Science.gov

Sample records for derived reference doses

  1. Derivation of a chronic oral reference dose for cobalt.

    PubMed

    Finley, Brent L; Monnot, Andrew D; Paustenbach, Dennis J; Gaffney, Shannon H

    2012-12-01

    Cobalt (Co) is an essential element in humans as a component of vitamin B12. However, at high levels Co exposure has been shown to have detrimental effects. This study was designed to identify a chronic oral reference dose (RfD) for Co. Currently available data indicate that non-cancer health effects associated with Co exposure may include hematological, neurological, immunological, reproductive, cardiovascular, and endocrine responses. This analysis employs the standard US EPA risk assessment methodology for establishing a chronic RfD. In this analysis, the Jaimet and Thode (1955) 10-week, multiple dose human study of thyroid effects (decreased iodine uptake) in children was determined to be the most robust and sensitive study for identifying a potential point of departure dose (POD). A dose of 0.9 mgCo/kg-day was chosen as the POD. Consistent with the US EPA's previous derivation of the perchlorate RfD, which is also based on decreased iodine uptake in humans, we considered several uncertainly factors (UFs), and determined that a factor of 10 for human variability was appropriate, as well as a factor of three for database adequacy. Applying an aggregate uncertainty factor of 30 to the POD yields a chronic oral RfD of 0.03 mg/kg-day. We believe this value would be protective of non-cancer health effects in the general population for a lifetime of daily exposure to Co. PMID:22982439

  2. Toxic Effects of Tetrabromobisphenol A on Thyroid Hormones in SD Rats and the Derived-reference Dose.

    PubMed

    Yang, Yan; Ni, Wei Wei; Yu, Lin; Cai, Ze; Yu, Yun Jiang

    2016-04-01

    The present study determined the thyroid hormone interference of tetrabromobisphenol A (TBBPA) in Sprague-Dawley (SD) rats, and the derived-reference dose (RfD) of different endpoint effects on mammals based on experimental results and data collection. Based on repeated exposure toxicity tests on mammals and extensive research, the present study used BMDS240 Software to derive a benchmark dose, and analyzed the accuracy and uncertainty, and similarity with other studies. Test results on triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH) demonstrated that all the indicators presented a non-monotonous dose-effect relationship clearly, except TSH in male rats exposed to 0-1000 mg/kg BW per day. Therefore, RfDs were derived from different critical effects. In summary, RfD for mammals in the present study was found to be 0.6 mg/kg per day. PMID:27241741

  3. Derivation of a reference dose and drinking water equivalent level for 1,2,3-trichloropropane.

    PubMed

    Tardiff, Robert G; Carson, M Leigh

    2010-06-01

    In some US potable water supplies, 1,2,3-trichloropropane (TCP) has been present at ranges of non-detect to less than 100 ppb, resulting from past uses. In subchronic oral studies, TCP produced toxicity in kidneys, liver, and other tissues. TCP administered by corn oil gavage in chronic studies produced tumors at multiple sites in rats and mice; however, interpretation of these studies was impeded by substantial premature mortality. Drinking water equivalent levels (DWELs) were estimated for a lifetime of consumption by applying biologically-based safety/risk assessment approaches, including Monte Carlo techniques, and with consideration of kinetics and modes of action, to possibly replace default assumptions. Internationally recognized Frameworks for human relevance of animal data were employed to interpret the findings. Calculated were a reference dose (=39 microg/kg d) for non-cancer and Cancer Values (CV) (=10-14 microg/kg d) based on non-linear dose-response relationships for mutagenicity as a precursor of cancer. Lifetime Average Daily Intakes (LADI) are 3130 and 790-1120 microg/person-d for non-cancer and cancer, respectively. DWELs, estimated by applying a relative source contribution (RSC) of 50% to the LADIs, are 780 and 200-280 microg/L for non-cancer and cancer, respectively. These DWELs may inform establishment of formal/informal guidelines and standards to protect public health. PMID:20303376

  4. Evidence of dose saving in routine CT practice using iterative reconstruction derived from a national diagnostic reference level survey

    PubMed Central

    Hayton, A; Beveridge, T; Marks, P; Wallace, A

    2015-01-01

    Objective: To assess the influence and significance of the use of iterative reconstruction (IR) algorithms on patient dose in CT in Australia. Methods: We examined survey data submitted to the Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) National Diagnostic Reference Level Service (NDRLS) during 2013 and 2014. We compared median survey dose metrics with categorization by scan region and use of IR. Results: The use of IR results in a reduction in volume CT dose index of between 17% and 44% and a reduction in dose–length product of between 14% and 34% depending on the specific scan region. The reduction was highly significant (p < 0.001, Wilcoxon rank-sum test) for all six scan regions included in the NDRLS. Overall, 69% (806/1167) of surveys included in the analysis used IR. Conclusion: The use of IR in CT is achieving dose savings of 20–30% in routine practice in Australia. IR appears to be widely used by participants in the ARPANSA NDRLS with approximately 70% of surveys submitted employing this technique. Advances in knowledge: This study examines the impact of the use of IR on patient dose in CT on a national scale. PMID:26133224

  5. Arterial input functions (AIFs) measured directly from arteries with low and standard doses of contrast agent, and AIFs derived from reference tissues

    PubMed Central

    Wang, Shiyang; Fan, Xiaobing; Medved, Milica; Pineda, Federico D.; Yousuf, Ambereen; Oto, Aytekin; Karczmar, Gregory S.

    2016-01-01

    Measurements of arterial input function (AIF) can have large systematic errors at standard contrast agent doses in dynamic contrast enhanced MRI (DCE-MRI). We compared measured AIFs from low dose (AIFLD) and standard dose (AIFSD) contrast agent injections, as well as the AIF derived from a muscle reference tissue and artery (AIFref). Twenty-two prostate cancer patients underwent DCE-MRI. Data were acquired on a 3 T scanner using an mDixon sequence. Gadobenate dimeglumine was injected twice, at doses of 0.015 and 0.085 mmol/kg. Directly measured AIFs were fitted with empirical mathematical models (EMMs) and compared to the AIF derived from a muscle reference tissue (AIFref). EMMs accurately fitted the AIFs. The 1st and 2nd pass peaks were visualized in AIFLD, but not in AIFSD, thus the peak and shape of AIFSD could not be accurately measured directly. The average scaling factor between AIFSD and AIFLD in the washout phase was only 56% of the contrast dose ratio (~6:1). The shape and magnitude of AIFref closely approximated that of AIFLD after empirically determined dose-dependent normalization. This suggests that AIFref may be a good approximation of the local AIF. PMID:26523650

  6. Derived reference doses for three compounds used in the photovoltaics industry: Copper indium diselenide, copper gallium diselenide, and cadmium telluride

    SciTech Connect

    Moskowitz, P.D.; Bernholc, N.; DePhillips, M.P.; Viren, J.

    1995-07-06

    Polycrystalline thin-film photovoltaic modules made from copper indium diselenide (CIS), copper gallium diselenide (CGS), and cadmium telluride (CdTe) arc nearing commercial development. A wide range of issues are being examined as these materials move from the laboratory to large-scale production facilities to ensure their commercial success. Issues of traditional interest include module efficiency, stability and cost. More recently, there is increased focus given to environmental, health and safety issues surrounding the commercialization of these same devices. An examination of the toxicological properties of these materials, and their chemical parents is fundamental to this discussion. Chemicals that can present large hazards to human health or the environment are regulated often more strictly than those that are less hazardous. Stricter control over how these materials are handled and disposed can increase the costs associated with the production and use of these modules dramatically. Similarly, public perception can be strongly influenced by the inherent biological hazard that these materials possess. Thus, this report: presents a brief background tutorial on how toxicological data are developed and used; overviews the toxicological data available for CIS, CGS and CdTe; develops ``reference doses`` for each of these compounds; compares the reference doses for these compounds with those of their parents; discusses the implications of these findings to photovoltaics industry.

  7. Derivation of a bisphenol A oral reference dose (RfD) and drinking-water equivalent concentration.

    PubMed

    Willhite, Calvin C; Ball, Gwendolyn L; McLellan, Clifton J

    2008-02-01

    Human exposure to bisphenol A (BPA) is due to that found in the diet, and BPA and its metabolites were detected at parts per billion (or less) concentrations in human urine, milk, saliva, serum, plasma, ovarian follicular fluid, and amniotic fluid. Adverse health effects in mice and rats may be induced after parenteral injection or after massive oral doses. Controlled ingestion trials in healthy adult volunteers with 5 mg d16-BPA were unable to detect parent BPA in plasma despite exquisitely sensitive (limit of detection = 6 nM) methods, but by 96 h 100% of the administered dose was recovered in urine as the glucuronide. The extensive BPA glucuronidation following ingestion is not seen after parenteral injection; only the parent BPA binds plasma proteins and estrogen receptors (ER). The hypothesis that BPA dose-response may be described by a J- or U-shape curve was not supported by toxicogenomic data collected in fetal rat testes and epididymes (after repeated parenteral exposure at 2-400,000 microg/kg-d), where a clear monotonic dose-response both in the numbers of genes and magnitude of individual gene expression was evident. There is no clear indication from available data that the BPA doses normally consumed by humans pose an increased risk for immunologic or neurologic disease. There is no evidence that BPA poses a genotoxic or carcinogenic risk and clinical evaluations of 205 men and women with high-performance liquid chromatography (HPLC)-verified serum or urinary BPA conjugates showed (1) no objective signs, (2) no changes in reproductive hormones or clinical chemistry parameters, and (3) no alterations in the number of children or sons:daughters ratio. Results of benchmark dose (BMD10 and BMDL10) calculations and no-observed-adverse-effect level (NOAEL) inspections of all available and reproducible rodent studies with oral BPA found BMD and NOAEL values all greater than the 5 mg/kg-d NOAELs from mouse and rat multigeneration reproduction toxicity studies

  8. Acute reference doses: theory and practical approaches.

    PubMed

    Moretto, A

    2000-07-01

    The approach of the Joint Meeting on Pesticide Residues to the establishment of the acute reference dose for pesticides is presented and related issues are discussed. Three main points seem relevant when discussing the acute reference dose: (1) what compounds should have an acute reference dose, (2) what toxicological database is required for the establishment of an acute reference dose; (3) what safety factors are to be used. It is concluded that (1) groups of compounds that need an acute reference dose can be identified, whereas general rules for identifying groups not requiring an acute reference dose cannot be easily given; (2) studies from the standard toxicological database can often be used to allocate an acute reference dose and the usefulness of refinements (by requesting specific studies) should be evaluated after intake assessment; general rules on study requirements cannot be easily given; (3) more thought should be given to what safety factors apply in certain circumstances. PMID:10983586

  9. Derived Reference Doses (RfDs) for the environmental degradates of the herbicides alachlor and acetochlor: results of an independent expert panel deliberation.

    PubMed

    Gadagbui, Bernard; Maier, Andrew; Dourson, Michael; Parker, Ann; Willis, Alison; Christopher, John P; Hicks, Lebelle; Ramasamy, Santhini; Roberts, Stephen M

    2010-01-01

    An independent peer expert panel was convened under the auspices of the Alliance for Risk Assessment (ARA) to review toxicology data and derive oral Reference Doses (RfDs) for four environmental degradates of the acetanilide herbicides, alachlor and acetochlor. The degradates included in this evaluation were (1) alachlor tertiary-ethanesulfonic acid (ESA), (2) alachlor tertiary-oxanilic acid (OXA), (3) acetochlor ESA, and (4) acetochlor OXA. Each degradate was judged to have sufficient data for developing low to medium confidence RfD, with use of an additional uncertainty factor (UF) to cover data gaps. Body weight decreases were identified as the most sensitive treatment-related adverse effect for RfD development. A composite UF of 1000 (10 for human variability in sensitivity, 10 for interspecies differences in sensitivity, and 10 for subchronic to chronic and database deficiency combined; i.e., 10(A)x10(H)x10(S&D)) for each degradate was considered reasonable, while noting that an argument could be made for an UF of 3000 (10(A)x10(H)x30(S&D)). Based on the available data, an oral RfD of 0.2 mg/kg-day is recommended for both acetochlor ESA and acetochlor OXA and an oral RfD of 0.8 mg/kg-day is recommended for both alachlor ESA and alachlor OXA. PMID:20206657

  10. Derivation of dose conversion factors for tritium

    SciTech Connect

    Killough, G. G.

    1982-03-01

    For a given intake mode (ingestion, inhalation, absorption through the skin), a dose conversion factor (DCF) is the committed dose equivalent to a specified organ of an individual per unit intake of a radionuclide. One also may consider the effective dose commitment per unit intake, which is a weighted average of organ-specific DCFs, with weights proportional to risks associated with stochastic radiation-induced fatal health effects, as defined by Publication 26 of the International Commission on Radiological Protection (ICRP). This report derives and tabulates organ-specific dose conversion factors and the effective dose commitment per unit intake of tritium. These factors are based on a steady-state model of hydrogen in the tissues of ICRP's Reference Man (ICRP Publication 23) and equilibrium of specific activities between body water and other tissues. The results differ by 27 to 33% from the estimate on which ICRP Publication 30 recommendations are based. The report also examines a dynamic model of tritium retention in body water, mineral bone, and two compartments representing organically-bound hydrogen. This model is compared with data from human subjects who were observed for extended periods. The manner of combining the dose conversion factors with measured or model-predicted levels of contamination in man's exposure media (air, drinking water, soil moisture) to estimate dose rate to an individual is briefly discussed.

  11. Chemical warfare agents: estimating oral reference doses.

    PubMed

    Opresko, D M; Young, R A; Faust, R A; Talmage, S S; Watson, A P; Ross, R H; Davidson, K A; King, J

    1998-01-01

    Health risk assessments for sites contaminated with chemical warfare agents require a comparison of the potential levels of exposure with a characterization of the toxic potency of each chemical. For noncancer health effects, toxic potency is expressed in terms of Reference Doses (RfD). A RfD is a daily exposure level or dose (usually expressed in units of milligrams of chemical per kilogram body weight per day) for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious effects. A daily exposure at or below the RfD is not likely to be associated with health risks, but as the amount of chemical that an individual is exposed to increases above the RfD, the probability that an adverse effect will occur also increases. A RfD is derived by first examining the available human or animal toxicity data to identify a dose or exposure that corresponds to a no-observed-adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL). The NOAEL is the exposure level at which there are no statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Effects may be produced at this level, but they are not considered to be adverse if they do not result in functional impairment or pathological lesions that affect the performance of the whole organism or which reduce an organism's ability to cope with additional challenge. The LOAEL is the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. If only a LOAEL is identified by the toxicity data, a NOAEL is estimated by dividing the LOAEL by a factor no greater than 10. This extrapolation factor of 10 or less is termed the LOAEL-to-NOAEL Uncertainty Factor (UFL). The NOAEL is also adjusted by the application of other

  12. Total dose performance of radiation hardened voltage regulators and references

    NASA Technical Reports Server (NTRS)

    McClure, S.; Gorelick, J.; Pease, R.; Rax, B.; Ladbury, R.

    2001-01-01

    Total dose test of commercially available radiation hardened bipolar voltage regulators and references show reduced sensitivity to dose rate and varying sensitivity to bias under pressure. Behavior of critical parameters in different dose rate and bias conditions is compared and the impact to hardness assurance methodology is discussed.

  13. National reference doses for common radiographic, fluoroscopic and dental X-ray examinations in the UK.

    PubMed

    Hart, D; Hillier, M C; Wall, B F

    2009-01-01

    The National Patient Dose Database (NPDD) is maintained by the Radiation Protection Division of the Health Protection Agency. The latest review of the database analysed the data collected from 316 hospitals over a 5-year period to the end of 2005. The information supplied amounted to a total of 23 000 entrance surface dose measurements and 57 000 dose-area product measurements for single radiographs, and 208 000 dose-area product measurements along with 187 000 fluoroscopy times for diagnostic examinations or interventional procedures. In addition, patient dose data for dental X-ray examinations were included for the first time in the series of 5-yearly reviews. This article presents a summary of a key output from the NPDD - national reference doses. These are based on the third quartile values of the dose distributions for 30 types of diagnostic X-ray examination and 8 types of interventional procedure on adults, and for 4 types of X-ray examination on children. The reference doses are approximately 16% lower than the corresponding values in the previous (2000) review, and are typically less than half the values of the original UK national reference doses that were derived from a survey in the mid-1980s. This commentary suggests that two of the national reference doses from the 2000 review be retained as diagnostic reference levels because the older sample size was larger than for the 2005 review. No clear evidence could be found for the use of digital imaging equipment having a significant effect on dose. PMID:18852213

  14. Construction of Taiwanese Adult Reference Phantoms for Internal Dose Evaluation.

    PubMed

    Chang, Shu-Jun; Hung, Shih-Yen; Liu, Yan-Lin; Jiang, Shiang-Huei

    2016-01-01

    In the internal dose evaluation, the specific absorbed fraction (SAF) and S-value are calculated from the reference phantom based on Caucasian data. The differences in height and weight between Caucasian and Asian may lead to inaccurate dose estimation. In this study, we developed the Taiwanese reference phantoms. 40 volunteers were recruited. Magnetic resonance images (MRI) were obtained, and the contours of 15 organs were drawn. The Taiwanese reference man (TRM) and Taiwanese reference woman (TRW) were constructed. For the SAF calculation, the differences in the self-absorption SAF (self-SAF) between the TRM, TRW, and Oak Ridge National Laboratory (ORNL) adult phantom were less than 10% when the difference in organ mass was less than 20%. The average SAF from liver to pancreas of TRM was 38% larger than that of the ORNL adult phantom, and the result of TRW was 2.02 times higher than that of the ORNL adult phantom. For the S-value calculation, the ratios of TRW and ORNL adult phantom ranged from 0.91 to 1.57, and the ratios of TRM and ORNL adult phantom ranged from 1.04 to 2.29. The SAF and S-value results were dominantly affected by the height, weight, organ mass, and geometric relationship between organs. By using the TRM and TRW, the accuracy of internal dose evaluation can be increased for radiation protection and nuclear medicine. PMID:27618708

  15. [A new toxicological concept-acute reference dose].

    PubMed

    Liu, Zhiwei; Chen, Bingheng

    2003-01-01

    Acute reference dose (ARfD) is a new concept in toxicology and risk assessment, and mainly used for assessing health effect from short-time exposure to environmental chemicals. The ARfD of a chemical was defined as "an estimate of a substance in food or drinking water, expressed on a body weight basis, that can be ingested over a short period of time, usually during one meal or one day, without appreciable health risk to the consumer on the basis of all the known facts at the time of the evaluation. It is usually expressed in milligrams per kilogram of body weight." ARfD is different from ADI and reference dose. In this review the principles and methods in establishing ARfD were explained. PMID:12731294

  16. Dose homogeneity specification for reference dosimetry of nonstandard fields

    SciTech Connect

    Chung, Eunah; Soisson, Emilie; Seuntjens, Jan

    2012-01-15

    Purpose: To investigate the sensitivity of the plan-class specific correction factor to dose distributions in composite nonstandard field dosimetry. Methods: A cylindrical water-filled PMMA phantom was constructed at the center of which reference absorbed dose could be measured. Ten different TomoTherapy-based IMRT fields were created on the CT images of the phantom. The dose distribution for each IMRT field was estimated at the position of a radiation detector or ionization chamber. The dose in each IMRT field normalized to that in a reference 10 x 10 cm{sup 2} field was measured using a PTW micro liquid ion chamber. Based on the new dosimetry formalism, a plan-class specific correction factor k{sub Q{sub p{sub c{sub s{sub r,Q}{sup f{sub p}{sub c}{sub s}{sub r},f{sub r}{sub e}{sub f}}}}}} for each field was measured for two Farmer-type chambers, Exradin A12 and NE2571, as well as for a smaller Exradin A1SL chamber. The dependence of the measured correction factor on parameters characterizing dose distribution was analyzed. Results: Uncertainty on the plan-class specific correction factor measurement was in the range of 0.3%-0.5% and 0.3%-0.8% for the Farmer-type chambers and the Exradin A1SL, respectively. When the heterogeneity of the central region of the target volume was less than 5%, the correction factor did not differ from unity by more than 0.7% for the three air-filled ionization chambers. For more heterogeneous dose deliveries, the correction factor differed from unity by up to 2.4% for the Farmer-type chambers. For the Exradin A1SL, the correction factor was closer to unity due to the reduced effect of dose gradients, while it was highly variable in different IMRT fields because of a more significant impact of positioning uncertainties on the response of this chamber. Conclusions: The authors have shown that a plan-class specific correction factor can be specified as a function of plan evaluation parameters especially for Farmer-type chambers. This work

  17. Development of a reference dose for BDE-47, 99, and 209 using benchmark dose methods.

    PubMed

    Li, Lu Xi; Chen, Li; Cao, Dan; Chen, Bing Heng; Zhao, Yan; Meng, Xiang Zhou; Xie, Chang Ming; Zhang, Yun Hui

    2014-09-01

    Eleven recently completed toxicological studies were critically reviewed to identify toxicologically significant endpoints and dose-response information. Dose-response data were compiled and entered into the USEPA's benchmark dose software (BMDS) for calculation of a benchmark dose (BMD) and a benchmark dose low (BMDL). After assessing 91 endpoints across the nine studies, a total of 23 of these endpoints were identified for BMD modeling, and BMDL estimates corresponding to various dose-response models were compiled for these separate endpoints. Thyroid, neurobehavior and reproductive endpoints for BDE-47, -99, -209 were quantitatively evaluated. According to methods and feature of each study, different uncertainty factor (UF) value was decided and subsequently reference doses (RfDs) were proposed. Consistent with USEPA, the lowest BMDLs of 2.10, 81.77, and 1698 µg/kg were used to develop RfDs for BDE-47, -99, and -209, respectively. RfDs for BDE-99 and BDE-209 were comparable to EPA results, and however, RfD of BDE-47 was much lower than that of EPA, which may result from that reproductive/developmental proves to be more sensitive than neurobehavior for BDE-47 and the principal study uses very-low-dose exposure. PMID:25256863

  18. Patient Dose Reference Levels for Interventional Radiology: A National Approach

    SciTech Connect

    Vano, Eliseo Sanchez, R.; Fernandez, J. M.; Gallego, J. J.; Verdu, J. F.; Garay, M. Gonzalez de; Azpiazu, A.; Segarra, A.; Hernandez, M. T.; Canis, M.; Diaz, F.; Moreno, F.; Palmero, J.

    2009-01-15

    A set of patient dose reference levels (RLs) for fluoroscopically guided interventional procedures was obtained in a survey launched by the National Society of Interventional Radiology (IR), involving 10 public hospitals, as recommended by the European Medical Exposures Directive. A sample of 1391 dose values (kerma area product [KAP]) was collected randomly during clinical procedures for seven of the most frequent procedures. Third quartiles of the KAP distributions were used to set the RLs. A regular quality control of the X-ray systems and a calibration of the dose meters were performed during the survey. The fluoroscopy time and total number of digital subtraction angiography images per procedure were also analyzed. The RL values proposed were 12 Gy cm{sup 2} for fistulography (hemodialysis access; sample of 180 cases), 73 Gy cm{sup 2} for lower limb arteriography (685 cases), 89 Gy cm{sup 2} for renal arteriography (55 cases), 80 Gy cm{sup 2} for biliary drainage (205 cases), 289 Gy cm{sup 2} for hepatic chemoembolization (151 cases), 94 Gy cm{sup 2} for iliac stent (70 cases), and 236 Gy cm{sup 2} for uterine embolization (45 cases). The provisional national RL values are lower than those obtained in a similar survey carried out in the United States from 2002 to 2004. These new values could be used to improve the practice of centers consistently working with doses higher than the RLs. This national survey also had a positive impact, as it helped increase the awareness of the members of the National Society of IR on a topic as crucial as patient dose values and programs on radiation protection.

  19. Site-Specific Reference Person Parameters and Derived Concentration Standards for the Savannah River Site

    DOE PAGESBeta

    Stone, Daniel K.; Higley, Kathryn A.; Jannik, G. Timothy

    2014-05-01

    The U.S. Department of Energy Order 458.1 states that the compliance with the 1 mSv annual dose constraint to a member of the public may be demonstrated by calculating dose to the maximally exposed individual (MEI) or to a representative person. Historically, the MEI concept was used for dose compliance at the Savannah River Site (SRS) using adult dose coefficients and adult male usage parameters. For future compliance, SRS plans to use the representative person concept for dose estimates to members of the public. The representative person dose will be based on the reference person dose coefficients from the U.S.more » DOE Derived Concentration Technical Standard and on usage parameters specific to SRS for the reference and typical person. Usage parameters and dose coefficients were determined for inhalation, ingestion and external exposure pathways. The parameters for the representative person were used to calculate and tabulate SRS-specific derived concentration standards (DCSs) for the pathways not included in DOE-STD-1196-2011.« less

  20. Site-Specific Reference Person Parameters and Derived Concentration Standards for the Savannah River Site

    SciTech Connect

    Stone, Daniel K.; Higley, Kathryn A.; Jannik, G. Timothy

    2014-05-01

    The U.S. Department of Energy Order 458.1 states that the compliance with the 1 mSv annual dose constraint to a member of the public may be demonstrated by calculating dose to the maximally exposed individual (MEI) or to a representative person. Historically, the MEI concept was used for dose compliance at the Savannah River Site (SRS) using adult dose coefficients and adult male usage parameters. For future compliance, SRS plans to use the representative person concept for dose estimates to members of the public. The representative person dose will be based on the reference person dose coefficients from the U.S. DOE Derived Concentration Technical Standard and on usage parameters specific to SRS for the reference and typical person. Usage parameters and dose coefficients were determined for inhalation, ingestion and external exposure pathways. The parameters for the representative person were used to calculate and tabulate SRS-specific derived concentration standards (DCSs) for the pathways not included in DOE-STD-1196-2011.

  1. Organ doses for reference pediatric and adolescent patients undergoing computed tomography estimated by Monte Carlo simulation

    SciTech Connect

    Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel J.; Bolch, Wesley E.

    2012-04-15

    Purpose: To establish an organ dose database for pediatric and adolescent reference individuals undergoing computed tomography (CT) examinations by using Monte Carlo simulation. The data will permit rapid estimates of organ and effective doses for patients of different age, gender, examination type, and CT scanner model. Methods: The Monte Carlo simulation model of a Siemens Sensation 16 CT scanner previously published was employed as a base CT scanner model. A set of absorbed doses for 33 organs/tissues normalized to the product of 100 mAs and CTDI{sub vol} (mGy/100 mAs mGy) was established by coupling the CT scanner model with age-dependent reference pediatric hybrid phantoms. A series of single axial scans from the top of head to the feet of the phantoms was performed at a slice thickness of 10 mm, and at tube potentials of 80, 100, and 120 kVp. Using the established CTDI{sub vol}- and 100 mAs-normalized dose matrix, organ doses for different pediatric phantoms undergoing head, chest, abdomen-pelvis, and chest-abdomen-pelvis (CAP) scans with the Siemens Sensation 16 scanner were estimated and analyzed. The results were then compared with the values obtained from three independent published methods: CT-Expo software, organ dose for abdominal CT scan derived empirically from patient abdominal circumference, and effective dose per dose-length product (DLP). Results: Organ and effective doses were calculated and normalized to 100 mAs and CTDI{sub vol} for different CT examinations. At the same technical setting, dose to the organs, which were entirely included in the CT beam coverage, were higher by from 40 to 80% for newborn phantoms compared to those of 15-year phantoms. An increase of tube potential from 80 to 120 kVp resulted in 2.5-2.9-fold greater brain dose for head scans. The results from this study were compared with three different published studies and/or techniques. First, organ doses were compared to those given by CT-Expo which revealed dose

  2. Electron spectra derived from depth dose distributions.

    PubMed

    Faddegon, B A; Blevis, I

    2000-03-01

    The technique of extracting electron energy spectra from measured distributions of dose along the central axis of clinical electron beams is explored in detail. Clinical spectra measured with this simple spectroscopy tool are shown to be sufficient in accuracy and resolution for use in Monte Carlo treatment planning. A set of monoenergetic depth dose curves of appropriate energy spacing, precalculated with Monte Carlo for a simple beam model, are unfolded from the measured depth dose curve. The beam model is comprised of a point electron and photon source placed in vacuum with a source-to-surface distance of 100 cm. Systematic error introduced by this model affects the calculated depth dose curve by no more than 2%/2 mm. The component of the dose due to treatment head bremsstrahlung, subtracted prior to unfolding, is estimated from the thin-target Schiff spectrum within 0.3% of the maximum total dose (from electrons and photons) on the beam axis. Optimal unfolding parameters are chosen, based on physical principles. Unfolding is done with the public-domain code FERDO. Comparisons were made to previously published spectra measured with magnetic spectroscopy and to spectra we calculated with Monte Carlo treatment head simulation. The approach gives smooth spectra with an average resolution for the 27 beams studied of 16+/-3% of the mean peak energy. The mean peak energy of the magnetic spectrometer spectra was calculated within 2% for the AECL T20 scanning beam accelerators, 3% for the Philips SL25 scattering foil based machine. The number of low energy electrons in Monte Carlo spectra is estimated by unfolding with an accuracy of 2%, relative to the total number of electrons in the beam. Central axis depth dose curves calculated from unfolded spectra are within 0.5%/0.5 mm of measured and simulated depth dose curves, except near the practical range, where 1%/1 mm errors are evident. PMID:10757603

  3. Establishment of dose reference levels for nuclear medicine in Greece.

    PubMed

    Vogiatzi, S; Kipouros, P; Chobis, M

    2011-09-01

    Greek Atomic Energy Commission's Department of Licensing and Inspections conducted a national survey for the establishment of nuclear medicine (NM) dose reference levels (DRLs) for adult patients, in Greece. The administered activities (AAs) (MBq) were collected from 120 NM departments (88 % of total), during on-site inspections for licensing purposes. Factors influencing the image quality were also investigated. The established national DRLs represent the AA value corresponding to the 75th percentile of the AA frequency distributions. In their majority, national DRLs and average AAs are comparable with the ones published in the international literature. In the light of new technologies, there might be potential for reducing the higher values of AAs, in co-operation with the nuclear medicine experts. PMID:21765158

  4. Dose Assessment in Computed Tomography Examination and Establishment of Local Diagnostic Reference Levels in Mazandaran, Iran

    PubMed Central

    Janbabanezhad Toori, A.; Shabestani-Monfared, A.; Deevband, M.R.; Abdi, R.; Nabahati, M.

    2015-01-01

    Background Medical X-rays are the largest man-made source of public exposure to ionizing radiation. While the benefits of Computed Tomography (CT) are well known in accurate diagnosis, those benefits are not risk-free. CT is a device with higher patient dose in comparison with other conventional radiation procedures. Objective This study is aimed at evaluating radiation dose to patients from Computed Tomography (CT) examination in Mazandaran hospitals and defining diagnostic reference level (DRL). Methods Patient-related data on CT protocol for four common CT examinations including brain, sinus, chest and abdomen & pelvic were collected. In each center, Computed Tomography Dose Index (CTDI) measurements were performed using pencil ionization chamber and CT dosimetry phantom according to AAPM report No. 96 for those techniques. Then, Weighted Computed Tomography Dose Index (CTDIW), Volume Computed Tomography Dose Index (CTDI vol) and Dose Length Product (DLP) were calculated. Results The CTDIw for brain, sinus, chest and abdomen & pelvic ranged (15.6-73), (3.8-25. 8), (4.5-16.3) and (7-16.3), respectively. Values of DLP had a range of (197.4-981), (41.8-184), (131-342.3) and (283.6-486) for brain, sinus, chest and abdomen & pelvic, respectively. The 3rd quartile of CTDIW, derived from dose distribution for each examination is the proposed quantity for DRL. The DRLs of brain, sinus, chest and abdomen & pelvic are measured 59.5, 17, 7.8 and 11 mGy, respectively. Conclusion Results of this study demonstrated large scales of dose for the same examination among different centers. For all examinations, our values were lower than international reference doses. PMID:26688796

  5. Re-evaluation of the reference dose for methylmercury and assessment of current exposure levels

    SciTech Connect

    Stern, A.H. )

    1993-06-01

    Methylmercury (Me-Hg) is widely distributed through freshwater and saltwater food chains and human consumption of fish and shellfish has lead to widespread exposure. Both the US EPA Reference Dose (0.3 [mu]g/kg/day) and the FAO/WHO Permissible Tolerable Weekly Intake (3.3 [mu]g/kg/week) are currently based on the prevention of paraesthesia in adult and older children. However, Me-Hg exposure in utero is known to result in a range of developmental neurologic effects including clinical CNS symptoms and delayed onset of walking. Based on a critical review of development toxicity data from human and animal studies, it is concluded that current guidelines for the prevention of paraesthesia are not adequate to address developmental effects. A dose of 0.07 [mu]g/kg/day is suggested as the best estimate of a potential reference dose for developmental effects. Data on nationwide fish consumption rates and Me-Hg levels in fish/seafood weighted by proportion of the catch intended for human consumption are analyzed in a Monte Carlo simulation to derive a probability distribution of background Me-Hg exposure. While various uncertainties in the toxicologic and exposure data limit the precision with which health risk can be estimated, this analysis suggests that at current levels of Me-Hg exposure, a significant fraction of women of childbearing age have exposures above this suggested reference dose.

  6. SITE SPECIFIC REFERENCE PERSON PARAMETERS AND DERIVED CONCENTRATION STANDARDS FOR THE SAVANNAH RIVER SITE

    SciTech Connect

    Jannik, T.

    2013-03-14

    The purpose of this report is twofold. The first is to develop a set of behavioral parameters for a reference person specific for the Savannah River Site (SRS) such that the parameters can be used to determine dose to members of the public in compliance with Department of Energy (DOE) Order 458.1 “Radiation Protection of the Public and the Environment.” A reference person is a hypothetical, gender and age aggregation of human physical and physiological characteristics arrived at by international consensus for the purpose of standardizing radiation dose calculations. DOE O 458.1 states that compliance with the annual dose limit of 100 mrem (1 mSv) to a member of the public may be demonstrated by calculating the dose to the maximally exposed individual (MEI) or to a representative person. Historically, for dose compliance, SRS has used the MEI concept, which uses adult dose coefficients and adult male usage parameters. Beginning with the 2012 annual site environmental report, SRS will be using the representative person concept for dose compliance. The dose to a representative person will be based on 1) the SRS-specific reference person usage parameters at the 95th percentile of appropriate national or regional data, which are documented in this report, 2) the reference person (gender and age averaged) ingestion and inhalation dose coefficients provided in DOE Derived Concentration Technical Standard (DOE-STD-1196-2011), and 3) the external dose coefficients provided in the DC_PAK3 toolbox. The second purpose of this report is to develop SRS-specific derived concentration standards (DCSs) for all applicable food ingestion pathways, ground shine, and water submersion. The DCS is the concentration of a particular radionuclide in water, in air, or on the ground that results in a member of the public receiving 100 mrem (1 mSv) effective dose following continuous exposure for one year. In DOE-STD-1196-2011, DCSs were developed for the ingestion of water, inhalation of

  7. Development of a chronic noncancer oral reference dose and drinking water screening level for sulfolane using benchmark dose modeling.

    PubMed

    Thompson, Chad M; Gaylor, David W; Tachovsky, J Andrew; Perry, Camarie; Carakostas, Michael C; Haws, Laurie C

    2013-12-01

    Sulfolane is a widely used industrial solvent that is often used for gas treatment (sour gas sweetening; hydrogen sulfide removal from shale and coal processes, etc.), and in the manufacture of polymers and electronics, and may be found in pharmaceuticals as a residual solvent used in the manufacturing processes. Sulfolane is considered a high production volume chemical with worldwide production around 18 000-36 000 tons per year. Given that sulfolane has been detected as a contaminant in groundwater, an important potential route of exposure is tap water ingestion. Because there are currently no federal drinking water standards for sulfolane in the USA, we developed a noncancer oral reference dose (RfD) based on benchmark dose modeling, as well as a tap water screening value that is protective of ingestion. Review of the available literature suggests that sulfolane is not likely to be mutagenic, clastogenic or carcinogenic, or pose reproductive or developmental health risks except perhaps at very high exposure concentrations. RfD values derived using benchmark dose modeling were 0.01-0.04 mg kg(-1) per day, although modeling of developmental endpoints resulted in higher values, approximately 0.4 mg kg(-1) per day. The lowest, most conservative, RfD of 0.01 mg kg(-1) per day was based on reduced white blood cell counts in female rats. This RfD was used to develop a tap water screening level that is protective of ingestion, viz. 365 µg l(-1). It is anticipated that these values, along with the hazard identification and dose-response modeling described herein, should be informative for risk assessors and regulators interested in setting health-protective drinking water guideline values for sulfolane. PMID:22936336

  8. Inhalation reference dose (RfDi): an application of interspecies dosimetry modeling for risk assessment of insoluble particles.

