential dose and cost savings. Patients are "normalized" with no more than two initial doses of 2 g/kg, identifying responders. A third dose is not administered until the patient's condition deteriorates, allowing a "dose interval" to be set. The dose is then reduced until relapse allowing dose optimization. Using this algorithm, we have individualized Ig doses for 71 chronic inflammatory neuropathy patients. The majority of patients had chronic inflammatory demyelinating polyradiculoneuropathy (n = 39) or multifocal motor neuropathy (n = 24). The mean (standard deviation) dose of Ig administered was 1.4 (0.6) g/kg, with a mean dosing interval of 4.3 weeks (median 4 weeks, range 0.5-10). Use of our standardized algorithm has allowed us to quickly optimize Ig dosing. PMID:26757367

  14. Animal models of complement-mediated hypersensitivity reactions to liposomes and other lipid-based nanoparticles.

    PubMed

    Szebeni, János; Alving, Carl R; Rosivall, László; Bünger, Rolf; Baranyi, Lajos; Bedöcs, Péter; Tóth, Miklós; Barenholz, Yezheckel

    2007-01-01

    Intravenous injection of some liposomal drugs, diagnostic agents, micelles and other lipid-based nanoparticles can cause acute hypersensitivity reactions (HSRs) in a high percentage (up to 45%) of patients, with hemodynamic, respiratory and cutaneous manifestations. The phenomenon can be explained with activation of the complement (C) system on the surface of lipid particles, leading to anaphylatoxin (C5a and C3a) liberation and subsequent release reactions of mast cells, basophils and possibly other inflammatory cells in blood. These reactions can be reproduced and studied in pigs, dogs and rats, animal models which differ from each other in sensitivity and spectrum of symptoms. In the most sensitive pig model, a few miligrams of liposome (phospholipid) can cause anaphylactoid shock, characterized by pulmonary hypertension, systemic hypotension, decreased cardiac output and major cardiac arrhythmias. Pigs also display cutaneous symptoms, such as flushing and rash. The sensitivity of dogs to hemodynamic changes is close to that of pigs, but unlike pigs, dogs also react to micellar lipids (such as Cremophor EL) and their response includes pronounced blood cell and vegetative neural changes (e.g., leukopenia followed by leukocytosis, thrombocytopenia, fluid excretions). Rats are relatively insensitive inasmuch as hypotension, their most prominent response to liposomes, is induced only by one or two orders of magnitude higher phospholipid doses (based on body weight) compared to the reactogenic dose in pigs and dogs. It is suggested that the porcine and dog models are applicable for measuring and predicting the (pseudo)allergic activity of particulate "nanodrugs". PMID:17613700

  15. 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.

  16. The use of safety or uncertainty factors in the setting of acute reference doses.

    PubMed

    Renwick, A G

    2000-07-01

    A 100-fold safety or uncertainty factor has been used for about 40 years to derive safe daily intakes for humans based on animal studies; the 100-fold factor comprises separate 10-fold factors to allow for species differences and inter-individual variability. Each factor has to allow for toxicokinetic and toxicodynamic differences. Sub-dividing the 10-fold factors into kinetic and dynamic defaults, which when multiplied give a product of 10, offers a number of advantages. The main rationale for this sub-division is so that chemical-specific data can be introduced to replace one or more of the default sub-factors, hence contributing to a chemical-related overall factor. However, sub-division of the 10-fold factors has allowed analysis of the appropriateness of the overall 10-fold defaults, and analysis of special situations, such as infants and children. The establishment of an acute reference dose based on animal studies has to allow for both species differences and inter-individual variability; comparison with the factors used for chronic effects suggests that modification of the usual defaults may be appropriate under certain specific circumstances, but that the usual default of 100 remains appropriate for most cases. PMID:10983588

  17. 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. PMID:23321424

  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. PMID:17243249

  19. 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.

  20. 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

  1. 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. PMID:25954313

  2. Reflex cardiopulmonary responses by stimulation to type J receptors in rats exposed to NO/sub 2/

    SciTech Connect

    Tsubone, H.; Suzuki, A.K.

    1984-01-01

    To examine the role of the vagal pathway on the cardiopulmonary functions in NO/sub 2/-exposed rats, phenyl diguanide, which stimulates type J receptors in the lungs, was injected to control and exposed rats at a constant dose. Based on a statistcal test, a decrease in the heart rate (HR) after the injection was observed in the groups exposed to 20 ppm NO/sub 2/ for 1.5 h and 3 h, and 10 ppm for 24 h. On the other hand, an increase in respiratory rate (RR) was observed in the groups exposed to 10 ppm for 3 h and 4 ppm for 1 wk. No change in HR and RR was found in the group exposed to 0.4 ppm for 4 wk. These results suggest that the augmentation of the reflex cardiopulmonary responses due to stimulation to the type J receptors was produced by exposures with a higher concentration of NO/sub 2/. 24 references, 7 figures, 2 tables.

  3. 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

  4. 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.

  5. Addressing proteolytic efficiency in enzymatic degradation therapy for celiac disease.

    PubMed

    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

  6. A proposal for scientific framework enabling specific population drug dosing recommendations.

    PubMed

    Jadhav, Pravin R; Cook, Jack; Sinha, Vikram; Zhao, Ping; Rostami-Hodjegan, Amin; Sahasrabudhe, Vaishali; Stockbridge, Norman; Powell, J Robert

    2015-10-01

    Over the last 3 decades, there has been little change in the paradigm to derive dosing recommendations for specific populations (e.g., renal failure, elderly, or obese patients) despite better understanding of clearance pathways in these groups and availability of modeling and simulation tools. Dosing recommendations for specific populations are often incomplete or unavailable at the time of drug approval. Currently, there is no regulatory framework to incorporate model-based dosing recommendations for specific populations. This paper proposes a scientific framework for using modeling and simulation to support specific population dosing recommendations. This framework creates a knowledgebase of drug and population attributes where model-based approaches can be developed to inform dosing recommendations. The framework may benefit patients by having reliable dosing information at the time of drug approval. Patients with conditions where studies are difficult to perform would benefit from dosing based on state-of-the-art knowledge. Industry and regulators would benefit from a scientific and efficient approach to improve specific population prediction. A research approach to determine specific population dose prediction is discussed along with challenges and risks. We hope to initiate a dialogue to explore the role of modeling based on data for drugs with similar clearance mechanisms to predict drug dosing. PMID:26109076

  7. 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

    2016-01-01

    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

  8. Monitoring of imatinib targeted delivery in human leukocytes.

    PubMed

    Kralj, Eva; Žakelj, Simon; Trontelj, Jurij; Pajič, Tadej; Preložnik Zupan, Irena; Černelč, Peter; Ostanek, Barbara; Marc, Janja; Kristl, Albin

    2013-09-27

    The success of imatinib therapy in chronic myeloid leukemia is highly influenced by its active transport into target cells. However, the methodology for analytical evaluation of intracellular drug concentration is rare and usually reliant upon the use of radioactively labeled drugs. More specifically, there is no published method available in the literature for the determination of imatinib concentration in granulocytes. To gain further insight into the intracellular drug uptake a very reliable two-stage sample concentration procedure was devised and coupled with a sensitive ultra-high performance liquid chromatography tandem mass spectrometry. The reliability of this sample preparation and sensitivity of the analysis was confirmed by a successful validation of all necessary method parameters to an impressive lower limit of quantification of 0.5 ng imatinib per 10(6) cells still at the signal to noise ratio of 670. The usefulness of the method is further improved with only 6 mL of blood being necessary for patient analysis. The method has been applied to blood samples of 13 CML patients treated with imatinib and all the measured intracellular drug concentrations were within the validated range. These and further measurements will enable the research of factors which may, besides blood plasma concentration, influence the individual's response to imatinib therapy. Furthermore, individualisation of dosing based on the directly measured targeted drug delivery could be possible. PMID:23643738

  9. MOSFET sensitivity dependence on integrated dose from high-energy photon beams.

    PubMed

    Tanyi, James A; Krafft, Shane P; Hagio, Tomoe; Fuss, Martin; Salter, Bill J

    2008-01-01

    The ability of a commercially available dual bias, dual MOSFET dosimetry system to measure therapeutic doses reproducibly throughout its vendor-defined dose-based lifetime has been evaluated by characterizing its sensitivity variation to integrated/cumulative doses from,high-energy (6 and 15 MV) photon radiotherapy beams. The variation of sensitivity as a function of total integrated dose was studied for three different dose-per-fraction levels; namely, 50, 200, and 1200 cGy/fraction. In standard sensitivity mode (i.e., measurements involving dose-per-fraction levels > or =100 cGy), the response of the MOSFET system to identical irradiations increased with integrated dose for both energies investigated. Dose measurement reproducibility for the low (i.e., 50 cGy) dose fractions was within 2.1% (if the system was calibrated before each in-phantom measurement) and 3.1% [if the system was calibrated prior to first use, with no intermediate calibration(s)]. Similarly, dose measurement reproducibility was between 2.2% and 6.6% for the conventional (i.e., 200 cGy) dose fractions and between 1.8% and 7.9% for escalated (i.e., 1200 cGy) dose fractions. The results of this study suggest that, due to the progressively increasing sensitivity resulting from the dual-MOSFET design, frequent calibrations are required to achieve measurement accuracy of < or =3% (within one standard deviation). PMID:18293559

  10. 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

  11. 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

  12. 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

    2011-01-01

    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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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)

  18. Web-Based Training on Reviewing Dose Modeling Aspects of NRC Decommissioning and License Termination Plans

    SciTech Connect

    LePoire, D.; Cheng, J.J.; Kamboj, S.; Arnish, J.; Richmond, P.; Chen, S.Y.; Barr, C.; McKenney, C.

    2008-01-15

    NRC licensees at decommissioning nuclear facilities submit License Termination Plans (LTP) or Decommissioning Plans (DP) to NRC for review and approval. To facilitate a uniform and consistent review of these plans, the NRC developed training for its staff. A live classroom course was first developed in 2005, which targeted specific aspects of the LTP and DP review process related to dose-based compliance demonstrations or modeling. A web-based training (WBT) course was developed in 2006 and 2007 to replace the classroom-based course. The advantage of the WBT is that it will allow for staff training or refreshers at any time, while the advantage of a classroom-based course is that it provides a forum for lively discussion and the sharing of experience of classroom participants. The objective of this course is to train NRC headquarters and regional office staff on how to review sections of a licensee's DP or LTP that pertain to dose modeling. The DP generally refers to the decommissioning of non-reactor facilities, while the LTP refers specifically to the decommissioning of reactors. This review is part of the NRC's licensing process, in which the NRC determines if a licensee has provided a suitable technical basis to support derived concentration guideline levels (DCGLs)1 or dose modeling analyses performed to demonstrate compliance with dose-based license termination rule criteria. This type of training is one component of an organizational management system. These systems 'use a range of practices to identify, create, represent, and distribute knowledge for reuse, awareness and learning'. This is especially important in an organization undergoing rapid change or staff turnover to retain organizational information and processes. NRC is committed to maintaining a dynamic program of training, development, and knowledge transfer to ensure that the NRC acquires and maintains the competencies needed to accomplish its mission. This paper discusses one specific project

  19. High-throughput sample processing and sample management; the functional evolution of classical cytogenetic assay towards automation.

    PubMed

    Ramakumar, Adarsh; Subramanian, Uma; Prasanna, Pataje G S

    2015-11-01

    High-throughput individual diagnostic dose assessment is essential for medical management of radiation-exposed subjects after a mass casualty. Cytogenetic assays such as the Dicentric Chromosome Assay (DCA) are recognized as the gold standard by international regulatory authorities. DCA is a multi-step and multi-day bioassay. DCA, as described in the IAEA manual, can be used to assess dose up to 4-6 weeks post-exposure quite accurately but throughput is still a major issue and automation is very essential. The throughput is limited, both in terms of sample preparation as well as analysis of chromosome aberrations. Thus, there is a need to design and develop novel solutions that could utilize extensive laboratory automation for sample preparation, and bioinformatics approaches for chromosome-aberration analysis to overcome throughput issues. We have transitioned the bench-based cytogenetic DCA to a coherent process performing high-throughput automated biodosimetry for individual dose assessment ensuring quality control (QC) and quality assurance (QA) aspects in accordance with international harmonized protocols. A Laboratory Information Management System (LIMS) is designed, implemented and adapted to manage increased sample processing capacity, develop and maintain standard operating procedures (SOP) for robotic instruments, avoid data transcription errors during processing, and automate analysis of chromosome-aberrations using an image analysis platform. Our efforts described in this paper intend to bridge the current technological gaps and enhance the potential application of DCA for a dose-based stratification of subjects following a mass casualty. This paper describes one such potential integrated automated laboratory system and functional evolution of the classical DCA towards increasing critically needed throughput. PMID:26520383

  20. Dabigatran versus warfarin major bleeding in practice: an observational comparison of patient characteristics, management and outcomes in atrial fibrillation patients.

    PubMed

    Smythe, Maureen A; Forman, Michael J; Bertran, Elizabeth A; Hoffman, Janet L; Priziola, Jennifer L; Koerber, John M

    2015-10-01

    Data comparing the patient characteristics, management and outcomes for dabigatran versus warfarin major bleeding in the practice setting are limited. We performed a retrospective single health system study of atrial fibrillation patients with dabigatran or warfarin major bleeding from October 2010 through September 2012. Patient identification occurred through both an internal adverse event reporting system and a structured stepwise data filtering approach using the International Classification of Diseases diagnosis codes. Thirty-five dabigatran major bleeding patients were identified and compared to 70 warfarin major bleeding patients. Intracranial bleed occurred in 4.3 % of warfarin patients and 8.6 % of dabigatran patients. Dabigatran patients tended to be older (79.9 vs. 76 years) and were more likely to have a creatinine clearance of 15-30 mL/min (40 vs. 18.6 %, p = 0.02). Over one-third of dabigatran patients had an excessive dose based on renal function. More dabigatran patients required a procedure for bleed management (37.1 vs. 17.1 %, p = 0.03) and received a hemostatic agent for reversal (11.4 vs. 1.4 %, p = 0.04). Dabigatran patients were twice as likely to spend time in an ICU (45.7 vs. 27.1 %, p = 0.06), be placed in hospice/comfort care (14.3 vs. 7.1 %, p = 0.24), expire during hospitalization (14.3 vs. 7.1 %, p = 0.24), and expire within 30-days (22.9 vs. 11.4 %, p = 0.28). In a single hospital center practice setting, as compared to warfarin, patients with dabigatran major bleeding were more likely to be older, have renal impairment, require a procedure for bleed management and receive a hemostatic agent. Patients with dabigatran major bleeding had an excessive dose for renal function in more than one-third of cases. PMID:25851800

  1. Enrofloxacin-based therapeutic strategy for the prevention of endometritis in susceptible mares.

    PubMed

    González, C; Moreno, L; Fumuso, E; García, J; Rivulgo, M; Confalonieri, A; Sparo, M; Sánchez Bruni, S

    2010-06-01

    Enrofloxacin (EFX) is often used empirically to prevent uterine infections in mares in order to improve efficiency on Commercial Embryo Transfer Farms. This study investigated the uterine distribution of EFX and its metabolite ciprofloxacin (CFX) in mares and assessed the minimal inhibitory concentrations (MIC) of EFX against various common pathogens as a basis for establishing a rational dosing schedule. Plasma and uterine pharmacokinetic (PK) studies were performed in two groups (n = 5) of healthy mares following intravenous (i.v.) administration of EFX at either 2.5 and at 5 mg/kg bodyweight. Plasma and endometrial tissue samples, taken before for up to 48 h after treatment were analysed by Reverse Phase HPLC. MIC values for wild strains of Gram-negative (Escherichia coli, Pseudomonas aeruginosa) and Gram-positive bacteria (beta-haemolytic streptococci) ranged from 0.25-2 and 1.5-3.0 microg/mL respectively. In terms of tissue distribution, the sum of the endometrial concentrations of the parent drug (EFX) and its active metabolite (CFX) (in terms of AUC), exceeded those in plasma by 249% and 941% following administration of EFX at 2.5 and 5 mg/kg respectively. After i.v. treatment with EFX at 5 mg/kg, endometrial concentrations of EFX and CFX above the MIC value were detected for 36-48 and 22-43 h posttreatment for Gram-negative and -positive isolates respectively. Concentrations above MIC were maintained for much shorter periods at the lower (2.5 mg/kg) treatment dose. Based on these results, a conventional dose (5 mg/kg) of EFX given prebreeding followed by two further doses at 36-48 h postbreeding are proposed as a rational strategy for using of EFX as a preventative therapy against a variety of common bacterial strains associated with equine endometritis. PMID:20557446

  2. 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. PMID:27110110

  3. Studies of the toxicological potential of capsinoids: II. A 26-week daily gavage dosing toxicity study of CH-19 Sweet extract in rats.

    PubMed

    Kodama, Terutaka; Watanabe, Eri; Masuyama, Takeshi; Tsubuku, Shoji; Otabe, Akira; Mochizuki, Masahiro; Bernard, Bruce K

    2008-01-01

    A 26-week oral toxicity study of capsinoids-containing CH-19 Sweet extract was conducted in Sprague-Dawley rats (20 males and 20 females per group) at 6 weeks of age. The test substance was administered by gavage for 26 weeks at dose levels of 0 (vehicle), 1.25, 2.5, and 5.0 ml/kg/day. The concentration of capsinoids in the CH-19 Sweet extract employed was 71.25 to 73.15 mg/ml, resulting in dose levels of capsinoids of 89.06 to 91.44, 178.13 to 182.88, and 356.25 to 365.75 mg/kg, respectively. Adverse test article-related changes were only observed in males, not in females, and within the males, only at the high dose (5.0 ml/kg). Within that group (high-dose males), increases were observed in the numbers of segmented neutrophils, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and lactate dehydrogenase (LDH) activities, liver weights, and in the incidence and severity of hepatocellular focal necrosis. No test substance-related changes were detected in clinical signs, body weight, food consumption, water intake, ophthalmology, or urinalysis. No adverse test article-related changes were observed in low- or mid-dose males or in females at any dose. Based on the results of this chronic gavage study, the target organ was the liver and the no observed adverse effect level (NOAEL) for CH-19 Sweet extract in the rat was 2.5 ml/kg/day in males and 5.0 ml/kg/day in females (178.13 to 182.88 mg/kg and 356.25 to 365.75 mg/kg as capsinoids, respectively). PMID:19037796

  4. Accuracy and optimal timing of activity measurements in estimating the absorbed dose of radioiodine in the treatment of Graves' disease

    NASA Astrophysics Data System (ADS)

    Merrill, S.; Horowitz, J.; Traino, A. C.; Chipkin, S. R.; Hollot, C. V.; Chait, Y.

    2011-02-01

    Calculation of the therapeutic activity of radioiodine 131I for individualized dosimetry in the treatment of Graves' disease requires an accurate estimate of the thyroid absorbed radiation dose based on a tracer activity administration of 131I. Common approaches (Marinelli-Quimby formula, MIRD algorithm) use, respectively, the effective half-life of radioiodine in the thyroid and the time-integrated activity. Many physicians perform one, two, or at most three tracer dose activity measurements at various times and calculate the required therapeutic activity by ad hoc methods. In this paper, we study the accuracy of estimates of four 'target variables': time-integrated activity coefficient, time of maximum activity, maximum activity, and effective half-life in the gland. Clinical data from 41 patients who underwent 131I therapy for Graves' disease at the University Hospital in Pisa, Italy, are used for analysis. The radioiodine kinetics are described using a nonlinear mixed-effects model. The distributions of the target variables in the patient population are characterized. Using minimum root mean squared error as the criterion, optimal 1-, 2-, and 3-point sampling schedules are determined for estimation of the target variables, and probabilistic bounds are given for the errors under the optimal times. An algorithm is developed for computing the optimal 1-, 2-, and 3-point sampling schedules for the target variables. This algorithm is implemented in a freely available software tool. Taking into consideration 131I effective half-life in the thyroid and measurement noise, the optimal 1-point time for time-integrated activity coefficient is a measurement 1 week following the tracer dose. Additional measurements give only a slight improvement in accuracy.