    PubMed

    Jarabek, A M; Menache, M G; Overton, J H; Dourson, M L; Miller, F J

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses [the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity] for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated (Overton and Miller 1988). Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation. PMID:2606680

  9. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, J.H. Jr.; Dourson, M.L.; Miller, F.J. )

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of this methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. Predictive physiologically based modeling of the inhalation of reactive gases has recently been demonstrated. Models that describe the deposition of hygroscopic particles and account for chemical factors that affect clearance mechanisms and gas uptake are under development. This paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The ratio of these two values serves as a scaling factor that can be applied in the R f D methodology to account for the dosimetric differences in the inhaled deposited dose. This application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

  10. A chronic oral reference dose for hexavalent chromium-induced intestinal cancer.

    PubMed

    Thompson, Chad M; Kirman, Christopher R; Proctor, Deborah M; Haws, Laurie C; Suh, Mina; Hays, Sean M; Hixon, J Gregory; Harris, Mark A

    2014-05-01

    High concentrations of hexavalent chromium [Cr(VI)] in drinking water induce villous cytotoxicity and compensatory crypt hyperplasia in the small intestines of mice (but not rats). Lifetime exposure to such cytotoxic concentrations increases intestinal neoplasms in mice, suggesting that the mode of action for Cr(VI)-induced intestinal tumors involves chronic wounding and compensatory cell proliferation of the intestine. Therefore, we developed a chronic oral reference dose (RfD) designed to be protective of intestinal damage and thus intestinal cancer. A physiologically based pharmacokinetic model for chromium in mice was used to estimate the amount of Cr(VI) entering each intestinal tissue section (duodenum, jejunum and ileum) from the lumen per day (normalized to intestinal tissue weight). These internal dose metrics, together with corresponding incidences for diffuse hyperplasia, were used to derive points of departure using benchmark dose modeling and constrained nonlinear regression. Both modeling techniques resulted in similar points of departure, which were subsequently converted to human equivalent doses using a human physiologically based pharmacokinetic model. Applying appropriate uncertainty factors, an RfD of 0.006 mg kg(-1) day(-1) was derived for diffuse hyperplasia-an effect that precedes tumor formation. This RfD is protective of both noncancer and cancer effects in the small intestine and corresponds to a safe drinking water equivalent level of 210 µg l(-1). This concentration is higher than the current federal maximum contaminant level for total Cr (100 µg l(-1)) and well above levels of Cr(VI) in US drinking water supplies (typically ≤ 5 µg l(-1)). PMID:23943231

  11. Inhalation reference dose (RfDi): An application of interspecies dosimetry modeling for risk assessment of insoluble particles

    SciTech Connect

    Jarabek, A.M.; Menache, M.G.; Overton, H.; Dourson, M.L.; Miller, F.J.

    1989-01-01

    Accurate extrapolation of animal toxicity data for human health risk assessment requires determination of the effective dose to the target tissue and the sensitivity of the target tissue to that dose. The methodology for deriving reference doses (the U.S. Environmental Protection Agency's (EPA) benchmark values for gauging systemic toxicity) for oral exposures has not included dosimetry modeling. Dosimetry data facilitate evaluation of concentration-response data with respect to the dose-response relationships used in quantitative risk assessment. Extension of the methodology to derivation of inhalation reference doses (RfDi) should account for the dynamics of the respiratory system as the portal of entry. The paper presents a method for calculating a dosimetric adjustment factor based on the values for the initial deposited dose of insoluble particles in an animal species and in humans. The application for insoluble particles illustrates the feasibility of interspecies dosimetry calculations for extrapolating the toxicological results of inhaled agents to human exposure conditions for more accurate risk estimation.

  12. Establishment of Reference Doses for residues of allergenic foods: report of the VITAL Expert Panel.

    PubMed

    Taylor, Steve L; Baumert, Joseph L; Kruizinga, Astrid G; Remington, Benjamin C; Crevel, Rene W R; Brooke-Taylor, Simon; Allen, Katrina J; Houben, Geert

    2014-01-01

    In 2011, an expert panel was assembled to establish appropriate Reference Doses for allergenic food residues as a part of the VITAL (Voluntary Incidental Trace Allergen Labeling) program of The Allergen Bureau of Australia & New Zealand (ABA). These Reference Doses would guide advisory labeling decisions for use on food labels. Individual NOAELs and LOAELs were obtained from clinical challenges of food-allergic subjects. Statistical dose-distribution models (log-normal, log-logistic, Weibull) were applied to the individual NOAELs and LOAELs for each allergenic food. The Reference Doses, in terms of mg of total protein from the allergenic food, were based upon either the ED01 (for peanut, cow's milk), the 95% lower confidence interval of the ED05 (for wheat, soybean, cashew, shrimp, sesame seed, mustard, and lupine), or both (egg, hazelnut) using all appropriate statistical dose-distribution models. Reference Doses were established for 11 allergenic foods ranging from 0.03 mg for egg protein to 10mg for shrimp protein. Reference Doses were not established for fish or celery due to poor model fits with existing data. Reference Doses were not established for other tree nuts beyond hazelnut and cashew because of the absence of data on NOAELs and LOAELs from individual subjects. PMID:24184597

  13. Absorbed dose to water reference dosimetry using solid phantoms in the context of absorbed-dose protocols

    SciTech Connect

    Seuntjens, Jan; Olivares, Marina; Evans, Michael; Podgorsak, Ervin

    2005-09-15

    For reasons of phantom material reproducibility, the absorbed dose protocols of the American Association of Physicists in Medicine (AAPM) (TG-51) and the International Atomic Energy Agency (IAEA) (TRS-398) have made the use of liquid water as a phantom material for reference dosimetry mandatory. In this work we provide a formal framework for the measurement of absorbed dose to water using ionization chambers calibrated in terms of absorbed dose to water but irradiated in solid phantoms. Such a framework is useful when there is a desire to put dose measurements using solid phantoms on an absolute basis. Putting solid phantom measurements on an absolute basis has distinct advantages in verification measurements and quality assurance. We introduce a phantom dose conversion factor that converts a measurement made in a solid phantom and analyzed using an absorbed dose calibration protocol into absorbed dose to water under reference conditions. We provide techniques to measure and calculate the dose transfer from solid phantom to water. For an Exradin A12 ionization chamber, we measured and calculated the phantom dose conversion factor for six Solid Water{sup TM} phantoms and for a single Lucite phantom for photon energies between {sup 60}Co and 18 MV photons. For Solid Water{sup TM} of certified grade, the difference between measured and calculated factors varied between 0.0% and 0.7% with the average dose conversion factor being low by 0.4% compared with the calculation whereas for Lucite, the agreement was within 0.2% for the one phantom examined. The composition of commercial plastic phantoms and their homogeneity may not always be reproducible and consistent with assumed composition. By comparing measured and calculated phantom conversion factors, our work provides methods to verify the consistency of a given plastic for the purpose of clinical reference dosimetry.

  14. Translating reference doses into allergen management practice: challenges for stakeholders.

    PubMed

    Crevel, René W R; Baumert, Joseph L; Luccioli, Stefano; Baka, Athanasia; Hattersley, Sue; Hourihane, Jonathan O'B; Ronsmans, Stefan; Timmermans, Frans; Ward, Rachel; Chung, Yong-joo

    2014-05-01

    Risk assessment describes the impact of a particular hazard as a function of dose and exposure. It forms the foundation of risk management and contributes to the overall decision-making process, but is not its endpoint. This paper outlines a risk analysis framework to underpin decision-making in the area of allergen cross-contact. Specifically, it identifies challenges relevant to each component of the risk analysis: risk assessment (data gaps and output interpretation); risk management (clear and realistic objectives); and risk communication (clear articulation of risk and benefit). Translation of the outputs from risk assessment models into risk management measures must be informed by a clear understanding of the model outputs and their limitations. This will lead to feasible and achievable risk management objectives, grounded in a level of risk accepted by the different stakeholders, thereby avoiding potential unintended detrimental consequences. Clear, consistent and trustworthy communications actively involving all stakeholders underpin these objectives. The conclusions, integrating the perspectives of different stakeholders, offer a vision where clear, science-based benchmarks form the basis of allergen management and labelling, cutting through the current confusion and uncertainty. Finally, the paper recognises that the proposed framework must be adaptable to new and emerging evidence. PMID:24491260

  15. Guidance on setting of acute reference dose (ARfD) for pesticides.

    PubMed

    Solecki, Roland; Davies, Les; Dellarco, Vicki; Dewhurst, Ian; Raaij, Marcel van; Tritscher, Angelika

    2005-11-01

    This paper summarises and extends the work developed over the last decade by the Joint FAO/WHO Meeting on Pesticide Residues (JMPR) for acute health risk assessment of agricultural pesticides. The general considerations in setting of acute reference doses (ARfDs) in a step-wise process, as well as specific considerations and guidance regarding selected toxicological endpoints are described in detail. The endpoints selected are based on the practical experience with agricultural pesticides by the JMPR and are not a comprehensive listing of all possible relevant endpoints. Haematotoxicity, immunotoxicity, neurotoxicity, liver and kidney toxicity, endocrine effects as well as developmental effects are taken into account as acute toxic alerts, relevant for the consideration of ARfDs for pesticides. The general biological background and the data available through standard toxicological testing for regulatory purposes, interpretation of the data, conclusions and recommendations for future improvements are described for each relevant endpoint. The paper also considers a single dose study protocol. This type of study is not intended to be included in routine toxicological testing for regulatory purposes, but rather to guide further testing when the current database indicates the necessity for an ARfD but does not allow a reliable derivation of the value. PMID:16040182

  16. Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations

    SciTech Connect

    Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel; Fisher, Ryan; Tien, Chris; Simon, Steven L.; Bouville, Andre; Bolch, Wesley E.

    2011-03-15

    Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantomsMethods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult male and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen/pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom. Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen/pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude. Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for different

  17. Organ doses for reference adult male and female undergoing computed tomography estimated by Monte Carlo simulations

    PubMed Central

    Lee, Choonsik; Kim, Kwang Pyo; Long, Daniel; Fisher, Ryan; Tien, Chris; Simon, Steven L.; Bouville, Andre; Bolch, Wesley E.

    2011-01-01

    Purpose: To develop a computed tomography (CT) organ dose estimation method designed to readily provide organ doses in a reference adult male and female for different scan ranges to investigate the degree to which existing commercial programs can reasonably match organ doses defined in these more anatomically realistic adult hybrid phantoms Methods: The x-ray fan beam in the SOMATOM Sensation 16 multidetector CT scanner was simulated within the Monte Carlo radiation transport code MCNPX2.6. The simulated CT scanner model was validated through comparison with experimentally measured lateral free-in-air dose profiles and computed tomography dose index (CTDI) values. The reference adult male and female hybrid phantoms were coupled with the established CT scanner model following arm removal to simulate clinical head and other body region scans. A set of organ dose matrices were calculated for a series of consecutive axial scans ranging from the top of the head to the bottom of the phantoms with a beam thickness of 10 mm and the tube potentials of 80, 100, and 120 kVp. The organ doses for head, chest, and abdomen∕pelvis examinations were calculated based on the organ dose matrices and compared to those obtained from two commercial programs, CT-EXPO and CTDOSIMETRY. Organ dose calculations were repeated for an adult stylized phantom by using the same simulation method used for the adult hybrid phantom. Results: Comparisons of both lateral free-in-air dose profiles and CTDI values through experimental measurement with the Monte Carlo simulations showed good agreement to within 9%. Organ doses for head, chest, and abdomen∕pelvis scans reported in the commercial programs exceeded those from the Monte Carlo calculations in both the hybrid and stylized phantoms in this study, sometimes by orders of magnitude. Conclusions: The organ dose estimation method and dose matrices established in this study readily provides organ doses for a reference adult male and female for

  18. Diagnostic reference levels and patient doses in computed tomography examinations in Greece.

    PubMed

    Simantirakis, G; Hourdakis, C J; Economides, S; Kaisas, I; Kalathaki, M; Koukorava, C; Manousaridis, G; Pafilis, C; Tritakis, P; Vogiatzi, S; Kamenopoulou, V; Dimitriou, P

    2015-02-01

    The purpose of this study is to present a national survey that was performed in Greece for the establishment of national Dose Reference Levels (DRLs) for seven common adult Computed Tomography (CT) examinations. Volumetric computed tomography dose index and dose-length product values were collected from the post-data page of 65 'modern' systems that incorporate tube current modulation. Moreover, phantom dose measurements on 26 'older' systems were performed. Finally, the effective dose to the patient from a typical acquisition during these examinations was estimated. The suggested national DRLs are generally comparable with respective published values from similar European studies, with the exception of sinuses CT, which presents significantly higher values. This fact, along with the large variation of the systems' dose values that were observed even for scanners of the same type, indicates a need for further patient protection optimisation without compromising the clinical outcome. PMID:24891405

  19. 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

  20. Deriving a geocentric reference frame for satellite positioning and navigation

    NASA Technical Reports Server (NTRS)

    Malla, R. P.; Wu, S.-C.

    1988-01-01

    With the advent of Earth-orbiting geodetic satellites, nongeocentric datums or reference frames have become things of the past. Accurate geocentric three-dimensional positioning is now possible and is of great importance for various geodetic and oceanographic applications. While relative positioning accuracy of a few centimeters has become a reality using very long baseline interferometry (VLBI), the uncertainty in the offset of the adopted coordinate system origin from the geocenter is still believed to be on the order of 1 meter. Satellite laser ranging (SLR), however, is capable of determining this offset to better than 10 cm, but this is possible only after years of measurements. Global Positioning System (GPS) measurements provide a powerful tool for an accurate determination of this origin offset. Two strategies are discussed. The first strategy utilizes the precise relative positions that were predetermined by VLBI to fix the frame orientation and the absolute scaling, while the offset from the geocenter is determined from GPS measurements. Three different cases are presented under this strategy. The reference frame thus adopted will be consistent with the VLBI coordinate system. The second strategy establishes a reference frame by holding only the longitude of one of the tracking sites fixed. The absolute scaling is determined by the adopted gravitational constant (GM) of the Earth; and the latitude is inferred from the time signature of the Earth rotation in the GPS measurements. The coordinate system thus defined will be a geocentric Earth-fixed coordinate system.

  1. PROPOSED ORAL REFERENCE DOSE (RFD) FOR BARIUM AND COMPOUNDS (Final Report) 2004

    EPA Science Inventory

    This document is the final report for the 2004 external peer review of the Proposed Oral Reference Dose (RfD) for Barium and Compounds, prepared by the U.S. Environmental Protection Agency (EPA), National Center for Environmental Assessment (NCEA), for the Integrated Risk Informa...

  2. Air kerma and absorbed dose standards for reference dosimetry in brachytherapy

    PubMed Central

    2014-01-01

    This article reviews recent developments in primary standards for the calibration of brachytherapy sources, with an emphasis on the currently most common photon-emitting radionuclides. The introduction discusses the need for reference dosimetry in brachytherapy in general. The following section focuses on the three main quantities, i.e. reference air kerma rate, air kerma strength and absorbed dose rate to water, which are currently used for the specification of brachytherapy photon sources and which can be realized with primary standards from first principles. An overview of different air kerma and absorbed dose standards, which have been independently developed by various national metrology institutes over the past two decades, is given in the next two sections. Other dosimetry techniques for brachytherapy will also be discussed. The review closes with an outlook on a possible transition from air kerma to absorbed dose to water-based calibrations for brachytherapy sources in the future. PMID:24814696

  3. Factors affecting quality for beta dose rate measurements using ISO 6980 series I reference sources

    SciTech Connect

    Burns, R.E. Jr.; O`Brien, J.M. Jr.

    1993-12-31

    Atlan-Tech, Inc. has performed several calibrations of ISO 6980 Series 1 reference beta sources over the past two to three years. There were many problems encountered in attempting to compare the results of these calibrations with those from other laboratories, indicating the need for more standardization in the methodology employed for the measurement of the absorbed dose rate from ISO 6980 Series 1 reference beta sources. This document describes some of the problems encountered in attempting to intercompare results of beta dose-rate measurements. It proposes some solutions in an attempt to open a dialogue among facilities using reference beta standards for the purpose of promoting better measurement quality assurance through data intercomparison.

  4. Development of a Reference Dose for Perchlorate: Current Issues and Status

    NASA Technical Reports Server (NTRS)

    Pleus, R. C.; Goodman, G.; Mattie, D. R.

    2000-01-01

    The perchlorate anion (ClO4) is typically manufactured as the ammonium salt. The most common use of ammonium perchlorate is in the aerospace program as a component of solid rocket fuel. The perchlorate anion is exceedingly stable under environmental conditions and has been found in ground and surface waters in CA, NV, UT, AZ, TX, AK, NY, MD, WV and FL. The National Center for Environmental Assessment (NCEA) of the U.S. Environmental Protection Agency (US EPA) is in the process of developing an oral reference dose (RfD) for perchlorate. An oral RfD is a body-weight-adjusted dose that can be consumed daily over an entire lifetime with the expectation of no adverse health effects. Once developed, the new RfD will be used by US EPA as the basis of a safe-drinking-water level (SDWL) guideline. US EPA and regional regulatory agencies will then jointly or separately propose clean-up action levels for ground and surface waters at contaminated sites. The toxicological database on CIO4- as of March 1997 was determined by an expert peer-review panel to be inadequate for the purpose of deriving an oral RfD. For example, little or no experimental data existed on the subchronic, reproductive, or developmental toxicity of perchlorate. To fill gaps in the toxicological database, eight animal studies were designed by a government-industry consortium that included US EPA and AFRL. These studies were performed in 1997-1998. It has been known for many years that in the thyroid, high doses of perchlorate block the function of iodide by competing for iodide binding sites. Perchlorate was used in the 1950s-60s as a treatment for Graves' disease (a hyperthyroid condition). Because of what was already known about the pharmacological mode of action of perchlorate, specific concerns addressed in the design of the recent animal studies included the potential for developmental toxicity, notably neurological development. Upon review of complete study reports from four of the studies and

  5. EURRECA-Estimating zinc requirements for deriving dietary reference values.

    PubMed

    Lowe, Nicola M; Dykes, Fiona C; Skinner, Anna-Louise; Patel, Sujata; Warthon-Medina, Marisol; Decsi, Tamás; Fekete, Katalin; Souverein, Olga W; Dullemeijer, Carla; Cavelaars, Adriënne E; Serra-Majem, Lluis; Nissensohn, Mariela; Bel, Silvia; Moreno, Luis A; Hermoso, Maria; Vollhardt, Christiane; Berti, Cristiana; Cetin, Irene; Gurinovic, Mirjana; Novakovic, Romana; Harvey, Linda J; Collings, Rachel; Hall-Moran, Victoria

    2013-01-01

    Zinc was selected as a priority micronutrient for EURRECA, because there is significant heterogeneity in the Dietary Reference Values (DRVs) across Europe. In addition, the prevalence of inadequate zinc intakes was thought to be high among all population groups worldwide, and the public health concern is considerable. In accordance with the EURRECA consortium principles and protocols, a series of literature reviews were undertaken in order to develop best practice guidelines for assessing dietary zinc intake and zinc status. These were incorporated into subsequent literature search strategies and protocols for studies investigating the relationships between zinc intake, status and health, as well as studies relating to the factorial approach (including bioavailability) for setting dietary recommendations. EMBASE (Ovid), Cochrane Library CENTRAL, and MEDLINE (Ovid) databases were searched for studies published up to February 2010 and collated into a series of Endnote databases that are available for the use of future DRV panels. Meta-analyses of data extracted from these publications were performed where possible in order to address specific questions relating to factors affecting dietary recommendations. This review has highlighted the need for more high quality studies to address gaps in current knowledge, in particular the continued search for a reliable biomarker of zinc status and the influence of genetic polymorphisms on individual dietary requirements. In addition, there is a need to further develop models of the effect of dietary inhibitors of zinc absorption and their impact on population dietary zinc requirements. PMID:23952091

  6. Estimating the population dose from nuclear medicine examinations towards establishing diagnostic reference levels

    PubMed Central

    Niksirat, Fatemeh; Monfared, Ali Shabestani; Deevband, Mohammad Reza; Amiri, Mehrangiz; Gholami, Amir

    2016-01-01

    Purpose of the Study: This study conducted a review on nuclear medicine (NM) services in Mazandaran Province with a view to establish adult diagnostic reference levels (DRLs) and provide updated data on population radiation exposure resulting from diagnostic NM procedures. Materials and Methods: The data were collected from all centers in all cities of Mazandaran Province in the North of Iran from March 2014 to February 2015. The 75th percentile of the distribution and the average administered activity (AAA) were calculated and the average effective dose per examination, collective effective dose to the population and annual effective dose per capita were estimated using dose conversion factors. The gathered data were analyzed via SPSS (version 18) software using descriptive statistics. Results: Based on the data of this study, the collective effective dose was 95.628 manSv, leading to a mean effective dose of 0.03 mSv per capita. It was also observed that the myocardial perfusion was the most common procedure (50%). The 75th percentile of the distribution of administered activity (AA) represents the DRL. The AAA and the 75th percentile of the distribution of AA are slightly higher than DRL of most European countries. Conclusions: Myocardial perfusion is responsible for most of the collective effective dose and it is better to establish national DRLs for myocardial perfusion and review some DRL values through the participation of NM specialists in the future. PMID:26917891

  7. Oral Reference Dose for ethylene glycol based on oxalate crystal-induced renal tubule degeneration as the critical effect

    SciTech Connect

    Snellings, William M.; Corley, Richard A.; McMartin, K. E.; Kirman, Christopher R.; Bobst, Sol M.

    2013-03-31

    Several risk assessments have been conducted for ethylene glycol (EG). These assessments identified the kidney as the primary target organ for chronic effects. None of these assessments have incorporated the robust database of species-specific toxicokinetic and toxicodynamic studies with EG and its metabolites in defining uncertainty factors used in reference value derivation. Pertinent in vitro and in vivo studies related to one of these metabolites, calcium oxalate, and its role in crystal-induced nephropathy are summarized, and the weight of evidence to establish the mode of action for renal toxicity is reviewed. Previous risk assessments were based on chronic rat studies using a strain of rat that was later determined to be less sensitive to the toxic effects of EG. A recently published 12-month rat study using the more sensitive strain (Wistar) was selected to determine the point of departure for a new risk assessment. This approach incorporated toxicokinetic and toxicodynamic data and used Benchmark Dose methods to calculate a Human Equivalent Dose. Uncertainty factors were chosen, depending on the quality of the studies available, the extent of the database, and scientific judgment. The Reference Dose for long-term repeat oral exposure to EG was determined to be 15 mg/kg bw/d.

  8. Evaluation of dose conversion coefficients for external exposure using Taiwanese reference man and woman.

    PubMed

    Chang, S J; Hung, S Y; Liu, Y L; Jiang, S H; Wu, J

    2015-11-01

    Reference man has been widely used for external and internal dose evaluation of radiation protection. The parameters of the mathematical model of organs suggested by the International Commission of Radiological Protection (ICRP) are adopted from the average data of Caucasians. However, the organ masses of Asians are significantly different from the data of Caucasians, leading to potentially dosimetric errors. In this study, a total of 40 volunteers whose heights and weights corresponded to the statistical average of Taiwanese adults were recruited. Magnetic resonance imaging was performed, and T2-weighted images were acquired. The Taiwanese reference man and woman were constructed according to the measured organ masses. The dose conversion coefficients (DCFs) for anterior-posterior (AP), posterior-anterior (PA), right lateral (RLAT) and left lateral (LLAT) irradiation geometries were simulated. For the Taiwanese reference man, the average differences of the DCFs compared with the results of ICRP-74 were 7.6, 5.1 and 11.1 % for 0.1, 1 and 10 MeV photons irradiated in the AP direction. The maximum difference reached 51.7 % for the testes irradiated by 10 MeV photons. The size of the trunk, the volume and the geometric position of organs can cause a significant impact on the DCFs for external exposure of radiation. The constructed Taiwanese reference man and woman can be used in radiation protection to increase the accuracy of dose evaluation for the Taiwanese population. PMID:25944957

  9. Neutron activation analysis for reference determination of the implantation dose of cobalt ions

    SciTech Connect

    Garten, R.P.H.; Bubert, H.; Palmetshofer, L.

    1992-05-15

    The authors prepared depth profilling reference materials by cobalt ion implantation at an ion energy of 300 keV into n-type silicon. The implanted Co dose was then determined by instrumental neutron activation analysis (INAA) giving an analytical dynamic range of almost 5 decades and uncertainty of 1.5%. This form of analysis allows sources of error (beam spreading, misalignment) to be corrected. 70 refs., 3 tabs.

  10. Organ dose conversion coefficients for pediatric reference computational phantoms in external photon radiation fields

    NASA Astrophysics Data System (ADS)

    Chang, Lienard A.

    In the event of a radiological accident or attack, it is important to estimate the organ doses to those exposed. In general, it is difficult to measure organ dose directly in the field and therefore dose conversion coefficients (DCC) are needed to convert measurable values such as air kerma to organ dose. Previous work on these coefficients has been conducted mainly for adults with a focus on radiation protection workers. Hence, there is a large gap in the literature for pediatric values. This study coupled a Monte Carlo N-Particle eXtended (MCNPX) code with International Council of Radiological Protection (ICRP)-adopted University of Florida and National Cancer Institute pediatric reference phantoms to calculate a comprehensive list of dose conversion coefficients (mGy/mGy) to convert air-kerma to organ dose. Parameters included ten phantoms (newborn, 1-year, 5-year, 10-year, 15-year old male and female), 28 organs over 33 energies between 0.01 and 20 MeV in six (6) irradiation geometries relevant to a child who might be exposed to a radiological release: anterior-posterior (AP), posterior-anterior (PA), right-lateral (RLAT), left-lateral (LLAT), rotational (ROT), and isotropic (ISO). Dose conversion coefficients to the red bone marrow over 36 skeletal sites were also calculated. It was hypothesized that the pediatric organ dose conversion coefficients would follow similar trends to the published adult values as dictated by human anatomy, but be of a higher magnitude. It was found that while the pediatric coefficients did yield similar patterns to that of the adult coefficients, depending on the organ and irradiation geometry, the pediatric values could be lower or higher than that of the adult coefficients.

  11. 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

  12. A Monte Carlo based three-dimensional dose reconstruction method derived from portal dose images

    SciTech Connect

    Elmpt, Wouter J. C. van; Nijsten, Sebastiaan M. J. J. G.; Schiffeleers, Robert F. H.; Dekker, Andre L. A. J.; Mijnheer, Ben J.; Lambin, Philippe; Minken, Andre W. H.

    2006-07-15

    The verification of intensity-modulated radiation therapy (IMRT) is necessary for adequate quality control of the treatment. Pretreatment verification may trace the possible differences between the planned dose and the actual dose delivered to the patient. To estimate the impact of differences between planned and delivered photon beams, a three-dimensional (3-D) dose verification method has been developed that reconstructs the dose inside a phantom. The pretreatment procedure is based on portal dose images measured with an electronic portal imaging device (EPID) of the separate beams, without the phantom in the beam and a 3-D dose calculation engine based on the Monte Carlo calculation. Measured gray scale portal images are converted into portal dose images. From these images the lateral scattered dose in the EPID is subtracted and the image is converted into energy fluence. Subsequently, a phase-space distribution is sampled from the energy fluence and a 3-D dose calculation in a phantom is started based on a Monte Carlo dose engine. The reconstruction model is compared to film and ionization chamber measurements for various field sizes. The reconstruction algorithm is also tested for an IMRT plan using 10 MV photons delivered to a phantom and measured using films at several depths in the phantom. Depth dose curves for both 6 and 10 MV photons are reconstructed with a maximum error generally smaller than 1% at depths larger than the buildup region, and smaller than 2% for the off-axis profiles, excluding the penumbra region. The absolute dose values are reconstructed to within 1.5% for square field sizes ranging from 5 to 20 cm width. For the IMRT plan, the dose was reconstructed and compared to the dose distribution with film using the gamma evaluation, with a 3% and 3 mm criterion. 99% of the pixels inside the irradiated field had a gamma value smaller than one. The absolute dose at the isocenter agreed to within 1% with the dose measured with an ionization

  13. Benchmark dose estimation of cadmium reference level for hypertension in a Chinese population.

    PubMed

    Chen, Xiao; Wang, Zhongqiu; Zhu, Guoying; Liang, Yihuai; Jin, Taiyi

    2015-01-01

    Cadmium exposure can cause high blood pressure or hypertension. Benchmark dose has been used to estimate the reference point of cadmium for kidney and bone damage. In this study, we observed the association of blood pressure and cadmium in blood (BCd) and evaluated the reference level of cadmium for hypertension using benchmark dose (BMD) approach. A total of 441 subjects were included in this study. Blood samples were collected from each individual for BCd determination. Blood pressure was measured by electronic sphygmomanometer. BMD and BMDL were calculated using BMD software corresponding to additional risk of 10%. The systolic blood pressure (SBP), diastolic blood pressure (DBP) and prevalence of hypertension increased with the increasing of BCd, especially for SBP (χ(2)=3.9, p=0.047 in men; χ(2)=4.3, p=0.037 in women). With a benchmark response of 10%, the BMDL10 for hypertension (high SBP) was 0.95μg/L and 1.02μg/L for women and men, respectively; the BMDL10 for hypertension (high DBP) was 1.8μg/L and 1.66μg/L for women and men, respectively. Our data evidenced that BCd was associated with elevation in blood pressure and hypertension, especially for women. The reference level of cadmium for hypertension with high SBP was lower than that of high DBP. PMID:25528411

  14. Establishment of air kerma reference standard for low dose rate Cs-137 brachytherapy sources.

    PubMed

    Sharma, Sunil Dutt; Kumar, Sudhir; Srinivasan, P; Chourasiya, G

    2011-01-01

    A guarded cylindrical graphite ionization chamber of nominal volume 1000 cm3 was designed and fabricated for use as a reference standard for low-dose rate 137Cs brachytherapy sources. The air kerma calibration coefficient (N(K)) of this ionization chamber was estimated analytically using Burlin's general cavity theory, as well as by the Monte Carlo simulation and validated experimentally using Amersham CDCS-J-type 137Cs reference source. In the analytical method, the N(K) was calculated for 662 keV gamma rays of 137Cs brachytherapy source. In the Monte Carlo method, the geometry of the measurement setup and physics-related input data of the 137Cs source and the surrounding material were simulated using the Monte Carlo N-Particle code. The photon energy fluence was used to arrive at the reference air kerma rate (RAKR) using mass energy absorption coefficient. The energy deposition rates were used to simulate the value of charge rate in the ionization chamber, and the N(K) was determined. The analytical and Monte Carlo values of N(K) of the cylindrical graphite ionization chamber for 137Cs brachytherapy source are in agreement within 1.07%. The deviation of analytical and Monte Carlo values from experimental values of N(K) is 0.36% and 0.72%, respectively. This agreement validates the analytical value, and establishes this chamber as a reference standard for RAKR or AKS measurement of 137Cs brachytherapy sources. PMID:22089009

  15. Reference air kerma and kerma-area product as estimators of peak skin dose for fluoroscopically guided interventions

    SciTech Connect

    Kwon, Deukwoo; Little, Mark P.; Miller, Donald L.

    2011-07-15

    Purpose: To determine more accurate regression formulas for estimating peak skin dose (PSD) from reference air kerma (RAK) or kerma-area product (KAP). Methods: After grouping of the data from 21 procedures into 13 clinically similar groups, assessments were made of optimal clustering using the Bayesian information criterion to obtain the optimal linear regressions of (log-transformed) PSD vs RAK, PSD vs KAP, and PSD vs RAK and KAP. Results: Three clusters of clinical groups were optimal in regression of PSD vs RAK, seven clusters of clinical groups were optimal in regression of PSD vs KAP, and six clusters of clinical groups were optimal in regression of PSD vs RAK and KAP. Prediction of PSD using both RAK and KAP is significantly better than prediction of PSD with either RAK or KAP alone. The regression of PSD vs RAK provided better predictions of PSD than the regression of PSD vs KAP. The partial-pooling (clustered) method yields smaller mean squared errors compared with the complete-pooling method.Conclusion: PSD distributions for interventional radiology procedures are log-normal. Estimates of PSD derived from RAK and KAP jointly are most accurate, followed closely by estimates derived from RAK alone. Estimates of PSD derived from KAP alone are the least accurate. Using a stochastic search approach, it is possible to cluster together certain dissimilar types of procedures to minimize the total error sum of squares.

  16. Developing patient-specific dose protocols for a CT scanner and exam using diagnostic reference levels.

    PubMed

    Strauss, Keith J

    2014-10-01

    The management of image quality and radiation dose during pediatric CT scanning is dependent on how well one manages the radiographic techniques as a function of the type of exam, type of CT scanner, and patient size. The CT scanner's display of expected CT dose index volume (CTDIvol) after the projection scan provides the operator with a powerful tool prior to the patient scan to identify and manage appropriate CT techniques, provided the department has established appropriate diagnostic reference levels (DRLs). This paper provides a step-by-step process that allows the development of DRLs as a function of type of exam, of actual patient size and of the individual radiation output of each CT scanner in a department. Abdomen, pelvis, thorax and head scans are addressed. Patient sizes from newborns to large adults are discussed. The method addresses every CT scanner regardless of vendor, model or vintage. We cover adjustments to techniques to manage the impact of iterative reconstruction and provide a method to handle all available voltages other than 120 kV. This level of management of CT techniques is necessary to properly monitor radiation dose and image quality during pediatric CT scans. PMID:25037975

  17. Patient radiation doses in interventional cardiology in the U.S.: Advisory data sets and possible initial values for U.S. reference levels

    SciTech Connect

    Miller, Donald L.; Hilohi, C. Michael; Spelic, David C.

    2012-10-15

    Purpose: To determine patient radiation doses from interventional cardiology procedures in the U.S and to suggest possible initial values for U.S. benchmarks for patient radiation dose from selected interventional cardiology procedures [fluoroscopically guided diagnostic cardiac catheterization and percutaneous coronary intervention (PCI)]. Methods: Patient radiation dose metrics were derived from analysis of data from the 2008 to 2009 Nationwide Evaluation of X-ray Trends (NEXT) survey of cardiac catheterization. This analysis used deidentified data and did not require review by an IRB. Data from 171 facilities in 30 states were analyzed. The distributions (percentiles) of radiation dose metrics were determined for diagnostic cardiac catheterizations, PCI, and combined diagnostic and PCI procedures. Confidence intervals for these dose distributions were determined using bootstrap resampling. Results: Percentile distributions (advisory data sets) and possible preliminary U.S. reference levels (based on the 75th percentile of the dose distributions) are provided for cumulative air kerma at the reference point (K{sub a,r}), cumulative air kerma-area product (P{sub KA}), fluoroscopy time, and number of cine runs. Dose distributions are sufficiently detailed to permit dose audits as described in National Council on Radiation Protection and Measurements Report No. 168. Fluoroscopy times are consistent with those observed in European studies, but P{sub KA} is higher in the U.S. Conclusions: Sufficient data exist to suggest possible initial benchmarks for patient radiation dose for certain interventional cardiology procedures in the U.S. Our data suggest that patient radiation dose in these procedures is not optimized in U.S. practice.

  18. [Basic principles for setting acute reference dose, ARfD in Japan].