  5. SU-E-I-57: Estimating the Occupational Eye Lens Dose in Interventional Radiology Using Active Personal Dosimeters Worn On the Chest

    SciTech Connect

    Omar, A; Marteinsdottir, M; Kadesjo, N; Fransson, A

    2015-06-15

    Purpose: To provide a general formalism for determination of occupational eye lens dose based on the response of an active personal dosimeter (APD) worn at chest level above the radiation protection apron. Methods: The formalism consists of three factors: (1) APD conversion factor converting the reading at chest level (APDchest) to the corresponding personal dose equivalent at eye level, (2) Dose conversion factor transferring the measured dose quantity, Hp(10), into a dose quantity relevant for the eye lens dose, (3) Correction factor accounting for differences in exposure of the eye(s) compared to the exposure at chest level (e.g., due to protective lead glasses).The different factors were investigated and evaluated based on phantom and clinical measurements performed in an x-ray angiography suite for interventional cardiology. Results: The eye lens dose can be conservatively estimated by assigning an appropriate numerical value to each factor entering the formalism that in most circumstances overestimates the dose. Doing so, the eye lens dose to the primary operator and assisting staff was estimated in this work as D-eye,primary = 2.0 APDchest and D-eye,assisting = 1.0 APDchest, respectively.The annual eye lens dose to three nurses and one cardiologist was estimated to be 2, 2, 2, and 13 mSv (Hp(0.07)), respectively, using a TLD dosimeter worn at eye level. In comparison, using the formalism and APDchest measurements, the respective doses were 2, 2, 2, and 16 mSv (Hp(3)). Conclusion: The formalism outlined in this work can be used to estimate the occupational eye lens dose from the response of an APD worn on the chest. The formalism is general and could be applied also to other types of dosimeters. However, the numerical value of the different factors may differ from those obtained with the APD’s used in this work due to differences in dosimeter properties.

  6. Management of venous thrombo-embolism: an update.

    PubMed

    Konstantinides, Stavros; Torbicki, Adam

    2014-11-01

    Venous thrombo-embolism is the third most frequent acute cardiovascular syndrome after myocardial infarction and stroke. Recently published landmark trials paved the way for significant progress in the management of the disease and provided the evidence for the ESC Pulmonary Embolism (PE) Guidelines 2014 update. Risk stratification strategies for non-high-risk PE continue to evolve, with an increasing emphasis on clinical prediction rules and right ventricular (RV) assessment on computed tomographic pulmonary angiography. In the field of anticoagulation treatment, pharmacogenetic testing for vitamin K antagonists on top of clinical parameters was not found to offer a significant benefit during the initiation phase; on the other hand, dosing based on the patient's clinical data seems superior to fixed loading regimens. The phase 3 trial programme of new oral anticoagulants in the treatment of venous thrombo-embolism has been completed, and the results indicate that these agents are at least as effective and probably cause less major bleeding than currently standard treatment. A multicentre prospective phase 4 trial will determine whether early discharge and out-of-hospital treatment of low-risk PE with the oral factor Xa inhibitor rivaroxaban is feasible, effective, and safe. For intermediate-risk PE defined on the basis of imaging tests and laboratory biomarkers, the bleeding risks of full-dose thrombolytic treatment appear too high to justify its use, unless clinical signs of haemodynamic decompensation appear. Patients in whom PE has resulted in chronic thrombo-embolic pulmonary hypertension and who are not suitable for pulmonary endarterectomy, may be expected to benefit from emerging pharmaceutical and interventional treatment options. PMID:25179762

  7. The psychiatric management of patients with alcohol dependence.

    PubMed

    Ritvo, Jonathan I; Park, Charles

    2007-09-01

    Alcohol dependence is a chronic, relapsing biobehavioral disease mediated by various parts of the brain, including reward systems, memory circuits, and the prefrontal cortex. It is characterized by loss of the ability to drink alcohol in moderation and continued drinking despite negative consequences. The alcohol withdrawal syndrome is a common but not universal diagnostic feature of alcohol dependence. Benzodiazepine detoxification of the alcohol withdrawal syndrome prevents the development of withdrawal seizures and delirium tremens, and makes patients more comfortable, which promotes engagement in treatment. Symptom-triggered dosing, based on a withdrawal rating scale such as the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised, is optimal for minimizing the total benzodiazepine dosage. Use of a long-acting benzodiazepine (eg, chlordiazepoxide) is preferred in uncomplicated patients. Thiamine should be administered routinely before the administration of intravenous fluids to prevent the development of Wernicke's encephalopathy and Wernicke-Korsakoff syndrome. In combination with psychosocial treatment, disulfiram, naltrexone, and acamprosate can reduce the frequency of relapse. Naltrexone may be more effective for reduction of loss of control with the first drink and cue-related craving, and acamprosate may be more effective for stabilizing the physiology of post-acute withdrawal. Disulfiram, an aversive deterrent, can be useful if administration can be monitored and tied to meaningful contingencies or when used prophylactically for situations anticipated to carry high risk of relapse. Psychiatric comorbidity, especially depression, is common and is best addressed concurrently, although definitive diagnosis may have to await a period of prolonged sobriety. Prescription of addictive substances, including benzodiazepines beyond the period of acute detoxification, should be avoided, and if necessary should be closely monitored (eg, by frequent

  8. 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. PMID:27423416

  9. VORICONAZOLE TOXICITY IN MULTIPLE PENGUIN SPECIES.

    PubMed

    Hyatt, Michael W; Georoff, Timothy A; Nollens, Hendrik H; Wells, Rebecca L; Clauss, Tonya M; Ialeggio, Donna M; Harms, Craig A; Wack, Allison N

    2015-12-01

    Aspergillosis is a common respiratory fungal disease in penguins managed under human care. Triazole antifungal drugs, including itraconazole, are most commonly used for treatment; however, itraconazole treatment failures from drug resistance are becoming more common, requiring newer treatment options. Voriconazole, a newer triazole, is being used more often. Until recently, no voriconazole pharmacokinetic studies had been performed in penguins, leading to empiric dosing based on other avian studies. This has led to increased anecdotal reporting of apparent voriconazole toxicity in penguins. This report describes 18 probable and 6 suspected cases of voriconazole toxicity in six penguin species from nine institutions: 12 African penguins (Spheniscus demersus), 5 Humboldt penguins (Spheniscus humboldti), 3 Magellanic penguins (Spheniscus magellanicus), 2 gentoo penguins (Pygoscelis papua papua), 1 macaroni penguin (Eudyptes chrysolophus), and 1 emperor penguin (Aptenodytes forsteri). Observed clinical signs of toxicity included anorexia, lethargy, weakness, ataxia, paresis, apparent vision changes, seizure-like activity, and generalized seizures. Similar signs of toxicity have also been reported in humans, in whom voriconazole therapeutic plasma concentration for Aspergillus spp. infections is 2-6 μg/ml. Plasma voriconazole concentrations were measured in 18 samples from penguins showing clinical signs suggestive of voriconazole toxicity. The concentrations ranged from 8.12 to 64.17 μg/ml, with penguins having plasma concentrations above 30 μg/ml exhibiting moderate to severe neurologic signs, including ataxia, paresis, and seizures. These concentrations were well above those known to result in central nervous system toxicity, including encephalopathy, in humans. This case series highlights the importance of species-specific dosing of voriconazole in penguins and plasma therapeutic drug monitoring. Further investigation, including pharmacokinetic studies, is

  10. Parenteral Adjuvant Effects of an Enterotoxigenic Escherichia coli Natural Heat-Labile Toxin Variant

    PubMed Central

    Braga, Catarina J. M.; Rodrigues, Juliana F.; Medina-Armenteros, Yordanka; Farinha-Arcieri, Luís E.; Ventura, Armando M.; Boscardin, Silvia B.; Sbrogio-Almeida, Maria E.; Ferreira, Luís C. S.

    2014-01-01

    Native type I heat-labile toxins (LTs) produced by enterotoxigenic Escherichia coli (ETEC) strains exert strong adjuvant effects on both antibody and T cell responses to soluble and particulate antigens following co-administration via mucosal routes. However, inherent enterotoxicity and neurotoxicity (following intra-nasal delivery) had reduced the interest in the use of these toxins as mucosal adjuvants. LTs can also behave as powerful and safe adjuvants following delivery via parenteral routes, particularly for activation of cytotoxic lymphocytes. In the present study, we evaluated the adjuvant effects of a new natural LT polymorphic form (LT2), after delivery via intradermal (i.d.) and subcutaneous (s.c.) routes, with regard to both antibody and T cell responses. A recombinant HIV-1 p24 protein was employed as a model antigen for determination of antigen-specific immune responses while the reference LT (LT1), produced by the ETEC H10407 strain, and a non-toxigenic LT form (LTK63) were employed as previously characterized LT types. LT-treated mice submitted to a four dose-base immunization regimen elicited similar p24-specific serum IgG responses and CD4+ T cell activation. Nonetheless, mice immunized with LT1 or LT2 induced higher numbers of antigen-specific CD8+ T cells and in vivo cytotoxic responses compared to mice immunized with the non-toxic LT derivative. These effects were correlated with stronger activation of local dendritic cell populations. In addition, mice immunized with LT1 and LT2, but not with LTK63, via s.c. or i.d. routes developed local inflammatory reactions. Altogether, the present results confirmed that the two most prevalent natural polymorphic LT variants (LT1 or LT2) display similar and strong adjuvant effects for subunit vaccines administered via i.d. or s.c. routes. PMID:24432018

  11. Corrections in dose assessment of 99mTc radiolabeled aerosol particles targeted to central human airways using planar gamma camera imaging.

    PubMed

    Möller, Winfried; Felten, Kathrin; Meyer, Gabriele; Meyer, Peter; Seitz, Jürgen; Kreyling, Wolfgang G

    2009-03-01

    The dose of inhaled radiolabeled aerosols is usually assessed using gamma (GC) camera imaging. Because of the complex and inhomogeneous structure of the lung, consisting of soft tissue, the thoracic skeleton, blood vessels, and air spaces, proper attenuation correction coefficients are difficult to evaluate and the estimated doses bear high uncertainty. One hundred milliliters of aerosol boli composed of 100 nm diameter (99m)Tc radiolabeled carbon particles (Technegas) were targeted either to the airways (AW) or to 800-mL volumetric lung depth (alveoli, AL) in 11 healthy volunteers. In addition, 750-mL full breaths (FB) of aerosol were inhaled to a 800-mL lung depth. The deposited dose was measured by collecting aerosol from inhaled and exhaled air stream on filters, which were analyzed for radioactivity. Lung imaging was performed using a planar GC (posterior). Ratios of GC counts to deposited dose (GC/DD) were similar after FB and AL administration, but twofold lower after AW administration (p < 0.01). Associated attenuation correction factors (ACF) were 2.5 +/- 0.5 (FB), 2.2 +/- 0.4 (AL), and 5.5 +/- 1.6 (AW, p < 0.01). Both GC/DD and ACF were highly correlated to the aerosol distribution index (central to peripheral ratio, C/P). After shallow bolus administration there was a negative correlation between body mass index and GC/DD. Inhalation of radioaerosols used in medical diagnosis and therapy in combination with high central airway deposition results in an underestimation of the deposited dose based on planar GC imaging. The aerosol distribution index C/P may provide one suitable indicator for corrections, which should be confirmed in future studies by individual attenuation analysis based on radiotracer transmission measurements. PMID:18844481

  12. Radionuclide concentrations in fish collected from Jemez, Nambe, and San Ildefonso Tribal Lakes

    SciTech Connect

    Fresquez, P.R.; Armstrong, D.R.; Salazar, J.G.

    1995-02-01

    Radionuclide concentrations ({sup 90}Sr, {sup 137}Cs, {sup 238}Pu, {sup 239}Pu,and total uranium) were determined in fish collected from Jemez, Nambe, and San Ildefonso tribal lakes. With the exception of {sup 137}Cs, all other radionuclides were not significantly different in (stocked) rainbow trout collected from Jemez and Nambe as compared with game fish collected from Abiquiu, Heron, and El Vado Reservoirs. Although {sup 137}Cs levels in trout from Jemez (3.2 {times} 10{sup -2} pCi per dry gram) and Nambe (7.5 {times} 10{sup -2} pCi per dry gram) were significantly higher than {sup 137}Cs concentrations in fish from Abiquiu, Heron, and El Vado, they were still well below the regional statistical (worldwide fallout) reference level (i.e., < 28 {times} 10{sup -2} pCi per dry gram). Game and nongame fish collected from San Ildefonso contained higher and significantly higher concentrations of uranium, respectively, as compared with fish collected from Abiquiu, Heron, and El Vado. The higher uranium concentrations in fish from San Ildefonso as compared with fish from Abiquiu, Heron, and El Vado were attributed to the higher natural soil uranium contents in the area as compared with the geology of the area upstream of San Ildefonso. The effective (radiation) dose equivalent (EDE) from consuming 46 lb of game fish from Jemez, Nambe, and San Ildefonso lakes, after natural background has been subtracted, was 0.013 ({+-}0.002), 0.019 ({+-}0.012), and 0.017 ({+-}0.028) mrem/yr, respectively. Similarly, the EDE from consuming nongame fish from San Ildefonso was 0.0092 ({+-}0.0084) mrem/yr. The highest calculated dose, based on the mean + 2 standard deviation (95% confidence level), was 0.073 mrem/yr; this was <0.08% of the International Commission on Radiological Protection permissible dose limit for protecting members of the public.

  13. 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.

  14. Carnosic Acid-combined Arsenic Trioxide Antileukaemia Cells in the Establishment of NB4/SCID Mouse Model.

    PubMed

    Hao, Li; Ran, Wang; Xiang-Xin, Li; Lu-Qun, Wang; Xiao-Ning, Yu

    2016-09-01

    Despite great improvement in the treatment outcome of APL, treatment failure still sometimes occurs due to the toxicity of arsenic trioxide (ATO). Damage to the heart and liver often occurs even when the dose is lower than the therapeutic dose. Based on the results of cell experiments in vitro in this study, we investigated the synergistic activity of carnosic acid (CA) combined with ATO in the SCID mouse model of human promyelocytic leukaemia in vivo. A NB4/SCID mouse model was established in this study. The NB4/SCID mice were randomly divided into three treatment groups (CA alone, ATO alone and CA combined with ATO) and a control group based on factorial design. The evaluation indicators of the curative effect of the drugs included expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins by immunohistochemistry, flow cytometry and Western blot analysis. The survival time was compared between the four groups. The results indicated that verification of the NB4/SCID mouse model was confirmed by histopathological examination. Compared with mice treated by CA or ATO alone, the mice in the combination of CA and ATO group had a higher rate of apoptosis, which was linked with expressions of cleaved caspase-3, PTEN, p27 gene mRNA and proteins. Also, the mice with the longest survival time were those treated with the combination of CA and ATO. In conclusion, the results of the present study indicated that CA and ATO in combination have strong synergistic antileukaemic effects on cell activity. PMID:26998898

  15. Five-year follow-up study on individual doses of Korean radiation workers based on ICRP 103 (2006-2010)

    NASA Astrophysics Data System (ADS)

    Lee, Jae-Seung; Ryu, Young-Hwan; Dong, Kyung-Rae; Goo, Eun-Hoe; Cho, Jae-Hwan; Lee, Hae-Kag; Kang, Seong-Jin; Choi, Eun-Jin; Chung, Woon-Kwan; Cha, Jang-Gyu

    2012-11-01

    This study examined individual doses of Korean radiation workers divided into deep and surface doses based on the dose limits recommended by the International Commission on Radiological Protection (ICRP) or ICRP 103 (approved on March 2007) for 5 years from 2006 to 2010. In addition, the exposure doses were compared according to occupation, departments and scale of the medical institutions (primary, secondary and tertiary) as well as between dental hospitals and hospitals, which is currently an issue, using 116,220 sets of data on the quarterly and yearly exposure doses of 5811 Korean radiation workers measured over a 5-year period (January 2006 to December 2010). For the mean exposure doses according to occupation, both deep and surface doses were higher in radiological technicians than in the other occupations and there was a significant difference between radiological technicians and others (researchers and assistants) (p<0.05). The results showed that none of the Korean radiation workers were exposed to radiation doses exceeding the maximum tolerant dose or 20 mSv/year recommended by the ICRP. When the mean exposure doses were compared according to the departments, both deep and surface doses were significantly higher (p<0.05) in the department of nuclear medicine than in the other departments (the department of biomedical engineering and the management team). For the mean exposure doses according to the scale of the medical institutions, the doses were highest in tertiary medical institutions followed in order by secondary and primary medical institutions (p<0.05). A comparison of the mean exposure doses in dental hospitals and hospitals revealed both deep and surface doses to be higher in hospitals than in dental hospitals (p<0.05). This study is considered to be used as basic data to establish a system for exposure dose management of radiation workers and more accurate studies on the radiation exposure are necessary in the future.

  16. SU-E-I-57: Evaluation and Optimization of Effective-Dose Using Different Beam-Hardening Filters in Clinical Pediatric Shunt CT Protocol

    SciTech Connect

    Gill, K; Aldoohan, S; Collier, J

    2014-06-01

    Purpose: Study image optimization and radiation dose reduction in pediatric shunt CT scanning protocol through the use of different beam-hardening filters Methods: A 64-slice CT scanner at OU Childrens Hospital has been used to evaluate CT image contrast-to-noise ratio (CNR) and measure effective-doses based on the concept of CT dose index (CTDIvol) using the pediatric head shunt scanning protocol. The routine axial pediatric head shunt scanning protocol that has been optimized for the intrinsic x-ray tube filter has been used to evaluate CNR by acquiring images using the ACR approved CT-phantom and radiation dose CTphantom, which was used to measure CTDIvol. These results were set as reference points to study and evaluate the effects of adding different filtering materials (i.e. Tungsten, Tantalum, Titanium, Nickel and Copper filters) to the existing filter on image quality and radiation dose. To ensure optimal image quality, the scanner routine air calibration was run for each added filter. The image CNR was evaluated for different kVps and wide range of mAs values using above mentioned beam-hardening filters. These scanning protocols were run under axial as well as under helical techniques. The CTDIvol and the effective-dose were measured and calculated for all scanning protocols and added filtration, including the intrinsic x-ray tube filter. Results: Beam-hardening filter shapes energy spectrum, which reduces the dose by 27%. No noticeable changes in image low contrast detectability Conclusion: Effective-dose is very much dependent on the CTDIVol, which is further very much dependent on beam-hardening filters. Substantial reduction in effective-dose is realized using beam-hardening filters as compare to the intrinsic filter. This phantom study showed that significant radiation dose reduction could be achieved in CT pediatric shunt scanning protocols without compromising in diagnostic value of image quality.

  17. Targeting JAK/STAT Signaling to Prevent Rejection After Kidney Transplantation: A Reappraisal.

    PubMed

    Baan, Carla C; Kannegieter, Nynke M; Felipe, Claudia Rosso; Tedesco Silva, Helio

    2016-09-01

    The profound involvement of cytokines in allograft rejection makes the molecules that control their actions, members of the Jak-Stat pathway, ideal targets for pharmacological intervention. Numerous studies have demonstrated that Jak3 is widely involved in the activation cascade and function of most immune cells. Tofacitinib, an oral Janus kinase inhibitor that targets Jak1/Jak3 dependent Stat activation, has been assessed as a substitute for calcineurin inhibitor therapy after low-to-moderate risk kidney transplantation in 3 randomized trials. Results using fixed-dose regimens showed a low incidence of rejection and better renal function with less interstitial fibrosis/tubular atrophy versus calcineurin inhibitor therapy. However, the safety profile of tofacitinib was poor, including increased incidences of cytomegalovirus disease, herpes zoster, BK virus, and nephropathy, which led to the discontinuation of its development for transplantation. High tofacitinib concentrations were independently associated with serious infection. Dosing according to exposure levels, coupled with pharmacodynamic monitoring based on phosphorylation of Stat5, could improve safety compared to the early fixed-dose regimens. Future studies could assess individualized dosing based on pharmacokinetic and pharmacodynamic monitoring. Additionally, because the increase of viral infections under tofacitinib may have been influenced by overlapping toxicity with concomitant mycophenolic acid, exploration of alternative adjunctive therapies (eg, a mammalian target of rapamycin inhibitor or belatacept) may demonstrate a better efficacy/safety profile. We believe that Jak inhibitors are a good and useful addition to the immunosuppressive armentarium for kidney transplant patients, and that new studies with personalized drug dosing, improved immune monitoring, and better patient selection should be performed. PMID:27163538

  18. Poster — Thur Eve — 06: Dose assessment of cone beam CT imaging protocols as part of SPECT/CT examinations

    SciTech Connect

    Tonkopi, E; Ross, AA

    2014-08-15

    Purpose: To assess radiation dose from the cone beam CT (CBCT) component of SPECT/CT studies and to compare with other CT examinations performed in our institution. Methods: We used an anthropomorphic chest phantom and the 6 cc ion chamber to measure entrance breast dose for several CBCT and diagnostic CT acquisition protocols. The CBCT effective dose was calculated with ImPACT software; the CT effective dose was evaluated from the DLP value and conversion factor, dependent on the anatomic region. The RADAR medical procedure radiation dose calculator was used to assess the nuclear medicine component of exam dose. Results: The entrance dose to the breast measured with the anthropomorphic phantom was 0.48 mGy and 9.41 mGy for cardiac and chest CBCT scans; and 4.59 mGy for diagnostic thoracic CT. The effective doses were 0.2 mSv, 3.2 mSv and 2.8 mSv respectively. For a small patient represented by the anthropomorphic phantom, the dose from the diagnostic CT was lower than from the CBCT scan, as a result of the exposure reduction options available on modern CT scanners. The CBCT protocols used the same fixed scanning techniques. The diagnostic CT dose based on the patient data was 35% higher than the phantom dose. For most SPECT/CT studies the dose from the CBCT component was comparable with the dose from the radiopharmaceutical. Conclusions: The patient radiation dose from the cone beam CT scan can be higher than that from a diagnostic CT and should be taken into consideration in evaluating total SPECT/CT patient dose.