    PubMed

    Yoshida, Midori; Suzuki, Daisetsu; Matsumoto, Kiyoshi; Shirota, Mariko; Inoue, Kaoru; Takahashi, Miwa; Morita, Takeshi; Ono, Atsushi

    2013-01-01

    Basic principles for simulation of acute reference dose (ARfD) setting were defined based on the work of Solecki et al. (2005). The principles are: (1) Appearance of acute toxicity within 24 h after oral administration. (2) Rationale for setting toxicity that appears or could appear after single oral administration. (3) ARfD setting is assumed to be necessary for all pesticides. (4) ARfD setting is not necessary when the value is at or above the cutoff level. (5) The setting basically applies to the general population. (6) ARfD is set based on the lowest NOAEL among all the available study data concerning endpoints for acute effects. (7) Effects of exposure during critical periods should be considered as endpoints for ARfD setting. (8) The approach for the safety coefficient is the same as that for acceptable daily intake. (9) If available, human data are acceptable as an endpoint for ARfD setting. PMID:24025213

  19. Comparison between CT-based volumetric calculations and ICRU reference-point estimates of radiation doses delivered to bladder and rectum during intracavitary radiotherapy for cervical cancer

    SciTech Connect

    Pelloski, Christopher E.; Palmer, Matthew B.S.; Chronowski, Gregory M.; Jhingran, Anuja; Horton, John; Eifel, Patricia J. . E-mail: peifel@mdanderson.org

    2005-05-01

    Purpose: To compare CT-based volumetric calculations and International Commission on Radiation Units and Measurements (ICRU) reference-point estimates of radiation doses to the bladder and rectum in patients with carcinoma of the uterine cervix treated with definitive low-dose-rate intracavitary radiotherapy (ICRT). Methods and Materials: Between November 2001 and March 2003, 60 patients were prospectively enrolled in a pilot study of ICRT with CT-based dosimetry. Most patients underwent two ICRT insertions. After insertion of an afterloading ICRT applicator, intraoperative orthogonal films were obtained to ensure proper positioning of the system and to facilitate subsequent planning. Treatments were prescribed using standard two-dimensional dosimetry and planning. Patients also underwent helical CT of the pelvis for three-dimensional reconstruction of the radiation dose distributions. The systems were loaded with {sup 137}Cs sources using the Selectron remote afterloading system according to institutional practice for low-dose-rate brachytherapy. Three-dimensional dose distributions were generated using the Varian BrachyVision treatment planning system. The rectum was contoured from the bottom of the ischial tuberosities to the sigmoid flexure. The entire bladder was contoured. The minimal doses delivered to the 2 cm{sup 3} of bladder and rectum receiving the highest dose (D{sub BV2} and D{sub RV2}, respectively) were determined from dose-volume histograms, and these estimates were compared with two-dimensionally derived estimates of the doses to the corresponding ICRU reference points. Results: A total of 118 unique intracavitary insertions were performed, and 93 were evaluated and the subject of this analysis. For the rectum, the estimated doses to the ICRU reference point did not differ significantly from the D{sub RV2} (p = 0.561); the mean ({+-} standard deviation) difference was 21 cGy ({+-} 344 cGy). The median volume of the rectum that received at least

  20. Construction of hybrid Chinese reference adult phantoms and estimation of dose conversion coefficients for muons.

    PubMed

    Dong, Liang; Li, Taosheng; Liu, Chunyu

    2015-04-01

    A set of fluence-to-effective dose conversion coefficients of external exposure to muons were investigated for Chinese hybrid phantom references, which include both male and female. Both polygon meshes and Non-Uniform Rational B-Spline (NURBS) surfaces were used to descried the boundary of the organs and tissues in these phantoms. The 3D-DOCTOR and Rhinoceros software were used to polygonise the colour slice images and generate the NURBS surfaces, respectively. The voxelisation is completed using the BINVOX software and the assembly finished by using MATLAB codes. The voxel resolutions were selected to be 0.22 × 0.22 × 0.22 cm(3) and 0.2 × 0.2 × 0.2 cm(3) for male and female phantoms, respectively. All parts of the final phantoms were matched to their reference organ masses within a tolerance of ±5%. The conversion coefficients for negative and positive muons were calculated with the FLUKA transport code. There were 21 external monoenergetic beams ranging from 0.01 GeV to 100 TeV in 5 different geometrical conditions of irradiation. PMID:25313173

  1. Intake ratio of 131I to 137Cs derived from thyroid and whole-body doses to Fukushima residents.

    PubMed

    Kim, Eunjoo; Kurihara, Osamu; Tani, Kotaro; Ohmachi, Yasushi; Fukutsu, Kumiko; Sakai, Kazuo; Akashi, Makoto

    2016-03-01

    This study deals with the intake ratio of (131)I to (137)Cs that allows for the utilisation of late whole-body measurements to reconstruct the internal thyroid doses to Fukushima residents. The ratio was derived from the thyroid dose distribution of children and the effective dose distribution of adults based on the assumption that various age groups of persons inhaled the two nuclides at the same activity ratio and at around the same time, while taking into account age-dependent ventilation rates. The two dose distributions were obtained from residents of Iitate village and Kawamata town, located northwest of Fukushima Daiichi nuclear power plant (FDNPP). As a result, the intake ratios for the residents were 2-3, which was much smaller than the activity ratio observed in air sampling. A main reason for this discrepancy presumably lies in the relatively smaller thyroid uptake for iodine in the Japanese subjects than that in the reference persons on whom the biokinetic model promulgated by International Commission on Radiological Protection is based. The actual intake ratio of the two nuclides is believed to have been higher south of the FDNPP; however, this would depend on which of three significant plume events dominantly contributed to the intake for individuals. Further studies are needed to clarify this issue as a part of the reconstruction of early internal doses related to the FDNPP accident. PMID:25982788

  2. No-reference image quality assessment based on log-derivative statistics of natural scenes

    NASA Astrophysics Data System (ADS)

    Zhang, Yi; Chandler, Damon M.

    2013-10-01

    We propose an efficient blind/no-reference image quality assessment algorithm using a log-derivative statistical model of natural scenes. Our method, called DErivative Statistics-based QUality Evaluator (DESIQUE), extracts image quality-related statistical features at two image scales in both the spatial and frequency domains. In the spatial domain, normalized pixel values of an image are modeled in two ways: pointwise-based statistics for single pixel values and pairwise-based log-derivative statistics for the relationship of pixel pairs. In the frequency domain, log-Gabor filters are used to extract the fine scales of the image, which are also modeled by the log-derivative statistics. All of these statistics can be fitted by a generalized Gaussian distribution model, and the estimated parameters are fed into combined frameworks to estimate image quality. We train our models on the LIVE database by using optimized support vector machine learning. Experiment results tested on other databases show that the proposed algorithm not only yields a substantial improvement in predictive performance as compared to other state-of-the-art no-reference image quality assessment methods, but also maintains a high computational efficiency.

  3. Simulation of acute reference dose (ARfD) settings for pesticides in Japan.

    PubMed

    Yoshida, Midori; Suzuki, Daisetsu; Matsumoto, Kiyoshi; Shirota, Mariko; Inoue, Kaoru; Takahashi, Miwa; Morita, Takeshi; Ono, Atsushi

    2013-01-01

    In order to develop guidelines for setting acute reference doses (ARfDs) for pesticides in Japan, we conducted simulations of ARfD settings based on evaluation reports for 201 pesticides assessed by the Food Safety Commission (FSC) in Japan over the last 8 years. Our conceptual principles were based on the concepts written by Solecki et al. (2005) and were adapted for toxicological data required in Japan. Through this process, we were able to set the ARfDs for over 90% of the 201 pesticides tested. The studies that provided the rationale for ARfD setting were primarily reproductive and developmental toxicity studies, acute neurotoxicity studies, and pharmacology studies. For approximately 30% of the pesticides simulated in the present study, it was not necessary to establish ARfDs. Some of the simulated ARfDs resulting from their endpoints may be conservative estimates, because the evaluation reports were written for acceptable daily intake settings. Thus, it was sometimes difficult to distinguish acute toxic alerts from repeated toxicities. We were unable to set an ARfD for 14 pesticides because of insufficient data on acute toxicities. This could be improved by more complete recordkeeping. Furthermore, we categorized the 201 pesticides by mechanism of action or chemical structure. Our simulation indicates that the conceptual framework presented here can be used as a basis for the development of guidelines on ARfD settings for pesticides in Japan. PMID:23535399

  4. Development of Diagnostic Reference Levels Using a Real-Time Radiation Dose Monitoring System at a Cardiovascular Center in Korea.

    PubMed

    Kim, Jungsu; Seo, Deoknam; Choi, Inseok; Nam, Sora; Yoon, Yongsu; Kim, Hyunji; Her, Jae; Han, Seonggyu; Kwon, Soonmu; Park, Hunsik; Yang, Dongheon; Kim, Jungmin

    2015-12-01

    Digital cardiovascular angiography accounts for a major portion of the radiation dose among the examinations performed at cardiovascular centres. However, dose-related information is neither monitored nor recorded systemically. This report concerns the construction of a radiation dose monitoring system based on digital imaging and communications in medicine (DICOM) data and its use at the cardiovascular centre of the University Hospitals in Korea. The dose information was analysed according to DICOM standards for a series of procedures, and the formulation of diagnostic reference levels (DRLs) at our cardiovascular centre represents the first of its kind in Korea. We determined a dose area product (DAP) DRL for coronary angiography of 75.6 Gy cm(2) and a fluoroscopic time DRL of 318.0 s. The DAP DRL for percutaneous transluminal coronary intervention was 213.3 Gy cm(2), and the DRL for fluoroscopic time was 1207.5 s. PMID:25700616

  5. Organ dose conversion coefficients for voxel models of the reference male and female from idealized photon exposures

    NASA Astrophysics Data System (ADS)

    Schlattl, H.; Zankl, M.; Petoussi-Henss, N.

    2007-04-01

    A new series of organ equivalent dose conversion coefficients for whole body external photon exposure is presented for a standardized couple of human voxel models, called Rex and Regina. Irradiations from broad parallel beams in antero-posterior, postero-anterior, left- and right-side lateral directions as well as from a 360° rotational source have been performed numerically by the Monte Carlo transport code EGSnrc. Dose conversion coefficients from an isotropically distributed source were computed, too. The voxel models Rex and Regina originating from real patient CT data comply in body and organ dimensions with the currently valid reference values given by the International Commission on Radiological Protection (ICRP) for the average Caucasian man and woman, respectively. While the equivalent dose conversion coefficients of many organs are in quite good agreement with the reference values of ICRP Publication 74, for some organs and certain geometries the discrepancies amount to 30% or more. Differences between the sexes are of the same order with mostly higher dose conversion coefficients in the smaller female model. However, much smaller deviations from the ICRP values are observed for the resulting effective dose conversion coefficients. With the still valid definition for the effective dose (ICRP Publication 60), the greatest change appears in lateral exposures with a decrease in the new models of at most 9%. However, when the modified definition of the effective dose as suggested by an ICRP draft is applied, the largest deviation from the current reference values is obtained in postero-anterior geometry with a reduction of the effective dose conversion coefficient by at most 12%.

  6. Organ dose conversion coefficients for voxel models of the reference male and female from idealized photon exposures.

    PubMed

    Schlattl, H; Zankl, M; Petoussi-Henss, N

    2007-04-21

    A new series of organ equivalent dose conversion coefficients for whole body external photon exposure is presented for a standardized couple of human voxel models, called Rex and Regina. Irradiations from broad parallel beams in antero-posterior, postero-anterior, left- and right-side lateral directions as well as from a 360 degrees rotational source have been performed numerically by the Monte Carlo transport code EGSnrc. Dose conversion coefficients from an isotropically distributed source were computed, too. The voxel models Rex and Regina originating from real patient CT data comply in body and organ dimensions with the currently valid reference values given by the International Commission on Radiological Protection (ICRP) for the average Caucasian man and woman, respectively. While the equivalent dose conversion coefficients of many organs are in quite good agreement with the reference values of ICRP Publication 74, for some organs and certain geometries the discrepancies amount to 30% or more. Differences between the sexes are of the same order with mostly higher dose conversion coefficients in the smaller female model. However, much smaller deviations from the ICRP values are observed for the resulting effective dose conversion coefficients. With the still valid definition for the effective dose (ICRP Publication 60), the greatest change appears in lateral exposures with a decrease in the new models of at most 9%. However, when the modified definition of the effective dose as suggested by an ICRP draft is applied, the largest deviation from the current reference values is obtained in postero-anterior geometry with a reduction of the effective dose conversion coefficient by at most 12%. PMID:17404459

  7. The reference dose for subchronic exposure of pigs to cadmium leading to early renal damage by benchmark dose method.

    PubMed

    Wu, Xiaosheng; Wei, Shuai; Wei, Yimin; Guo, Boli; Yang, Mingqi; Zhao, Duoyong; Liu, Xiaoling; Cai, Xianfeng

    2012-08-01

    Pigs were exposed to cadmium (Cd) (in the form of CdCl(2)) concentrations ranging from 0 to 32mg Cd/kg feed for 100 days. Urinary cadmium (U-Cd) and blood cadmium (B-Cd) levels were determined as indicators of Cd exposure. Urinary levels of β(2)-microglobulin (β(2)-MG), α(1)-microglobulin (α(1)-MG), N-acetyl-β-D-glucosaminidase (NAG), cadmium-metallothionein (Cd-MT), and retinol binding protein (RBP) were determined as biomarkers of tubular dysfunction. U-Cd concentrations were increased linearly with time and dose, whereas B-Cd reached two peaks at 40 days and 100 days in the group exposed to 32mg Cd/kg. Hyper-metallothionein-urinary (HyperMTuria) and hyper-N-acetyl-β-D-glucosaminidase-urinary (hyperNAGuria) emerged from 80 days onwards in the group exposed to 32mg Cd/kg feed, followed by hyper-β2-microglobulin-urinary (hyperβ2-MGuria) and hyper-retinol-binding-protein-urinary (hyperRBPuria) from 100 days onwards. The relationships between the Cd exposure dose and biomarkers of exposure (as well as the biomarkers of effect) were examined, and significant correlations were found between them (except for α(1)-MG). Dose-response relationships between Cd exposure dose and biomarkers of tubular dysfunction were studied. The critical concentration of Cd exposure dose was calculated by the benchmark dose (BMD) method. The BMD(10)/BMDL(10) was estimated to be 1.34/0.67, 1.21/0.88, 2.75/1.00, and 3.73/3.08mg Cd/kg feed based on urinary RBP, NAG, Cd-MT, and β(2)-MG, respectively. The calculated tolerable weekly intake of Cd for humans was 1.4 μg/kg body weight based on a safety factor of 100. This value is lower than the currently available values set by several different countries. This indicates a need for further studies on the effects of Cd and a re-evaluation of the human health risk assessment for the metal. PMID:22610606

  8. Derivation of a screening methodology for evaluating radiation dose to aquatic and terrestrial biota.

    PubMed

    Higley, Kathryn A; Domotor, Stephen L; Antonio, Ernest J; Kocher, David C

    2003-01-01

    The United States Department of Energy (DOE) currently has in place a radiation dose standard for the protection of aquatic animals, and is considering additional dose standards for terrestrial biota. These standards are: 10 mGy/d for aquatic animals, 10 mGy/d for terrestrial plants, and, 1 mGy/d for terrestrial animals. Guidance on suitable approaches to the implementation of these standards is needed. A screening methodology, developed through DOE's Biota Dose Assessment Committee (BDAC), serves as the principal element of DOE's graded approach for evaluating radiation doses to aquatic and terrestrial biota. Limiting concentrations of radionuclides in water, soil, and sediment were derived for 23 radionuclides. Four organism types (aquatic animals; riparian animals; terrestrial animals; and terrestrial plants) were selected as the basis for development of the screening method. Internal doses for each organism type were calculated as the product of contaminant concentration, bioaccumulation factor(s) and dose conversion factors. External doses were calculated based on the assumption of immersion of the organism in soil, sediment, or water. The assumptions and default parameters used provide for conservative screening values. The screening methodology within DOE's graded approach should prove useful in demonstrating compliance with biota dose limits and for conducting screening assessments of radioecological impact. It provides a needed evaluation tool that can be employed within a framework for protection of the environment. PMID:12590069

  9. Overview of the ICRP/ICRU adult reference computational phantoms and dose conversion coefficients for external idealised exposures.

    PubMed

    Endo, Akira; Petoussi-Henss, Nina; Zankl, Maria; Bolch, Wesley E; Eckerman, Keith F; Hertel, Nolan E; Hunt, John G; Pelliccioni, Maurizio; Schlattl, Helmut; Menzel, Hans-Georg

    2014-10-01

    This paper reviews the ICRP Publications 110 and 116 describing the reference computational phantoms and dose conversion coefficients for external exposures. The International Commission on Radiological Protection (ICRP) in its 2007 Recommendations made several revisions to the methods of calculation of the protection quantities. In order to implement these recommendations, the DOCAL task group of the ICRP developed computational phantoms representing the reference adult male and female and then calculated a set of dose conversion coefficients for various types of idealised external exposures. This paper focuses on the dose conversion coefficients for neutrons and investigates their relationship with the conversion coefficients of the protection and operational quantities of ICRP Publication 74. Contributing factors to the differences between these sets of conversion coefficients are discussed in terms of the changes in phantoms employed and the radiation and tissue weighting factors. PMID:24285286

  10. Organ doses, effective doses, and risk indices in adult CT: Comparison of four types of reference phantoms across different examination protocols

    SciTech Connect

    Zhang Yakun; Li Xiang; Paul Segars, W.; Samei, Ehsan

    2012-06-15

    Purpose: Radiation exposure from computed tomography (CT) to the public has increased the concern among radiation protection professionals. Being able to accurately assess the radiation dose patients receive during CT procedures is a crucial step in the management of CT dose. Currently, various computational anthropomorphic phantoms are used to assess radiation dose by different research groups. It is desirable to better understand how the dose results are affected by different choices of phantoms. In this study, the authors assessed the uncertainties in CT dose and risk estimation associated with different types of computational phantoms for a selected group of representative CT protocols. Methods: Routinely used CT examinations were categorized into ten body and three neurological examination categories. Organ doses, effective doses, risk indices, and conversion coefficients to effective dose and risk index (k and q factors, respectively) were estimated for these examinations for a clinical CT system (LightSpeed VCT, GE Healthcare). Four methods were used, each employing a different type of reference phantoms. The first and second methods employed a Monte Carlo program previously developed and validated in our laboratory. In the first method, the reference male and female extended cardiac-torso (XCAT) phantoms were used, which were initially created from the Visible Human data and later adjusted to match organ masses defined in ICRP publication 89. In the second method, the reference male and female phantoms described in ICRP publication 110 were used, which were initially developed from tomographic data of two patients and later modified to match ICRP 89 organ masses. The third method employed a commercial dosimetry spreadsheet (ImPACT group, London, England) with its own hermaphrodite stylized phantom. In the fourth method, another widely used dosimetry spreadsheet (CT-Expo, Medizinische Hochschule, Hannover, Germany) was employed together with its associated

  11. Computed organ doses to an Indian reference adult during brachytherapy treatment of esophagus, breast, and neck cancers

    PubMed Central

    Keshavkumar, Biju

    2012-01-01

    This study aims to generate the normalized mean organ dose factors (mGy min-1 GBq-1) to healthy organs during brachytherapy treatment of esophagus, breast, and neck cancers specific to the patient population in India. This study is in continuation to the earlier published studies on the estimation of organ doses during uterus brachytherapy treatments. The results are obtained by Monte Carlo simulation of radiation transport through MIRD type anthropomorphic mathematical phantom representing reference Indian adult with 192Ir and 60Co high dose rate sources in the esophagus, breast, and neck of the phantom. The result of this study is compared with a published computational study using voxel-based phantom model. The variation in the organ dose of this study to the published values is within 50%. PMID:22973082

  12. Bayesian methods for uncertainty factor application for derivation of reference values.

    PubMed

    Simon, Ted W; Zhu, Yiliang; Dourson, Michael L; Beck, Nancy B

    2016-10-01

    In 2014, the National Research Council (NRC) published Review of EPA's Integrated Risk Information System (IRIS) Process that considers methods EPA uses for developing toxicity criteria for non-carcinogens. These criteria are the Reference Dose (RfD) for oral exposure and Reference Concentration (RfC) for inhalation exposure. The NRC Review suggested using Bayesian methods for application of uncertainty factors (UFs) to adjust the point of departure dose or concentration to a level considered to be without adverse effects for the human population. The NRC foresaw Bayesian methods would be potentially useful for combining toxicity data from disparate sources-high throughput assays, animal testing, and observational epidemiology. UFs represent five distinct areas for which both adjustment and consideration of uncertainty may be needed. NRC suggested UFs could be represented as Bayesian prior distributions, illustrated the use of a log-normal distribution to represent the composite UF, and combined this distribution with a log-normal distribution representing uncertainty in the point of departure (POD) to reflect the overall uncertainty. Here, we explore these suggestions and present a refinement of the methodology suggested by NRC that considers each individual UF as a distribution. From an examination of 24 evaluations from EPA's IRIS program, when individual UFs were represented using this approach, the geometric mean fold change in the value of the RfD or RfC increased from 3 to over 30, depending on the number of individual UFs used and the sophistication of the assessment. We present example calculations and recommendations for implementing the refined NRC methodology. PMID:27211295

  13. Long-term stability of liquid ionization chambers with regard to their qualification as local reference dosimeters for low dose-rate absorbed dose measurements in water.

    PubMed

    Bahar-Gogani, J; Grindborg, J E; Johansson, B E; Wickman, G

    2001-03-01

    The long-term sensitivity and calibration stability of liquid ionization chambers (LICs) has been studied at a local and a secondary standards dosimetry laboratory over a period of 3 years. The chambers were transported several times by mail between the two laboratories for measurements. The LICs used in this work are designed for absorbed dose measurements in the dose rate region of 0.1-100 mGy min(-1) and have a liquid layer thickness of 1 mm and a sensitive volume of 16.2 mm3. The liquids used as sensitive media in the chambers are mixtures of isooctane (C8H18) and tetramethylsilane (Si(CH3)4) in different proportions (about 2 to 1). Operating at a polarizing voltage of 300 V the leakage current of the chambers was stable and never exceeded 3% of the observable current at a dose rate of about 1 mGy min(-1). The volume sensitivity of the chambers was measured to be of the order of 10(-9) C Gy(-1) mm3. No systematic changes in the absorbed dose to water calibration was observed for any of the chambers during the test period (sigma < 0.2%). Variations in chamber dose response with small changes in the polarizing voltage as well as sensitivity changes with accumulated absorbed dose were also investigated. Measurements showed that the LIC response varies by 0.15% per 1% change in applied voltage around 300 V. No significant change could be observed in the LIC sensitivity after a single absorbed dose of 15 kGy. The results indicate that the LIC can be made to serve as a calibration transfer instrument and a reference detector for absorbed dose to water determinations providing good precision and long-term reproducibility. PMID:11277221

  14. Monitoring Satellite-derived Surface Solar Radiation with Near Real Time Reference Data

    NASA Astrophysics Data System (ADS)

    Kim, H. Y.; Laszlo, I.; Liu, H.

    2015-12-01

    Geostationary satellite observations of the Earth are increasingly made more frequent. For example, Himawari-8 of Japanese Meteorological Agency takes images of the planet every 10 minutes in multiple bands. Similarly, the GOES-R satellite of the US National Oceanic and Atmospheric Administration (NOAA) will make observations every 5 to 15 minutes. Products, like shortwave (solar) radiation budget at the surface, derived from these observations have or will have similar rapid refresh rates. Routine, near-real time assessment of the quality of these products ideally requires the availability of near-real time reference data. Such near-real time data has recently become available from the NOAA Surface Radiation Budget Network (SURFRAD). These data are disseminated every 15 minutes. However, in contrast to non-real-time data with fully quality control, which have a latency of 24 hours or more, the near-real time data have less quality control applied to them in order to achieve low latency. To assess applicability of this near-real time SURFRAD data for the evaluation satellite products we are using them experimentally to evaluate the quality of Downward Shortwave Radiation at the surface (DSR) retrieved operationally every hour from GOES and made available in the Geostationary Surface and Insolation Product (GSIP) . Metrics (accuracy and precision) are computed to characterize the level of agreement between satellite retrievals and the near-real time reference data. These metrics are then compared with metrics from the evaluation with the non-real time, fully quality controlled reference. The comparison shows that monitoring of DSR with near-real time data is not very different from monitoring it with non-real time data and so DSR retrievals can be evaluated hourly or shorter times depending on reference data availability.

  15. Derivation of a Screening Methodology for Evaluating Radiation Dose to Aquatic and Terrestrial Biota

    SciTech Connect

    Higley, Kathryn A.; Domotor, S L.; Antonio, Ernest J. ); Kocher, David

    2003-06-06

    The United States Department of Energy (DOE) currently has in place a radiation dose standard for the protection of aquatic organisms, and is considering proposing dose standards for both aquatic and terrestrial biota. These standards are: 10 mGy/d for aquatic animals; 10 mGy/d for terrestrial plants; and 1 mGy/d for terrestrial animals. Guidance on suitable approaches to implementation of these standards is needed. A screening methodology was developed as the first part of DOE's three-step graded approach for evaluating radiation doses to aquatic and terrestrial biota. Limiting concentrations of radionuclides in water, soil, and sediment media were derived for twenty-three target radionuclides. Four organism types (aquatic animals; riparian animals; terrestrial animals; and terrestrial plants) were selected as the basis for methods development. Internal doses for each organism type were calculated as the product of media concentration, bioaccumulation factors(s) and dose conversion factors. External doses were calculated based on the assumption of immersion of the organism in soil, sediment, or water. The assumptions and default parameters used provide for conservative screening values.

  16. Phase-derivative-based estimation of a digital reference wave from a single off-axis digital hologram.

    PubMed

    Khodadad, Davood

    2016-03-01

    This paper describes a method to obtain an estimated digital reference wave from a single off-axis digital hologram that matches the actual experimental reference wave as closely as possible. The proposed method is independent of a reference flat plate and speckles. The digital reference wave parameters are estimated directly from the recorded phase information. The parameters include both the off-axis tilt angle and the curvature of the reference wave. Phase derivatives are used to extract the digital reference wave parameters without the need for a phase unwrapping process. Thus, problems associated with phase wrapping are avoided. Experimental results for the proposed method are provided. The simulated effect of the digital reference wave parameters on the reconstructed image phase distribution is shown. The pseudo phase gradient originating from incorrect estimation of the digital reference wave parameters and its effect on object reconstruction are discussed. PMID:26974627

  17. Impact of A Priori Gradients on VLBI-Derived Terrestrial Reference Frames

    NASA Astrophysics Data System (ADS)

    Böhm, J.; Spicakova, H.; Urquhart, L.; Steigenberger, P.; Schuh, H.

    2011-07-01

    Tropospheric gradients are usually estimated in the analysis of space geodetic observations to account for the azimuthal asymmetry of troposphere delays. Whereas some analysis centres use a priori gradients for the analysis of Very Long Baseline Interferometry (VLBI) observations, no a priori information is generally applied in the analysis of Global Navigation Satellite Systems (GNSS) observations. We introduce a spherical harmonic expansion of total gradients derived from climatology data of the European Centre for Medium-Range Weather Forecasts (ECMWF), and we compare it to the gradients which have been determined for selected VLBI sites from data of the Data Assimilation Office (DAO) at Goddard Space Flight Center. The latter are usually applied in VLBI analysis. We show the effect of using both types of a priori gradients on the terrestrial and celestial reference frames which are determined from GNSS and VLBI analysis.

  18. EURRECA-Estimating vitamin D requirements for deriving dietary reference values.

    PubMed

    Cashman, Kevin D; Kiely, Mairead

    2013-01-01

    The time course of the EURRECA from 2008 to 2012, overlapped considerably with the timeframe of the process undertaken by the North American Institute of Medicine (IOM) to revise dietary reference intakes for vitamin D and calcium (published November 2010). Therefore the aims of the vitamin D-related activities in EURRECA were formulated to address knowledge requirements that would complement the activities undertaken by the IOM and provide additional resources for risk assessors and risk management agencies charged with the task of setting dietary reference values for vitamin D. A total of three systematic reviews were carried out. The first, which pre-dated the IOM review process, identified and evaluated existing and novel biomarkers of vitamin D status and confirmed that circulating 25-hydroxyvitamin D (25(OH)D) concentrations is a robust and reliable marker of vitamin D status. The second systematic review conducted a meta-analysis of the dose-response of serum 25(OH)D to vitamin D intake from randomized controlled trials (RCT) among adults to explore the most appropriate model of the vitamin D intake-serum 25(OH)D) relationship to estimate requirements. The third review also carried out a meta-analysis to evaluate evidence of efficacy from RCT using foods fortified with vitamin D, and found they increased circulating 25(OH)D concentrations in a dose-dependent manner but identified a need for stronger data on the efficacy of vitamin D-fortified food on deficiency prevention and potential health outcomes, including adverse effects. Finally, narrative reviews provided estimates of the prevalence of inadequate intakes of vitamin D in adults and children from international dietary surveys, as well as a compilation of research requirements for vitamin D to inform current and future assessments of vitamin D requirements. [Supplementary materials are available for this article. Go to the publisher's onilne edition of Critical Reviews in Food Science and Nutrion for

  19. Cytotoxicity of the MEIC reference chemicals in rat hepatoma-derived Fa32 cells.

    PubMed

    Dierickx, P J

    2000-09-01

    The cytotoxicity of the MEIC reference chemicals was investigated in rat hepatoma-derived Fa32 cells. The total protein content was measured as an endpoint after exposure times of 30 min and 24 h, both in normal and glutathione-depleted cells. The neutral red uptake inhibition and the MTT conversion were also measured after 30 min. On average, the cytotoxicity was higher in glutathione-depleted cells when compared to normal cells, and was lower after 30 min than after 24 h. Evidence was obtained for lysosomal attack (of five chemicals) or mitochondrial dysfunction (of six chemicals) as the primary intoxication mechanism. Malathion and mercuric chloride belong to both series of chemicals. Good to excellent correlations were observed when the 50% inhibitory concentrations of the six different in vitro assays were compared. When the six in vitro assays in Fa32 cells were compared with the human toxicity, the correlation coefficient was almost always identical to that obtained previously in human hepatoma-derived Hep G2 cells. The latter was the best acute in vitro assay for the prediction of human toxicity within the MEIC study. Altogether the results integrate very well with the basal cytotoxicity concept (Ekwall, B., 1995. The basal cytotoxicity concept. In: Goldberg, A.M., Van Zutphen, L.F.M. (Eds.), The World Congress on Alternatives and Animal Use in the Life Sciences: Education, Research, Testing. Mary Ann Liebert Publishers, New York, pp. 721-725). PMID:10996672

  20. Dose coefficients and derived guidance and clinical decision levels for contaminated wounds

    SciTech Connect

    Bertelli, Luiz; Toohey, Richard E

    2009-01-01

    The NCRP Wound Model describing the retention of selected radionuclides at the site of a contaminated wound and their uptake into the transfer compartment has been combined with the ICRP element-specific systemic models for those radionuclides to derive dose coefficients for intakes via contaminated wounds. Those coefficients have been used to generate derived guidance levels (i.e., the activity in a wound that would result in an effective dose of 20 or 50 mSv, or in some cases, a committed organ equivalent dose of 500 mSv), and clinical decision levels (i.e., activity levels that would indicate the need for consideration of medical intervention to remove activity from the wound site or administration of decorporation therapy or both), typically set at 5 times the derived guidance levels. Data are provided for the radionuclides commonly encountered at nuclear power plants and nuclear weapons, fuel fabrication or recycling, waste disposal, medical and research facilities. These include: {sup 60}Co, {sup 90}Sr, {sup 99m}Tc, {sup 131}I, {sup 137}Cs, {sup 192}Ir, {sup 210}Po, {sup 226,228}Ra, {sup 228,232}Th, {sup 235,238}U, {sup 237}Np, {sup 238,239}Pu, {sup 241}Am, {sup 242,244}Cm, and {sup 252}Cf.

  1. Patient grouping for dose surveys and establishment of diagnostic reference levels in paediatric computed tomography.

    PubMed

    Vassileva, J; Rehani, M

    2015-07-01

    There has been confusion in literature on whether paediatric patients should be grouped according to age, weight or other parameters when dealing with dose surveys. The present work aims to suggest a pragmatic approach to achieve reasonable accuracy for performing patient dose surveys in countries with limited resources. The analysis is based on a subset of data collected within the IAEA survey of paediatric computed tomography (CT) doses, involving 82 CT facilities from 32 countries in Asia, Europe, Africa and Latin America. Data for 6115 patients were collected, in 34.5 % of which data for weight were available. The present study suggests that using four age groups, <1, >1-5, >5-10 and >10-15 y, is realistic and pragmatic for dose surveys in less resourced countries and for the establishment of DRLs. To ensure relevant accuracy of results, data for >30 patients in a particular age group should be collected if patient weight is not known. If a smaller sample is used, patient weight should be recorded and the median weight in the sample should be within 5-10 % from the median weight of the sample for which the DRLs were established. Comparison of results from different surveys should always be performed with caution, taking into consideration the way of grouping of paediatric patients. Dose results can be corrected for differences in patient weight/age group. PMID:25836695

  2. Direction distributions of neutrons and reference values of the personal dose equivalent in workplace fields.

    PubMed

    Luszik-Bhadra, M; Bolognese-Milsztajn, T; Boschung, M; Coeck, M; Curzio, G; d'Errico, F; Fiechtner, A; Lacoste, V; Lindborg, L; Reginatto, M; Schuhmacher, H; Tanner, R; Vanhavere, F

    2007-01-01

    Within the EC project EVIDOS, double-differential (energy and direction) fluence spectra were determined by means of novel direction spectrometers. By folding the spectra with fluence-to-dose equivalent conversion coefficients, contributions to H*(10) for 14 directions, and values of the personal dose equivalent Hp(10) and the effective dose E for 6 directions of a person's orientation in the field were determined. The results of the measurements and calculations obtained within the EVIDOS project in workplace fields in nuclear installations in Europe, i.e., at Krümmel (boiling water reactor and transport cask), at Mol (Venus research reactor and fuel facility Belgonucléaire) and at Ringhals (pressurised reactor and transport cask) are presented. PMID:17369265

  3. Calculated organ doses using Monte Carlo simulations in a reference male phantom undergoing HDR brachytherapy applied to localized prostate carcinoma

    SciTech Connect

    Candela-Juan, Cristian; Perez-Calatayud, Jose; Ballester, Facundo; Rivard, Mark J.

    2013-03-15

    Purpose: The aim of this study was to obtain equivalent doses in radiosensitive organs (aside from the bladder and rectum) when applying high-dose-rate (HDR) brachytherapy to a localized prostate carcinoma using {sup 60}Co or {sup 192}Ir sources. These data are compared with results in a water phantom and with expected values in an infinite water medium. A comparison with reported values from proton therapy and intensity-modulated radiation therapy (IMRT) is also provided. Methods: Monte Carlo simulations in Geant4 were performed using a voxelized phantom described in International Commission on Radiological Protection (ICRP) Publication 110, which reproduces masses and shapes from an adult reference man defined in ICRP Publication 89. Point sources of {sup 60}Co or {sup 192}Ir with photon energy spectra corresponding to those exiting their capsules were placed in the center of the prostate, and equivalent doses per clinical absorbed dose in this target organ were obtained in several radiosensitive organs. Values were corrected to account for clinical circumstances with the source located at various positions with differing dwell times throughout the prostate. This was repeated for a homogeneous water phantom. Results: For the nearest organs considered (bladder, rectum, testes, small intestine, and colon), equivalent doses given by {sup 60}Co source were smaller (8%-19%) than from {sup 192}Ir. However, as the distance increases, the more penetrating gamma rays produced by {sup 60}Co deliver higher organ equivalent doses. The overall result is that effective dose per clinical absorbed dose from a {sup 60}Co source (11.1 mSv/Gy) is lower than from a {sup 192}Ir source (13.2 mSv/Gy). On the other hand, equivalent doses were the same in the tissue and the homogeneous water phantom for those soft tissues closer to the prostate than about 30 cm. As the distance increased, the differences of photoelectric effect in water and soft tissue, and appearance of other materials

  4. Two non-parametric methods for derivation of constraints from radiotherapy dose-histogram data

    NASA Astrophysics Data System (ADS)

    Ebert, M. A.; Gulliford, S. L.; Buettner, F.; Foo, K.; Haworth, A.; Kennedy, A.; Joseph, D. J.; Denham, J. W.

    2014-07-01

    Dose constraints based on histograms provide a convenient and widely-used method for informing and guiding radiotherapy treatment planning. Methods of derivation of such constraints are often poorly described. Two non-parametric methods for derivation of constraints are described and investigated in the context of determination of dose-specific cut-points—values of the free parameter (e.g., percentage volume of the irradiated organ) which best reflect resulting changes in complication incidence. A method based on receiver operating characteristic (ROC) analysis and one based on a maximally-selected standardized rank sum are described and compared using rectal toxicity data from a prostate radiotherapy trial. Multiple test corrections are applied using a free step-down resampling algorithm, which accounts for the large number of tests undertaken to search for optimal cut-points and the inherent correlation between dose-histogram points. Both methods provide consistent significant cut-point values, with the rank sum method displaying some sensitivity to the underlying data. The ROC method is simple to implement and can utilize a complication atlas, though an advantage of the rank sum method is the ability to incorporate all complication grades without the need for grade dichotomization.

  5. Cancer risks after diagnostic doses of 131I with special reference to thyroid cancer

    SciTech Connect

    Holm, L.E. )

    1991-01-01

    Between 1951 and 1969 a total of 35,074 patients less than 75 years of age (mean = 44 years) were examined with diagnostic doses of 131I. The mean administered activity of 131I was 52 microCi and the radiation dose to the thyroid gland was on the average of 0.5 Gy. The cohort was matched with the Swedish Cancer Register for the years 1958-1984. During this period, 3746 cancers occurred more than 5 years after the 131I examination, and the resulting standardized incidence ratio (SIR) was 1.01 (95% confidence interval (CI) = 0.98 to 1.04). SIR for thyroid cancer was 1.18 (95% CI = 0.88 to 1.56). The risks for both cancer of all sites and for thyroid cancer were highest 5 to 9 years after examination (SIR = 1.07 and 2.06, respectively) and did not differ from unity thereafter. With greater than or equal to 10 years of follow-up, risk was not statistically associated with the dose of 131I.

  6. Impact of oral bisphenol A at reference doses on intestinal barrier function and sex differences after perinatal exposure in rats.

    PubMed

    Braniste, Viorica; Jouault, Aurore; Gaultier, Eric; Polizzi, Arnaud; Buisson-Brenac, Claire; Leveque, Mathilde; Martin, Pascal G; Theodorou, Vassilia; Fioramonti, Jean; Houdeau, Eric

    2010-01-01

    Bisphenol A (BPA), a chemical estrogen widely used in the food-packaging industry and baby bottles, is recovered in human fluids (0.1-10 nM). Recent studies have reported that BPA is hormonally active at low doses, emphasizing the debate of a risk for human health. Estrogen receptors are expressed in the colon, and although the major route of BPA exposure is food, the effects on gut have received no attention. We first examined the endocrine disrupting potency of BPA on colonic paracellular permeability (CPP), experimental colitis, and visceral sensitivity in ovariectomized rats orally exposed to 5 mg/kg/d BPA (i.e., the no observed adverse effect level), 50 microg/kg/d BPA (i.e., tolerable daily intake), or lower doses. BPA dose-dependently decreased basal CPP, with a half-maximal inhibitory dose of 5.2 microg/kg/d, 10-fold below the tolerable daily intake. This correlated with an increase in epithelial tight junction sealing, also observed in Caco-2 cells exposed to 10 nM BPA. When ovariectomized rats were fed with BPA at the no observed adverse effect level, the severity of colitis was reduced, whereas the same dose increased pain sensitivity to colorectal stimuli. We then examined the impact of perinatal exposure to BPA on intestinal permeability and inflammatory response in the offspring. In female rats, but not in male rats, perinatal BPA evoked a decrease of CPP in adulthood, whereas the proinflammatory response of colonic mucosa was strengthened. This study first demonstrates that the xenoestrogen BPA at reference doses influences intestinal barrier function and gut nociception. Moreover, perinatal exposure promotes the development of severe inflammation in adult female offspring only. PMID:20018722

  7. Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields.

    PubMed

    Azcona, Juan Diego; Barbés, Benigno; Wang, Lilie; Burguete, Javier

    2016-01-01

    This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac's head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was

  8. Satellite-derived UV climatology over Europe: daily doses maps from January 1984 to October 2002

    NASA Astrophysics Data System (ADS)

    Verdebout, J.; Groebner, J.

    2003-04-01

    The paper presents a first version of a European satellite-derived ultraviolet (UV) radiation climatology over Europe, covering the period from January 1984 to October 2002. It consists in maps of the surface dose rates and daily doses, covering Europe (12E-32E, 34N-74N) with a spatial resolution of 0.05 deg. The method basically uses a standard radiative transfer code (UVspec) and exploits various sources of information to assign values to the influencing parameters. GOME, TOMS or TOVS data are used for the total column ozone. The attenuation of radiation by clouds is estimated using the MVIRI/METEOSAT visible channel data. In practice, for each METEOSAT pixel, the cloud optical thickness is derived from the enhancement of the signal with respect to the cloudless situation. Other influencing factors taken into account include tropospheric aerosols (using observations by ground meteorological stations), snow cover and surface elevation. The generated data set is made of daily maps of near noontime dose rates from which daily and monthly doses are extrapolated. The maps are available for several action spectra: UVA, UVB, erythemal, SCUPh, DNA and PLANT. The year-to-year variability of the UV radiation during the 19 years period, as deduced from this data set is illustrated. It varies according to the month and can reach ±50% over large areas. Variations are essentially due to changes in total column and cloudiness. These two factors are also documented separately. The validity of the results is discussed. Over such a period, the consistency of the input data and the impact on the modelled surface UV radiation is a critical issue for drawing conclusions on possible changes and trends. A partial validation of the results is demonstrated by comparison with ground UV measurements performed at Ispra, from 1992 to 2002.

  9. Experimental pencil beam kernels derivation for 3D dose calculation in flattening filter free modulated fields

    NASA Astrophysics Data System (ADS)

    Diego Azcona, Juan; Barbés, Benigno; Wang, Lilie; Burguete, Javier

    2016-01-01

    This paper presents a method to obtain the pencil-beam kernels that characterize a megavoltage photon beam generated in a flattening filter free (FFF) linear accelerator (linac) by deconvolution from experimental measurements at different depths. The formalism is applied to perform independent dose calculations in modulated fields. In our previous work a formalism was developed for ideal flat fluences exiting the linac’s head. That framework could not deal with spatially varying energy fluences, so any deviation from the ideal flat fluence was treated as a perturbation. The present work addresses the necessity of implementing an exact analysis where any spatially varying fluence can be used such as those encountered in FFF beams. A major improvement introduced here is to handle the actual fluence in the deconvolution procedure. We studied the uncertainties associated to the kernel derivation with this method. Several Kodak EDR2 radiographic films were irradiated with a 10 MV FFF photon beam from two linacs from different vendors, at the depths of 5, 10, 15, and 20cm in polystyrene (RW3 water-equivalent phantom, PTW Freiburg, Germany). The irradiation field was a 50mm diameter circular field, collimated with a lead block. The 3D kernel for a FFF beam was obtained by deconvolution using the Hankel transform. A correction on the low dose part of the kernel was performed to reproduce accurately the experimental output factors. Error uncertainty in the kernel derivation procedure was estimated to be within 0.2%. Eighteen modulated fields used clinically in different treatment localizations were irradiated at four measurement depths (total of fifty-four film measurements). Comparison through the gamma-index to their corresponding calculated absolute dose distributions showed a number of passing points (3%, 3mm) mostly above 99%. This new procedure is more reliable and robust than the previous one. Its ability to perform accurate independent dose calculations was

  10. Local patient dose diagnostic reference levels in pediatric interventional cardiology in Chile using age bands and patient weight values

    SciTech Connect

    Ubeda, Carlos; Miranda, Patricia; Vano, Eliseo

    2015-02-15

    Purpose: To present the results of a patient dose evaluation program in pediatric cardiology and propose local diagnostic reference levels (DRLs) for different types of procedure and age range, in addition to suggesting approaches to correlate patient dose values with patient weight. This study was the first conducted in Latin America for pediatric interventional cardiology under the auspices of the International Atomic Energy Agency. Methods: Over three years, the following data regarding demographic and patient dose values were collected: age, gender, weight, height, number of cine series, total number of cine frames, fluoroscopy time (FT), and two dosimetric quantities, dose-area product (DAP) and cumulative dose (CD), at the patient entrance reference point. The third quartile values for FT, DAP, CD, number of cine series, and the DAP/body weight ratio were proposed as the set of quantities to use as local DRLs. Results: Five hundred and seventeen patients were divided into four age groups. Sample sizes by age group were 120 for <1 yr; 213 for 1 to <5 yr; 82 for 5 to <10 yr; and 102 for 10 to <16 yr. The third quartile values obtained for DAP by diagnostic and therapeutic procedures and age range were 1.17 and 1.11 Gy cm{sup 2} for <1 yr; 1.74 and 1.90 Gy cm{sup 2} for 1 to <5 yr; 2.83 and 3.22 Gy cm{sup 2} for 5 to <10 yr; and 7.34 and 8.68 Gy cm{sup 2} for 10 to <16 yr, respectively. The third quartile value obtained for the DAP/body weight ratio for the full sample of procedures was 0.17 (Gy cm{sup 2}/kg) for diagnostic and therapeutic procedures. Conclusions: The data presented in this paper are an initial attempt at establishing local DRLs in pediatric interventional cardiology, from a large sample of procedures for the standard age bands used in Europe, complemented with the values of the ratio between DAP and patient weight. This permits a rough estimate of DRLs for different patient weights and the refining of these values for the age bands when there

  11. Reference computations of public dose and cancer risk from airborne releases of plutonium. Nuclear safety technical report

    SciTech Connect

    Peterson, V.L.

    1993-12-23

    This report presents results of computations of doses and the associated health risks of postulated accidental atmospheric releases from the Rocky Flats Plant (RFP) of one gram of weapons-grade plutonium in a form that is respirable. These computations are intended to be reference computations that can be used to evaluate a variety of accident scenarios by scaling the dose and health risk results presented here according to the amount of plutonium postulated to be released, instead of repeating the computations for each scenario. The MACCS2 code has been used as the basis of these computations. The basis and capabilities of MACCS2 are summarized, the parameters used in the evaluations are discussed, and results are presented for the doses and health risks to the public, both the Maximum Offsite Individual (a maximally exposed individual at or beyond the plant boundaries) and the population within 50 miles of RFP. A number of different weather scenarios are evaluated, including constant weather conditions and observed weather for 1990, 1991, and 1992. The isotopic mix of weapons-grade plutonium will change as it ages, the {sup 241}Pu decaying into {sup 241}Am. The {sup 241}Am reaches a peak concentration after about 72 years. The doses to the bone surface, liver, and whole body will increase slightly but the dose to the lungs will decrease slightly. The overall cancer risk will show almost no change over this period. This change in cancer risk is much smaller than the year-to-year variations in cancer risk due to weather. Finally, x/Q values are also presented for other applications, such as for hazardous chemical releases. These include the x/Q values for the MOI, for a collocated worker at 100 meters downwind of an accident site, and the x/Q value integrated over the population out to 50 miles.

  12. Construction of spherical harmonic series for the potential derivatives of arbitrary orders in the geocentric Earth-fixed reference frame

    NASA Astrophysics Data System (ADS)

    Petrovskaya, M. S.; Vershkov, A. N.

    2010-03-01

    The derivatives of the Earth gravitational potential are considered in the global Cartesian Earth-fixed reference frame. Spherical harmonic series are constructed for the potential derivatives of the first and second orders on the basis of a general expression of Cunningham (Celest Mech 2:207-216, 1970) for arbitrary order derivatives of a spherical harmonic. A common structure of the series for the potential and its first- and second-order derivatives allows to develop a general procedure for constructing similar series for the potential derivatives of arbitrary orders. The coefficients of the derivatives are defined by means of recurrence relations in which a coefficient of a certain order derivative is a linear function of two coefficients of a preceding order derivative. The coefficients of the second-order derivatives are also presented as explicit functions of three coefficients of the potential. On the basis of the geopotential model EGM2008, the spherical harmonic coefficients are calculated for the first-, second-, and some third-order derivatives of the disturbing potential T, representing the full potential V, after eliminating from it the zero- and first-degree harmonics. The coefficients of two lowest degrees in the series for the derivatives of T are presented. The corresponding degree variances are estimated. The obtained results can be applied for solving various problems of satellite geodesy and celestial mechanics.

  13. Wavelength and light-dose dependence in tumour phototherapy with haematoporphyrin derivative.

    PubMed Central

    van Gemert, J. C.; Berenbaum, M. C.; Gijsbers, G. H.

    1985-01-01

    Red light (c. 630 nm) is almost universally used in tumour phototherapy as it is the most penetrating of the porphyrin excitation wavebands. However, measurements of tumour attenuation of light of different wavelengths and of the excitation spectrum of haematoporphyrin derivative in vitro suggested that green light might be more efficient than red in destroying thin tumours. Experimentally, we confirmed this for tumours up to approximately 1.2 mm thick, a depth exceeding that of most carcinomas-in-situ. The superiority of green light over red in terms of the illumination time required to produce equivalent depths of necrosis may extend to greater depths (3-4 mm) if the former is produced by an argon laser and the latter by an argon-pumped dye laser. The relation between depth of necrosis Zn and light dose D is shown to be Zn = sigma gamma-1 1n(D/theta gamma) where sigma gamma is the attenuation coefficient for light at wavelength gamma and theta gamma the threshold light dose for producing necrosis at that wavelength. This logarithmic relationship suggests that it may be difficult to eradicate large tumours merely by increasing the light dose, and indicates the need for other approaches. Images Figure 2 PMID:3160379

  14. The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

    PubMed

    Habeck, C; Gazes, Y; Razlighi, Q; Steffener, J; Brickman, A; Barulli, D; Salthouse, T; Stern, Y

    2016-01-15

    Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the

  15. Evaluation of alanine as a reference dosimeter for therapy level dose comparisons in megavoltage electron beams

    NASA Astrophysics Data System (ADS)

    McEwen, Malcolm; Sharpe, Peter; Vörös, Sándor

    2015-04-01

    When comparing absorbed dose standards from different laboratories (e.g. National Measurement Institutes, NMIs, for Key or Supplementary comparisons) it is rarely possible to carry out a direct comparison of primary standard instruments, and therefore some form of transfer detector is required. Historically, air-filled, unsealed ionization chambers have been used because of the long history of using these instruments, very good stability over many years, and ease of transport. However, the use of ion chambers for therapy-level comparisons is not without its problems. Findings from recent investigations suggest that ion chambers are prone to non-random variations, they are not completely robust to standard courier practices, and failure at any step in a comparison can render all measurements potentially useless. An alternative approach is to identify a transfer system that is insensitive to some of these concerns—effectively a dosimeter that is inexpensive, simple to use, robust, but with sufficient precision and of a size relevant to the disseminated quantity in question. The alanine dosimetry system has been successfully used in a number of situations as an audit dosimeter and therefore the purpose of this investigation was to determine whether alanine could also be used as the transfer detector for dosimetric comparisons, which require a lower value for the measurement uncertainty. A measurement protocol was developed for comparing primary standards of absorbed dose to water in high-energy electron beams using alanine pellets irradiated in a water-equivalent plastic phantom. A trial comparison has been carried out between three NMIs and has indicated that alanine is a suitable alternative to ion chambers, with the system used achieving a precision of 0.1%. Although the focus of the evaluation was on the performance of the dosimeter, the comparison results are encouraging, showing agreement at the level of the combined uncertainties (~0.6%). Based on this

  16. GPS derived ground motions (2005-2014) within the Gulf of Mexico region referred to a stable Gulf of Mexico reference frame

    NASA Astrophysics Data System (ADS)

    Yu, J.; Wang, G.

    2015-11-01

    This study investigates current ground motions derived from the GPS geodesy infrastructure in the Gulf of Mexico region. The positions and velocity vectors of 161 continuous GPS (CGPS) stations are presented with respect to a newly established local reference frame, the Stable Gulf of Mexico Reference Frame (SGOMRF). Thirteen long-term (> 5 years) CGPS are used to realize the local reference frame. The root-mean-square (RMS) of the velocities of the 13 SGOMRF reference stations achieves 0.2 mm yr-1 in the horizontal and 0.3 mm yr-1 in the vertical directions. GPS observations presented in this study indicate significant land subsidence in the coastal area of southeastern Louisiana, the greater Houston metropolitan area, and two cities in Mexico (Aguascalientes and Mexico City). The most rapid subsidence is recorded at the Mexico City International airport, which is up to 26.6 cm yr-1 (2008-2014). Significant spatial variation of subsidence rates is observed in both Mexico City and the Houston area. The overall subsidence rate in the Houston area is decreasing. GPS observations in southeastern Louisiana indicate minor (4.0-6.0 mm yr-1) but consistent subsidence over time and space. This poses a potential threat to the safety of costal infrastructure in the long-term.

  17. GPS-derived ground deformation (2005-2014) within the Gulf of Mexico region referred to a stable Gulf of Mexico reference frame

    NASA Astrophysics Data System (ADS)

    Yu, Jiangbo; Wang, Guoquan

    2016-07-01

    This study investigates current ground deformation derived from the GPS geodesy infrastructure in the Gulf of Mexico region. The positions and velocity vectors of 161 continuous GPS (CGPS) stations are presented with respect to a newly established local reference frame, the Stable Gulf of Mexico Reference Frame (SGOMRF). Thirteen long-term (> 5 years) CGPS are used to realize the local reference frame. The root mean square (RMS) of the velocities of the 13 SGOMRF reference stations achieves 0.2 mm yr-1 in the horizontal and 0.3 mm yr-1 in the vertical directions. GPS observations presented in this study indicate significant land subsidence in the coastal area of southeastern Louisiana, the greater Houston metropolitan area, and two cities in Mexico (Aguascalientes and Mexico City). The most rapid subsidence is recorded at the Mexico City International airport, which is up to 26.6 cm yr-1 (2008-2014). Significant spatial variation of subsidence rates is observed in both Mexico City and the Houston area. The overall subsidence rate in the Houston area is decreasing. The subsidence rate in southeastern Louisiana is relatively smaller (4.0-6.0 mm yr-1) but tends to be steady over time. This poses a potential threat to the safety of coastal infrastructure in the long-term.

  18. Using physiologically based pharmacokinetic modeling to address nonlinear kinetics and changes in rodent physiology and metabolism due to aging and adaptation in deriving reference values for propylene glycol methyl ether and propylene glycol methyl ether acetate.

    SciTech Connect

    Kirman, C R.; Sweeney, Lisa M.; Corley, Rick A.; Gargas, M L.

    2005-04-01

    Reference values, including an oral reference dose (RfD) and an inhalation reference concentration (RfC), were derived for propylene glycol methyl ether (PGME), and an oral RfD was derived for its acetate (PGMEA). These values were based upon transient sedation observed in F344 rats and B6C3F1 mice during a two-year inhalation study. The dose-response relationship for sedation was characterized using internal dose measures as predicted by a physiologically based pharmacokinetic (PBPK) model for PGME and its acetate. PBPK modeling was used to account for changes in rodent physiology and metabolism due to aging and adaptation, based on data collected during weeks 1, 2, 26, 52, and 78 of a chronic inhalation study. The peak concentration of PGME in richly perfused tissues was selected as the most appropriate internal dose measure based upon a consideration of the mode of action for sedation and similarities in tissue partitioning between brain and other richly perfused tissues. Internal doses (peak tissue concentrations of PGME) were designated as either no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) based upon the presence or absence of sedation at each time-point, species, and sex in the two year study. Distributions of the NOAEL and LOAEL values expressed in terms of internal dose were characterized using an arithmetic mean and standard deviation, with the mean internal NOAEL serving as the basis for the reference values, which was then divided by appropriate uncertainty factors. Where data were permitting, chemical-specific adjustment factors were derived to replace default uncertainty factor values of ten. Nonlinear kinetics are were predicted by the model in all species at PGME concentrations exceeding 100 ppm, which complicates interspecies and low-dose extrapolations. To address this complication, reference values were derived using two approaches which differ with respect to the order in which these extrapolations

  19. FMA-RadLex: An application ontology of radiological anatomy derived from the foundational model of anatomy reference ontology.

    PubMed

    Mejino, Jose L V; Rubin, Daniel L; Brinkley, James F

    2008-01-01

    Domain reference ontologies are being developed to serve as generalizable and reusable sources designed to support any application specific to the domain. The challenge is how to develop ways to derive or adapt pertinent portions of reference ontologies into application ontologies. In this paper we demonstrate how a subset of anatomy relevant to the domain of radiology can be derived from an anatomy reference ontology, the Foundational Model of Anatomy (FMA) Ontology, to create an application ontology that is robust and expressive enough to incorporate and accommodate all salient anatomical knowledge necessary to support existing and emerging systems for managing anatomical information related to radiology. The principles underlying this work are applicable to domains beyond radiology, so our results could be extended to other areas of biomedicine in the future. PMID:18999035

  20. Derived Intervention Levels for Tritium Based on Food and Drug Administration Methodology Using ICRP 56 Dose Coefficients

    SciTech Connect

    Blanchard, A

    1999-06-09

    In 1998, the FDA released its recommendations for age-dependent derived intervention levels for several radionuclides involved in nuclear accidents. One radionuclide that is not included in that document is tritium. Therefore an analysis is presented here using dose coefficients from ICRP 56 to develop Derived Intervention Levels (DILs) for tritium in two forms: water (HTO) and organically bound tritium (OBT).

  1. An integrated clinical pharmacology approach for deriving dosing recommendations in a regulatory setting: review of recent cases in psychiatry drugs.

    PubMed

    Younis, Islam R; Rogers, Hobart; Zhang, Huixia; Zhu, Hao; Uppoor, Ramana S; Mehta, Mehul U

    2013-10-01

    Clinical pharmacology as an interdisciplinary science is unique in its capacity and the diversity of the methods and approaches it can provide to derive dosing recommendations in various subpopulations. This article illustrates cases where an integrated clinical pharmacology approach was used to derive dosing recommendations for psychiatry drugs within regulatory settings. The integrated approach is based on the view that once a drug is shown to be effective in the general population, it is reasonable to take into consideration other relevant findings and the use of alternative scientific tools and analysis to derive dosing recommendations in specific populations. The method provides useful means to solve the challenges of the paucity of available data and lead to clear dosing instructions. This in turn expands the benefits of any given drug to all individuals in which the drug is likely to be effective. PMID:23842865

  2. Conversion factors for external gamma dose derived from natural radionuclides in soils.

    PubMed

    Quindos, L S; Fernández, P L; Ródenas, C; Gómez-Arozamena, J; Arteche, J

    2004-01-01

    Field in situ gamma radiation exposure rates and laboratory measured radioactivity contents of 1500 Spanish soils were compared. The main objective was to determine if published theoretically derived conversion factors would yield accurate quantitative activity concentration (Bq kg(-1)) for the data carried out in different surveys developed by our laboratory during the last ten years. The in situ external gamma dose rate results were compared to laboratory gamma analysis of soils samples gathered from each site, considering the concentrations of seven radionuclides: 40K, 214Pb, 214Bi, 212Bi, 212Pb, 208Tl and 228Ac. The coefficient of correlation found between these variables indicate a good relationship. A discussion of the factors contributing to the uncertainties as well as measurement procedure are also given in this paper. PMID:14567949

  3. Dose- and time-dependent effects of triamcinolone acetonide on human rotator cuff-derived cells

    PubMed Central

    Harada, Y.; Kokubu, T.; Mifune, Y.; Inui, A.; Sakata, R.; Muto, T.; Takase, F.; Kurosaka, M.

    2014-01-01

    Objectives To investigate the appropriate dose and interval for the administration of triamcinolone acetonide (TA) in treating tendinopathy to avoid adverse effects such as tendon degeneration and rupture. Methods Human rotator cuff-derived cells were cultured using three media: regular medium (control), regular medium with 0.1 mg/mL of TA (low TA group), and with 1.0 mg/mL of TA (high TA group). The cell morphology, apoptosis, and viability were assessed at designated time points. Results In the low TA group, the cells became flattened and polygonal at seven days then returned to normal at 21 days. The cell apoptosis ratio and messenger ribonucleic acid expression of caspase-3, 7, 8, and 9 increased, and viability was reduced in the low and high groups at seven days. In the low TA group, apoptosis and viability returned to normal at 21 days, however, in the high TA group, the cell morphology, apoptosis ratio, caspase-3, 7, 8, and 9 and viability did not return by day 21. Re-administration was performed in the low TA group at 7-, 14-, and 21-day intervals, and cell viability did not return to the control level at the 7- and 14-day intervals. Conclusion A 0.1 mg/mL dose of TA temporarily decreased cell viability and increased cell apoptosis, which was recovered at 21 days, however, 1 mg/mL of TA caused irreversible damage to cell morphology and viability. An interval > three weeks was needed to safely re-administer TA. These findings may help determine the appropriate dose and interval for TA injection therapy. Cite this article: Bone Joint Res 2014;3:328–34. PMID:25477418

  4. Low doses of arginine butyrate derivatives improve dystrophic phenotype and restore membrane integrity in DMD models.

    PubMed

    Vianello, Sara; Consolaro, Francesca; Bich, Claudia; Cancela, José-Manuel; Roulot, Morgane; Lanchec, Erwan; Touboul, David; Brunelle, Alain; Israël, Maurice; Benoit, Evelyne; de la Porte, Sabine

    2014-06-01

    A new approach to treating Duchenne muscular dystrophy was investigated by using the ester or amide covalent association of arginine [nitric oxide (NO) pathway] and butyrate [histone deacetylase (HDAC) inhibition] in mdx mice and patient myotubes. Two prodrugs were synthesized, and the beneficial effects on dystrophic phenotype were studied. Nerve excitability abnormalities detected in saline-treated mice were almost totally rescued in animals treated at low doses (50-100 mg/kg/d). Force and fatigue resistance were improved ≈60% and 3.5-fold, respectively, and the percentage of necrosis in heart sections was reduced ≈90% in the treated mice. A decrease of >50% in serum creatine kinase indicated an overall improvement in the muscles. Restoration of membrane integrity was studied directly by measuring the reduction (≈74%) of Evans blue incorporation in the limb muscles of the treated animals, the increase in utrophin level, and the normalization of lipid composition of the heart. In cultures of human myotubes (primary cells and cell line), both prodrugs and HDAC inhibitors increased by 2- to 4-fold the utrophin level, which was correctly localized at the membrane. β-Dystroglycan and embryonic myosin protein levels were also increased. Finally, a 50% reduction in the number of spontaneous Ca(2+) spikes was observed after treatment with NO synthase substrate and HDAC inhibitors. Overall, the beneficial effects were obtained with doses 10 (in vivo) and 5 (in vitro) times lower than those of the salt formulation. Altogether, these data constitute proof of principle of the beneficial effects of low doses of arginine butyrate derivatives on muscular dystrophy, enhancing the NO pathway and inhibiting HDAC. PMID:24604079

  5. Looking for systematic error in scale from terrestrial reference frames derived from DORIS data

    NASA Technical Reports Server (NTRS)

    Willis, Pascal; Soudarin, L.; Lemoine, F. G.

    2005-01-01

    The long-term stability of the scale of Terrestrial Reference Frames is directly linked with station height determination and is critical for several scientific studies, such as global mean sea level rise or ocean circulation with consequences on global warming studies. In recent International Terrestrial Reference Frame solutions, the DORIS technique was not sonsidered able to provide any useful information on scale. We have analyzed three different DORIS time series of coordinates performed independently using different software packages.

  6. Reference computations of public dose and cancer risk from airborne releases of uranium and Class W plutonium

    SciTech Connect

    Peterson, V.L.

    1995-06-06

    This report presents ``reference`` computations that can be used by safety analysts in the evaluations of the consequences of postulated atmospheric releases of radionuclides from the Rocky Flats Environmental Technology Site. These computations deal specifically with doses and health risks to the public. The radionuclides considered are Class W Plutonium, all classes of Enriched Uranium, and all classes of Depleted Uranium. (The other class of plutonium, Y, was treated in an earlier report.) In each case, one gram of the respirable material is assumed to be released at ground leveL both with and without fire. The resulting doses and health risks can be scaled to whatever amount of release is appropriate for a postulated accident being investigated. The report begins with a summary of the organ-specific stochastic risk factors appropriate for alpha radiation, which poses the main health risk of plutonium and uranium. This is followed by a summary of the atmospheric dispersion factors for unfavorable and typical weather conditions for the calculation of consequences to both the Maximum Offsite Individual and the general population within 80 km (50 miles) of the site.

  7. Mitochondrial-Derived Oxidants and Cellular Responses to Low Dose/Low LET Ionizing Radiation

    SciTech Connect

    Spitz, Douglas R.

    2009-11-09

    Exposure to ionizing radiation results in the immediate formation of free radicals and other reactive oxygen species (ROS). It has been assumed that the subsequent injury processes leading to genomic instability and carcinogenesis following radiation, derive from the initial oxidative damage caused by these free radicals and ROS. It is now becoming increasingly obvious that metabolic oxidation/reduction (redox) reactions can be altered by irradiation leading to persistent increases in steady-state levels of intracellular free radicals and ROS that contribute to the long term biological effects of radiation exposure by causing chronic oxidative stress. The objective during the last period of support (DE-FG02-05ER64050; 5/15/05-12/31/09) was to determine the involvement of mitochondrial genetic defects in metabolic oxidative stress and the biological effects of low dose/low LET radiation. Aim 1 was to determine if cells with mutations in succinate dehydrogenase (SDH) subunits C and D (SDHC and SDHD in mitochondrial complex II) demonstrated increases in steady-state levels of reactive oxygen species (ROS; O2•- and H2O2) as well as demonstrating increased sensitivity to low dose/low LET radiation (10 cGy) in cultured mammalian cells. Aim #2 was to determine if mitochondrially-derived ROS contributed to increased sensitivity to low dose/low LET radiation in mammalian cells containing mutations in SDH subunits. Aim #3 was to determine if a causal relationship existed between increases in mitochondrial ROS production, alterations in electron transport chain proteins, and genomic instability in the progeny of irradiated cells. Evidence gathered in the 2005-2009 period of support demonstrated that mutations in genes coding for mitochondrial electron transport chain proteins (ETC); either Succinate Dehydrogenase (SDH) subunit C (SDHC) or subunit D (SDHD); caused increased ROS production, increased genomic instability, and increased sensitivity to low dose/low LET radiation

  8. Comparison of doses to the rectum derived from treatment planning system with in-vivo dose values in vaginal vault brachytherapy using cylinder applicators

    PubMed Central

    Obed, Rachel Ibhade; Akinlade, Bidemi Idayat; Ntekim, Atara

    2015-01-01

    Purpose In-vivo measurements to determine doses to organs-at-risk can be an essential part of brachytherapy quality assurance (QA). This study compares calculated doses to the rectum with measured dose values as a means of QA in vaginal vault brachytherapy using cylinder applicators. Material and methods At the Department of Radiotherapy, University College Hospital (UCH), Ibadan, Nigeria, intracavitary brachytherapy (ICBT) was delivered by a GyneSource high-dose-rate (HDR) unit with 60Co. Standard 2D treatment plans were created with HDR basic 2.6 software for prescription doses 5-7 Gy at points 5 mm away from the posterior surface of vaginal cylinder applicators (20, 25, and 30 mm diameters). The LiF:Mg, Ti thermoluminescent dosimeter rods (1 x 6 mm) were irradiated to a dose of 7 Gy on Theratron 60Co machine for calibration purpose prior to clinical use. Measurements in each of 34 insertions involving fourteen patients were performed with 5 TLD-100 rods placed along a re-usable rectal marker positioned in the rectum. The dosimeters were read in Harshaw 3500 TLD reader and compared with doses derived from the treatment planning system (TPS) at 1 cm away from the dose prescription points. Results The mean calculated and measured doses ranged from 2.1-3.8 Gy and 1.2-5.6 Gy with averages of 3.0 ± 0.5 Gy and 3.1 ± 1.1 Gy, respectively, for treatment lengths 2-8 cm along the cylinder-applicators. The mean values correspond to 48.9% and 50.8% of the prescribed doses, respectively. The deviations of the mean in-vivo doses from the TPS values ranged from –1.9 to 2.1 Gy with a p-value of 0.427. Conclusions This study was part of efforts to verify rectal dose obtained from the TPS during vaginal vault brachytherapy. There was no significant difference in the dose to the rectum from the two methods of measurements. PMID:26816506

  9. Spatial Mental Representations Derived from Survey and Route Descriptions: When Individuals Prefer Extrinsic Frame of Reference

    ERIC Educational Resources Information Center

    Meneghetti, Chiara; Pazzaglia, Francesca; De Beni, Rossana

    2011-01-01

    The present research investigates the role of individual differences in preference for adopting extrinsic frame of reference (EFR) in ability to represent mentally spatial information learned through survey and route descriptions. A sample of 191 participants (100 females and 91 males) was categorized as four groups with high (H-EFR), medium-high…

  10. Deriving and Measuring Group Knowledge Structure from Essays: The Effects of Anaphoric Reference

    ERIC Educational Resources Information Center

    Clariana, Roy B.; Wallace, Patricia E.; Godshalk, Veronica M.

    2009-01-01

    Essays are an important measure of complex learning, but pronouns can confound an author's intended meaning for both readers and text analysis software. This descriptive investigation considers the effect of pronouns on a computer-based text analysis approach, "ALA-Reader," which uses students' essays as the data source for deriving individual and…

  11. Comprehensive Reference Ranges for Hematology and Clinical Chemistry Laboratory Parameters Derived from Normal Nigerian Adults

    PubMed Central

    Miri-Dashe, Timzing; Osawe, Sophia; Tokdung, Monday; Daniel, Nenbammun; Choji, Rahila Pam; Mamman, Ille; Deme, Kurt; Damulak, Dapus; Abimiku, Alash’le

    2014-01-01

    Background Interpretation of laboratory test results with appropriate diagnostic accuracy requires reference or cutoff values. This study is a comprehensive determination of reference values for hematology and clinical chemistry in apparently healthy voluntary non-remunerated blood donors and pregnant women. Methods and findings Consented clients were clinically screened and counseled before testing for HIV, Hepatitis B, Hepatitis C and Syphilis. Standard national blood donors’ questionnaire was administered to consented blood donors. Blood from qualified volunteers was used for measurement of complete hematology and chemistry parameters. Blood samples were analyzed from a total of 383 participants, 124 (32.4%) males, 125 (32.6%) non-pregnant females and 134 pregnant females (35.2%) with a mean age of 31 years. Our results showed that the red blood cells count (RBC), Hemoglobin (HB) and Hematocrit (HCT) had significant gender difference (p = 0.000) but not for total white blood count (p>0.05) which was only significantly higher in pregnant verses non-pregnant women (p = 0.000). Hemoglobin and Hematocrit values were lower in pregnancy (P = 0.000). Platelets were significantly higher in females than men (p = 0.001) but lower in pregnant women (p = 0.001) with marked difference in gestational period. For clinical chemistry parameters, there was no significant difference for sodium, potassium and chloride (p>0.05) but gender difference exists for Bicarbonate (HCO3), Urea nitrogen, Creatinine as well as the lipids (p<0.05). Total bilirubin was significantly higher in males than females (p = 0.000). Significant differences exist for all chemistry parameters between pregnant and non-pregnant women in this study (p<0.05), except Amylase and total cholesterol (p>0.05). Conclusions Hematological and Clinical Chemistry reference ranges established in this study showed significant gender differences. Pregnant women also differed from non

  12. Patient Dose During Carotid Artery Stenting With Embolic-Protection Devices: Evaluation With Radiochromic Films and Related Diagnostic Reference Levels According to Factors Influencing the Procedure

    SciTech Connect

    D'Ercole, Loredana; Quaretti, Pietro; Cionfoli, Nicola; Klersy, Catherine; Bocchiola, Milena; Rodolico, Giuseppe; Azzaretti, Andrea; Lisciandro, Francesco; Cascella, Tommaso; Zappoli Thyrion, Federico

    2013-04-15

    To measure the maximum entrance skin dose (MESD) on patients undergoing carotid artery stenting (CAS) using embolic-protection devices, to analyze the dependence of dose and exposure parameters on anatomical, clinical, and technical factors affecting the procedure complexity, to obtain some local diagnostic reference levels (DRLs), and to evaluate whether overcoming DRLs is related to procedure complexity. MESD were evaluated with radiochromic films in 31 patients (mean age 72 {+-} 7 years). Five of 33 (15 %) procedures used proximal EPD, and 28 of 33 (85 %) procedures used distal EPD. Local DRLs were derived from the recorded exposure parameters in 93 patients (65 men and 28 women, mean age 73 {+-} 9 years) undergoing 96 CAS with proximal (33 %) or distal (67 %) EPD. Four bilateral lesions were included. MESD values (mean 0.96 {+-} 0.42 Gy) were <2 Gy without relevant dependence on procedure complexity. Local DRL values for kerma area product (KAP), fluoroscopy time (FT), and number of frames (N{sub FR}) were 269 Gy cm{sup 2}, 28 minutes, and 251, respectively. Only simultaneous bilateral treatment was associated with KAP (odds ratio [OR] 10.14, 95 % confidence interval [CI] 1-102.7, p < 0.05) and N{sub FR} overexposures (OR 10.8, 95 % CI 1.1-109.5, p < 0.05). Type I aortic arch decreased the risk of FT overexposure (OR 0.4, 95 % CI 0.1-0.9, p = 0.042), and stenosis {>=} 90 % increased the risk of N{sub FR} overexposure (OR 2.8, 95 % CI 1.1-7.4, p = 0.040). At multivariable analysis, stenosis {>=} 90 % (OR 2.8, 95 % CI 1.1-7.4, p = 0.040) and bilateral treatment (OR 10.8, 95 % CI 1.1-109.5, p = 0.027) were associated with overexposure for two or more parameters. Skin doses are not problematic in CAS with EPD because these procedures rarely lead to doses >2 Gy.

  13. Identification of stable reference genes for quantitative PCR in cells derived from chicken lymphoid organs.

    PubMed

    Borowska, D; Rothwell, L; Bailey, R A; Watson, K; Kaiser, P

    2016-02-01

    Quantitative polymerase chain reaction (qPCR) is a powerful technique for quantification of gene expression, especially genes involved in immune responses. Although qPCR is a very efficient and sensitive tool, variations in the enzymatic efficiency, quality of RNA and the presence of inhibitors can lead to errors. Therefore, qPCR needs to be normalised to obtain reliable results and allow comparison. The most common approach is to use reference genes as internal controls in qPCR analyses. In this study, expression of seven genes, including β-actin (ACTB), β-2-microglobulin (B2M), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-glucuronidase (GUSB), TATA box binding protein (TBP), α-tubulin (TUBAT) and 28S ribosomal RNA (r28S), was determined in cells isolated from chicken lymphoid tissues and stimulated with three different mitogens. The stability of the genes was measured using geNorm, NormFinder and BestKeeper software. The results from both geNorm and NormFinder were that the three most stably expressed genes in this panel were TBP, GAPDH and r28S. BestKeeper did not generate clear answers because of the highly heterogeneous sample set. Based on these data we will include TBP in future qPCR normalisation. The study shows the importance of appropriate reference gene normalisation in other tissues before qPCR analysis. PMID:26872627

  14. Relative accuracy of grid references derived from postcode and address in UK epidemiological studies of overhead power lines.

    PubMed

    Swanson, J; Vincent, T J; Bunch, K J

    2014-12-01

    In the UK, the location of an address, necessary for calculating the distance to overhead power lines in epidemiological studies, is available from different sources. We assess the accuracy of each. The grid reference specific to each address, provided by the Ordnance Survey product Address-Point, is generally accurate to a few metres, which will usually be sufficient for calculating magnetic fields from the power lines. The grid reference derived from the postcode rather than the individual address is generally accurate to tens of metres, and may be acceptable for assessing effects that vary in the general proximity of the power line, but is probably not acceptable for assessing magnetic-field effects. PMID:25325707

  15. Using physiologically based pharmacokinetic modeling and benchmark dose methods to derive an occupational exposure limit for N-methylpyrrolidone.