  19. A Safety Evaluation of DAS181, a Sialidase Fusion Protein, in Rodents

    PubMed Central

    Larson, Jeffrey L.; Kang, Seong-Kwi; Choi, Bo In; Hedlund, Maria; Aschenbrenner, Laura M.; Cecil, Beth; Machado, GloriaMay; Nieder, Matthew; Fang, Fang

    2011-01-01

    DAS181 is a novel inhaled drug candidate blocking influenza virus (IFV) and parainfluenza virus (PIV) infections through removal of sialic acid receptors from epithelial surface of the respiratory tract. To support clinical development, a 28-day Good Laboratory Practices inhalation toxicology study was conducted in Sprague-Dawley rats. In this study, achieved average daily doses based on exposure concentrations were 0.47, 0.90, 1.55, and 3.00 mg/kg/day of DAS181 in a dry powder formulation. DAS181 was well tolerated at all dose levels, and there were no significant toxicological findings. DAS181 administration did not affect animal body weight, food consumption, clinical signs, ophthalmology, respiratory parameters, or organ weight. Gross pathology evaluations were unremarkable. Histological examination of the lungs was devoid of pulmonary tissue damage, and findings were limited to mild and transient changes indicative of exposure and clearance of a foreign protein. DAS181 did not show any cytotoxic effects on human and animal primary cells, including hepatocytes, skeletal muscle cells, osteoblasts, or respiratory epithelial cells. DAS181 did not cause direct or indirect hemolysis. A laboratory abnormality observed in the 28-day toxicology study was mild and transient anemia in male rats at the 3.00 mg/kg dose, which is an expected outcome of enhanced clearance of desialylated red blood cells resulting from systemic exposure with DAS181. Another laboratory observation was a transient dose-dependent elevation in alkaline phosphatase (ALP), which can be attributed to reduced ALP clearance resulting from increased protein desialylation due to DAS181 systemic exposure. These laboratory parameters returned to normal at the end of the recovery period. PMID:21572096

  20. Pharmacokinetic modeling optimizes inhibition of the ‘undruggable’ EWS-FLI1 transcription factor in Ewing Sarcoma

    PubMed Central

    Hong, S. Peter; Kallakury, Bhaskar; Monroe, Phillip; Erkizan, Hayriye V; Barber-Rotenberg, Julie S.; Houghton, Peter; Üren, Aykut; Toretsky, Jeffrey A.

    2014-01-01

    Transcription factors have long been deemed ‘undruggable’ targets for therapeutics. Enhanced recognition of protein biochemistry as well as the need to have more targeted approaches to treat cancer has rendered transcription factors approachable for therapeutic development. Since transcription factors lack enzymatic domains, the specific targeting of these proteins has unique challenges. One challenge is the hydrophobic microenvironment that affects small molecules gaining access to block protein interactions. The most attractive transcription factors to target are those formed from tumor specific chromosomal translocations that are validated oncogenic driver proteins. EWS-FLI1 is a fusion protein that results from the pathognomonic translocation of Ewing sarcoma (ES). Our past work created the small molecule YK-4-279 that blocks EWS-FLI1 from interacting with RNA Helicase A (RHA). To fulfill long-standing promise in the field by creating a clinically useful drug, steps are required to allow for in vivo administration. These investigations identify the need for continuous presence of the small molecule protein-protein inhibitor for a period of days. We describe the pharmacokinetics of YK-4-279 and its individual enantiomers. In vivo studies confirm prior in vitro experiments showing (S)-YK-4-279 as the EWS-FLI1 specific enantiomer demonstrating both induction of apoptosis and reduction of EWS-FLI1 regulated caveolin-1 protein. We have created the first rat xenograft model of ES, treated with (S)-YK-4-279 dosing based upon PK modeling leading to a sustained complete response in 2 of 6 ES tumors. Combining laboratory studies, pharmacokinetic measurements, and modeling has allowed us to create a paradigm that can be optimized for in vivo systems using both in vitro data and pharmacokinetic simulations. Thus, (S)-YK-4-279 as a small molecule drug is ready for continued development towards a first-in-human, first-in-class, clinical trial. PMID:24481407

  1. Similar efficacy and safety of artemether-lumefantrine (Coartem®) in African infants and children with uncomplicated falciparum malaria across different body weight ranges

    PubMed Central

    2011-01-01

    Background Artemisinin-based combination therapy, including artemether-lumefantrine (AL), is currently recommended for the treatment of uncomplicated Plasmodium falciparum malaria. The objectives of the current analysis were to compare the efficacy and safety of AL across different body weight ranges in African children, and to examine the age and body weight relationship in this population. Methods Efficacy, safety and pharmacokinetic data from a randomized, investigator-blinded, multicentre trial of AL for treatment of acute uncomplicated P. falciparum malaria in infants and children in Africa were analysed according to body weight group. Results The trial included 899 patients (intent-to-treat population 886). The modified intent-to-treat (ITT) population (n = 812) comprised 143 children 5 to < 10 kg, 334 children 10 to < 15 kg, 277 children 15 to < 25 kg, and 58 children 25 to < 35 kg. The 28-day PCR cure rate, the primary endpoint, was comparable across all four body weight groups (97.2%, 98.9%, 97.8% and 98.3%, respectively). There were no clinically relevant differences in safety or tolerability between body weight groups. In the three AL body weight dosing groups (5 to < 15 kg, 15 to < 25 kg and 25 to < 35 kg), 80% of patients were aged 10-50 months, 46-100 months and 90-147 months, respectively. Conclusion Efficacy of AL in uncomplicated falciparum malaria is similar across body weight dosing groups as currently recommended in the label with no clinically relevant differences in safety or tolerability. AL dosing based on body weight remains advisable. PMID:22176931

  2. 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. PMID:27008040

  3. Impact of Pre-Existing Elastic Matrix on TGF-β1 and HA Oligomer-Induced Regenerative Repair by Rat Aortic Smooth Muscle Cells

    PubMed Central

    Gacchina, Carmen E.; Ramamurthi, Anand

    2010-01-01

    Regenerating elastic matrices lost to disease (e.g. in aneurysms) is vital to re-establishing vascular homeostasis but is challenged by poor elastogenicity of post-neonatal cells. We previously showed exogenous hyaluronan oligomers (HA-o) and TGF-β1 to synergistically enhance tropo and matrix elastin deposition by healthy adult rat aortic SMCs (RASMCs). Towards treating aortic aneurysms (AAs), which exhibit cause- and site-specific heterogeneity in matrix content/structure and contain proteolytically-injured SMCs, we investigated impact of pre-existing elastic matrix degeneration on elastogenic induction of injured RASMCs. Elastin-rich RASMC layers at 21 days of culture, were treated with 0.15 U/ml (PPE15) and 0.75 U/ml (PPE75) of porcine pancreatic elastase to degrade the elastic matrix variably, or left uninjured (control). One set of cultures was harvested at 21d, before and after injury, to quantify viable cell count, matrix elastin loss. Other injured cell layers were cultured to 42d with or without factors (0.2 μg/ml HA oligomers, 1 ng/ml TGF-β1). We showed that (a)ability of cultures to self-repair and regenerate elastic matrices following proteolysis is limited when elastolysis is severe, (b)HA oligomers and TGF-β1 elastogenically stimulate RASMCs in mildly-injured (i.e., PPE15) cultures to restore both elastic matrix amounts and elastic-fiber deposition to levels in healthy cultures, and (c) in severely injured (i.e., PPE75) cultures, the factors stimulate matrix elastin synthesis and crosslinking, though not to control levels. The outcomes underscore need to enhance elastogenic factor doses based on severity of elastin loss. This study will help customize therapies for elastin regeneration within AAs based on cause and location. PMID:20653044

  4. 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 Central

    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. PMID:27110110

  5. Predictive value of phase I trials for safety in later trials and final approved dose: analysis of 61 approved cancer drugs.

    PubMed

    Jardim, Denis L; Hess, Kenneth R; Lorusso, Patricia; Kurzrock, Razelle; Hong, David S

    2014-01-15

    Phase I trials use a small number of patients to define a maximum tolerated dose (MTD) and the safety of new agents. We compared data from phase I and registration trials to determine whether early trials predicted later safety and final dose. We searched the U.S. Food and Drug Administration (FDA) website for drugs approved in nonpediatric cancers (January 1990-October 2012). The recommended phase II dose (R2PD) and toxicities from phase I were compared with doses and safety in later trials. In 62 of 85 (73%) matched trials, the dose from the later trial was within 20% of the RP2D. In a multivariable analysis, phase I trials of targeted agents were less predictive of the final approved dose (OR, 0.2 for adopting ± 20% of the RP2D for targeted vs. other classes; P = 0.025). Of the 530 clinically relevant toxicities in later trials, 70% (n = 374) were described in phase I. A significant relationship (P = 0.0032) between increasing the number of patients in phase I (up to 60) and the ability to describe future clinically relevant toxicities was observed. Among 28,505 patients in later trials, the death rate that was related to drug was 1.41%. In conclusion, dosing based on phase I trials was associated with a low toxicity-related death rate in later trials. The ability to predict relevant toxicities correlates with the number of patients on the initial phase I trial. The final dose approved was within 20% of the RP2D in 73% of assessed trials. PMID:24190980

  6. 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.