    PubMed

    Poet, T S; Schlosser, P M; Rodriguez, C E; Parod, R J; Rodwell, D E; Kirman, C R

    2016-04-01

    The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. PMID:26776754

  16. SU-E-T-516: Measurement of the Absorbed Dose Rate in Water Under Reference Conditions in a CyberKnife Unit

    SciTech Connect

    Aragon-Martinez, N; Hernandez-Guzman, A; Gomez-Munoz, A; Massillon-JL, G

    2014-06-01

    Purpose: This paper aims to measure the absorbed-dose-rate in a CyberKnife unit reference-field (6cm diameter) using three ionization chambers (IC) following the new IAEA/AAPM formalism and Gafchromic film (MD-V3-55 and EBT3) protocol according to our work reported previously. Methods: The absorbed-dose-rates were measured at 90cm and 70cm SSD in a 10cmx10cm field and at 70cm SSD in a 5.4cmx5.4cm equivalent to 6cm diameter field using a linac Varian iX. All measurements were performed at 10cm depth in water. The correction factors that account for the difference between the IC response on the reference field and the CyberKnife reference field, k-(Q-msr,Q)^(f-msr,f-ref), were evaluated and Gafchromic film were calibrated using the results obtained above. Under the CyberKnife reference conditions, the factors were used to measure the absorbed-dose-rate with IC according to the new formalism and the calibrated film was irradiated in water. The film calibration curve was used to evaluate the absorbed-dose-rate in the CyberKnife unit. Results: Difference up to 2.56% is observed between dose-rate measured with IC in the reference 10cmx10cm field, depending where the chamber was calibrated, which was not reflected in the correction factor k-(Q-msr,Q)^(f-msr,f-ref ) where variations of ~0.15%-0.5% were obtained. Within measurements uncertainties, maximum difference of 1.8% on the absorbed-dose-rate in the CyberKnife reference field is observed between all IC and the films Conclusion: Absorbed-dose-rate to water was measured in a CyberKnife reference field with acceptable accuracy (combined uncertainties ~1.32%-1.73%, k=1) using three IC and films. The MD-V3-55 film as well as the new IAEA/AAPM formalism can be considered as a suitable dosimetric method to measure absorbed-dose-rate to water in small and non-standard CyberKnife fields used in clinical treatments However, the EBT3 film is not appropriated due to the high uncertainty provided (combined uncertainty ~9%, k=1

  17. Evaluation of an X-Ray Dose Profile Derived from an Optically Stimulated Luminescent Dosimeter during Computed Tomographic Fluoroscopy

    PubMed Central

    Hasegawa, Hiroaki; Sato, Masanori; Tanaka, Hiroshi

    2015-01-01

    The purpose of this study was to evaluate scatter radiation dose to the subject surface during X-ray computed tomography (CT) fluoroscopy using the integrated dose ratio (IDR) of an X-ray dose profile derived from an optically stimulated luminescent (OSL) dosimeter. We aimed to obtain quantitative evidence supporting the radiation protection methods used during previous CT fluoroscopy. A multislice CT scanner was used to perform this study. OSL dosimeters were placed on the top and the lateral side of the chest phantom so that the longitudinal direction of dosimeters was parallel to the orthogonal axis-to-slice plane for measurement of dose profiles in CT fluoroscopy. Measurement of fluoroscopic conditions was performed at 120 kVp and 80 kVp. Scatter radiation dose was evaluated by calculating the integrated dose determined by OSL dosimetry. The overall percent difference of the integrated doses between OSL dosimeters and ionization chamber was 5.92%. The ratio of the integrated dose of a 100-mm length area to its tails (−50 to −6 mm, 50 to 6 mm) was the lowest on the lateral side at 80 kVp and the highest on the top at 120 kVp. The IDRs for different measurement positions were larger at 120 kVp than at 80 kVp. Similarly, the IDRs for the tube voltage between the primary X-ray beam and scatter radiation was larger on the lateral side than on the top of the phantom. IDR evaluation suggested that the scatter radiation dose has a high dependence on the position and a low dependence on tube voltage relative to the primary X-ray beam for constant dose rate fluoroscopic conditions. These results provided quantitative evidence supporting the radiation protection methods used during CT fluoroscopy in previous studies. PMID:26151914

  18. Evaluation of an X-Ray Dose Profile Derived from an Optically Stimulated Luminescent Dosimeter during Computed Tomographic Fluoroscopy.

    PubMed

    Hasegawa, Hiroaki; Sato, Masanori; Tanaka, Hiroshi

    2015-01-01

    The purpose of this study was to evaluate scatter radiation dose to the subject surface during X-ray computed tomography (CT) fluoroscopy using the integrated dose ratio (IDR) of an X-ray dose profile derived from an optically stimulated luminescent (OSL) dosimeter. We aimed to obtain quantitative evidence supporting the radiation protection methods used during previous CT fluoroscopy. A multislice CT scanner was used to perform this study. OSL dosimeters were placed on the top and the lateral side of the chest phantom so that the longitudinal direction of dosimeters was parallel to the orthogonal axis-to-slice plane for measurement of dose profiles in CT fluoroscopy. Measurement of fluoroscopic conditions was performed at 120 kVp and 80 kVp. Scatter radiation dose was evaluated by calculating the integrated dose determined by OSL dosimetry. The overall percent difference of the integrated doses between OSL dosimeters and ionization chamber was 5.92%. The ratio of the integrated dose of a 100-mm length area to its tails (-50 to -6 mm, 50 to 6 mm) was the lowest on the lateral side at 80 kVp and the highest on the top at 120 kVp. The IDRs for different measurement positions were larger at 120 kVp than at 80 kVp. Similarly, the IDRs for the tube voltage between the primary X-ray beam and scatter radiation was larger on the lateral side than on the top of the phantom. IDR evaluation suggested that the scatter radiation dose has a high dependence on the position and a low dependence on tube voltage relative to the primary X-ray beam for constant dose rate fluoroscopic conditions. These results provided quantitative evidence supporting the radiation protection methods used during CT fluoroscopy in previous studies. PMID:26151914

  19. Evaluation of absorbed and effective doses to patients from radiopharmaceuticals using the ICRP 110 reference computational phantoms and ICRP 103 formulation.

    PubMed

    Hadid, Lama; Gardumi, Anna; Desbrée, Aurélie

    2013-09-01

    In diagnostic nuclear medicine, mean absorbed doses to patients' organs and effective doses are published for standard stylised anatomic models. To provide more realistic and detailed geometries of the human morphology, the International Commission on Radiological Protection (ICRP) has recently adopted male and female voxel phantoms to represent the reference adult. This work investigates the impact of the use of these new computational phantoms. The absorbed doses were calculated for 11 different radiopharmaceuticals currently used in diagnostic nuclear medicine. They were calculated for the ICRP 110 reference computational phantoms using the OEDIPE software and the MCNP extended Monte Carlo code. The biokinetic models were issued from ICRP Publications 53, 80 and 106. The results were then compared with published values given in these ICRP Publications. To discriminate the effect of anatomical differences on organ doses from the effect of the calculation method, the Monte Carlo calculations were repeated for the reference adult stylised phantom. The voxel effect, the influence of the use of different densities and nuclear decay data were also investigated. Effective doses were determined for the ICRP 110 adult reference computational phantom with the tissue weighting factor of ICRP Publication 60 and the tissue weighting factors of ICRP Publication 103. The calculation method and, in particular, the simulation of the electron transport have a significant influence on the calculated doses, especially, for small and walled organs. Overestimates of >200 % were observed for the urinary bladder wall of the stylised phantom compared with the computational phantoms. The unrealistic organ topology of the stylised phantom leads to important dose differences, sometimes by an order of magnitude. The effective doses calculated using the new computational phantoms and the new tissue weighting factors are globally lower than the published ones, except for some

  20. Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment

    NASA Astrophysics Data System (ADS)

    Ramola, R. C.; Prasad, Mukesh; Kandari, Tushar; Pant, Preeti; Bossew, Peter; Mishra, Rosaline; Tokonami, S.

    2016-08-01

    The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13–52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses.

  1. Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment.

    PubMed

    Ramola, R C; Prasad, Mukesh; Kandari, Tushar; Pant, Preeti; Bossew, Peter; Mishra, Rosaline; Tokonami, S

    2016-01-01

    The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13-52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses. PMID:27499492

  2. Dose estimation derived from the exposure to radon, thoron and their progeny in the indoor environment

    PubMed Central

    Ramola, R. C.; Prasad, Mukesh; Kandari, Tushar; Pant, Preeti; Bossew, Peter; Mishra, Rosaline; Tokonami, S.

    2016-01-01

    The annual exposure to indoor radon, thoron and their progeny imparts a major contribution to inhalation doses received by the public. In this study, we report results of time integrated passive measurements of indoor radon, thoron and their progeny concentrations that were carried out in Garhwal Himalaya with the aim of investigating significant health risk to the dwellers in the region. The measurements were performed using recently developed LR-115 detector based techniques. The experimentally determined values of radon, thoron and their progeny concentrations were used to estimate total annual inhalation dose and annual effective doses. The equilibrium factors for radon and thoron were also determined from the observed data. The estimated value of total annual inhalation dose was found to be 1.8 ± 0.7 mSv/y. The estimated values of the annual effective dose were found to be 1.2 ± 0.5 mSv/y and 0.5 ± 0.3 mSv/y, respectively. The estimated values of radiation doses suggest no important health risk due to exposure of radon, thoron and progeny in the study area. The contribution of indoor thoron and its progeny to total inhalation dose ranges between 13–52% with mean value of 30%. Thus thoron cannot be neglected when assessing radiation doses. PMID:27499492

  3. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia

    PubMed Central

    Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I.; Sue, Carolyn M.; Mackay-Sim, Alan

    2014-01-01

    ABSTRACT Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

  4. Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia.

    PubMed

    Fan, Yongjun; Wali, Gautam; Sutharsan, Ratneswary; Bellette, Bernadette; Crane, Denis I; Sue, Carolyn M; Mackay-Sim, Alan

    2014-01-01

    Hereditary Spastic Paraplegia (HSP) is a genetically heterogeneous group of disorders, diagnosed by progressive gait disturbances with muscle weakness and spasticity, for which there are no treatments targeted at the underlying pathophysiology. Mutations in spastin are a common cause of HSP. Spastin is a microtubule-severing protein whose mutation in mouse causes defective axonal transport. In human patient-derived olfactory neurosphere-derived (ONS) cells, spastin mutations lead to lower levels of acetylated α-tubulin, a marker of stabilised microtubules, and to slower speed of peroxisome trafficking. Here we screened multiple concentrations of four tubulin-binding drugs for their ability to rescue levels of acetylated α-tubulin in patient-derived ONS cells. Drug doses that restored acetylated α-tubulin to levels in control-derived ONS cells were then selected for their ability to rescue peroxisome trafficking deficits. Automated microscopic screening identified very low doses of the four drugs (0.5 nM taxol, 0.5 nM vinblastine, 2 nM epothilone D, 10 µM noscapine) that rescued acetylated α-tubulin in patient-derived ONS cells. These same doses rescued peroxisome trafficking deficits, restoring peroxisome speeds to untreated control cell levels. These results demonstrate a novel approach for drug screening based on high throughput automated microscopy for acetylated α-tubulin followed by functional validation of microtubule-based peroxisome transport. From a clinical perspective, all the drugs tested are used clinically, but at much higher doses. Importantly, epothilone D and noscapine can enter the central nervous system, making them potential candidates for future clinical trials. PMID:24857849

  5. [F-18]-Fluoromisonidazole Quantification of Hypoxia in Human Cancer Patients using Image-derived Blood Surrogate Tissue Reference Regions

    PubMed Central

    Muzi, Mark; Peterson, Lanell M.; O’Sullivan, Janet N.; Fink, James R.; Rajendran, Joseph G.; McLaughlin, Lena J.; Muzi, John P.; Mankoff, David A.; Krohn, Kenneth A.

    2015-01-01

    18F-FMISO is the most widely used PET agent for imaging hypoxia, a condition associated with resistance to tumor therapy. 18F-FMISO equilibrates in normoxic tissues, but is retained under hypoxic conditions because of reduction and binding to macromolecules. A simple tissue-to-blood ratio (TB) is suitable for quantifying hypoxia. A threshold of TB ≥ 1.2 is useful in discriminating the hypoxic volume (HV) of tissue; TBmax is the maximum intensity of the hypoxic region and does not invoke a threshold. Because elimination of blood sampling would simplify clinical use, we tested the validity of using imaging regions as a surrogate for blood sampling. Methods Patients underwent 20 min 18F-FMISO scans during the 90–140 min interval post-injection with venous blood sampling. 223 18F-FMISO patient studies had detectable surrogate blood regions in the field-of-view. Quantitative parameters of hypoxia (TBmax, HV) derived from blood samples were compared to values using surrogate blood regions derived from heart, aorta and/or cerebellum. In a subset of brain cancer patients, parameters from blood samples and from cerebellum were compared for their ability to independently predict outcome. Results Vascular regions of heart showed the highest correlation to measured blood activity (R2 = 0.84). For brain studies, cerebellar activity was similarly correlated to blood samples. In brain cancer patients, Kaplan-Meier analysis showed that image-derived reference regions had nearly identical predictive power as parameters derived from blood, thus obviating the need for venous sampling in these patients. Conclusions Simple static analysis of 18F-FMISO PET captures both the intensity (TBmax) and spatial extent (HV) of tumor hypoxia. An image-derived region to assess blood activity can be used as a surrogate for blood sampling in quantification of hypoxia. PMID:26112020

  6. (Depth-dose curves of the beta reference fields (147)Pm, (85)Kr and (90)Sr/(90)Y produced by the beta secondary standard BSS2.

    PubMed

    Brunzendorf, Jens

    2012-08-01

    The most common reference fields in beta dosimetry are the ISO 6980 series 1 radiation fields produced by the beta secondary standard BSS2 and its predecessor BSS. These reference fields require sealed beta radiation sources ((147)Pm, (85)Kr or (90)Sr/(90)Y) in combination with a source-specific beam-flattening filter, and are defined only at a given distance from the source. Every radiation sources shipped with the BSS2 is sold with a calibration certificate of the Physikalisch-Technische Bundesanstalt. The calibration workflow also comprises regular depth-dose measurements. This work publishes complete depth-dose curves of the series 1 sources (147)Pm, (85)Kr and (90)Sr/(90)Y in ICRU tissue up to a depth of 11 mm,when all electrons are stopped. For this purpose, the individual depth-dose curves of all BSS2 sources calibrated so far have been determined, i.e. the complete datasets of all BSS2 beta sources have been re-evaluated. It includes 191 depth-dose curves of 116 different sources comprising more than 2200 data points in total. Appropriate analytical representations of the nuclide-specific depth-dose curves are provided for the first time. PMID:22267274

  7. SU-E-J-19: Accuracy of Dual-Energy CT-Derived Relative Electron Density for Proton Therapy Dose Calculation

    SciTech Connect

    Mullins, J; Duan, X; Kruse, J; Herman, M; Bues, M

    2014-06-01

    Purpose: To determine the suitability of dual-energy CT (DECT) to calculate relative electron density (RED) of tissues for accurate proton therapy dose calculation. Methods: DECT images of RED tissue surrogates were acquired at 80 and 140 kVp. Samples (RED=0.19−2.41) were imaged in a water-equivalent phantom in a variety of configurations. REDs were calculated using the DECT numbers and inputs of the high and low energy spectral weightings. DECT-derived RED was compared between geometric configurations and for variations in the spectral inputs to assess the sensitivity of RED accuracy versus expected values. Results: RED accuracy was dependent on accurate spectral input influenced by phantom thickness and radius from the phantom center. Material samples located at the center of the phantom generally showed the best agreement to reference RED values, but only when attenuation of the surrounding phantom thickness was accounted for in the calculation spectra. Calculated RED changed by up to 10% for some materials when the sample was located at an 11 cm radius from the phantom center. Calculated REDs under the best conditions still differed from reference values by up to 5% in bone and 14% in lung. Conclusion: DECT has previously been used to differentiate tissue types based on RED and Z for binary tissue-type segmentation. To improve upon the current standard of empirical conversion of CT number to RED for treatment planning dose calculation, DECT methods must be able to calculate RED to better than 3% accuracy throughout the image. The DECT method is sensitive to the accuracy of spectral inputs used for calculation, as well as to spatial position in the anatomy. Effort to address adjustments to the spectral calculation inputs based on position and phantom attenuation will be required before DECT-determined RED can achieve a consistent level of accuracy for application in dose calculation.

  8. Using physiologically-based pharmacokinetic modeling to address nonlinear kinetics and changes in rodent physiology and metabolism due to aging and adaptation in deriving reference values for propylene glycol methyl ether and propylene glycol methyl ether acetate.

    PubMed

    Kirman, C R; Sweeney, L M; Corley, R; Gargas, M L

    2005-04-01

    Reference values, including an oral reference dose (RfD) and an inhalation reference concentration (RfC), were derived for propylene glycol methyl ether (PGME), and an oral RfD was derived for its acetate (PGMEA). These values were based on transient sedation observed in F344 rats and B6C3F1 mice during a two-year inhalation study. The dose-response relationship for sedation was characterized using internal dose measures as predicted by a physiologically-based pharmacokinetic (PBPK) model for PGME and its acetate. PBPK modeling was used to account for changes in rodent physiology and metabolism due to aging and adaptation, based on data collected during Weeks 1, 2, 26, 52, and 78 of a chronic inhalation study. The peak concentration of PGME in richly perfused tissues (i.e., brain) was selected as the most appropriate internal dose measure based on a consideration of the mode of action for sedation and similarities in tissue partitioning between brain and other richly perfused tissues. Internal doses (peak tissue concentrations of PGME) were designated as either no-observed-adverse-effect levels (NOAELs) or lowest-observed-adverse-effect levels (LOAELs) based on the presence or the absence of sedation at each time point, species, and sex in the two-year study. Distributions of the NOAEL and LOAEL values expressed in terms of internal dose were characterized using an arithmetic mean and standard deviation, with the mean internal NOAEL serving as the basis for the reference values, which was then divided by appropriate uncertainty factors. Where data were permitting, chemical-specific adjustment factors were derived to replace default uncertainty factor values of 10. Nonlinear kinetics, which was predicted by the model in all species at PGME concentrations exceeding 100 ppm, complicate interspecies, and low-dose extrapolations. To address this complication, reference values were derived using two approaches that differ with respect to the order in which these

  9. Acute necrotising pancreatitis derived from low-dose corticosteroid use: an important reminder of clinical management.

    PubMed

    Sabre, Alexander; Guthrie, Morgan Mary; Maleknia, Reza

    2015-01-01

    Although the exact mechanism is unknown, incidence of drug-induced pancreatitis from corticosteroids is well established in the medical literature. Commonly reported in chronic steroid-dependent individuals who require large doses for a wide array of pathologies, the incidence of damage to the pancreas from low-doses have not been well described. We report a case of a 68-year-old woman who presented with severe abdominal pain, nausea and vomiting, 3 days after the initiation of low-dose methylprednisolone for osteoarthritis. Inpatient laboratory analysis revealed an elevated lipase of 1770 U/L and CT scan showing extensive necrotising pancreatitis involving the head, body and tail. Cessation of the causative medication and conservative treatment successfully led to resolution of symptoms. We present this case to inform clinicians of the precipitance of pancreatitis from modest strength corticosteroid management, so that more accurate and improved performance in pharmacological decisions can be made for patient care. PMID:26150628

  10. Do Glioma Patients Derive Any Therapeutic Benefit From Taking a Higher Cumulative Dose of Temozolomide Regimens?

    PubMed Central

    Sun, Hao; Du, Shasha; Liao, Guixiang; Xie, Xiao; Ren, Chen; Yuan, Ya Wei

    2015-01-01

    Abstract Temozolomide (TMZ) is an oral alkylating agent with established effects on the central nervous system of glioblastoma (GBM) patients. Clinical trials have demonstrated a significant impact on overall survival (OS) with TMZ. Ever since, several TMZ regimens have been designed to improve treatment efficacy by increasing the cumulative dose per cycle. We report a meta-analysis to systematically evaluate different treatment schedules of TMZ in GBM patients. All searches that were conducted in the Cochrane library, Science Direct, and PubMed Databases, and 3 randomized controlled trials (1141 patients) were included. OS and progression-free survival (PFS) were the primary outcomes to be pooled. Unexpectedly, this analysis did not reveal any OS or PFS advantage for the high cumulative dose (HCD) regimen compared with the normal cumulative dose regimen (1141 total patients; hazard ratio [HR] 1.07, 95% CI 0.94–1.22, P = 0.31). Then after analyzing the characteristics of the results from each trial, we found that the regimen with a higher peak concentration during a short-term period (daily doses ≥150 mg/m2/d within ≤7 days/cycle) always had a more superior clinical benefit. So we generated a new pooled HR of 1.10 with a 95% CI of 0.96–1.25 (P = 0.17), which prefers the high peak concentration schedule even without a significant difference. The adverse outcome also indicates a significant increased risk of leukopenia (risk ratio 1.59, 95% CI 1.03–2.46, P = 0.04) among the HCD group. Our study suggests that increasing the cumulative dose per cycle is not an ideal way to improve the efficacy of TMZ, and it will lead to increased risk for leukopenia. Future trials should be designed to examine schedules of higher peak concentration rather than the cumulative dose per cycle. PMID:25997057

  11. Contribution for the derivation of a soil screening value (SSV) for uranium, using a natural reference soil.

    PubMed

    Caetano, Ana Luisa; Marques, Catarina R; Gavina, Ana; Carvalho, Fernando; Gonçalves, Fernando; da Silva, Eduardo Ferreira; Pereira, Ruth

    2014-01-01

    In order to regulate the management of contaminated land, many countries have been deriving soil screening values (SSV). However, the ecotoxicological data available for uranium is still insufficient and incapable to generate SSVs for European soils. In this sense, and so as to make up for this shortcoming, a battery of ecotoxicological assays focusing on soil functions and organisms, and a wide range of endpoints was carried out, using a natural soil artificially spiked with uranium. In terrestrial ecotoxicology, it is widely recognized that soils have different properties that can influence the bioavailability and the toxicity of chemicals. In this context, SSVs derived for artificial soils or for other types of natural soils, may lead to unfeasible environmental risk assessment. Hence, the use of natural regional representative soils is of great importance in the derivation of SSVs. A Portuguese natural reference soil PTRS1, from a granitic region, was thereby applied as test substrate. This study allowed the determination of NOEC, LOEC, EC20 and EC50 values for uranium. Dehydrogenase and urease enzymes displayed the lowest values (34.9 and <134.5 mg U Kg, respectively). Eisenia andrei and Enchytraeus crypticus revealed to be more sensitive to uranium than Folsomia candida. EC50 values of 631.00, 518.65 and 851.64 mg U Kg were recorded for the three species, respectively. Concerning plants, only Lactuca sativa was affected by U at concentrations up to 1000 mg U kg(1). The outcomes of the study may in part be constrained by physical and chemical characteristics of soils, hence contributing to the discrepancy between the toxicity data generated in this study and that available in the literature. Following the assessment factor method, a predicted no effect concentration (PNEC) value of 15.5 mg kg-1dw was obtained for U. This PNEC value is proposed as a SSV for soils similar to the PTRS1. PMID:25353962

  12. Contribution for the Derivation of a Soil Screening Value (SSV) for Uranium, Using a Natural Reference Soil

    PubMed Central

    Caetano, Ana Luisa; Marques, Catarina R.; Gavina, Ana; Carvalho, Fernando; Gonçalves, Fernando; da Silva, Eduardo Ferreira; Pereira, Ruth

    2014-01-01

    In order to regulate the management of contaminated land, many countries have been deriving soil screening values (SSV). However, the ecotoxicological data available for uranium is still insufficient and incapable to generate SSVs for European soils. In this sense, and so as to make up for this shortcoming, a battery of ecotoxicological assays focusing on soil functions and organisms, and a wide range of endpoints was carried out, using a natural soil artificially spiked with uranium. In terrestrial ecotoxicology, it is widely recognized that soils have different properties that can influence the bioavailability and the toxicity of chemicals. In this context, SSVs derived for artificial soils or for other types of natural soils, may lead to unfeasible environmental risk assessment. Hence, the use of natural regional representative soils is of great importance in the derivation of SSVs. A Portuguese natural reference soil PTRS1, from a granitic region, was thereby applied as test substrate. This study allowed the determination of NOEC, LOEC, EC20 and EC50 values for uranium. Dehydrogenase and urease enzymes displayed the lowest values (34.9 and <134.5 mg U Kg, respectively). Eisenia andrei and Enchytraeus crypticus revealed to be more sensitive to uranium than Folsomia candida. EC50 values of 631.00, 518.65 and 851.64 mg U Kg were recorded for the three species, respectively. Concerning plants, only Lactuca sativa was affected by U at concentrations up to 1000 mg U kg1. The outcomes of the study may in part be constrained by physical and chemical characteristics of soils, hence contributing to the discrepancy between the toxicity data generated in this study and that available in the literature. Following the assessment factor method, a predicted no effect concentration (PNEC) value of 15.5 mg kg−1dw was obtained for U. This PNEC value is proposed as a SSV for soils similar to the PTRS1. PMID:25353962

  13. Copper toxicity in a natural reference soil: ecotoxicological data for the derivation of preliminary soil screening values.

    PubMed

    Caetano, Ana Luísa; Marques, Catarina Ribeiro; Gonçalves, Fernando; da Silva, Eduardo Ferreira; Pereira, Ruth

    2016-01-01

    The risk assessment of contaminated soils is conventionally done with the support of soil screening values (SSVs). Since SSVs are still unavailable for many European countries, including Portugal, standardized toxicity tests are urgently claimed for their derivation. Hence, this work aimed the generation of toxicity values for copper (Cu) in a natural reference soil (PTRS1) targeting different terrestrial species, endpoints and soil functions, as to derive a preliminary Cu SSV. For this, the Assessment Factor approach was applied, which allowed calculating predicted no effect concentrations (PNEC) for Cu that will be the basis for SSV proposal. In order to increase the reliability of the PNEC, and hence of the SSV, a lab/field factor was applied to correct the toxicity values used for PNEC determination. Cu affected urease, cellulase and nitrogen mineralization activities. The EC50 values calculated for the invertebrates reproduction were 130.9, 165.1 and 191.6 mg Cu Kg(-1) soildw for Eisenia andrei, Enchytraeus crypticus and Folsomia candida, respectively. Cu inhibited seed germination mainly for Lactuca sativa, whilst it was toxic for the growth of different plant species (EC50s between 89 and 290.5 mg Cu Kg(-1) soildw). Based on the outcomes gathered, we proposed SSVs for Cu ranging between 26.3 and 31.8 mg Kg(-1) soildw, which is above the background values reported and below all the EC20s recorded for the species and endpoints herein analyzed. Overall, this work describes a procedure that could be easily followed by other European countries wishing to derive SSVs adjusted to their soils. PMID:26520436

  14. Boron neutron capture therapy (BNCT) for malignant melanoma with special reference to absorbed doses to the normal skin and tumor.

    PubMed

    Fukuda, H; Hiratsuka, J; Kobayashi, T; Sakurai, Y; Yoshino, K; Karashima, H; Turu, K; Araki, K; Mishima, Y; Ichihashi, M

    2003-09-01

    Twenty-two patients with malignant melanoma were treated with boron neutron capture therapy (BNCT) using 10B-p-boronophenylalanine (BPA). The estimation of absorbed dose and optimization of treatment dose based on the pharmacokinetics of BPA in melanoma patients is described. The doses of gamma-rays were measured using small TLDs of Mg2SiO4 (Tb) and thermal neutron fluence was measured using gold foil and wire. The total absorbed dose to the tissue from BNCT was obtained by summing the primary and capture gamma-ray doses and the high LET radiation doses from 10B(n, alpha)7Li and 14N(n,p)14C reactions. The key point of the dose optimization is that the skin surrounding the tumour is always irradiated to 18 Gy-Eq, which is the maximum tolerable dose to the skin, regardless of the 10B-concentration in the tumor. The neutron fluence was optimized as follows. (1) The 10B concentration in the blood was measured 15-40 min after the start of neutron irradiation. (2) The 10B-concentration in the skin was estimated by multiplying the blood 10B value by a factor of 1.3. (3) The neutron fluence was calculated. Absorbed doses to the skin ranged from 15.7 to 37.1 Gy-Eq. Among the patients, 16 out of 22 patients exhibited tolerable skin damage. Although six patients showed skin damage that exceeded the tolerance level, three of them could be cured within a few months after BNCT and the remaining three developed severe skin damage requiring skin grafts. The absorbed doses to the tumor ranged from 15.7 to 68.5 Gy-Eq and the percentage of complete response was 73% (16/22). When BNCT is used in the treatment of malignant melanoma, based on the pharmacokinetics of BPA and radiobiological considerations, promising clinical results have been obtained, although many problems and issues remain to be solved. PMID:14626847

  15. Dose-dependent Effect of Boric Acid on Myogenic Differentiation of Human Adipose-derived Stem Cells (hADSCs).

    PubMed

    Apdik, Hüseyin; Doğan, Ayşegül; Demirci, Selami; Aydın, Safa; Şahin, Fikrettin

    2015-06-01

    Boron, a vital micronutrient for plant metabolism, is not fully elucidated for embryonic and adult body development, and tissue regeneration. Although optimized amount of boron supplement has been shown to be essential for normal gestational development in zebrafish and frog and beneficial for bone regeneration in higher animals, effects of boron on myogenesis and myo-regeneration remains to be solved. In the current study, we investigated dose-dependent activity of boric acid on myogenic differentiation of human adipose-derived stem cells (hADSCs) using immunocytochemical, gene, and protein expression analysis. The results revealed that while low- (81.9 μM) and high-dose (819.6 μM) boron treatment increased myogenic gene expression levels such as myosin heavy chain (MYH), MyoD, myogenin, and desmin at day 4 of differentiation, high-dose treatment decreased myogenic-related gene and protein levels at day 21 of differentiation, confirmed by immunocytochemical analysis. The findings of the study present not only an understanding of boron's effect on myogenic differentiation but also an opportunity for the development of scaffolds to be used in skeletal tissue engineering and supplements for embryonic muscle growth. However, fine dose tuning and treatment period arranging are highly warranted as boron treatment over required concentrations and time might result in detrimental outcomes to myogenesis and myo-regeneration. PMID:25637568

  16. Area dose rate values derived from NaI or LaBr3 spectra.

    PubMed

    Dombrowski, H

    2014-08-01

    More and more spectrometric systems are being installed in environmental radiation monitoring stations instead of or in addition to dosimetric detectors, because novel spectrometric systems have been developed which do not need any cooling and because the necessary electronics, especially digital multichannel analysers, have become more manageable and more affordable. The advantage of obtaining information about nuclide vectors can justify the operation of a more complex spectroscopic measuring system, but if spectrometers are also used for dose rate measurements in the natural environment, ambient dose equivalent rate values have to be calculated from measured spectra. Different approaches to achieve this goal will be presented in this article. Some practical recommendations will also be presented to avoid known errors. PMID:24478307

  17. Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms

    PubMed Central

    Scheerans, Christian; Heinig, Roland; Mueck, Wolfgang

    2015-01-01

    Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show ‘relevant’ drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration–time curve (AUC) outside the dosing interval (τ) after SD administration, %AUC(τ-∞)SD; and third, the rationale for a threshold of %AUC(τ-∞)SD that predicts ‘relevant’ drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC, derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the ‘preferred’ MEDA for MR formulations. A causal relationship was derived between %AUC(τ-∞)SD and RA,AUC, which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration–time curve. Considering AUC thresholds from other guidelines together with the causal relationship between %AUC(τ-∞)SD and RA,AUC indicates that values of %AUC(τ-∞)SD ≤ 20%, resulting in RA,AUC ≤ 1.25, can be considered as leading to non-relevant drug accumulation. Hence, the authors suggest that 20% for %AUC(τ-∞)SD is a reasonable threshold and selection criterion between SD or MD study designs for bioequivalence studies of new MR formulations. © 2014 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd. PMID:25327367

  18. Proposal for defining the relevance of drug accumulation derived from single dose study data for modified release dosage forms.

    PubMed

    Scheerans, Christian; Heinig, Roland; Mueck, Wolfgang

    2015-03-01

    Recently, the European Medicines Agency (EMA) published the new draft guideline on the pharmacokinetic and clinical evaluation of modified release (MR) formulations. The draft guideline contains the new requirement of performing multiple dose (MD) bioequivalence studies, in the case when the MR formulation is expected to show 'relevant' drug accumulation at steady state (SS). This new requirement reveals three fundamental issues, which are discussed in the current work: first, measurement for the extent of drug accumulation (MEDA) predicted from single dose (SD) study data; second, its relationship with the percentage residual area under the plasma concentration-time curve (AUC) outside the dosing interval (τ) after SD administration, %AUC(τ-∞)SD ; and third, the rationale for a threshold of %AUC(τ-∞)SD that predicts 'relevant' drug accumulation at SS. This work revealed that the accumulation ratio RA,AUC , derived from the ratio of the time-averaged plasma concentrations during τ at SS and after SD administration, respectively, is the 'preferred' MEDA for MR formulations. A causal relationship was derived between %AUC(τ-∞)SD and RA,AUC , which is valid for any drug (product) that shows (dose- and time-) linear pharmacokinetics regardless of the shape of the plasma concentration-time curve. Considering AUC thresholds from other guidelines together with the causal relationship between %AUC(τ-∞)SD and RA,AUC indicates that values of %AUC(τ-∞)SD ≤ 20%, resulting in RA,AUC ≤ 1.25, can be considered as leading to non-relevant drug accumulation. Hence, the authors suggest that 20% for %AUC(τ-∞)SD is a reasonable threshold and selection criterion between SD or MD study designs for bioequivalence studies of new MR formulations. PMID:25327367

  19. Quality audit of megavoltage radiotherapy units: intercomparison of dose at a reference point using a mailed TL-dosimetry system.

    PubMed

    Davis, B; Faessler, P

    1993-07-01

    A dosimetry intercomparison based on mailed TL-dosimeters and the well proven IAEA/EORTC phantom is described. Its aim is to identify discrepancies in dosimetry larger than +/- 3%. Dosimeters were mailed to all radiotherapy centres in Switzerland for irradiation with 2 Gy at a reference point in a water container, using photons and electrons. Thirty-six beams were monitored. The results show an agreement of within 2% for the majority of the beams monitored. Two electron beams were at 6% of the reference value. PMID:8234874

  20. TU-F-BRE-09: Towards the Establishment of Dosimetric References in Small Fields Using the New Concept of Dose-Area Product

    SciTech Connect

    Dufreneix, S; Bordy, J; Delaunay, F; Delaunay, F; Daures, J; Gouriou, J; Le Roy, M; Ostrowsky, A; Rapp, B; Sommier, L

    2014-06-15

    Purpose: To establish dosimetric references of absorbed dose in water in radiation fields smaller than 2 cm used in radiotherapy thanks to a new methodology based on the use of dosimeters larger than the field size. Methods: A new graphite calorimeter was constructed with a large sensitive volume (diameter of the core: 30 mm). This primary dosimeter was fully characterized and compared to previous LNE-LNHB graphite calorimeters in a 60Co large field. A specially designed graphite parallel-plate ionization chamber with a 30 mm collecting electrode was also assembled and tested. Measurements were then conducted in two 6 MV small circular fields of 2 cm and 1 cm diameter respectively, using the new concept of dose-area product instead of punctual dose commonly used in radiotherapy. Results: The dose rate established in a large 60Co field with the new calorimeter is in agreement within 0.4% with previous calorimeters. The ionization chamber shows good characteristics except for a 0.06% drift per hour in water. The ratio of calorimetric against ionometric measurements in the 2 cm diameter field is 1.1% higher than the one in the 1 cm diameter field (with respectively 0.30% and 1.03% type A uncertainty for each field). Conclusion: Results presented here highlight the possibility of measuring dose-area products in small fields with a graphite calorimeter and a parallel-plate ionization chamber. Measurements in a 0.75 cm diameter field are already underway to confirm the trend observed in the 2 cm and 1 cm diameter fields. The last step to establish precise dosimetric references in small fields is to calculate correction factors thanks to Monte Carlo simulations.

  1. Derivation of Geometry Factors for Internal Gamma Dose Calculations for a Cylindrical Radioactive Waste Package

    SciTech Connect

    Lewis, Brent J.; Husain, Aamir

    2002-12-15

    A general methodology was developed to estimate geometry factors for internal gamma dose rate calculations within a cylindrical radioactive waste container. In particular, an average geometry factor is needed to calculate the average energy deposition rate within the container for determination of the internal gas generation rate. Such a calculation is required in order to assess the potential for radioactive waste packages to radiolytically generate combustible gases.This work therefore provides a method for estimating the point and average geometry factors for internal dose assessment for a cylindrical geometry. This analysis is compared to other results where it is shown that the classical work of Hine and Brownell do not correspond to the average geometry factors for a cylindrical body but rather to values at the center of its top or bottom end. The current treatment was further developed into a prototype computer code (PC-CAGE) that calculates the geometry factors numerically for a cylindrical body of any size and material, accounting both for gamma absorption and buildup effects.

  2. Low-Dose Oxygen Enhances Macrophage-Derived Bacterial Clearance following Cigarette Smoke Exposure

    PubMed Central

    Bain, William G.; Tripathi, Ashutosh; Mandke, Pooja; Gans, Jonathan H.; D'Alessio, Franco R.; Sidhaye, Venkataramana K.; Aggarwal, Neil R.

    2016-01-01

    Background. Chronic obstructive pulmonary disease (COPD) is a common, smoking-related lung disease. Patients with COPD frequently suffer disease exacerbations induced by bacterial respiratory infections, suggestive of impaired innate immunity. Low-dose oxygen is a mainstay of therapy during COPD exacerbations; yet we understand little about whether oxygen can modulate the effects of cigarette smoke on lung immunity. Methods. Wild-type mice were exposed to cigarette smoke for 5 weeks, followed by intratracheal instillation of Pseudomonas aeruginosa (PAO1) and 21% or 35–40% oxygen. After two days, lungs were harvested for PAO1 CFUs, and bronchoalveolar fluid was sampled for inflammatory markers. In culture, macrophages were exposed to cigarette smoke and oxygen (40%) for 24 hours and then incubated with PAO1, followed by quantification of bacterial phagocytosis and inflammatory markers. Results. Mice exposed to 35–40% oxygen after cigarette smoke and PAO1 had improved survival and reduced lung CFUs and inflammation. Macrophages from these mice expressed less TNF-α and more scavenger receptors. In culture, macrophages exposed to cigarette smoke and oxygen also demonstrated decreased TNF-α secretion and enhanced phagocytosis of PAO1 bacteria. Conclusions. Our findings demonstrate a novel, protective role for low-dose oxygen following cigarette smoke and bacteria exposure that may be mediated by enhanced macrophage phagocytosis. PMID:27403445

  3. Leukemia patient-derived lymphoblastoid cell lines exhibit increased induction of leukemia-associated transcripts following high-dose irradiation.