  7. Assessment of asbestos body formation by high resolution FEG-SEM after exposure of Sprague-Dawley rats to chrysotile, crocidolite, or erionite.

    PubMed

    Gandolfi, Nicola Bursi; Gualtieri, Alessandro F; Pollastri, Simone; Tibaldi, Eva; Belpoggi, Fiorella

    2016-04-01

    This work presents a comparative FEG-SEM study of the morphological and chemical characteristics of both asbestos bodies and fibres found in the tissues of Sprague-Dawley rats subjected to intraperitoneal or intrapleural injection of UICC chrysotile, UICC crocidolite and erionite from Jersey, Nevada (USA), with monitoring up to 3 years after exposure. Due to unequal dosing based on number of fibres per mass for chrysotile with respect to crocidolite and erionite, excessive fibre burden and fibre aggregation during injection that especially for chrysotile would likely not represent what humans would be exposed to, caution must be taken in extrapolating our results based on instillation in experimental animals to human inhalation. Notwithstanding, the results of this study may help to better understand the mechanism of formation of asbestos bodies. For chrysotile and crocidolite, asbestos bodies are systematically formed on long asbestos fibres. The number of coated fibres is only 3.3% in chrysotile inoculated tissues. In UICC crocidolite, Mg, Si, and Fe are associated with the fibres whereas Fe, P and Ca are associated with the coating. Even for crocidolite, most of the observed fibres are uncoated as coated fibres are about 5.7%. Asbestos bodies do not form on erionite fibres. The crystal habit, crystallinity and chemistry of all fibre species do not change with contact time, with the exception of chrysotile which shows signs of leaching of Mg. A model for the formation of asbestos bodies from mineral fibres is postulated. Because the three fibre species show limited signs of dissolution in the tissue, they cannot act as source of elements (primarily Fe, P and Ca) promoting nucleation and growth of asbestos bodies. Hence, the limited number of coated fibres should be due to the lack of nutrients or organic nature. PMID:26705886

  8. Fixed-Dose Subcutaneous Methylnaltrexone in Patients with Advanced Illness and Opioid-Induced Constipation: Results of a Randomized, Placebo-Controlled Study and Open-Label Extension

    PubMed Central

    Wellman, Charles V.; Israel, Robert J.; Barrett, Andrew C.; Paterson, Craig; Forbes, William P.

    2015-01-01

    Abstract Background: Subcutaneous methylnaltrexone (MNTX), dosed based on body weight, is efficacious and well tolerated in inducing bowel movements in patients with advanced illness and opioid-induced constipation (OIC); however, fixed-dose administration of MNTX may improve ease of administration. Objective: The study objective was to assess safety and efficacy of fixed-dose MNTX in two phase 4 trials. Methods: In a double-blind, randomized, placebo-controlled trial (RCT), patients with advanced illness and OIC received MNTX (8 mg or 12 mg by body weight [38 kg to <62 kg or ≥62 kg, respectively]) or placebo every other day (QOD) for two weeks. Patients completing the RCT could enroll in an open-label extension (OLE) study with MNTX administered as needed (PRN). The primary endpoint was percentage of patients with a rescue-free bowel movement (RFBM) within four hours after ≥2 of the first 4 doses in the first week. Results: In the RCT, 116 and 114 patients received MNTX and placebo, respectively, and 149 patients continued to the OLE study. The percentage of patients achieving primary endpoint was 62.9% and 9.6% for MNTX and placebo groups, respectively (p<0.0001). Median time to RFBM after the first dose was 0.8 hour and 23.6 hours in MNTX and placebo groups, respectively (p<0.0001). Efficacy results during the OLE study were consistent with the RCT. MNTX demonstrated a favorable safety profile in the RCT and OLE study. Conclusion: Fixed-dose MNTX administered QOD in the RCT and PRN in the OLE study demonstrated robust efficacy and was well tolerated in treating OIC in patients with advanced illness. PMID:25973526

  9. Impact of titanium dioxide nanoparticles on the bacterial communities of biological activated carbon filter intended for drinking water treatment.

    PubMed

    Zhiyuan, Liu; Shuili, Yu; Heedeung, Park; Qingbin, Yuan; Guicai, Liu; Qi, Li

    2016-08-01

    Titanium dioxide nanoparticles (TiO2 NPs) are inevitably present in the aquatic environment owing to their increasing production and use. However, knowledge of the potential effects of TiO2 NPs on the treatment of drinking water is scarce. Herein, the effects of two types of anatase TiO2 NPs (TP1, 25 nm; TP2, 100 nm) on the bacterial community in a biological activated carbon (BAC) filter were investigated via quantitative polymerase chain reaction (Q-PCR) analysis, ATP quantification, and 454 pyrosequencing analysis. Both TP1 and TP2 significantly inhibited the bacterial ATP level (p < 0.01) and induced a decrease in the abundance of bacterial 16S rDNA gene copies at doses of 0.1 and 100 mg L(-1). Simultaneously, the diversity and evenness of the bacterial communities were considerably reduced. The relative abundances of bacteria annotated to OTUs from Nitrospira class and Betaproteobacteria class decreased upon TiO2 NP treatment, whereas those of Bacilli class and Gammaproteobacteria class increased. TiO2 NP size showed a greater effect on the bacterial composition than did the dose based on Bray-Curtis distances. These findings identified negative effects of TiO2 NPs on the bacterial community in the BAC filter. Given the fact that BAC filters are used widely in drinking water treatment plants, these results suggested a potential threat by TiO2 NP to drinking water treatment system. PMID:27126871

  10. Using laboratory x-ray and cobalt-60 irradiations to predict CMOS device response in strategic and space environments

    SciTech Connect

    Fleetwood, D.M.; Winokur, P.S.; Schwank, J.R.

    1988-12-01

    The postirradiation response of CMOS transistors with 30-60 nm gate oxides is investigated as a function of radiation energy, total dose, dose rate, and annealing time. Measurements of threshold voltage, oxide-trapped charge, and interface traps are reported for times ranging from 10 ms to 4 months following LINAC, Co-60, Cs-137, and 10-keV x-ray irradiations. Exposure dose rates vary by 11 orders of magnitude: from 0.05 to 6 x 10/sup 9/ rad(SiO/sub 2/)/s. To within the +- 10 percent uncertainty in the overall dosimetry, no true dose rate effects on MOS device response are observed. Further, for these devices, interface trap and oxide-trapped charge densities are found to be linear with total dose. Based on these results, and subject to future verification, preliminary recommendations are made for lot acceptance testing of hardened CMOS circuits and devices intended for use in space and strategic environments. These include an endorsement of Co-60 exposure and elevated temperature annealing for qualification of devices for use in space environments and a recommendation for the use of x-ray exposures at dose rates greater than -- 2000 rad (SiO/sub 2/)/s, in addition to Co-60 irradiations according to MIL-STD method 1019.3, for strategic applications. These tests are practical to implement, and should provide greatly improved confidence in CMOS performance in space and strategic applications over that obtained with MIL-STD 1019.3 testing.

  11. Wound Healing Essentials: Let There Be Oxygen

    PubMed Central

    Sen, Chandan K.

    2009-01-01

    The state of wound oxygenation is a key determinant of healing outcomes. From a diagnostic standpoint, measurements of wound oxygenation are commonly used to guide treatment planning such as amputation decision. In preventive applications, optimizing wound perfusion and providing supplemental O2 in the peri-operative period reduces the incidence of post-operative infections. Correction of wound pO2 may, by itself, trigger some healing responses. Importantly, approaches to correct wound pO2 favorably influence outcomes of other therapies such as responsiveness to growth factors and acceptance of grafts. Chronic ischemic wounds are essentially hypoxic. Primarily based on the tumor literature, hypoxia is generally viewed as being angiogenic. This is true with the condition that hypoxia be acute and mild to modest in magnitude. Extreme near-anoxic hypoxia, as commonly noted in problem wounds, is not compatible with tissue repair. Adequate wound tissue oxygenation is required but may not be sufficient to favorably influence healing outcomes. Success in wound care may be improved by a personalized health care approach. The key lies in our ability to specifically identify the key limitations of a given wound and in developing a multifaceted strategy to specifically address those limitations. In considering approaches to oxygenate the wound tissue it is important to recognize that both too little as well as too much may impede the healing process. Oxygen dosing based on the specific need of a wound therefore seems prudent. Therapeutic approaches targeting the oxygen sensing and redox signaling pathways are promising. PMID:19152646

  12. 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

  13. Comparison of the analgesic effect of patient-controlled oxycodone and fentanyl for pain management in patients undergoing colorectal surgery.

    PubMed

    Jung, Kyeo-Woon; Kang, Hyeon-Wook; Park, Chan-Hye; Choi, Byung-Hyun; Bang, Ji-Yeon; Lee, Soo-Han; Lee, Eun-Kyung; Choi, Byung-Moon; Noh, Gyu-Jeong

    2016-08-01

    Oxycodone is a μ-opioid receptor agonist and is generally indicated for the relief of moderate to severe pain. The aim of this study was to compare the analgesic efficacy of patient-controlled oxycodone and fentanyl for postoperative pain in patients undergoing colorectal surgery. Patients scheduled to undergo elective colorectal surgery (n=82) were allocated to receive oxycodone (n=41, concentration of 1 mg/mL) or fentanyl (n=41, concentration of 15 μg/mL) for postoperative pain management. After the operation, pain using a numerical rating scale (NRS), delivery to demand ratio, infused dose of patient-controlled analgesia (PCA), side effects, and sedation levels were evaluated. Median (25%-75%) cumulative PCA dose of oxycodone group at 48 hours (66.9, 58.4-83.7 mL) was significantly less than that of fentanyl group (80.0, 63.4-103.3 mL, P=.037). Six hours after surgery, the mean (SD) NRS scores of the oxycodone and fentanyl groups were 6.2 (2.4) and 6.8 (1.9), respectively (P=.216). The mean equianalgesic potency ratio of oxycodone to fentanyl was 55:1. The groups did not differ in postoperative nausea, vomiting, and level of sedation. Patient-controlled oxycodone provides similar effects for pain relief compared to patient-controlled fentanyl in spite of less cumulative PCA dose. Based on these results, oxycodone can be a useful alternative to fentanyl for PCA in patients after colorectal surgery. PMID:27128496

  14. 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

  15. 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. PMID:26226448

  16. Nevirapine exposure with WHO pediatric weight band dosing: enhanced therapeutic concentrations predicted based on extensive international pharmacokinetic experience.

    PubMed

    Nikanjam, Mina; Kabamba, Desiré; Cressey, Tim R; Burger, David; Aweeka, Francesca T; Acosta, Edward P; Spector, Stephen A; Capparelli, Edmund V

    2012-10-01

    Nevirapine (NVP) is a nonnucleoside reverse transcriptase inhibitor (NNRTI) used worldwide as part of combination antiretroviral therapy in infants and children to treat HIV infection. Dosing based on either weight or body surface area has been approved by the U.S. Food and Drug Administration (FDA) but can be difficult to implement in resource-limited settings. The World Health Organization (WHO) has developed simplified weight band dosing for NVP, but it has not been critically evaluated. NVP pharmacokinetic data were combined from eight pediatric clinical trials (Pediatric AIDS Clinical Trials Group [PACTG] studies 245, 356, 366, 377, 403, 1056, and 1069 and Children with HIV in Africa Pharmacokinetics and Adherence of Simple Antiretroviral Regimens [CHAPAS]) representing subjects from multiple continents and across the pediatric age continuum. A population pharmacokinetic model was developed to characterize developmental changes in NVP disposition, identify potential sources of NVP pharmacokinetic variability, and assess various pediatric dosing strategies and their impact on NVP exposure. Age, CYP2B6 genotype, and ritonavir were independent predictors of oral NVP clearance. The Triomune fixed-dose tablet was an independent predictor of bioavailability compared to the liquid and other tablet formulations. Monte Carlo simulations of the final model were used to assess WHO weight band dosing recommendations. The final pharmacokinetic model indicated that WHO weight band dosing is likely to result in a percentage of children with NVP exposure within the target range similar to that obtained with FDA dosing. Weight band dosing of NVP proposed by the WHO has the potential to provide a simple and effective dosing strategy for resource limited settings. PMID:22869579

  17. 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

  18. Modelling PK/QT relationships from Phase I dose-escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations.

    PubMed

    Sinclair, Karen; Kinable, Els; Grosch, Kai; Wang, Jixian

    2016-05-01

    In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose-escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose-concentration and concentration-QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug-drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose-escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision-making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26991506

  19. Tailoring iron chelation by iron intake and serum ferritin: the prospective EPIC study of deferasirox in 1744 patients with transfusion-dependent anemias

    PubMed Central

    Cappellini, Maria Domenica; Porter, John; El-Beshlawy, Amal; Li, Chi-Kong; Seymour, John F.; Elalfy, Mohsen; Gattermann, Norbert; Giraudier, Stéphane; Lee, Jong-Wook; Chan, Lee Lee; Lin, Kai-Hsin; Rose, Christian; Taher, Ali; Thein, Swee Lay; Viprakasit, Vip; Habr, Dany; Domokos, Gabor; Roubert, Bernard; Kattamis, Antonis

    2010-01-01

    Background Following a clinical evaluation of deferasirox (Exjade®) it was concluded that, in addition to baseline body iron burden, ongoing transfusional iron intake should be considered when selecting doses. The 1-year EPIC study, the largest ever investigation conducted for an iron chelator, is the first to evaluate whether fixed starting doses of deferasirox, based on transfusional iron intake, with dose titration guided by serum ferritin trends and safety markers, provides clinically acceptable chelation in patients (aged ≥2 years) with transfusional hemosiderosis from various types of anemia. Design and Methods The recommended initial dose was 20 mg/kg/day for patients receiving 2–4 packed red blood cell units/month and 10 or 30 mg/kg/day was recommended for patients receiving less or more frequent transfusions, respectively. Dose adjustments were based on 3-month serum ferritin trends and continuous assessment of safety markers. The primary efficacy end-point was change in serum ferritin after 52 weeks compared with baseline. Results The 1744 patients enrolled had the following conditions; thalassemia (n=1115), myelodysplastic syndromes (n=341), aplastic anemia (n=116), sickle cell disease (n=80), rare anemias (n=43) and other transfused anemias (n=49). Overall, there was a significant reduction in serum ferritin from baseline (−264 ng/mL; P<0.0001), reflecting dosage adjustments and ongoing iron intake. The most common (>5%) adverse events were gastrointestinal disturbances (28%) and skin rash (10%). Conclusions Analysis of this large, prospectively collected data set confirms the response to chelation therapy across various anemias, supporting initial deferasirox doses based on transfusional iron intake, with subsequent dose titration guided by trends in serum ferritin and safety markers (clinicaltrials.gov identifier: NCT00171821). PMID:19951979

  20. A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice

    PubMed Central

    Eckhoff, Grace; Charles, Richelle C.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Qadri, Firdausi; Vann, W. F.; Kováč, Pavol; Ryan, Edward T.

    2015-01-01

    Background Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Methodology Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 μg), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. Principle Findings Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 μg). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. Conclusion We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. PMID:26154421

  1. Intrinsic dosimetry of glass containers used to transport nuclear materials: Potential implications to the fields of waste management and nuclear forensics

    SciTech Connect

    Schwantes, Jon M.; Miller, Steve D.; Piper, Roman K.; Murphy, Mark K.; Amonette, James E.; Bonde, Steven E.; Duckworth, Douglas C.

    2009-04-12

    Thermoluminescence (TL) and Electron Paramagnetic Resonance (EPR) dosimetry were used to measure dose effects in borosilicate glass with time, from 10 min to w60 days following exposure to a dose of up to 100 Gy. TL and EPR results were consistent and performed similarly, with both techniques capable of achieving an estimated limit of detection of between 0.5 and 1 Gy. Three peaks were identified in the TL glow curve at roughly 110 C, 205 C, and 225 C. The intensity of the 205 C peak was the dominant peak over the time period of this study. The stability of all of the peaks with time since irradiation increased with their corresponding temperature and no significant variation was observed in the glow curve response to a specified total dose attained at different dose rates. The intensity of the 205 C peak decreased logarithmically with time regardless of total dose. Based upon a conservative limit of detection of 3.3 Gy, a 100 Gy dose would still be detected 2.7E3 years after exposure. Here, we introduce the concept of intrinsic dosimetry, the measurement of the total absorbed dose received by the walls of a container containing radioactive material. The foreseen advantage of intrinsic dosimetry comes from considering the measured absorbed dose received by containers in concert with the characteristics (amount, type) of the source of that dose, the radioactive material contained within the walls of the container, in order to provide enhanced information about the history of an unknown sample in question. Three hypothetical scenarios are presented to introduce this method and to illustrate how intrinsic dosimetry might benefit the fields of nuclear forensics and waste management.

  2. Evaluation of vegetables in Tsukuba for contamination with radioactive materials from the accident at Fukushima Daiichi nuclear power plant.

    PubMed

    Isobe, Tomonori; Mori, Yutaro; Takada, Kenta; Sato, Eisuke; Takahashi, Hideki; Sekiguchi, Takao; Yoshimura, Yousuke; Sakurai, Hideyuki; Sakae, Takeji

    2013-10-01

    A large amount of radioactive material was released into the atmosphere after the accident of the Fukushima Daiichi Nuclear Power Plant following the Tohoku earthquake on 11 March 2011, and traces of these materials were detected in Tsukuba. Because radioactive materials can adhere to vegetables, the authors made a qualitative evaluation of vegetables in Tsukuba, estimated internal exposure dose based on quantitative measurement results, and investigated several decontamination methods. Qualitative analysis of vegetable contamination was done by autoradiography. Quantitative analysis was done using a high-purity germanium detector. To assess decontamination, two methods were tested: one with running water and the other with boiling water. In addition, boiled soup stock was measured. In the qualitative evaluation by autoradiography, radioactive materials were not uniformly distributed but adhered to vegetables in clumps and hot spots. In the quantitative evaluation to measure contamination of outer and inner leaves of sanchu lettuce, it was observed that the concentration of I was 8,031.35 ± 764.79 Bq kg in the outer leaves and 115.28 ± 20.63 Bq kg in the inner leaves. In addition, the concentration of Cs was 1,371.93 ± 366.45 Bq kg in the outer leaves and 9.68 ± 15.03 Bq kg in the inner leaves. This suggests that one can greatly reduce internal exposure dose by removing the outer leaves if one has to eat vegetables just after a nuclear accident. In the decontamination assessment, a decontamination efficiency of up to 70% was achieved by boiling vegetables for 20 min. PMID:23982606

  3. Adjusting Cyclophosphamide Dose in Obese Patients with Lymphoma Is Safe and Yields Favorable Outcomes after Autologous Hematopoietic Cell Transplantation.

    PubMed

    Bachanova, Veronika; Rogosheske, John; Shanley, Ryan; Burns, Linda J; Smith, Sara M; Weisdorf, Daniel J; Brunstein, Claudio G

    2016-03-01

    No clear dosing guidelines exist for cyclophosphamide (Cy) dose adjustments in obese patients treated with high-dose chemoradiotherapy followed by autologous hematopoietic cell transplantation (HCT). We prospectively compared the outcomes of high-dose Cy/total body irradiation (TBI) conditioning in 147 non-Hodgkin lymphoma (NHL) patients in 3 weight groups: nonobese (<120% ideal body weight [IBW]; n = 72), overweight (120% to 149% IBW; n = 46), and obese (≥150% IBW; n = 29). Nonobese and overweight patients received Cy (120 mg/kg of total body weight, intravenously) and TBI (1320 cGy), whereas obese patients (median body mass index, 36) received an adjusted Cy dose based on IBW plus 50% of the difference between total body weight and IBW (AdjBW50). The median patient age was 57 years (range, 19 to 73). The most common diagnoses were diffuse large B cell lymphoma (n = 57) and mantle cell lymphoma (n = 51). Three-year overall survival was 61% (95% confidence interval [CI], 48% to 72%) for nonobese patients, 68% (95% CI, 52% to 82%) for overweight patients, and 80% (95% CI, 62% to 93%) for obese patients. Cumulative incidence of relapse (48%, 43%, and 38%, respectively) and nonrelapse mortality (∼4%) were similar in all groups. Hemorrhagic cystitis and cardiac toxicity were rare events. Our data show that the AdjBW50 formula can be safely and effectively used for Cy dose adjustments in obese patients treated for NHL with high-dose Cy/TBI conditioning followed by autologous HCT. PMID:26497907