    PubMed

    Spencer, A; Granter, N

    1999-09-01

    Improvement in diagnostic cytogenetic techniques has led to the recognition of an increasing number of leukemia-associated chromosomal translocations and inversions. These genetic lesions frequently are associated with the disruption of putative transcription factors and the production of hybrid transcripts that are implicated in leukemogenesis. Epidemiologic evidence suggests that some, but not all, individuals with a history of gamma-irradiation exposure are at increased risk of developing chronic myeloid leukemia (CML). CML is characterized by the Philadelphia chromosome and transcription of the resulting hybrid BCR-ABL gene. Utilizing the leukemia-associated BCR-ABL p210 transcript as a marker, we sought differences in the induction of illegitimate genetic recombination following high-dose gamma-irradiation of karyotypically normal lymphoblastoid cell lines (LCL) derived from individuals with and without a history of myeloid leukemias. Six LCL [4 leukemia patient derived [2 acute myeloid leukemia and 2 CML] and 2 from normal individuals were analyzed with reverse transcriptase polymerase chain reaction for BCR-ABL under stringent conditions following exposure to 0, 50, or 100 Gy of LET gamma-irradiation delivered via a Varian linear accelerator at 4 MV. Transcripts identical to disease-associated b2a2 and b3a2 transcripts were detected both spontaneously (background illegitimate genetic recombination) and following gamma-irradiation. Background BCR-ABL positivity was demonstrable in 4 of the 6 LCL, with no significant difference in detection between leukemic- and nonleukemic-derived LCL. Overall, increasing gamma-irradiation dose resulted in an increased frequency of BCR-ABL transcript detection (0 Gy vs 50 Gy vs 100 Gy,p = 0.0023, Chi-square test). Within the leukemic- but not the nonleukemic-derived LCL there was significantly greater BCR-ABL positivity after gamma-irradiation compared to unirradiated equivalents. Furthermore, the BCR-ABL positivity of both

  4. Radiation dose in coronary angiography and intervention: initial results from the establishment of a multi-centre diagnostic reference level in Queensland public hospitals

    SciTech Connect

    Crowhurst, James A; Whitby, Mark; Thiele, David; Halligan, Toni; Westerink, Adam; Crown, Suzanne; Milne, Jillian

    2014-09-15

    Radiation dose to patients undergoing invasive coronary angiography (ICA) is relatively high. Guidelines suggest that a local benchmark or diagnostic reference level (DRL) be established for these procedures. This study sought to create a DRL for ICA procedures in Queensland public hospitals. Data were collected for all Cardiac Catheter Laboratories in Queensland public hospitals. Data were collected for diagnostic coronary angiography (CA) and single-vessel percutaneous intervention (PCI) procedures. Dose area product (P{sub KA}), skin surface entrance dose (K{sub AR}), fluoroscopy time (FT), and patient height and weight were collected for 3 months. The DRL was set from the 75th percentile of the P{sub KA.} 2590 patients were included in the CA group where the median FT was 3.5 min (inter-quartile range = 2.3–6.1). Median K{sub AR} = 581 mGy (374–876). Median P{sub KA} = 3908 uGym{sup 2} (2489–5865) DRL = 5865 uGym{sup 2}. 947 patients were included in the PCI group where median FT was 11.2 min (7.7–17.4). Median K{sub AR} = 1501 mGy (928–2224). Median P{sub KA} = 8736 uGym{sup 2} (5449–12,900) DRL = 12,900 uGym{sup 2}. This study established a benchmark for radiation dose for diagnostic and interventional coronary angiography in Queensland public facilities.

  5. Comparison BIPM.RI(I)-K8 of high dose-rate Ir-192 brachytherapy standards for reference air kerma rate of the PTB and the BIPM

    NASA Astrophysics Data System (ADS)

    Kessler, C.; Allisy-Roberts, P. J.; Selbach, H. J.

    2015-01-01

    An indirect comparison of the standards for reference air kerma rate (RAKR) for 192Ir high dose rate (HDR) brachytherapy sources of the Physikalisch-Technische Bundesanstalt (PTB), Germany, and of the Bureau International des Poids et Mesures (BIPM) was carried out at the PTB in September 2011. The comparison result, based on the calibration coefficients for a transfer standard and expressed as a ratio of the PTB and the BIPM standards for reference air kerma rate, is 1.0003 with a combined standard uncertainty of 0.0099. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  6. Comparison BIPM.RI(I)-K8 of high dose-rate Ir-192 brachytherapy standards for reference air kerma rate of the NRC and the BIPM

    NASA Astrophysics Data System (ADS)

    Kessler, C.; Downton, B.; Mainegra-Hing, E.

    2015-01-01

    An indirect comparison of the standards for reference air kerma rate for 192Ir high dose rate (HDR) brachytherapy sources of the National Research Council (NRC), Canada, and of the Bureau International des Poids et Mesures (BIPM) was carried out at the NRC in August 2014. The comparison result, based on the calibration coefficients for a transfer standard and expressed as a ratio of the NRC and the BIPM standards for reference air kerma rate, is 0.9966 with a combined standard uncertainty of 0.0050. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  7. Report on the technical review workshop on the reference dose for Aroclor 1016. Held in Washington, DC on May 24-25, 1994

    SciTech Connect

    1994-11-01

    The report includes information and material from a technical review workshop organized by the U.S. Environmental Protection Agency`s (EPA`s) Risk Assessment Forum for EPA`s Reference Dose/Reference Concentration (RfD/RfC) Work Group. The meeting was held in Washington, DC, at the Barcelo Washington Hotel on May 24-25, 1994. The subject of the technical review was the Integrated Risk Information System (IRIS) RfD entry for Aroclor 1016, a polychlorinated biphenyl (PCB). The expert technical review panel was convened to independently evaluate whether the RfD for Aroclor 1016 is based on a scientifically responsible analysis that represents full consideration of the available data and clean articulation of that analysis in the IRIS RfD entry. EPA also requested panel members to consider four broad options for the Aroclor 1016 RfD as potential recommendations to the RfD/RfC Work Group.

  8. Comparison BIPM.RI(I)-K8 of high dose-rate Ir-192 brachytherapy standards for reference air kerma rate of the NMIJ and the BIPM

    NASA Astrophysics Data System (ADS)

    Kessler, C.; Kurosawa, T.; Mikamoto, T.

    2016-01-01

    An indirect comparison of the standards for reference air kerma rate for 192Ir high dose rate (HDR) brachytherapy sources of the National Metrology Institute of Japan (AIST-NMIJ), Japan, and of the Bureau International des Poids et Mesures (BIPM) was carried out at the Japan Radioisotope Association (JRIA) in April 2015. The comparison result, based on the calibration coefficients for a transfer standard and expressed as a ratio of the NMIJ and the BIPM standards for reference air kerma rate, is 1.0036 with a combined standard uncertainty of 0.0054. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  9. Selection of Reference Genes for Quantitative Gene Expression in Porcine Mesenchymal Stem Cells Derived from Various Sources along with Differentiation into Multilineages

    PubMed Central

    Lee, Won-Jae; Jeon, Ryoung-Hoon; Jang, Si-Jung; Park, Ji-Sung; Lee, Seung-Chan; Baregundi Subbarao, Raghavendra; Lee, Sung-Lim; Park, Bong-Wook; King, William Allan; Rho, Gyu-Jin

    2015-01-01

    The identification of stable reference genes is a prerequisite for ensuring accurate validation of gene expression, yet too little is known about stable reference genes of porcine MSCs. The present study was, therefore, conducted to assess the stability of reference genes in porcine MSCs derived from bone marrow (BMSCs), adipose (AMSCs), and skin (SMSCs) with their in vitro differentiated cells into mesenchymal lineages such as adipocytes, osteocytes, and chondrocytes. Twelve commonly used reference genes were investigated for their threshold cycle (Ct) values by qRT-PCR. The Ct values of candidate reference genes were analyzed by geNorm software to clarify stable expression regardless of experimental conditions. Thus, Pearson's correlation was applied to determine correlation between the three most stable reference genes (NF3) and optimal number of reference genes (NFopt). In assessment of stability of reference gene across experimental conditions by geNorm analysis, undifferentiated MSCs and each differentiated status into mesenchymal lineages showed slightly different results but similar patterns about more or less stable rankings. Furthermore, Pearson's correlation revealed high correlation (r > 0.9) between NF3 and NFopt. Overall, the present study showed that HMBS, YWHAZ, SDHA, and TBP are suitable reference genes for qRT-PCR in porcine MSCs. PMID:25972899

  10. Letter report: References for radioactive releases to the atmosphere from Hanford operations, 1944--1957. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Hall, R.B.

    1991-11-01

    A search was made for published documents related to discharges of radioactive material from Hanford Site facilities to the atmosphere from 1944--1957. The purpose was to list documents that contain data that might be useful in developing a source term for airborne releases. The source term for the radionuclide that contributes most to dose, ioidine-131, is a separate effort. Other source terms will be developed later. This tabulation of published summaries of atmospheric release data shows the type of measurements that were being made from 1944--1957 and the magnitude of the discharges to the atmosphere. In the early years, very little data were collected that related to specific radionuclides. However, most of the key radionuclides were known to be present in effluents from occasional specific radionuclide analyses. 2 refs.

  11. Monte Carlo derivation of filtered tungsten anode X-ray spectra for dose computation in digital mammography*

    PubMed Central

    Paixão, Lucas; Oliveira, Bruno Beraldo; Viloria, Carolina; de Oliveira, Marcio Alves; Teixeira, Maria Helena Araújo; Nogueira, Maria do Socorro

    2015-01-01

    Objective Derive filtered tungsten X-ray spectra used in digital mammography systems by means of Monte Carlo simulations. Materials and Methods Filtered spectra for rhodium filter were obtained for tube potentials between 26 and 32 kV. The half-value layer (HVL) of simulated filtered spectra were compared with those obtained experimentally with a solid state detector Unfors model 8202031-H Xi R/F & MAM Detector Platinum and 8201023-C Xi Base unit Platinum Plus w mAs in a Hologic Selenia Dimensions system using a direct radiography mode. Results Calculated HVL values showed good agreement as compared with those obtained experimentally. The greatest relative difference between the Monte Carlo calculated HVL values and experimental HVL values was 4%. Conclusion The results show that the filtered tungsten anode X-ray spectra and the EGSnrc Monte Carlo code can be used for mean glandular dose determination in mammography. PMID:26811553

  12. Correlation of In Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study.

    PubMed

    Soeteman-Hernández, Lya G; Fellows, Mick D; Johnson, George E; Slob, Wout

    2015-12-01

    In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement). PMID:26443842

  13. Low dose gemcitabine-loaded lipid nanocapsules target monocytic myeloid-derived suppressor cells and potentiate cancer immunotherapy.

    PubMed

    Sasso, Maria Stella; Lollo, Giovanna; Pitorre, Marion; Solito, Samantha; Pinton, Laura; Valpione, Sara; Bastiat, Guillaume; Mandruzzato, Susanna; Bronte, Vincenzo; Marigo, Ilaria; Benoit, Jean-Pierre

    2016-07-01

    Tumor-induced expansion of myeloid-derived suppressor cells (MDSCs) is known to impair the efficacy of cancer immunotherapy. Among pharmacological approaches for MDSC modulation, chemotherapy with selected drugs has a considerable interest due to the possibility of a rapid translation to the clinic. However, such approach is poorly selective and may be associated with dose-dependent toxicities. In the present study, we showed that lipid nanocapsules (LNCs) loaded with a lauroyl-modified form of gemcitabine (GemC12) efficiently target the monocytic (M-) MDSC subset. Subcutaneous administration of GemC12-loaded LNCs reduced the percentage of spleen and tumor-infiltrating M-MDSCs in lymphoma and melanoma-bearing mice, with enhanced efficacy when compared to free gemcitabine. Consistently, fluorochrome-labeled LNCs were preferentially uptaken by monocytic cells rather than by other immune cells, in both tumor-bearing mice and human blood samples from healthy donors and melanoma patients. Very low dose administration of GemC12-loaded LNCs attenuated tumor-associated immunosuppression and increased the efficacy of adoptive T cell therapy. Overall, our results show that GemC12-LNCs have monocyte-targeting properties that can be useful for immunomodulatory purposes, and unveil new possibilities for the exploitation of nanoparticulate drug formulations in cancer immunotherapy. PMID:27135716

  14. Serum levels of brain-derived neurotrophic factor in alcohol-dependent patients receiving high-dose baclofen.

    PubMed

    Geisel, Olga; Hellweg, Rainer; Müller, Christian A

    2016-06-30

    The neurotrophin brain-derived neurotrophic factor (BDNF) has been suggested to be involved in the development and maintenance of addictive and other psychiatric disorders. Also, interactions of γ-aminobutyric acid (GABA)-ergic compounds and BDNF have been reported. The objective of this study was to investigate serum levels of BDNF over time in alcohol-dependent patients receiving individually titrated high-dose treatment (30-270mg/d) with the GABA-B receptor agonist baclofen or placebo for up to 20 weeks. Serum levels of BDNF were measured in patients of the baclofen/placebo group at baseline (t0), 2 weeks after reaching individual high-dose of baclofen/placebo treatment (t1) and after termination of study medication (t2) in comparison to carefully matched healthy controls. No significant differences in serum levels of BDNF between the baclofen and the placebo group or healthy controls were found at t0, t1, or at t2. Based on these findings, it seems unlikely that baclofen exerts a direct effect on serum levels of BDNF in alcohol-dependent patients. Future studies are needed to further explore the mechanism of action of baclofen and its possible relationship to BDNF in alcohol use disorders. PMID:27107672

  15. The Importance of Measurement Errors for Deriving Accurate Reference Leaf Area Index Maps for Validation of Moderate-Resolution Satellite LAI Products

    NASA Technical Reports Server (NTRS)

    Huang, Dong; Yang, Wenze; Tan, Bin; Rautiainen, Miina; Zhang, Ping; Hu, Jiannan; Shabanov, Nikolay V.; Linder, Sune; Knyazikhin, Yuri; Myneni, Ranga B.

    2006-01-01

    The validation of moderate-resolution satellite leaf area index (LAI) products such as those operationally generated from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor data requires reference LAI maps developed from field LAI measurements and fine-resolution satellite data. Errors in field measurements and satellite data determine the accuracy of the reference LAI maps. This paper describes a method by which reference maps of known accuracy can be generated with knowledge of errors in fine-resolution satellite data. The method is demonstrated with data from an international field campaign in a boreal coniferous forest in northern Sweden, and Enhanced Thematic Mapper Plus images. The reference LAI map thus generated is used to assess modifications to the MODIS LAI/fPAR algorithm recently implemented to derive the next generation of the MODIS LAI/fPAR product for this important biome type.

  16. Identification of Novel Low-Dose Bisphenol A Targets in Human Foreskin Fibroblast Cells Derived from Hypospadias Patients

    PubMed Central

    Qin, Xian-Yang; Kojima, Yoshiyuki; Mizuno, Kentaro; Ueoka, Katsuhiko; Muroya, Koji; Miyado, Mami; Zaha, Hiroko; Akanuma, Hiromi; Zeng, Qin; Fukuda, Tomokazu; Yoshinaga, Jun; Yonemoto, Junzo; Kohri, Kenjiro; Hayashi, Yutaro; Fukami, Maki; Ogata, Tsutomu; Sone, Hideko

    2012-01-01

    Background/Purpose The effect of low-dose bisphenol A (BPA) exposure on human reproductive health is still controversial. To better understand the molecular basis of the effect of BPA on human reproductive health, a genome-wide screen was performed using human foreskin fibroblast cells (hFFCs) derived from child hypospadias (HS) patients to identify novel targets of low-dose BPA exposure. Methodology/Principal Findings Gene expression profiles of hFFCs were measured after exposure to 10 nM BPA, 0.01 nM 17β-estradiol (E2) or 1 nM 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for 24 h. Differentially expressed genes were identified using an unpaired Student's t test with P value cut off at 0.05 and fold change of more than 1.2. These genes were selected for network generation and pathway analysis using Ingenuity Pathways Analysis, Pathway Express and KegArray. Seventy-one genes (42 downregulated and 29 upregulated) were identified as significantly differentially expressed in response to BPA, among which 43 genes were found to be affected exclusively by BPA compared with E2 and TCDD. Of particular interest, real-time PCR analysis revealed that the expression of matrix metallopeptidase 11 (MMP11), a well-known effector of development and normal physiology, was found to be inhibited by BPA (0.47-fold and 0.37-fold at 10 nM and 100 nM, respectively). Furthermore, study of hFFCs derived from HS and cryptorchidism (CO) patients (n = 23 and 11, respectively) indicated that MMP11 expression was significantly lower in the HS group than in the CO group (0.25-fold, P = 0.0027). Conclusions/Significance This present study suggests that an involvement of BPA in the etiology of HS might be associated with the downregulation of MMP11. Further study to elucidate the function of the novel target genes identified in this study during genital tubercle development might increase our knowledge of the effects of low-dose BPA exposure on human reproductive health. PMID:22574217

  17. Assessment of Local Dose Reference Values for Recanalization of Chronic Total Occlusions and Other Occlusions in a High-Volume Catheterization Center.

    PubMed

    Maccia, Carlo; Malchair, Françoise; Gobert, Isabelle; Louvard, Yves; Lefevre, Thierry

    2015-10-15

    The increasing number and complexity of these procedures have led to a higher number of patients at risk for tissue reactions like skin injuries. Monitoring of their dose indicators is essential in recognizing these patients. The aim of this work was to determine local diagnostic reference levels (DRLs) for recanalization of chronic total occlusion (CTO) and other occlusions procedures. All data from patients who underwent cardiac procedures were reviewed and classified according to their complexity. Dose indicators such as fluoroscopy time (FT), dose area product (DAP), and air kerma at patient entrance reference point (AKr) were recorded. Correlations with patient's body mass index, operators, procedure strategy, and complexity were studied. For CTO, the mean DAP, AKr, and FT were 252 ± 234 Gycm(2), 3,985 ± 3,579 mGy, and 47 ± 36 minutes, respectively. To better reflect the non-Gaussian distribution of data, the median and the 75th percentile values were also reported: median DAP, 172 Gycm(2); 75th percentile DAP, 350 Gycm(2); median AKr, 2,714 mGy; and 75th percentile AKr, 5,921 mGy. A tentative new set of values were suggested to take into account the complexity difference in recanalization of total occlusions according to their antegrade or retrograde approach. These approach-specific DRLs for total occlusions were mean DAP (120 ± 114 Gycm(2)), mean AKr (1,789 ± 1,933 mGy), and mean FT (22 ± 18 minutes) for antegrade approach and mean DAP (459 ± 304 Gycm(2)), mean AKr (6,881 ± 4,243 mGy), and mean FT (82 ± 40 minutes) for retrograde approach. The other significant values were median DAP (84 Gycm(2)), 75th percentile DAP (147 Gycm(2)), median AKr (1,160 mGy), and 75th percentile AKr (2,176 mGy) for antegrade approach and median DAP (422 Gycm(2)), 75th percentile DAP (552 Gycm(2)), median AKr (6,295 mGy), and 75th percentile AKr (8,064 mGy) for retrograde approach. In conclusion, a set of local DRL values from a large center were assessed

  18. A comparison of mean glandular dose diagnostic reference levels within the all-digital Irish National Breast Screening Programme and the Irish Symptomatic Breast Services.

    PubMed

    O'Leary, Desiree; Rainford, Louise

    2013-03-01

    Data on image quality, compression and radiation dose were collected from symptomatic breast units within the Republic of Ireland. Quantitative and qualitative data were analysed using SPSS. Recommendations of mean glandular dose (MGD) diagnostic reference levels were made at various levels for film-screen and full field digital mammography units to match levels published worldwide. MGDs received by symptomatic breast patients within Ireland are higher than those received in the all-digital Irish Breast Screening service; 55-65 mm breast: 1.75 mGy (screening) vs. 2.4 mGy (symptomatic) at the 95th percentile; various reasons are proposed for the differences. MGDs achieved in the screening service may be lower because of the exacting requirements for radiographer training, characteristics of the patients and equipment quality assurance levels. More precise imaging guidelines, standards and training of symptomatic radiographers performing mammography are suggested to remediate MGDs delivered to the breasts of Irish women attending the symptomatic breast services. PMID:22740646

  19. Fluence-to-dose conversion coefficients based on the posture modification of Adult Male (AM) and Adult Female (AF) reference phantoms of ICRP 110

    NASA Astrophysics Data System (ADS)

    Galeano, D. C.; Santos, W. S.; Alves, M. C.; Souza, D. N.; Carvalho, A. B.

    2016-04-01

    The aim of this work was to modify the standing posture of the anthropomorphic reference phantoms of ICRP publication 110, AM (Adult Male) and AF (Adult Female), to the sitting posture. The change of posture was performed using the Visual Monte Carlo software (VMC) to rotate the thigh region of the phantoms and position it between the region of the leg and trunk. Scion Image software was used to reconstruct and smooth the knee and hip contours of the phantoms in a sitting posture. For 3D visualization of phantoms, the VolView software was used. In the change of postures, the organ and tissue masses were preserved. The MCNPX was used to calculate the equivalent and effective dose conversion coefficients (CCs) per fluence for photons for six irradiation geometries suggested by ICRP publication 110 (AP, PA, RLAT, LLAT, ROT and ISO) and energy range 0.010-10 MeV. The results were compared between the standing and sitting postures, for both sexes, in order to evaluate the differences of scattering and absorption of radiation for different postures. Significant differences in the CCs for equivalent dose were observed in the gonads, colon, prostate, urinary bladder and uterus, which are present in the pelvic region, and in organs distributed throughout the body, such as the lymphatic nodes, muscle, skeleton and skin, for the phantoms of both sexes. CCs for effective dose showed significant differences of up to 16% in the AP irradiation geometry, 27% in the PA irradiation geometry and 13% in the ROT irradiation geometry. These results demonstrate the importance of using phantoms in different postures in order to obtain more precise conversion coefficients for a given exposure scenario.

  20. DOSE RESPONSE ASSESSMENT FOR DEVELOPMENTAL TOXICITY: II. COMPARISON OF GENERIC BENCHMARK DOSE ESTIMATES WITH NO OBSERVED ADVERSE EFFECT LEVELS

    EPA Science Inventory

    The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large data base of 246 developmental toxicity experiments compiled for use in comparing alternative approaches to developmental toxicity risk assessment. BMD estimates derived w...

  1. An accurate derivation of the air dose-rate and the deposition concentration distribution by aerial monitoring in a low level contaminated area

    NASA Astrophysics Data System (ADS)

    Nishizawa, Yukiyasu; Sugita, Takeshi; Sanada, Yukihisa; Torii, Tatsuo

    2015-04-01

    Since 2011, MEXT (Ministry of Education, Culture, Sports, Science and Technology, Japan) have been conducting aerial monitoring to investigate the distribution of radioactive cesium dispersed into the atmosphere after the accident at the Fukushima Dai-ichi Nuclear Power Plant (FDNPP), Tokyo Electric Power Company. Distribution maps of the air dose-rate at 1 m above the ground and the radioactive cesium deposition concentration on the ground are prepared using spectrum obtained by aerial monitoring. The radioactive cesium deposition is derived from its dose rate, which is calculated by excluding the dose rate of the background radiation due to natural radionuclides from the air dose-rate at 1 m above the ground. The first step of the current method of calculating the dose rate due to natural radionuclides is calculate the ratio of the total count rate of areas where no radioactive cesium is detected and the count rate of regions with energy levels of 1,400 keV or higher (BG-Index). Next, calculate the air dose rate of radioactive cesium by multiplying the BG-Index and the integrated count rate of 1,400 keV or higher for the area where the radioactive cesium is distributed. In high dose-rate areas, however, the count rate of the 1,365-keV peak of Cs-134, though small, is included in the integrated count rate of 1,400 keV or higher, which could cause an overestimation of the air dose rate of natural radionuclides. We developed a method for accurately evaluating the distribution maps of natural air dose-rate by excluding the effect of radioactive cesium, even in contaminated areas, and obtained the accurate air dose-rate map attributed the radioactive cesium deposition on the ground. Furthermore, the natural dose-rate distribution throughout Japan has been obtained by this method.

  2. Derivation and representation of dose-volume response from large clinical trial data sets: an example from the RADAR prostate radiotherapy trial

    NASA Astrophysics Data System (ADS)

    Ebert, M. A.; Foo, K.; Haworth, A.; Gulliford, S. L.; Kearvall, R.; Kennedy, A.; Richardson, S.; Krawiec, M.; Stewart, N.; Joseph, D. J.; Denham, J. W.

    2014-03-01

    Large multicentre radiotherapy trials incorporating assessment of multiple outcomes at multiple timepoints can generate extensive datasets. We have investigated graphical techniques for presentation of this data and the associated underlying dose-volume response information, necessary for guiding statistical analyses and translating outcomes to future patient treatments. A relational database was used to archive reviewed plan data for patients accrued to the TROG 03.04 RADAR trial. Viewing software was used to clean and enhance the data. Scripts were developed to export arbitrary dose-histogram data which was combined with clinical toxicity data with a median follow-up of 72 months. Graphical representations of dose-volume response developed include prevalence atlasing, univariate logistic regression and dose-volume-point odds ratios, and continuous cut-point derivation via ROC analysis. These representations indicate variable association of toxicities across structures and time-points.

  3. n-3 fatty acids effectively improve the reference memory-related learning ability associated with increased brain docosahexaenoic acid-derived docosanoids in aged rats.

    PubMed

    Hashimoto, Michio; Katakura, Masanori; Tanabe, Yoko; Al Mamun, Abdullah; Inoue, Takayuki; Hossain, Shahdat; Arita, Makoto; Shido, Osamu

    2015-02-01

    We investigated whether a highly purified eicosapentaenoic acid (EPA) and a concentrated n-3 fatty acid formulation (prescription TAK-085) containing EPA and docosahexaenoic acid (DHA) ethyl ester could improve the learning ability of aged rats and whether this specific outcome had any relation with the brain levels of EPA-derived eicosanoids and DHA-derived docosanoids. The rats were tested for reference memory errors (RMEs) and working memory errors (WMEs) in an eight-arm radial maze. Fatty acid compositions were analyzed by GC, whereas brain eicosanoid/docosanoids were measured by LC-ESI-MS-MS-based analysis. The levels of lipid peroxides (LPOs) were measured by thiobarbituric acid reactive substances. The administration of TAK-085 at 300 mg·kg⁻¹day⁻¹ for 17 weeks reduced the number of RMEs in aged rats compared with that in the control rats. Both TAK-085 and EPA administration increased plasma EPA and DHA levels in aged rats, with concurrent increases in DHA and decreases in arachidonic acid in the corticohippocampal brain tissues. TAK-085 administration significantly increased the formation of EPA-derived 5-HETE and DHA-derived 7-, 10-, and 17-HDoHE, PD1, RvD1, and RvD2. ARA-derived PGE2, PGD2, and PGF2α significantly decreased in TAK-085-treated rats. DHA-derived mediators demonstrated a significantly negative correlation with the number of RMEs, whereas EPA-derived mediators did not exhibit any relationship. Furthermore, compared with the control rats, the levels of LPO in the plasma, cerebral cortex, and hippocampus were significantly reduced in TAK-085-treated rats. The findings of the present study suggest that long-term EPA+DHA administration may be a possible preventative strategy against age-related cognitive decline. PMID:25450447

  4. Effects of photosensitizer (hematoporphyrin derivative-HPD) and light dose on vascular targets in the albino mouse ear

    SciTech Connect

    Davis, R.K.; Davis, K.; Straight, R.C.; Waner, M.

    1988-01-01

    Photodynamic damage to normal tissues, including skin, appears to occur by photooxidative damage to the normal microvasculature as the primary target sensitized by HPD bound to the vascular wall or endothelial cell. Initial damage to the microvasculature was measured by the increase in vascular permeability (VP) as measured by Evans Blue dye (EB) extravasation as a function of HPD and laser light (632 nm) dose. Albino, Swiss-Webster mice (female 122-25 g, 5 mice per group) were injected intraperitoneally (IP) with incremental doses of HPD (1, 10, 20, 30, 40 and 50 mg/kg). After 48 hours the left ear of each mouse was masked as a control and the right ear was irradiated at 632 nm using the Aurora-Lexel Argon-dye laser with an intensity of 50 mW/cm2 and light doses of 0, 25, 50, 75, and 100 J/cm2 directed to a 3-mm spot on the mouse ear. No EB leakage occurred in the absence of HPD at any light dose or in the absence of light at any HPC dose. Vascular permeability increased as a function of HPD dose up to 30 mg/kg. AT 50 mg/kg HPD, there was a decrease in VP. At each HPD dose above 10 mg/kg, the VP increased as a function of light dose up to 75 J/cm2. Further increase in light dose was without effect. The amount of HPD porphyrin recovered from irradiated ears decreased as a function of light dose. There appeared to be an irreversible photo destruction of the porphyrin exposed to light.

  5. Empirical derivation of the reference region for computing diagnostic sensitive ¹⁸fluorodeoxyglucose ratios in Alzheimer's disease based on the ADNI sample.

    PubMed

    Rasmussen, Jerod M; Lakatos, Anita; van Erp, Theo G M; Kruggel, Frithjof; Keator, David B; Fallon, James T; Macciardi, Fabio; Potkin, Steven G

    2012-03-01

    Careful selection of the reference region for non-quantitative positron emission tomography (PET) analyses is critically important for Region of Interest (ROI) data analyses. We introduce an empirical method of deriving the most suitable reference region for computing neurodegeneration sensitive (18)fluorodeoxyglucose (FDG) PET ratios based on the dataset collected by the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. Candidate reference regions are selected based on a heat map of the difference in coefficients of variation (COVs) of FDG ratios over time for each of the Automatic Anatomical Labeling (AAL) atlas regions normalized by all other AAL regions. Visual inspection of the heat map suggests that the portion of the cerebellum and vermis superior to the horizontal fissure is the most sensitive reference region. Analyses of FDG ratio data show increases in significance on the order of ten-fold when using the superior portion of the cerebellum as compared with the traditionally used full cerebellum. The approach to reference region selection in this paper can be generalized to other radiopharmaceuticals and radioligands as well as to other disorders where brain changes over time are hypothesized and longitudinal data is available. Based on the empirical evidence presented in this study, we demonstrate the usefulness of the COV heat map method and conclude that intensity normalization based on the superior portion of the cerebellum may be most sensitive to measuring change when performing longitudinal analyses of FDG-PET ratios as well as group comparisons in Alzheimer's disease. This article is part of a Special Issue entitled: Imaging Brain Aging and Neurodegenerative disease. PMID:21958592

  6. A reference genetic linkage map of apomictic Hieracium species based on expressed markers derived from developing ovule transcripts

    PubMed Central

    Shirasawa, Kenta; Hand, Melanie L.; Henderson, Steven T.; Okada, Takashi; Johnson, Susan D.; Taylor, Jennifer M.; Spriggs, Andrew; Siddons, Hayley; Hirakawa, Hideki; Isobe, Sachiko; Tabata, Satoshi; Koltunow, Anna M. G.

    2015-01-01

    Background and Aims Apomixis in plants generates clonal progeny with a maternal genotype through asexual seed formation. Hieracium subgenus Pilosella (Asteraceae) contains polyploid, highly heterozygous apomictic and sexual species. Within apomictic Hieracium, dominant genetic loci independently regulate the qualitative developmental components of apomixis. In H. praealtum, LOSS OF APOMEIOSIS (LOA) enables formation of embryo sacs without meiosis and LOSS OF PARTHENOGENESIS (LOP) enables fertilization-independent seed formation. A locus required for fertilization-independent endosperm formation (AutE) has been identified in H. piloselloides. Additional quantitative loci appear to influence the penetrance of the qualitative loci, although the controlling genes remain unknown. This study aimed to develop the first genetic linkage maps for sexual and apomictic Hieracium species using simple sequence repeat (SSR) markers derived from expressed transcripts within the developing ovaries. Methods RNA from microdissected Hieracium ovule cell types and ovaries was sequenced and SSRs were identified. Two different F1 mapping populations were created to overcome difficulties associated with genome complexity and asexual reproduction. SSR markers were analysed within each mapping population to generate draft linkage maps for apomictic and sexual Hieracium species. Key Results A collection of 14 684 Hieracium expressed SSR markers were developed and linkage maps were constructed for Hieracium species using a subset of the SSR markers. Both the LOA and LOP loci were successfully assigned to linkage groups; however, AutE could not be mapped using the current populations. Comparisons with lettuce (Lactuca sativa) revealed partial macrosynteny between the two Asteraceae species. Conclusions A collection of SSR markers and draft linkage maps were developed for two apomictic and one sexual Hieracium species. These maps will support cloning of controlling genes at LOA and LOP loci

  7. Analytical equations for CT dose profiles derived using a scatter kernel of Monte Carlo parentage with broad applicability to CT dosimetry problems

    SciTech Connect

    Dixon, Robert L.; Boone, John M.

    2011-07-15

    Purpose: Knowledge of the complete axial dose profile f(z), including its long scatter tails, provides the most complete (and flexible) description of the accumulated dose in CT scanning. The CTDI paradigm (including CTDI{sub vol}) requires shift-invariance along z (identical dose profiles spaced at equal intervals), and is therefore inapplicable to many of the new and complex shift-variant scan protocols, e.g., high dose perfusion studies using variable (or zero) pitch. In this work, a convolution-based beam model developed by Dixon et al.[Med. Phys. 32, 3712-3728, (2005)] updated with a scatter LSF kernel (or DSF) derived from a Monte Carlo simulation by Boone [Med. Phys. 36, 4547-4554 (2009)] is used to create an analytical equation for the axial dose profile f(z) in a cylindrical phantom. Using f(z), equations are derived which provide the analytical description of conventional (axial and helical) dose, demonstrating its physical underpinnings; and likewise for the peak axial dose f(0) appropriate to stationary phantom cone beam CT, (SCBCT). The methodology can also be applied to dose calculations in shift-variant scan protocols. This paper is an extension of our recent work Dixon and Boone [Med. Phys. 37, 2703-2718 (2010)], which dealt only with the properties of the peak dose f(0), its relationship to CTDI, and its appropriateness to SCBCT. Methods: The experimental beam profile data f(z) of Mori et al.[Med. Phys. 32, 1061-1069 (2005)] from a 256 channel prototype cone beam scanner for beam widths (apertures) ranging from a = 28 to 138 mm are used to corroborate the theoretical axial profiles in a 32 cm PMMA body phantom. Results: The theoretical functions f(z) closely-matched the central axis experimental profile data{sup 11} for all apertures (a = 28 -138 mm). Integration of f(z) likewise yields analytical equations for all the (CTDI-based) dosimetric quantities of conventional CT (including CTDI{sub L} itself) in addition to the peak dose f(0) relevant to

  8. Effects of realistic doses of atrazine, metolachlor, and glyphosate on lipid peroxidation and diet-derived antioxidants in caged honey bees (Apis mellifera).