  4. 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

  5. Prandial Insulin Dosing Using the Carbohydrate Counting Technique in Hospitalized Patients With Type 2 Diabetes

    PubMed Central

    Dungan, Kathleen M.; Sagrilla, Colleen; Abdel-Rasoul, Mahmoud; Osei, Kwame

    2013-01-01

    OBJECTIVE To compare a modified fixed meal dosing strategy to flexible meal dosing in hospitalized patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Patients (N = 126) with refractory hyperglycemia or requiring at least 20 units of insulin per day were randomly assigned to fixed meal dosing (including withholding the dose if less than half of the meal tray was consumed) or flexible meal dosing based upon carbohydrate intake. The inpatient diabetes management team made all treatment adjustments. Outcomes included day 3 mean glucose, 72-h glucose trend analysis, hypoglycemia (<3.9 mmol/L), and inpatient diabetes treatment satisfaction. RESULTS The mean glucose on day 3 was 9.5 and 8.8 mmol/L in the fixed and flexible meal groups, respectively (P = 0.26). The frequency of hypoglycemia was 23 and 39% overall in the fixed and flexible meal groups (P = 0.08), with half of events occurring in the morning. There was a wide range of carbohydrate intake (median 51 g/meal, 10–90% range 26–72 g on day 3). The fixed dose group required significantly more prandial insulin overall and more correction insulin over time. There was no difference in composite treatment satisfaction or dosing miscalculations between groups. CONCLUSIONS A fixed meal dosing strategy provided similar glucose control as flexible meal dosing, when managed by an inpatient diabetes treatment team. However, a larger sample size would be needed to definitively evaluate a treatment effect of flexible meal dosing in the hospital. Further study is needed to improve the delivery of bolus insulin in hospitalized patients. PMID:24062326

  6. 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. PMID:26826355

  7. INTRINSIC DOSIMETRY OF GLASS CONTAINERS USED TO TRANSPORT NUCLEAR MATERIALS: Potential Implications to the Field of Nuclear Forensics

    SciTech Connect

    Schwantes, Jon M.; Miller, Steven D.; Piper, Roman K.; Murphy, Mark K.; Amonette, James E.; Bonde, Steven E.; Duckworth, Douglas C.

    2008-09-15

    Thermoluminescence (TL) and Electron Paramagnetic Resonance (EPR) dosimetry were used to measure dose effects in borosilicate glass with time, from 10 minutes to ~60 days following exposure to a dose of up to 10,000 Rad. TL and EPR results were consistent and performed similarly, with both techniques capable of achieving an estimated limit of detection of between 50-100 Rad. Three peaks were identified in the TL glow curve at roughly 110oC, 205oC, and 225oC. The intensity of the 205oC peak was the dominant peak over the time period of this study. The stability of all of the peaks with time since irradiation increased with their corresponding temperature and little or no variation was observed in the glow curve response to a specified total dose attained at different dose rates. The intensity of the 205oC peak decreased logarithmically with time regardless of total dose. Based upon a conservative limit of detection of 330 Rad, a 10,000 Rad dose would still be detected 2.7E3 years after exposure. This paper introduces the concept of intrinsic dosimetry, the consideration of a measured dose received to container walls in concert with the physical characteristics of the radioactive material contained inside those walls, as a method for gathering rather unique pathway information about the history of that sample. Three hypothetical scenarios are presented to introduce this method and to illustrate how intrinsic dosimetry might benefit the fields of nuclear forensics and waste management.

  8. Biosphere model for assessing doses from nuclear waste disposal

    SciTech Connect

    Sheppard, M.I.; Zach, R.; Sheppard, S.C.; Amiro, B.D.

    1996-12-01

    In Canada`s nuclear fuel waste disposal concept, the waste would be placed in corrosion-resistant metal containers, surrounded by clay-based buffer and backfill materials, in a vault deep in plutonic rock of the Canadian Shield. The engineered and natural barriers of the disposal system are designed to isolate the waste from the surface environment. Nevertheless, isolation may not be complete for all time and nuclides could reach the surface environment. Because this would likely occur far in the future, the impact on the environment and humans must be predicted with the help of mathematical models. The Atomic Energy Control Board (AECB), a key regulator of Canada`s nuclear industry, requires that quantitative model simulations extend to at least 10,000 years. The AECB has established an individual risk limit for human exposure of 10{sup -6} serious health effects per year. This limit corresponds to a radiological dose of 0.05 mSv/a or about 2.5% of the natural background dose, based on the AECB`s risk conversion factor of 0.02. To demonstrate environmental and human safety, radiological doses are predicted to a member of a self-sufficient critical group, the most exposed people for up to 10,000 years. For times longer than 10,000 years, reasoned arguments are required to show that no sudden or dramatic increases will occur that would be unacceptable by today`s standards. Our predictions are based on linked vault, geosphere and biosphere models, which compose the system model.

  9. MO-E-17A-04: Size-Specific Dose Estimate (SSDE) Provides a Simple Method to Calculate Organ Dose for Pediatric CT Examinations

    SciTech Connect

    Moore, B; Brady, S; Kaufman, R; Mirro, A

    2014-06-15

    Purpose: Investigate the correlation of SSDE with organ dose in a pediatric population. Methods: Four anthropomorphic phantoms, representing a range of pediatric body habitus, were scanned with MOSFET dosimeters placed at 23 organ locations to determine absolute organ dosimetry. Phantom organ dosimetry was divided by phantom SSDE to determine correlation between organ dose and SSDE. Correlation factors were then multiplied by patient SSDE to estimate patient organ dose. Patient demographics consisted of 352 chest and 241 abdominopelvic CT examinations, 22 ± 15 kg (range 5−55 kg) mean weight, and 6 ± 5 years (range 4 mon to 23 years) mean age. Patient organ dose estimates were compared to published pediatric Monte Carlo study results. Results: Phantom effective diameters were matched with patient population effective diameters to within 4 cm. 23 organ correlation factors were determined in the chest and abdominopelvic region across nine pediatric weight subcategories. For organs fully covered by the scan volume, correlation in the chest (average 1.1; range 0.7−1.4) and abdominopelvic (average 0.9; range 0.7−1.3) was near unity. For organs that extended beyond the scan volume (i.e., skin, bone marrow, and bone surface), correlation was determined to be poor (average 0.3; range: 0.1−0.4) for both the chest and abdominopelvic regions, respectively. Pediatric organ dosimetry was compared to published values and was found to agree in the chest to better than an average of 5% (27.6/26.2) and in the abdominopelvic region to better than 2% (73.4/75.0). Conclusion: Average correlation of SSDE and organ dosimetry was found to be better than ± 10% for fully covered organs within the scan volume. This study provides a list of organ dose correlation factors for the chest and abdominopelvic regions, and describes a simple methodology to estimate individual pediatric patient organ dose based on patient SSDE.

  10. SU-E-J-204: Radiation Dose to Patients Resulting From Image Guidance Procedures and AAPM TG-180 Update

    SciTech Connect

    Ding, G; Alaei, P

    2014-06-01

    Purpose: Image-guided radiation therapy (IGRT) is the new paradigm for patient positioning and target localization in radiotherapy. Daily imaging procedures add additional dose to the patient's treatment volume and normal tissues and may expose the organs at risk to unaccounted doses. This presentation is to update the progress of AAPM TG-180 which aims to provide strategies to quantify and account the dose from both MV and kV imaging in patient treatment planning. Methods: Our current knowledge on image guidance dose is presented. A summary of doses from image guidance procedures delivered to patients in relationship with therapeutic doses is given. Different techniques in reducing the image guidance dose are summarized. Typical organ doses resulting from different image acquisition procedures used in IGRT are tabulated. Results: Many techniques to reduce the imaging doses are available in clinical applications. There are large variations between dose to bone and dose to soft tissues for x-rays at kilovoltage energy range. Methods for clinical implementation of accounting for the imaging dose from an imaging procedure are available. Beam data from imaging systems can be generated by combining Monte Carlo simulations and experimental measurements for commissioning imaging beams in the treatment planning. Conclusion: The current treatment planning systems are not yet equipped to perform patient specific dose calculations resulting from kV imaging procedures. The imaging dose from current kV image devices has been significantly reduced and is generally much less than that resulting from MV. Because the magnitude of kV imaging dose is significantly low and the variation between patients is modest, it is feasible to estimate dose based on imaging producers or protocols using tabulated values which provides an alternative to accomplish the task of accounting and reporting imaging doses.

  11. Magnetomotive optical coherence elastography (MM-OCE) for thermal therapy dosimetry (Conference Presentation)

    NASA Astrophysics Data System (ADS)

    Huang, Pin-Chieh; Marjanovic, Marina; Spillman, Darold R.; Odintsov, Boris M.; Boppart, Stephen A.

    2016-03-01

    Biomechanical properties of tissues have been utilized for disease detection, diagnosis, and progression, however they have not been extensively utilized for therapy dosimetry. Magnetic hyperthermia aims to kill cells and ablate tumors using magnetic nanoparticles (MNPs) either injected in or targeted to tumors. Upon application of an appropriate AC magnetic field, MNPs can heat target tissue while sparing non-targeted healthy tissue. However, a sensitive monitoring technique for the dose of magnetic hyperthermia is needed to prevent over-treatment and collateral injury. During hyperthermia treatments, the viscoelastic properties of tissues are altered due to protein denaturation, coagulation, and tissue dehydration, making these properties candidates for dosimetry. Magnetomotive optical coherence elastography (MM-OCE) utilizes MNPs as internal force transducers to probe the biomechanical properties of tissues. Therefore, we aim to evaluate the hyperthermia dose based on the elastic changes revealed by MM-OCE. In this study, MNPs embedded in tissues were utilized for both hyperthermia and MM-OCE measurements. Tissue temperature and elastic modulus were obtained, where the elastic modulus was extracted from the resonance frequency detected by MM-OCE. Results showed a correlation between stiffness and temperature change following treatment. To investigate the thermal-dose-dependent changes, intervals of hyperthermia treatment were repeatedly performed on the same tissue sequentially, interspersed with MM-OCE. With increasing times of treatment, tissue stiffness increased, while temperature rise remained relatively constant. These results suggest that MM-OCE may potentially identify reversible and irreversible tissue changes during thermal therapy, supporting the use of MM-OCE for dosimetric control of hyperthermia in future applications.

  12. 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.

  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 d