    PubMed

    Helmer, Stephanie Hedrei; Kerbaol, Anahi; Aras, Philippe; Jumarie, Catherine; Boily, Monique

    2015-06-01

    The decline in the population of pollinators is a worrying phenomenon worldwide. In North America, the extensive use of herbicides in maize and soya crops may affect the health of nontarget organisms like the honey bee. In this study, caged honey bees were exposed to realistic doses of atrazine, metolachlor, and glyphosate for 10 days via contaminated syrup. Peroxidation of lipids was evaluated using the thiobarbituric acid reactive substance (TBARS) test, and diet-derived antioxidants-carotenoids, all-trans-retinol (at-ROH) and α-tocopherol-were detected and quantified using reversed-phase HPLC techniques. Significant increases in syrup consumption were observed in honey bees exposed to metolachlor, and a lower TBARS value was recorded for the highest dose. No relationship was observed between the peroxidation of lipids and the levels of antioxidants. However, β-carotene, which was found to be the most abundant carotenoid, and at-ROH (derived from β-carotene) both decreased with increasing doses of atrazine and glyphosate. In contrast, metolachlor increased levels of at-ROH without any effects on β-carotene. These results show that the honey bee carotenoid-retinoid system may be altered by sublethal field-realistic doses of herbicides. PMID:24728576

  9. Identification of two putative reference genes from grapevine suitable for gene expression analysis in berry and related tissues derived from RNA-Seq data

    PubMed Central

    2013-01-01

    Background Data normalization is a key step in gene expression analysis by qPCR. Endogenous control genes are used to estimate variations and experimental errors occurring during sample preparation and expression measurements. However, the transcription level of the most commonly used reference genes can vary considerably in samples obtained from different individuals, tissues, developmental stages and under variable physiological conditions, resulting in a misinterpretation of the performance of the target gene(s). This issue has been scarcely approached in woody species such as grapevine. Results A statistical criterion was applied to select a sub-set of 19 candidate reference genes from a total of 242 non-differentially expressed (NDE) genes derived from a RNA-Seq experiment comprising ca. 500 million reads obtained from 14 table-grape genotypes sampled at four phenological stages. From the 19 candidate reference genes, VvAIG1 (AvrRpt2-induced gene) and VvTCPB (T-complex 1 beta-like protein) were found to be the most stable ones after comparing the complete set of genotypes and phenological stages studied. This result was further validated by qPCR and geNorm analyses. Conclusions Based on the evidence presented in this work, we propose to use the grapevine genes VvAIG1 or VvTCPB or both as a reference tool to normalize RNA expression in qPCR assays or other quantitative method intended to measure gene expression in berries and other tissues of this fruit crop, sampled at different developmental stages and physiological conditions. PMID:24330674

  10. Increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acid levels in human plasma after a single dose of long-chain omega-3 PUFA

    PubMed Central

    Schuchardt, Jan Philipp; Schneider, Inga; Willenberg, Ina; Yang, Jun; Hammock, Bruce D.; Hahn, Andreas; Schebb, Nils Helge

    2014-01-01

    Introduction Several supplementation studies with long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) describe an increase of EPA-derived hydroxy, epoxy and dihydroxy fatty acids in blood, while changes in levels of other LC n-3 and n-6 PUFA-derived oxylipins were minor. In order to investigate the kinetics of changes in oxylipin levels in response to LC n-3 PUFA ingestion, we conducted a single dose treatment study with healthy subjects. Subjects and methods In the present kinetic study, we compared patterns of hydroxy, epoxy and dihydroxy fatty acids in plasma of 6 healthy men before and after 6, 8, 24, and 48 h of fish oil (1008 mg EPA and 672 mg DHA) ingestion. Levels of EPA- as well as other LC PUFA-derived hydroxy, epoxy and dihydroxy fatty acids were analyzed in plasma by LC–MS. Additionally, levels of these oxylipins were compared with their parent PUFA levels in plasma phospholipids. Results All EPA-derived oxylipin levels were significantly increased 6 h after LC n-3 PUFA ingestion and gradually drop thereafter reaching the baseline levels about 48 h after treatment. The relative increase in EPA plasma phospholipid levels highly correlated with the increase of plasma EPA-derived oxylipin levels at different time points. In contrast, plasma levels of arachidonic acid- and DHA-derived oxylipins as well as parent PUFA levels in plasma phospholipids were hardly changed. Discussion and conclusions Our findings demonstrate that a single dose of LC n-3 PUFAs can rapidly induce a shift in the EPA oxylipin profile of healthy subjects within a few hours. Taking the high biological activity of the EPA-derived epoxy fatty acids into account, even short-term treatment with LC n-3 PUFAs may cause systemic effects, which warrant further investigation. PMID:24667634

  11. Low-dose radiation pretreatment improves survival of human ceiling culture-derived proliferative adipocytes (ccdPAs) under hypoxia via HIF-1 alpha and MMP-2 induction

    SciTech Connect

    Adachi, Naoki; Kubota, Yoshitaka; Kosaka, Kentarou; Akita, Shinsuke; Sasahara, Yoshitarou; Kira, Tomoe; Kuroda, Masayuki; Mitsukawa, Nobuyuki; Bujo, Hideaki; Satoh, Kaneshige

    2015-08-07

    Poor survival is a major problem of adipocyte transplantation. We previously reported that VEGF and MMPs secreted from transplanted adipocytes are essential for angiogenesis and adipogenesis. Pretreatment with low-dose (5 Gy) radiation (LDR) increased VEGF, MMP-2, and HIF-1 alpha mRNA expression in human ceiling culture-derived proliferative adipocytes (hccdPAs). Gene expression after LDR differed between adipose-derived stem cells (hASCs) and hccdPAs. Pretreatment with LDR improved the survival of hccdPAs under hypoxia, which is inevitable in the early stages after transplantation. Upregulation of VEGF and MMP-2 after LDR in hccdPAs is mediated by HIF-1 alpha expression. Our results suggest that pretreatment with LDR may improve adipocyte graft survival in a clinical setting through upregulation of VEGF and MMP-2 via HIF-1 alpha. - Highlights: • Ceiling culture-derived proliferative adipocytes (ccdPAs) react to radiation. • Low-dose radiation (LDR) pretreatment improves survival of ccdPAs under hypoxia. • Gene expression after LDR differs between ccdPAs and adipose-derived stem cells. • LDR-induced increase in MMP-2 and VEGF is dependent on HIF-1 alpha induction. • LDR pretreatment may improve the adipocyte graft survival rate in clinical settings.

  12. Brain-derived neurotrophic factor, acting at the spinal cord level, participates in bladder hyperactivity and referred pain during chronic bladder inflammation.

    PubMed

    Frias, B; Allen, S; Dawbarn, D; Charrua, A; Cruz, F; Cruz, C D

    2013-03-27

    Brain-derived neurotrophic factor (BDNF) is a neurotrophin (NT) known to participate in chronic somatic pain. A recent study has indicated that BDNF may participate in chronic cystitis at the peripheral level. However, the principal site of action for this NT is the central nervous system, most notably the spinal cord. The effects of centrally-acting BDNF on bladder function in normal animals and its central role during chronic cystitis are presently unknown. The present study was undertaken to clarify this issue. For that purpose, control non-inflamed animals were intrathecally injected with BDNF, after which bladder function was evaluated. This treatment caused short-lasting bladder hyperactivity; whereas chronic intrathecal administration of BDNF did not elicit this effect. Cutaneous sensitivity was assessed by mechanical allodynia as an internal control of BDNF action. To ascertain the role of BDNF in bladder inflammation, animals with cyclophosphamide-induced cystitis received intrathecal injections of either a general Trk receptor antagonist or a BDNF scavenger. Blockade of Trk receptors or BDNF sequestration notably improved bladder function. In addition, these treatments also reduced referred pain, typically observed in rats with chronic cystitis. Reduction of referred pain was accompanied by a decrease in the spinal levels of extracellular signal-regulated kinase (ERK) phosphorylation, a marker of increased sensory barrage in the lumbosacral spinal cord, and spinal BDNF expression. Results obtained here indicate that BDNF, acting at the spinal cord level, contributes to bladder hyperactivity and referred pain, important hallmarks of chronic cystitis. In addition, these data also support the development of BDNF modulators as putative therapeutic options for the treatment of chronic bladder inflammation. PMID:23313710

  13. Combined effect of clinically relevant doses of emitefur, a new 5-fluorouracil derivative, and radiation in murine tumours.

    PubMed Central

    Shibamoto, Y.; Murata, R.; Miyauchi, S.; Hirohashi, M.; Takagi, T.; Sasai, K.; Shibata, T.; Oya, N.; Takahashi, M.

    1996-01-01

    We investigated the combined effect of radiation and clinically relevant doses of emitefur (BOF-A2), a newly developed anti-cancer agent consisting of a masked form of 5-fluorouracil (5-FU) and a potent inhibitor of 5-FU degradation, in two types of murine tumours. In preliminary pharmacokinetic studies, the area under the curve for 5-FU in plasma, after administration of 12.5 mg kg-1 and 25 mg kg-1 emitefur in mice, appeared to be similar to that obtained on the first day and that on the seventh day, respectively, after starting administration of 400-600 mg day-1 in humans. These doses (12.5 and 25 mg kg-1) of emitefur were evaluated either alone or in combination with single (15 Gy), five-fraction (4 Gy each) or ten-fraction (2.8 Gy each) irradiation using a tumour growth delay assay for SCCVII tumours and in combination with four-fraction (5 Gy each) irradiation using an in vivo-in vitro assay for EMT6 tumours. The anti-tumour and radiation-enhancing effects of 12.5 mg kg-1 emitefur were not significant in any except the ten-fraction experiment. On the other hand, multiple doses of 25 mg kg-1 emitefur given either alone or in combination with radiation produced marked effects. The mean tumour growth delay time (the time to double in volume for treated tumours minus that for untreated tumours) was 8.1 days for five administrations of 25 mg kg-1 emitefur. 10.4 days for five fractions of 4 Gy and 22.1 days for five treatments with the combination of the two. Thus, the increase in growth delay afforded by this combination was at least additive. The effect of four fractions of 5 Gy with 25 mg kg-1 emitefur in EMT6 tumours was lower than that of four fractions of 7.5 Gy, but the effect of five fractions of 4 Gy with this dose of emitefur in SCCVII tumours was similar to the effect of five fractions of 6 Gy, and the effect of ten fractions of 2.8 Gy with 25 mg kg-1 emitefur was much higher than that of ten fractions of 4.2 Gy. In conclusion, emitefur given either alone

  14. Calculation of internal dose from ingested soil-derived uranium in humans: Application of a new method.

    PubMed

    Träber, S C; Li, W B; Höllriegl, V; Nebelung, K; Michalke, B; Rühm, W; Oeh, U

    2015-08-01

    The aim of the present study was to determine the internal dose in humans after the ingestion of soil highly contaminated with uranium. Therefore, an in vitro solubility assay was performed to estimate the bioaccessibility of uranium for two types of soil. Based on the results, the corresponding bioavailabilities were assessed by using a recently published method. Finally, these bioavailability data were used together with the biokinetic model of uranium to assess the internal doses for a hypothetical but realistic scenario characterized by a daily ingestion of 10 mg of soil over 1 year. The investigated soil samples were from two former uranium mining sites of Germany with (238)U concentrations of about 460 and 550 mg/kg. For these soils, the bioavailabilities of (238)U were quantified as 0.18 and 0.28 % (geometric mean) with 2.5th percentiles of 0.02 and 0.03 % and 97.5th percentiles of 1.48 and 2.34 %, respectively. The corresponding calculated annual committed effective doses for the assumed scenario were 0.4 and 0.6 µSv (GM) with 2.5th percentiles of 0.2 and 0.3 µSv and 97.5th percentiles of 1.6 and 3.0 µSv, respectively. These annual committed effective doses are similar to those from natural uranium intake by food and drinking water, which is estimated to be 0.5 µSv. Based on the present experimental data and the selected ingestion scenario, the investigated soils-although highly contaminated with uranium-are not expected to pose any major health risk to humans related to radiation. PMID:25980738

  15. Diversification of existing reference phantoms in nuclear medicine: Calculation of specific absorbed fractions for 21 mathematical phantoms and validation through dose estimates resulting from the administration of (18)F-FDG.

    PubMed

    Blaickner, Matthias; Kindl, Peter

    2008-12-01

    Current dose assessment in nuclear medicine patient studies relies on published S-values, which are, in turn, based on calculated specific absorbed fractions (SAFs) available for a limited number of anthro-pomorphic computational phantoms. In order to take the individual physiognomy of patients more into account, this study aimed to broaden the supply of phantoms and their respective SAFs. An ensemble of 21 mathematical phantoms was submitted to the Monte Carlo Code MCNP4c2 for the purpose of calculation of SAFs for annihilation radiation. These values were incorporated into an internal dose assessment following the Medical Internal Radiation Dose (MIRD) schema and relying on published biokinetic data for intravenous administration of (18)F-FDG. The results were compared with data from the ICRP, MIRD reports and concurrent calculations with OLINDA/EXM. A very good agreement with sources relying on the SAFs of Cristy and Eckerman (i.e., the ICRP and OLINDA/EXM) was observed, with the absorbed dose in lung being the only exception. In the case of dose to red marrow, the King Spiers factors were omitted in the three-factor approximation, which led to a precise accordance with the Cristy/Eckerman values. Summarizing, one can say that the coincidence with published data justifies the method chosen and demonstrates successfully the expansion of available reference phantoms for dose assessment in nuclear medicine. PMID:19111050

  16. In vitro lymphotoxicity and selective T cell immunotoxicity of high doses of acyclovir and its derivatives in mice.

    PubMed

    Poluektova, L; Krzystyniak, K; Desjardins, R; Flipo, D; Fournier, M

    1996-01-01

    The antiviral drug acyclovir [9-(2-hydroxyethoxymethyl)guanine (ACV)], its 7-isomer (7-ACV) and its two derivatives: N2-acetyl ACV (ac-ACV) and N2,O-diacetyl ACV (diac-ACV) were examined for their potential in vitro lymphotoxicity and in vivo immunotoxicity in mice. In vitro lymphotoxicity of ACV and its acetylated derivatives was low, whereas the 7-ACV isomer enhanced the in vitro cell proliferation in PHA-stimulated cultures. Addition of 2'-deoxyguanosine (dGuo) did not exhibit any inhibitory potential of ACV. However, reduction in the absolute number of CD3+, CD8+, and CD25+ cells, but not Ig+ cells, was noted at high concentrations of ACV and its derivatives, suggesting a selective T cell cytotoxicity. Similarly, the in vivo exposure revealed selective T cell immunotoxicity of ACV and its derivatives since the reduced number of Thy 1.2+ and CD8+ cells was not accompanied with any marked changes in the Ig+ population. The CD4+/CD8+ ratio was affected both in vitro and in vivo by high concentrations of ACV. PMID:9024946

  17. Low-dose tacrolimus combined with donor-derived mesenchymal stem cells after renal transplantation: a prospective, non-randomized study

    PubMed Central

    Pan, Guang-hui; Chen, Zheng; Xu, Lu; Zhu, Jing-hui; Xiang, Peng; Ma, Jun-jie; Peng, Yan-wen; Li, Guang-hui; Chen, Xiao-yong; Fang, Jia-li; Guo, Yu-he; Zhang, Lei; Liu, Long-shan

    2016-01-01

    Calcineurin inhibitors, including tacrolimus, are largely responsible for advances in allotransplantation. However, the nephrotoxicity associated with these immunosuppressants impairs patients' long-term survival after renal allograft. Therefore, novel regimens that minimize or even eliminate calcineurin inhibitors could improve transplantation outcomes. In this pilot study, we investigated the use of low-dose tacrolimus in combination with mesenchymal stem cells (MSCs), which are immunosuppressive and prolong allograft survival in experimental organ transplant models. Donor-derived, bone marrow MSCs combined with a sparing dose of tacrolimus (0.04-0.05 mg/kg/day) were administered to 16 de novo living-related kidney transplant recipients; 16 other patients received a standard dose of tacrolimus (0.07-0.08 mg/kg/day). The safety of MSC infusion, acute rejection, graft function, graft survival, and patient survival were evaluated over ≥24 months following kidney transplantation. All patients survived and had stable renal function at the 24 month follow-up. The combination of low-dose tacrolimus and MSCs was as effective as standard dose tacrolimus in maintaining graft survival at least 2 years after transplantation. In addition, both groups had similar urea, urine protein, urinary RBC, urinary WBC, 24-h urine protein, and creatinine clearance rates from 7 days to 24 months after transplantation. Furthermore, no differences in the proportion of lymphocytes, CD19, CD3, CD34, CD38, and natural killer cells were detected between the control and experimental groups. None of the MSC recipients experienced immediate or long-term toxicity from the treatment. This preliminary data suggests that the addition of MSCs permits the use of lower dosages of nephrotoxic calcineurin inhibitors following renal transplantation. PMID:26933811

  18. Comparison of internal doses calculated using the specific absorbed fractions of the average adult Japanese male phantom with those of the reference computational phantom-adult male of ICRP publication 110

    NASA Astrophysics Data System (ADS)

    Manabe, Kentaro; Sato, Kaoru; Endo, Akira

    2014-03-01

    In order to study the effects of body sizes and masses of organs and tissues on internal dose assessment, the values corresponding to effective dose coefficients for intakes of radionuclides were calculated using the specific absorbed fractions (SAFs) of two phantoms: the average adult Japanese male phantom (JM-103) and the reference computational phantom-adult male (RCP-AM) of the International Commission on Radiological Protection. SAFs were evaluated using the phantoms and Monte Carlo radiation transport code MCNPX or were taken from published data. As a result of a comparison for 2894 cases of 923 radionuclides, the maximum discrepancy in the effective dose coefficients between the JM-103 and RCP-AM was about 40%. However, the discrepancies were smaller than 10% in 97% of all cases.

  19. Effects of low-dose gamma-irradiation on production of shikonin derivatives in callus cultures of Lithospermum erythrorhizon S.

    NASA Astrophysics Data System (ADS)

    Chung, B. Y.; Lee, Y.-B.; Baek, M.-H.; Kim, J.-H.; Wi, S. G.; Kim, J.-S.

    2006-09-01

    The yield increase of secondary metabolite production was examined in plant cell cultures with the use of relatively low to high doses gamma irradiation. Suspension culture of Lithospermum erythrorhizon cells was irradiated to 2, 16, and 32 Gy. The gamma irradiation significantly stimulated the shikonin biosynthesis of the cells and increased the total shikonin yields (intracellular+extracellular shikonin yields) by 400% at 16 Gy and by only 240% and 180% at 2 and 32 Gy, respectively. One of the key enzymes for the shikonin biosynthesis of cells, p-hydroxylbenzoic acid (PHB) geranyltransferase, was found to be stimulated by the gamma-radiation treatments. The activity of PHB geranyltransferase was increased at 2 and 16 Gy with a negligible change at 32 Gy. In contrast, the activity of PHB glucosyltransferase was slightly changed at all doses of gamma radiation compared with the control cells. Therefore, the increase in PHB geranyltransferase activity leads to the accumulation of secondary metabolites such as a shikonin, which may contribute to plant defense against the stresses induced by gamma irradiation.

  20. Use of In Vivo and In Vitro Data to Derive a Chronic Reference Value for Crotonaldehyde Based on Relative Potency to Acrolein

    PubMed Central

    Grant, Roberta L.; Jenkins, Allison F.

    2015-01-01

    The Texas Commission on Environmental Quality (TCEQ) conducted a chronic inhalation noncancer toxicity assessment for crotonaldehyde (CRO). Since there were limited toxicity data for CRO, a reference value (ReV) was derived using a relative potency factor (RPF) approach with acrolein as the index chemical. Both CRO and acrolein are α,β-unsaturated carbonyls and share common steps in their mode of action (MOA). Only studies that investigated the effects of CRO and acrolein in the same study were used to calculate a CRO:acrolein RPF. In vivo findings measuring both 50% respiratory depression in rats and two species of mice and subcutaneous 50% lethality in rats and mice were used to calculate an RPF of 3 (rounded to one significant figure). In vitro data were useful to compare the MOA of CRO and acrolein and to support the RPF determined using in vivo data. In vitro cell culture studies investigating cytotoxicity in normal human lung fibroblast cultures using the propidium iodide cytotoxicity assay and in mouse lymphocyte cultures using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay were used to calculate an in vitro RPF of 3, which supports the in vivo RPF. The chronic ReV for acrolein of 1.2 ppb derived by TCEQ was multiplied by the RPF of 3 to calculate the ReV for CRO of 3.6 ppb (10 μg/m3). The ReV for CRO was developed to protect the general public from adverse health effects from chronic exposure to CRO in ambient air. PMID:26580244

  1. Universal immunization of infants with low doses of a low-cost, plasma-derived hepatitis B vaccine in South Africa.

    PubMed Central

    Schoub, B. D.; Matai, U.; Singh, B.; Blackburn, N. K.; Levin, J. B.

    2002-01-01

    OBJECTIVE: To evaluate the effectiveness of universal vaccination against viral hepatitis B in South Africa among 18-month-old rural children. METHODS: Children were immunized with a course of low-dose (1.5 microg), plasma-derived hepatitis B vaccine at 6, 10 and 14 weeks of age, and blood samples from the children were tested for three hepatitis B markers: hepatitis B surface antigen (HBsAg), anti-HBs and anti-HBc. FINDINGS: One year after vaccination, a protective anti-HBs antibody titre of at least 10 IU/l was present in 669/769 (87.0%) of blood serum samples tested. Only 3/756 children (0.4%) were HBsAg positive and a fourth child was anti-HBc positive (HBsAg negative). This is a marked decrease compared to the hepatitis B prevalences reported in previous studies. Among rural migrant mine-workers, for example, HBsAg prevalence was 9.9%, and was 10.1% among children 0-6 years of age in the Eastern Cape Province. CONCLUSION: The low-dose, plasma-derived hepatitis B vaccine, which is affordable to most developing countries, was very successful in controlling endemic hepatitis B infection, where the virus is predominantly spread by horizontal transmission among infants and young children. PMID:12075363

  2. Safety and immunogenicity in man of a cell culture derived trivalent live attenuated seasonal influenza vaccine: a Phase I dose escalating study in healthy volunteers.

    PubMed

    Heldens, Jacco; Hulskotte, Ellen; Voeten, Theo; Breedveld, Belinda; Verweij, Pierre; van Duijnhoven, Wilbert; Rudenko, Larissa; van Damme, Pierre; van den Bosch, Han

    2014-09-01

    Live attenuated influenza vaccine (LAIV) offers the promise of inducing a variety of immune responses thereby conferring protection to circulating field strains. LAIVs are based on cold adapted and temperature sensitive phenotypes of master donor viruses (MDVs) containing the surface glycoprotein genes of seasonal influenza strains. Two types of MDV lineages have been described, the Ann Arbor lineages and the A/Leningrad/17 and B/USSR/60 lineages. Here the safety and immunogenicity of a Madin Darby Canine Kidney - cell culture based, intranasal LAIV derived from A/Leningrad/17 and B/USSR, was evaluated in healthy influenza non-naive volunteers 18-50 years of age. In a double-blind, randomized, placebo-controlled design, single escalating doses of 1×10(5), 1×10(6), or 1×10(7) tissue culture infectious dose 50% (TCID50) of vaccine containing each of the three influenza virus re-assortants recommended by the World Health Organization for the 2008-2009 season were administered intranasally. A statistically significant geometric mean increase in hemagglutination inhibition titer was reached for influenza strain A/H3N2 after immunization with all doses of LAIV. For the A/H1N1 and B strains, the GMI in HI titer did not increase for any of the doses. Virus neutralization antibody titers showed a similar response pattern. A dose-response effect could not be demonstrated for any of the strains, neither for the HI antibody nor for the VN antibody responses. No influenza like symptoms, no nasal congestions, no rhinorrhea, or other influenza related upper respiratory tract symptoms were observed. In addition, no difference in the incidence or nature of adverse events was found between vaccine and placebo treated subjects. Overall, the results indicated that the LAIV for nasal administration is immunogenic (i.e. able to provoke an immune response) and safe both from the perspective of the attenuated virus and the MDCK cell line from which it was derived, and it warrants

  3. The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji.

    PubMed

    Kimura, Eisaku

    2011-03-01

    Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in

  4. The Global Programme to Eliminate Lymphatic Filariasis: History and achievements with special reference to annual single-dose treatment with diethylcarbamazine in Samoa and Fiji

    PubMed Central

    Kimura, Eisaku

    2011-01-01

    Diethylcarbamazine (DEC), first introduced in 1947, was shown to have strong efficacy and safety for treatment of human lymphatic filariasis, which is caused mostly by a species Wuchereria bancrofti. Many studies to optimize the dosage and treatment schedule of DEC followed, and, based on the results, control programs with various regimens were implemented in different endemic areas/countries. By the mid 1970s, with endorsement by the WHO Expert Committee on Filariasis (3rd report, 1974), the standard DEC regimen for W. bancrofti infection in mass treatment had been established in principle: a total dose of 72 mg/kg of body weight given in 12 divided doses, once weekly or monthly, at 6 mg/kg each. Not long after the committee report, the efficacy of annual single-dose treatment at 6 mg/kg, which is only one twelfth of the WHO-recommended dose in a year, was reported effective in French Polynesia (study period: 1973-78), and later in Samoa (study period: 1979-81). These results were published between 1978 and 1985 in the Bulletin of WHO but received little attention. In the mid 1980s, the efficacy of ivermectin, the first-choice drug for onchocerciasis, against lymphatic filariae came to light. Since the effect at a single dose was remarkable, and often better than DEC, it was predicted that the newly introduced drug would replace DEC. Treatment experiments with ivermectin increased quickly in number. Meanwhile, annual single-dose mass drug administration (MDA) with DEC at 6 mg/kg was under scrutiny in Samoa and Fiji. In the early 1990s, the Samoan study, which covered the entire population of 160,000 with 3 annual MDAs, reported a significant reduction in microfilaria (mf) prevalence and mean mf density, while in Fiji, the efficacy of 5 rounds of annual MDA (total dose, 30 mg/kg) was shown to be as effective as 28 multi-dose MDA spread over 2 years (6 weekly plus 22 monthly treatments at 5 mg/kg; total dose, 140 mg/kg). Several additional studies carried out in

  5. Preliminary results of trace element contents in mantle derived specimens from Kakanui, New Zealand, of the Jarosewich's Microbeam Reference Samples Collection: The first step of a new program

    NASA Astrophysics Data System (ADS)

    Logan, M.

    2009-12-01

    Over the last two decades, microbeam instrumentation has been the subject of a great technological development—ever more sophisticated analytical capabilities including lower detection limits and better mass- and spectral resolution. Nevertheless, the accuracy of microananalysis is limited because of the lack of reliable reference materials for trace elements (<0.1 wt. %) with a similar composition to the unknown. The program started at the Department of Mineral Sciences, NMNH, Smithsonian Institution (Logan, 2009) has the long-term objective of establishing working values for the trace element contents of the 59 specimens (including silicates, oxides, carbonates, REE orthoposphates, and volcanic and synthetic glasses) from the Jarosewich Microbeam Reference Samples Collection. During the 1970s and 1980s Eugene Jarosewich characterized these specimens for major and minor elements by wet chemistry to be used as RM for microanalysis, Jarosewich et al., (1980). Currently, more than 600 reference samples from this collection are yearly requested by laboratories all over the world. Suitable homogeneous crystals for reference samples can only grow in an environment with constant P-T conditions for a long time such as the mantle. However, during the ascent of mantle nodules to the surface of the earth, their original composition could be affected by metasomatism. Therefore, this program focuses on a rigorous analysis of the degree and scale of homogeneity of trace element contents in mantle derived specimens, as they are the most likely to satisfy the requirements to become RMs. Because the most frequently requested specimens of this collection are from the well know locality Kakanui, New Zealand, a statistical analysis was performed based on 640 electron microprobe analyses (P, Sc, V, Cr, Ni and Zn) on the tschermakitic augite (NMNH 122142), kaersutitic hornblende (NMNH 143965) and a pyrope garnet,(NMNH 143968) in traverses across three randomly selected grains. In

  6. Derivation and validation of simple anthropometric equations to predict adipose tissue mass and total fat mass with MRI as the reference method.

    PubMed

    Al-Gindan, Yasmin Y; Hankey, Catherine R; Govan, Lindsay; Gallagher, Dympna; Heymsfield, Steven B; Lean, Michael E J

    2015-12-14

    The reference organ-level body composition measurement method is MRI. Practical estimations of total adipose tissue mass (TATM), total adipose tissue fat mass (TATFM) and total body fat are valuable for epidemiology, but validated prediction equations based on MRI are not currently available. We aimed to derive and validate new anthropometric equations to estimate MRI-measured TATM/TATFM/total body fat and compare them with existing prediction equations using older methods. The derivation sample included 416 participants (222 women), aged between 18 and 88 years with BMI between 15·9 and 40·8 (kg/m2). The validation sample included 204 participants (110 women), aged between 18 and 86 years with BMI between 15·7 and 36·4 (kg/m2). Both samples included mixed ethnic/racial groups. All the participants underwent whole-body MRI to quantify TATM (dependent variable) and anthropometry (independent variables). Prediction equations developed using stepwise multiple regression were further investigated for agreement and bias before validation in separate data sets. Simplest equations with optimal R (2) and Bland-Altman plots demonstrated good agreement without bias in the validation analyses: men: TATM (kg)=0·198 weight (kg)+0·478 waist (cm)-0·147 height (cm)-12·8 (validation: R 2 0·79, CV=20 %, standard error of the estimate (SEE)=3·8 kg) and women: TATM (kg)=0·789 weight (kg)+0·0786 age (years)-0·342 height (cm)+24·5 (validation: R (2) 0·84, CV=13 %, SEE=3·0 kg). Published anthropometric prediction equations, based on MRI and computed tomographic scans, correlated strongly with MRI-measured TATM: (R (2) 0·70-0·82). Estimated TATFM correlated well with published prediction equations for total body fat based on underwater weighing (R (2) 0·70-0·80), with mean bias of 2·5-4·9 kg, correctable with log-transformation in most equations. In conclusion, new equations, using simple anthropometric measurements, estimated MRI-measured TATM with correlations and

  7. Reference crop evapotranspiration derived from geo-stationary satellite imagery: a case study for the Fogera flood plain, NW-Ethiopia and the Jordan Valley, Jordan

    NASA Astrophysics Data System (ADS)

    de Bruin, H. A. R.; Trigo, I. F.; Jitan, M. A.; Temesgen Enku, N.; van der Tol, C.; Gieske, A. S. M.

    2010-11-01

    First results are shown of a project aiming to estimate daily values of reference crop evapotranspiration ET0 from geo-stationary satellite imagery. In particular, for Woreta, a site in the Ethiopian highland at an elevation of about 1800 m, we tested a radiation-temperature based approximate formula proposed by Makkink (MAK), adopting ET0 evaluated with the version of the Penman-Monteith equation described in the FAO Irrigation and Drainage paper 56 as the most accurate estimate. More precisely we used the latter with measured daily solar radiation as input (denoted by PMFAO-Rs). Our data set for Woreta concerns a period where the surface was fully covered with short green non-stressed vegetation. Our project was carried out in the context of the Satellite Application Facility on Land Surface Analysis (LANDSAF) facility. Among others, the scope of LANDSAF is to increase benefit from the EUMETSAT Satellite Meteosat Second Generation (MSG). In this study we applied daily values of downward solar radiation at the surface obtained from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) radiometer. In addition, air temperature at 2 m was obtained from 3-hourly forecasts provided by the European Centre for Medium-Range Weather Forecasts (ECMWF). Both MAK and PMFAO-Rs contain the psychrometric "constant", which is proportional to air pressure, which, in turn, decreases with elevation. In order to test elevation effects we tested MAK and its LANDSAF input data for 2 sites in the Jordan Valley located about 250 m b.s.l. Except for a small underestimation of air temperature at the Ethiopian site at 1800 m, the first results of our LANDSAF-ET0 project are promising. If our approach to derive ET0 proves successfully, then the LANDSAF will be able to initiate nearly real time free distribution of ET0 for the full MSG disk.

  8. Reference crop evapotranspiration derived from geo-stationary satellite imagery - a case study for the Fogera flood plain, NW-Ethiopia and the Jordan Valley, Jordan

    NASA Astrophysics Data System (ADS)

    de Bruin, H. A. R.; Trigo, I. F.; Jitan, M. A.; Temesgen Enku, N.; van der Tol, C.; Gieske, A. S. M.

    2010-07-01

    First results are shown of a project aiming to estimate daily values of reference crop evapotranspiration ET0 from geo-stationary satellite imagery. In particular, for Woreta, a site in the Ethiopian highland at an elevation of about 1800 m, we tested a radiation-temperature based approximate formula proposed by Makkink (MAK) adopting ET0 evaluated with the version of the Penman-Monteith equation described in the FAO Irrigation and Drainage paper 56 as the most accurate estimate. More precisely we used the latter with measured daily solar radiation as input (denoted by PMFAO-Rs). Our data set for Woreta concerns a period where the surface was fully covered with short green non-stressed vegetation. Our project was carried out in the context of the Satellite Application Facility on Land Surface Analysis (LANDSAF) facility. Among others, the scope of LANDSAF is to increase benefit from the EUMETSAT Satellite Meteosat Second Generation (MSG). In this study we applied daily values of downward solar radiation at the surface obtained from the Spinning Enhanced Visible and Infrared Imager (SEVIRI) radiometer. In addition, air temperature at 2 m was obtained from 3-hourly forecasts provided by the European Centre for Medium-Range Weather Forecasts (ECMWF). Both MAK and PMFAO-Rs contain the psychrometric "constant", which is proportional to air pressure, which, in turn, decreases with elevation. In order to test elevation effects we tested MAK and its LANDSAF input data for 2 sites in the Jordan Valley located about 250 m b.s.l. Except for a small underestimation of air temperature at the Ethiopian site at 1800 m, the first results of our LANDSAF-ET0 project are promising. If our approach to derive ET0 proves successfully, then the LANDSAF will be able to initiate nearly real time free distribution of ET0 for the full MSG disk.

  9. Pharmacokinetics of a Once-Daily Dose of Tacrolimus Early After Liver Transplantation: With Special Reference to CYP3A5 and ABCB1 Single Nucleotide Polymorphisms.

    PubMed

    Miyata, Yoichi; Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Kaneko, Junichi; Yamamoto, Takehito; Suzuki, Hiroshi; Arita, Junichi; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Tamura, Sumihito; Kokudo, Norihiro

    2016-01-01

    BACKGROUND The aim of the present study was to investigate the pharmacokinetics of the once-daily tacrolimus formulation (QD form) in relation to polymorphisms of the donor cytochrome P450 family 3 sub-family A polypeptide 5 (CYP3A5) gene and recipient adenosine triphosphate-binding cassette sub-family B member 1 (ABCB1) gene. MATERIAL AND METHODS A total of 80 consecutive living-donor liver transplant (LDLT) recipients were started on the QD form of tacrolimus (day 1), and 60 patients were completely followed for 7 days early after liver transplantation in order to evaluate the pharmacokinetics. RESULTS The concentration/dose (C/D) ratio in recipients with the donor CYP3A5 *1 allele was significantly lower throughout the observation period compared with those with the CYP3A5 genotype *3/*3 (p<0.001), while no effect of single-nucleotide polymorphisms (SNPs) of ABCB1 was observed. The administered doses required to achieve the target trough level were significantly higher on day 7 than on day 1 among all groups, regardless of the differences in the SNPs, especially among those with donor CYP3A5 *1 allele. The tacrolimus concentration was kept within the targeted level all through the study regardless of SNPs. CONCLUSIONS The donor CYP3A5 *1 allele correlated with the lower C/D ratio after administration of the QD form, and higher doses of QD-form tacrolimus and careful monitoring for the trough level should be considered, especially in recipients with the donor CYP3A5 *1 allele. PMID:27503662

  10. Correlation of In  Vivo Versus In Vitro Benchmark Doses (BMDs) Derived From Micronucleus Test Data: A Proof of Concept Study

    PubMed Central

    Soeteman-Hernández, Lya G.; Fellows, Mick D.; Johnson, George E.; Slob, Wout

    2015-01-01

    In this study, we explored the applicability of using in vitro micronucleus (MN) data from human lymphoblastoid TK6 cells to derive in vivo genotoxicity potency information. Nineteen chemicals covering a broad spectrum of genotoxic modes of action were tested in an in vitro MN test using TK6 cells using the same study protocol. Several of these chemicals were considered to need metabolic activation, and these were administered in the presence of S9. The Benchmark dose (BMD) approach was applied using the dose-response modeling program PROAST to estimate the genotoxic potency from the in vitro data. The resulting in vitro BMDs were compared with previously derived BMDs from in vivo MN and carcinogenicity studies. A proportional correlation was observed between the BMDs from the in vitro MN and the BMDs from the in vivo MN assays. Further, a clear correlation was found between the BMDs from in vitro MN and the associated BMDs for malignant tumors. Although these results are based on only 19 compounds, they show that genotoxicity potencies estimated from in vitro tests may result in useful information regarding in vivo genotoxic potency, as well as expected cancer potency. Extension of the number of compounds and further investigation of metabolic activation (S9) and of other toxicokinetic factors would be needed to validate our initial conclusions. However, this initial work suggests that this approach could be used for in vitro to in vivo extrapolations which would support the reduction of animals used in research (3Rs: replacement, reduction, and refinement). PMID:26443842

  11. Sensitivity to Low-Dose/Low-LET Ionizing Radiation in Mammalian Cells Harboring Mutations in Succinate Dehydrogenase Subunit C is Governed by Mitochondria-Derived Reactive Oxygen Species

    PubMed Central

    Aykin-Burns, Nukhet; Slane, Benjamin G.; Liu, Annie T. Y.; Owens, Kjerstin M.; O'Malley, Malinda S.; Smith, Brian J.; Domann, Frederick E.; Spitz, Douglas R.

    2011-01-01

    It has been hypothesized that ionizing radiation-induced disruptions in mitochondrial O2 metabolism lead to persistent heritable increases in steady-state levels of intracellular superoxide (O2•−) and hydrogen peroxide (H2O2) that contribute to the biological effects of radiation. Hamster fibroblasts (B9 cells) expressing a mutation in the gene coding for the mitochondrial electron transport chain protein succinate dehydrogenase subunit C (SDHC) demonstrate increases in steady-state levels of O2•− and H2O2. When B9 cells were exposed to low-dose/low-LET radiation (5–50 cGy), they displayed significantly increased clonogenic cell killing compared with parental cells. Clones derived from B9 cells overexpressing a wild-type human SDHC (T4, T8) demonstrated significantly increased surviving fractions after exposure to 5–50 cGy relative to B9 vector controls. In addition, pretreatment with polyethylene glycol-conjugated CuZn superoxide dismutase and catalase as well as adenoviral-mediated overexpression of MnSOD and/or mitochondria-targeted catalase resulted in significantly increased survival of B9 cells exposed to 10 cGy ionizing radiation relative to vector controls. Adenoviral-mediated overexpression of either MnSOD or mitochondria-targeted catalase alone was equally as effective as when both were combined. These results show that mammalian cells over expressing mutations in SDHC demonstrate low-dose/low-LET radiation sensitization that is mediated by increased levels of O2•− and H2O2. These results also support the hypothesis that mitochondrial O2•− and H2O2 originating from SDH are capable of playing a role in low-dose ionizing radiation-induced biological responses. PMID:21268708

  12. Monte Carlo-derived TLD cross-calibration factors for treatment verification and measurement of skin dose in accelerated partial breast irradiation.

    PubMed

    Garnica-Garza, H M

    2009-03-21

    Monte Carlo simulation was employed to calculate the response of TLD-100 chips under irradiation conditions such as those found during accelerated partial breast irradiation with the MammoSite radiation therapy system. The absorbed dose versus radius in the last 0.5 cm of the treated volume was also calculated, employing a resolution of 20 microm, and a function that fits the observed data was determined. Several clinically relevant irradiation conditions were simulated for different combinations of balloon size, balloon-to-surface distance and contents of the contrast solution used to fill the balloon. The thermoluminescent dosemeter (TLD) cross-calibration factors were derived assuming that the calibration of the dosemeters was carried out using a Cobalt 60 beam, and in such a way that they provide a set of parameters that reproduce the function that describes the behavior of the absorbed dose versus radius curve. Such factors may also prove to be useful for those standardized laboratories that provide postal dosimetry services. PMID:19229101

  13. Construction of an Algorithm for Stem Recognition in the Hebrew Language. Application of Hebrew Morphology to Computer Techniques for Investigation of Word Roots. Final Report, Part II. Noun Reference Dictionary, Verbal Derivatives. Part I.

    ERIC Educational Resources Information Center

    Lazewnik, Grainom

    This document comprises the first part of the section of the Noun Reference Dictionary concerned with nouns derived from verb roots. See AL 002 270 for Part II. The format of this section is the same as that described in AL 002 267 for the pure nominal section of the dictionary. Roots are indicated. For other related documents, see ED 019 668, AL…

  14. Determination of absorbed dose in water at the reference point D(r{sub 0},{theta}{sub 0}) for an {sup 192}Ir HDR brachytherapy source using a Fricke system

    SciTech Connect

    Austerlitz, C.; Mota, H. C.; Sempau, J.; Benhabib, S. M.; Campos, D.; Allison, R.; Almeida, C. E. de; Zhu, D.; Sibata, C. H.

    2008-12-15

    A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a {sup 192}Ir high dose rate (HDR) source at 1 cm from its center in water, D(r{sub 0},{theta}{sub 0}). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the {sup 192}Ir radioactive source. A ring cavity around the source with 1.5 mm thickness and 5 mm height is centered at 1 cm from the central axis of the source. This ring cavity is etched in a disk shaped base with 2.65 cm diameter and 0.90 cm thickness. The cavity has a wall around it 0.25 cm thick. This ring is filled with Fricke solution, sealed, and the whole assembly is immersed in water during irradiations. The device takes advantage of the cylindrical geometry to measure D(r{sub 0},{theta}{sub 0}). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an {sup 192}Ir Alpha Omega radioactive source. A Spectronic 1001 spectrophotometer was used to measure the optical absorbance using a 1 mL quartz cuvette with 1.00 cm light pathlength. The PENELOPE Monte Carlo code (MC) was utilized to simulate the Fricke device and the {sup 192}Ir Alpha Omega source in detail to calculate the perturbation introduced by the PMMA material. A NIST traceable calibrated well type ionization chamber was used to determine the air-kerma strength, and a published dose-rate constant was used to determine the dose rate at the reference point. The time to deliver 30.00 Gy to the reference point was calculated. This absorbed dose was then compared to the absorbed dose measured by the Fricke solution. Based on MC simulation, the PMMA of the Fricke device increases the D(r{sub 0},{theta}{sub 0}) by 2.0%. Applying the corresponding correction factor, the D(r{sub 0},{theta}{sub 0}) value assessed with the Fricke device agrees within 2.0% with the expected value with a total combined uncertainty of 3.43%(k=1). The Fricke device provides a promising

  15. Antiaggregant activity of a new benzimidazole derivative.

    PubMed

    Kucheryavenko, A F; Spasov, A A; Petrov, V I; Anisimova, V A

    2014-04-01

    Antiaggregant activity of a new tricyclic benzimidazole derivative, RU-891 compound, was studied on the model of ADP-induced platelet aggregation in vitro and intravascular platelet aggregation in vivo. We evaluated the effect of this substance on blood coagulation potential. Antiaggregant agent acetylsalicylic acid was used as the reference drug. RU-891 produced a dose-dependent antiaggregant effect in vivo and in vitro that exceeded the effect of the reference drug. This compound did not modulate blood coagulation potential. PMID:24824700

  16. Age- and sex-related reference ranges for eight plasma constituents derived from randomly selected adults in a Scottish new town.

    PubMed Central

    Gardner, M D; Scott, R

    1980-01-01

    The results of analysis of blood specimens from randomly selected adults aged 19-88 years in the new town of Cumbernauld were used to establish age- and sex-related reference ranges by the centile method (central 95%) for plasma calcium, phosphate, total protein, albumin, globulins, urea, creatinine, and urate. The possible existence of a subpopulation with a higher reference range for urea is mooted. PMID:7400337

  17. Pharmacokinetics and disposition of monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) after intravenous dosing of antiseptic XueBiJing injection in human subjects and rats

    PubMed Central

    Cheng, Chen; Lin, Jia-zhen; Li, Li; Yang, Jun-ling; Jia, Wei-wei; Huang, Yu-hong; Du, Fei-fei; Wang, Feng-qing; Li, Mei-juan; Li, Yan-fen; Xu, Fang; Zhang, Na-ting; Olaleye, Olajide E.; Sun, Yan; Li, Jian; Sun, Chang-hai; Zhang, Gui-ping; Li, Chuan

    2016-01-01

    Aim: Monoterpene glycosides derived from Paeonia lactiflora roots (Chishao) are believed to be pharmacologically important for the antiseptic herbal injection XueBiJing. This study was designed to characterize the pharmacokinetics and disposition of monoterpene glycosides. Methods: Systemic exposure to Chishao monoterpene glycosides was assessed in human subjects receiving an intravenous infusion and multiple infusions of XueBiJing injection, followed by assessment of the pharmacokinetics of the major circulating compounds. Supportive rat studies were also performed. Membrane permeability and plasma-protein binding were assessed in vitro. Results: A total of 18 monoterpene glycosides were detected in XueBiJing injection (content levels, 0.001–2.47 mmol/L), and paeoniflorin accounted for 85.5% of the total dose of monoterpene glycosides detected. In human subjects, unchanged paeoniflorin exhibited considerable levels of systemic exposure with elimination half-lives of 1.2–1.3 h; no significant metabolite was detected. Oxypaeoniflorin and albiflorin exhibited low exposure levels, and the remaining minor monoterpene glycosides were negligible or undetected. Glomerular-filtration-based renal excretion was the major elimination pathway of paeoniflorin, which was poorly bound to plasma protein. In rats, the systemic exposure level of paeoniflorin increased proportionally as the dose was increased. Rat lung, heart, and liver exposure levels of paeoniflorin were lower than the plasma level, with the exception of the kidney level, which was 4.3-fold greater than the plasma level; brain penetration was limited by the poor membrane permeability. Conclusion: Due to its significant systemic exposure and appropriate pharmacokinetic profile, as well as previously reported antiseptic properties, paeoniflorin is a promising XueBiJing constituent of therapeutic importance. PMID:26838074

  18. Estimating Toxicity Pathway Activating Doses for High Throughput Chemical Risk Assessments

    EPA Science Inventory

    Estimating a Toxicity Pathway Activating Dose (TPAD) from in vitro assays as an analog to a reference dose (RfD) derived from in vivo toxicity tests would facilitate high throughput risk assessments of thousands of data-poor environmental chemicals. Estimating a TPAD requires def...

  19. Retention of tritium in reference persons: a metabolic model. Derivation of parameters and application of the model to the general public and to workers.

    PubMed

    Galeriu, D; Melintescu, A

    2010-09-01

    Tritium ((3)H) is a radioactive isotope of hydrogen that is ubiquitous in environmental and biological systems. Following debate on the human health risk from exposure to tritium, there have been claims that the current biokinetic model recommended by the International Commission on Radiological Protection (ICRP) may underestimate tritium doses. A new generic model for tritium in mammals, based on energy metabolism and body composition, together with all its input data, has been described in a recent paper and successfully tested for farm and laboratory mammals. That model considers only dietary intake of tritium and was extended to humans. This paper presents the latest development of the human model with explicit consideration of brain energy metabolism. Model testing with human experimental data on organically bound tritium (OBT) in urine after tritiated water (HTO) or OBT intakes is presented. Predicted absorbed doses show a moderate increase for OBT intakes compared with doses recommended by the ICRP. Infants have higher tritium retention-a factor of 2 longer than the ICRP estimate. The highest tritium concentration is in adipose tissue, which has a very low radiobiological sensitivity. The ranges of uncertainty in retention and doses are investigated. The advantage of the new model is its ability to be applied to the interpretation of bioassay data. PMID:20798471

  20. Comparative Validation of Conventional and RNA-Seq Data-Derived Reference Genes for qPCR Expression Studies of Colletotrichum kahawae

    PubMed Central

    Vieira, Ana; Cabral, Ana; Fino, Joana; Azinheira, Helena G.; Loureiro, Andreia; Talhinhas, Pedro; Pires, Ana Sofia; Varzea, Vitor; Moncada, Pilar; Oliveira, Helena; Silva, Maria do Céu; Paulo, Octávio S.; Batista, Dora

    2016-01-01

    Colletotrichum kahawae is an emergent fungal pathogen causing severe epidemics of Coffee Berry Disease on Arabica coffee crops in Africa. Currently, the molecular mechanisms underlying the Coffea arabica—C. kahawae interaction are still poorly understood, as well as the differences in pathogen aggressiveness, which makes the development of functional studies for this pathosystem a crucial step. Quantitative real time PCR (qPCR) has been one of the most promising approaches to perform gene expression analyses. However, proper data normalization with suitable reference genes is an absolute requirement. In this study, a set of 8 candidate reference genes were selected based on two different approaches (literature and Illumina RNA-seq datasets) to assess the best normalization factor for qPCR expression analysis of C. kahawae samples. The gene expression stability of candidate reference genes was evaluated for four isolates of C. kahawae bearing different aggressiveness patterns (Ang29, Ang67, Zim12 and Que2), at different stages of fungal development and key time points of the plant-fungus interaction process. Gene expression stability was assessed using the pairwise method incorporated in geNorm and the model-based method used by NormFinder software. For C. arabica—C. kahawae interaction samples, the best normalization factor included the combination of PP1, Act and ck34620 genes, while for C. kahawae samples the combination of PP1, Act and ck20430 revealed to be the most appropriate choice. These results suggest that RNA-seq analyses can provide alternative sources of reference genes in addition to classical reference genes. The analysis of expression profiles of bifunctional catalase-peroxidase (cat2) and trihydroxynaphthalene reductase (thr1) genes further enabled the validation of the selected reference genes. This study provides, for the first time, the tools required to conduct accurate qPCR studies in C. kahawae considering its aggressiveness pattern

  1. Pigment epithelium-derived factor expression prolongs survival and enhances the cytotoxicity of low-dose chemotherapy in castration-refractory prostate cancer

    PubMed Central

    Nelius, T; Martinez-Marin, D; Hirsch, J; Miller, B; Rinard, K; Lopez, J; de Riese, W; Filleur, S

    2014-01-01

    There is currently no cure for advanced castration-refractory prostate cancer (CRPC) despite the recent approval of several new therapeutic agents. We report here the anti-tumor effect of the angio-inhibitory pigment epithelium-derived factor (PEDF) in the metastatic LNCaP-derivative CRPC CL1 model and explore PEDF anti-neoplasic efficacy in combination with low-dose chemotherapy. Androgen-sensitive LNCaP and CRPC PC3 cell lines were examined as comparison. Using a retroviral expression system, we showed that PEDF limited the proliferation of all prostatic cell lines tested; an effect attributed to interleukin 8 (IL8)-CXCR1/IL8RA inhibition. PEDF also reduced the number and size of 3D tumor spheroids in vitro, but only induced cell differentiation in CRPC spheroids. Similarly, PEDF inhibited the migration of CRPC cells suggesting both anti-proliferative and anti-migratory functions. In vivo, PEDF decreased by 85% and 65% the growth of subcutaneous (s.c.) PC3 and CL1 tumors, respectively. In the CL1 orthotopic model, tumor intake with lethal metastases was found in all animals; nevertheless, PEDF prolonged the median survival of tumor-bearing mice (95% confidence interval: 53±0.001 to 57±1 days). Accordingly, PEDF delayed the emergence of skeletal-related event in intra-tibial xenografts. Next, we evaluated low-dose docetaxel (DTX; 5, 1, 0.5 mg/kg) or cyclophosphamide (CTX; 10–20 mg/kg) on established s.c. PC3 tumors that conditionally express PEDF anti-tumoral epitope/NT3. Although NT3–DTX-5 mg/kg combination was inefficient, NT3–DTX-1 mg/kg and -0.5 mg/kg inhibited by 95% and 87.8%, respectively, tumor growth compared with control and induced tumor stasis. Both NT3–CTX combinations were advantageous. Inversely, PEDF–DTX-5 mg/kg and PEDF–CTX-10 mg/kg delayed the most CL1 tumor growth (15, 11 and 5 days for PEDF–DTX-5 mg/kg, PEDF–CTX-10 mg/kg and single treatments, respectively) with elevated apoptosis and serum thrombospondin-1

  2. Dose constraints to the individual annual doses of exposed workers in the medical sector.

    PubMed

    Kamenopoulou, V; Drikos, G; Dimitriou, P

    2001-03-01

    The study is an attempt, within the process of the optimization of radiation protection, to propose constraints to the individual annual doses of classified workers employed in the medical sector of ionizing radiation applications in Greece. These exposed workers were grouped according to their specialties, i.e. medical doctors, technicians and nurses and their occupational category with common or similar tasks, such as diagnostic radiology, interventional radiology, nuclear medicine and radiotherapy. The last 5 years' annual dose distributions of these occupational groups, coming from the National Dose Registry Information System (NDRIS) of the Greek Atomic Energy Commission (GAEC) were analyzed. The proposed dose constraints (DCs) were set at levels, below which the annual doses of the 70 or 75% of the exposed workers per category are expected to be included. At the present stage the derived values may be considered achievable ceiling values referring to acceptably applied practices rather than to optimized ones, taking into account social and economic criteria. PMID:11274851

  3. Meta-analysis for deriving age- and gender-specific dose-response relationships between urinary cadmium concentration and {beta} {sub 2}-microglobulinuria under environmental exposure

    SciTech Connect

    Gamo, Masashi . E-mail: masashi-gamo@aist.go.jp; Ono, Kyoko; Nakanishi, Junko

    2006-05-15

    A meta-analysis was conducted to derive age- and gender-specific dose-response relationships between urinary cadmium (Cd) concentration and {beta} {sub 2}-microglobulinuria ({beta}2MG-uria) under environmental exposure. {beta}2MG-uria was defined by a cutoff point of 1000 {mu}g {beta} {sub 2}-microglobulin/g creatinine. We proposed a model for describing the relationships among the interindividual variabilities in urinary Cd concentration, the ratio of Cd concentrations in the target organ and in urine, and the threshold Cd concentration in the target organ. The parameters in the model were determined so that good agreement might be achieved between the prevalence rates of {beta}2MG-uria reported in the literature and those estimated by the model. In this analysis, only the data from the literature on populations environmentally exposed to Cd were used. Using the model and estimated parameters, the prevalence rate of {beta}2MG-uria can be estimated for an age- and gender-specific subpopulation for which the distribution of urinary Cd concentrations is known. The maximum permissible level of urinary Cd concentration was defined as the maximum geometric mean of the urinary Cd concentration in an age- and gender-specific subpopulation that would not result in a statistically significant increase in the prevalence rate of {beta}2MG-uria. This was estimated to be approximately 3 {mu}g/g creatinine for a population in a small geographical area and approximately 2 {mu}g/g creatinine for a nationwide population.

  4. Spliced stromal cell-derived factor-1α analog stimulates endothelial progenitor cell migration and improves cardiac function in a dose-dependent manner after myocardial infarction

    PubMed Central

    Hiesinger, William; Frederick, John R.; Atluri, Pavan; McCormick, Ryan C.; Marotta, Nicole; Muenzer, Jeffrey R.; Woo, Y. Joseph

    2011-01-01

    Objectives Stromal cell-derived factor (SDF)-1α is a potent endogenous endothelial progenitor cell (EPC) chemokine and key angiogenic precursor. Recombinant SDF-1α has been demonstrated to improve neovasculogenesis and cardiac function after myocardial infarction (MI) but SDF-1α is a bulky protein with a short half-life. Small peptide analogs might provide translational advantages, including ease of synthesis, low manufacturing costs, and the potential to control delivery within tissues using engineered biomaterials. We hypothesized that a minimized peptide analog of SDF-1α, designed by splicing the N-terminus (activation and binding) and C-terminus (extracellular stabilization) with a truncated amino acid linker, would induce EPC migration and preserve ventricular function after MI. Methods EPC migration was first determined in vitro using a Boyden chamber assay. For in vivo analysis, male rats (n=48) underwent left anterior descending coronary artery ligation. At infarction, the rats were randomized into 4 groups and received peri-infarct intramyocardial injections of saline, 3 μg/kg of SDF-1α, 3 μg/kg of spliced SDF analog, or 6 μg/kg spliced SDF analog. After 4 weeks, the rats underwent closed chest pressure volume conductance catheter analysis. Results EPCs showed significantly increased migration when placed in both a recombinant SDF-1α and spliced SDF analog gradient. The rats treated with spliced SDF analog at MI demonstrated a significant dose-dependent improvement in end-diastolic pressure, stroke volume, ejection fraction, cardiac output, and stroke work compared with the control rats. Conclusions A spliced peptide analog of SDF-1α containing both the N- and C- termini of the native protein induced EPC migration, improved ventricular function after acute MI, and provided translational advantages compared with recombinant human SDF-1α. PMID:20951261

  5. REFERENCE DOSE FOR METHYLMERCURY (EXTERNAL REVIEW DRAFT)

    EPA Science Inventory

    In 1997, U.S. EPA issued the Mercury Study Report to Congress (MSRC). Among the assessments in the MSRC was a state-of-the-science evaluation of the health effects of methylmercury. There has been considerable discussion within the scientific community regarding the level of e...

  6. The reference individual of radiation protection

    SciTech Connect

    Eckerman, K.F.; Cristy, M.

    1995-12-31

    The 70-kg {open_quotes}standard man{close_quotes} representing a typical Western adult male has been used in physiological models since at least the 1920s. In 1949 at the Chalk River conference, health physicists from the U.S., UK, and Canada agreed on the concept of a standard man to facilitate comparison of internal dose estimates. The 70-kg standard man included specifications of the masses of 25 organs and tissues, total body content of 15 elements, total water intake and output, water content of the body, and some anatomical and physiological data for the respiratory and gastrointestinal tracts. In 1959, in its Publication 2{sup 2} on permissible doses for internal radiation the International Commission on Radiological Protection (ICRP) modified standard man. In 1963 the ICRP established a task group to revise and extend the standard man concept. The name was changed later to Reference Man and the task group`s work was published in 1975 as ICRP Publication 23{sup 3}. Publication 23 similar to Publication 2, updates and documents the sources of the data. Data on women, children, and fetuses were also collected, where available, but these data were limited primarily to anatomical data and only a few reference values were established for these groups. Information assembled during the course of the effort on the Reference Man report was used at Oak Ridge National Laboratory (ORNL) to construct a mathematical representation of the body (a phantom) that was suitable for use with Monte Carlo methods in the calculation of organ doses. That effort was undertaken to improve estimates of dose from photon-emitting radionuclides residing within organs, so-called internal emitters. The phantom, although updated throughout the years, remains today as the basis for organ dose estimates in nuclear medicine and radiation protection and underlies the radiation risk data derived from the epidemiologic studies of the atomic bomb survivors of Hiroshima and Nagasaki.

  7. 76 FR 10591 - Notice of Availability; Recommended Use of Body Weight3∕4 as the Default Method in Derivation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-25

    ... AGENCY Notice of Availability; Recommended Use of Body Weight as the Default Method in Derivation of the... Method in Derivation of the Oral Reference Dose'' (referred to hereafter as BW 3/4 ). This document was... physiologically based toxicokinetic ] modeling. As a default method to account for differences in...

  8. Dose characterization in the near-source region for two high dose rate brachytherapy sources.

    PubMed

    Wang, Ruqing; Li, X Allen

    2002-08-01

    High dose rate (HDR) 192Ir sources are currently used in intravascular brachytherapy (IVB) for the peripheral arterial system. This poses a demand on evaluating accurate dose parameters in the near-source region for such sources. The purpose of this work is to calculate the dose parameters for the old VariSource HDR 192Ir source and the new microSelectron HDR 192Ir source, using Monte Carlo electron and photon transport simulation. The two-dimensional (2D) dose rate distributions and the air kerma strengths for the two HDR sources were calculated by EGSnrc and EGS4 Monte Carlo codes. Based on these data, the dose parameters proposed in the AAPM TG-60 protocol were derived. The dose rate constants obtained are 13.119+/-0.028 cGy h(-1) U(-1) for the old VariSource source, and 22.751+/-0.031 cGy h(-1) U(-1) for the new microSelectron source at the reference point (r0 = 2 mm, theta = pi/2). The 2D dose rate distributions, the radial dose functions, and the anisotropy functions presented for the two sources cover radial distances ranging from 0.5 to 10 mm. In the near-source region on the transverse plane, the dose effects of the charged particle nonequilibrium and the beta-particle dose contribution were studied. It is found that at radial distances ranging from 0.5 to 2 mm, these effects increase the calculated dose rates by up to 29% for the old VariSource source, and by up to 12% for the new microSelectron source, which, in turn, change values of the radial dose function and the anisotropy function. The present dose parameters, which account for the charged particle nonequilibrium and the beta particle contribution, may be used for accurate IVB dose calculation. PMID:12201413

  9. Comparing results from two continental geochemical surveys to world soil composition and deriving Predicted Empirical Global Soil (PEGS2) reference values

    NASA Astrophysics Data System (ADS)

    de Caritat, Patrice; Reimann, Clemens; Bastrakov, E.; Bowbridge, D.; Boyle, P.; Briggs, S.; Brown, D.; Brown, M.; Brownlie, K.; Burrows, P.; Burton, G.; Byass, J.; de Caritat, P.; Chanthapanya, N.; Cooper, M.; Cranfield, L.; Curtis, S.; Denaro, T.; Dhnaram, C.; Dhu, T.; Diprose, G.; Fabris, A.; Fairclough, M.; Fanning, S.; Fidler, R.; Fitzell, M.; Flitcroft, P.; Fricke, C.; Fulton, D.; Furlonger, J.; Gordon, G.; Green, A.; Green, G.; Greenfield, J.; Harley, J.; Heawood, S.; Hegvold, T.; Henderson, K.; House, E.; Husain, Z.; Krsteska, B.; Lam, J.; Langford, R.; Lavigne, T.; Linehan, B.; Livingstone, M.; Lukss, A.; Maier, R.; Makuei, A.; McCabe, L.; McDonald, P.; McIlroy, D.; McIntyre, D.; Morris, P.; O'Connell, G.; Pappas, B.; Parsons, J.; Petrick, C.; Poignand, B.; Roberts, R.; Ryle, J.; Seymon, A.; Sherry, K.; Skinner, J.; Smith, M.; Strickland, C.; Sutton, S.; Swindell, R.; Tait, H.; Tang, J.; Thomson, A.; Thun, C.; Uppill, B.; Wall, K.; Watkins, J.; Watson, T.; Webber, L.; Whiting, A.; Wilford, J.; Wilson, T.; Wygralak, A.; Albanese, S.; Andersson, M.; Arnoldussen, A.; Baritz, R.; Batista, M. J.; Bel-lan, A.; Birke, M.; Cicchella, C.; Demetriades, A.; Dinelli, E.; De Vivo, B.; De Vos, W.; Duris, M.; Dusza-Dobek, A.; Eggen, O. A.; Eklund, M.; Ernstsen, V.; Filzmoser, P.; Finne, T. E.; Flight, D.; Forrester, S.; Fuchs, M.; Fugedi, U.; Gilucis, A.; Gosar, M.; Gregorauskiene, V.; Gulan, A.; Halamić, J.; Haslinger, E.; Hayoz, P.; Hobiger, G.; Hoffmann, R.; Hoogewerff, J.; Hrvatovic, H.; Husnjak, S.; Janik, L.; Johnson, C. C.; Jordan, G.; Kirby, J.; Kivisilla, J.; Klos, V.; Krone, F.; Kwecko, P.; Kuti, L.; Ladenberger, A.; Lima, A.; Locutura, J.; Lucivjansky, P.; Mackovych, D.; Malyuk, B. I.; Maquil, R.; McLaughlin, M.; Meuli, R. G.; Miosic, N.; Mol, G.; Négrel, P.; O'Connor, P.; Oorts, K.; Ottesen, R. T.; Pasieczna, A.; Petersell, V.; Pfleiderer, S.; Poňavič, M.; Prazeres, C.; Rauch, U.; Reimann, C.; Salpeteur, I.; Schedl, A.; Scheib, A.; Schoeters, I.; Sefcik, P.; Sellersjö, E.; Skopljak, F.; Slaninka, I.; Šorša, A.; Srvkota, R.; Stafilov, T.; Tarvainen, T.; Trendavilov, V.; Valera, P.; Verougstraete, V.; Vidojević, D.; Zissimos, A. M.; Zomeni, Z.

    2012-02-01

    Analytical data for 10 major oxides (Al2O3, CaO, Fe2O3, K2O, MgO, MnO, Na2O, P2O5, SiO2 and TiO2), 16 total trace elements (As, Ba, Ce, Co, Cr, Ga, Nb, Ni, Pb, Rb, Sr, Th, V, Y, Zn and Zr), 14 aqua regia extracted elements (Ag, As, Bi, Cd, Ce, Co, Cs, Cu, Fe, La, Li, Mn, Mo and Pb), Loss On Ignition (LOI) and pH from 3526 soil samples from two continents (Australia and Europe) are presented and compared to (1) the composition of the upper continental crust, (2) published world soil average values, and (3) data from other continental-scale soil surveys. It can be demonstrated that average upper continental crust values do not provide reliable estimates for natural concentrations of elements in soils. For many elements there exist substantial differences between published world soil averages and the median concentrations observed on two continents. Direct comparison with other continental datasets is hampered by the fact that often mean, instead of the statistically more robust median, is reported. Using a database of the worldwide distribution of lithological units, it can be demonstrated that lithology is a poor predictor of soil chemistry. Climate-related processes such as glaciation and weathering are strong modifiers of the geochemical signature inherited from bedrock during pedogenesis. To overcome existing shortcomings of predicted global or world soil geochemical reference values, we propose Preliminary Empirical Global Soil reference values based on analytical results of a representative number of soil samples from two continents (PEGS2).

  10. Capture and analysis of radiation dose reports for radiology.

    PubMed

    Midgley, S M

    2014-12-01

    Radiographic imaging systems can produce records of exposure and dose parameters for each patient. A variety of file formats are in use including plain text, bit map images showing pictures of written text and radiation dose structured reports as text or extended markup language files. Whilst some of this information is available with image data on the hospital picture archive and communication system, access is restricted to individual patient records, thereby making it difficult to locate multiple records for the same scan protocol. This study considers the exposure records and dose reports from four modalities. Exposure records for mammography and general radiography are utilized for repeat analysis. Dose reports for fluoroscopy and computed tomography (CT) are utilized to study the distribution of patient doses for each protocol. Results for dosimetric quantities measured by General Radiography, Fluoroscopy and CT equipment are summarised and presented in the Appendix. Projection imaging uses the dose (in air) area product and derived quantities including the dose to the reference point as a measure of the air kerma reaching the skin, ignoring movement of the beam for fluoroscopy. CT uses the dose indices CTDIvol and dose length product as a measure of the dose per axial slice, and to the scanned volume. Suitable conversion factors are identified and used to estimate the effective dose to an average size patient (for CT and fluoroscopy) and the entrance skin dose for fluoroscopy. PMID:25315104

  11. THE APPLICATION OF DIAGNOSTIC REFERENCE LEVELS FOR OPTIMISATION OF X-RAY IMAGING IN THE UK.

    PubMed

    Martin, Colin J

    2016-06-01

    The concept of diagnostic reference levels (DRLs) has been introduced to provide standard doses against which hospital patient dose measurements can be compared to evaluate practices. DRLs are defined in terms of measured dose quantities. National DRLs can be derived from surveys of patient doses for common types of examinations in 20-30 large hospitals. The International Commission on Radiological Protection proposes that median doses for each type of examination at every hospital be collated and DRLs based on the third quartile value of the distribution. Once DRLs have been set, periodic audits of patient dose should be undertaken for examinations that reflect the clinical workload. Median doses from these distributions should be compared with relevant DRLs to identify procedures for which further optimisation is required and appropriate corrective action taken. This paper discusses factors that should be considered in the optimisation process and gives examples of experiences in application of DRLs in Scotland. PMID:26589349

  12. Reference Assessment

    ERIC Educational Resources Information Center

    Bivens-Tatum, Wayne

    2006-01-01

    This article presents interesting articles that explore several different areas of reference assessment, including practical case studies and theoretical articles that address a range of issues such as librarian behavior, patron satisfaction, virtual reference, or evaluation design. They include: (1) "Evaluating the Quality of a Chat Service"…

  13. Reference Services.

    ERIC Educational Resources Information Center

    Bunge, Charles A.

    1999-01-01

    Discusses library reference services. Topics include the historical development of reference services; instruction in library use, particularly in college and university libraries; guidance; information and referral services and how they differ from traditional question-answering service; and future concerns, including user fees and the planning…

  14. Reference frames and reference networks

    NASA Astrophysics Data System (ADS)

    Bosy, Jaroslaw; Krynski, Jan

    2015-12-01

    The summary of research activities concerning reference frames and reference networks performed in Poland in a period of 2011-2014 is presented. It contains the results of research on implementation of IUGG2011 and IAU2012 resolutions on reference systems, implementation of the ETRS89 in Poland, operational work of permanent IGS/ EUREF stations in Poland, operational work of ILRS laser ranging station in Poland, active GNSS station networks in Poland, maintenance of vertical control in Poland, maintenance and modernization of gravity control, and maintenance of magnetic control in Poland. The bibliography of the related works is given in references.

  15. Application of the hybrid approach to the benchmark dose of urinary cadmium as the reference level for renal effects in cadmium polluted and non-polluted areas in Japan

    SciTech Connect

    Suwazono, Yasushi; Nogawa, Kazuhiro; Uetani, Mirei; Nakada, Satoru; Kido, Teruhiko; Nakagawa, Hideaki

    2011-02-15

    Objectives: The aim of this study was to evaluate the reference level of urinary cadmium (Cd) that caused renal effects. An updated hybrid approach was used to estimate the benchmark doses (BMDs) and their 95% lower confidence limits (BMDL) in subjects with a wide range of exposure to Cd. Methods: The total number of subjects was 1509 (650 men and 859 women) in non-polluted areas and 3103 (1397 men and 1706 women) in the environmentally exposed Kakehashi river basin. We measured urinary cadmium (U-Cd) as a marker of long-term exposure, and {beta}2-microglobulin ({beta}2-MG) as a marker of renal effects. The BMD and BMDL that corresponded to an additional risk (BMR) of 5% were calculated with background risk at zero exposure set at 5%. Results: The U-Cd BMDL for {beta}2-MG was 3.5 {mu}g/g creatinine in men and 3.7 {mu}g/g creatinine in women. Conclusions: The BMDL values for a wide range of U-Cd were generally within the range of values measured in non-polluted areas in Japan. This indicated that the hybrid approach is a robust method for different ranges of cadmium exposure. The present results may contribute further to recent discussions on health risk assessment of Cd exposure.

  16. Evaluation of Radiation Doses Due to Consumption of Contaminated Food Items and Calculation of Food Class-Specific Derived Intervention Levels

    SciTech Connect

    Heinzelman, K M; Mansfield, W G

    2010-04-27

    This document evaluates the expected radiation dose due to the consumption of several specific food classes (dairy, meat, produce, etc.) contaminated with specific radionuclides, and relates concentration levels in food to the detection abilities of typical aboratory analysis/measurement methods. The attached charts present the limiting organ dose as a function of the radionuclide concentration in a particular food class, and allow the user to compare these concentrations and doses to typical analytical detection apabilities. The expected radiation dose depends on several factors: the age of the individual; the radionuclide present in the food; the concentration of the radionuclide in the food; and the amount of food consumed. Food consumption rates for individuals of various ges were taken from the 1998 United States Food and Drug Administration (FDA) document, Accidental Radioactive Contamination of HUman Food and Animal Feeds: Recommendations for State and Local Agencies. In that document, the FDA defines the erived Intervention Level (DIL), which is the concentration of a particular radionuclide in food that if consumed could result in an individual receiving a radiation dose exceeding the Protection Action Guide (PAG) thresholds for intervention. This document also resents odified, food class specific DIL, which is calculated using a somewhat modified version of the FDA's procedure. This document begins with an overview of the FDA's DIL calculation, followed by a description of the food class specific DIL calculations, and finally charts of the radiation dose per radioactivity concentration for several food class/radionuclide combinations.

  17. Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn-177Lu is superior to 90Y-177Lu in peptide receptor radiotherapy

    NASA Astrophysics Data System (ADS)

    Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

    2012-07-01

    Clinical trials on 177Lu-90Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1-25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93Y, 90Y and 125Sn in combination with 177Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75-25% combination of 177Lu and 90Y activity. However, 125Sn-177Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125Sn is the best RN for combination with 177Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125Sn-labelled somatostatin analogues.

  18. Ready Reference.

    ERIC Educational Resources Information Center

    Koltay, Emery

    1999-01-01

    Includes the following ready reference information: "Publishers' Toll-Free Telephone Numbers"; "How to Obtain an ISBN (International Standard Book Number)"; "How to Obtain an ISSN (International Standard Serial Number)"; and "How to Obtain an SAN (Standard Address Number)". (AEF)

  19. A steady state solution for ditch drainage problem with special reference to seepage face and unsaturated zone flow contribution: Derivation of a new drainage spacing eqaution

    NASA Astrophysics Data System (ADS)

    Yousfi, Ammar; Mechergui, Mohammed

    2016-04-01

    al. (2001). In this work, a novel solution based on theoretical approach will be adapted to incorporate both the seepage face and the unsaturated zone flow contribution for solving ditch drained aquifers problems. This problem will be tackled on the basis of the approximate 2D solution given by Castro-Orgaz et al. (2012). This given solution yields the generalized water table profile function with a suitable boundary condition to be determined and provides a modified DF theory which permits as an outcome the analytical determination of the seepage face. To assess the ability of the developed equation for water-table estimations, the obtained results were compared with numerical solutions to the 2-D problem under different conditions. It is shown that results are in fair agreement and thus the resulting model can be used for designing ditch drainage systems. With respect to drainage design, the spacings calculated with the newly derived equation are compared with those computed from the DF theory. It is shown that the effect of the unsaturated zone flow contribution is limited to sandy soils and The calculated maximum increase in drain spacing is about 30%. Keywords: subsurface ditch drainage; unsaturated zone; seepage face; water-table, ditch spacing equation

  20. Flexibility of mouse classical and plasmacytoid-derived dendritic cells in directing T helper type 1 and 2 cell development: dependency on antigen dose and differential toll-like receptor ligation.

    PubMed

    Boonstra, André; Asselin-Paturel, Carine; Gilliet, Michel; Crain, Chad; Trinchieri, Giorgio; Liu, Yong-Jun; O'Garra, Anne

    2003-01-01

    Distinct dendritic cell (DC) subsets have been suggested to be preprogrammed to direct either T helper cell (Th) type 1 or Th2 development, although more recently different pathogen products or stimuli have been shown to render these DCs more flexible. It is still unclear how distinct mouse DC subsets cultured from bone marrow precursors, blood, or their lymphoid tissue counterparts direct Th differentiation. We show that mouse myeloid and plasmacytoid precursor DCs (pDCs) cultured from bone marrow precursors and ex vivo splenic DC subsets can induce the development of both Th1 and Th2 effector cells depending on the dose of antigen. In general, high antigen doses induced Th1 cell development whereas low antigen doses induced Th2 cell development. Both cultured and ex vivo splenic plasmacytoid-derived DCs enhanced CD4(+) T cell proliferation and induced strong Th1 cell development when activated with the Toll-like receptor (TLR)9 ligand CpG, and not with the TLR4 ligand lipopolysaccharide (LPS). The responsiveness of plasmacytoid pDCs to CpG correlated with high TLR9 expression similarly to human plasmacytoid pDCs. Conversely, myeloid DCs generated with granulocyte/macrophage colony-stimulating factor enhanced Th1 cell development when stimulated with LPS as a result of their high level of TLR4 expression. Polarized Th1 responses resulting from high antigen dose were not additionally enhanced by stimulation of DCs by TLR ligands. Thus, the net effect of antigen dose, the state of maturation of the DCs together with the stimulation of DCs by pathogen-derived products, will determine whether a Th1 or Th2 response develops. PMID:12515817

  1. Poroelastic references

    SciTech Connect

    Morency, Christina

    2014-12-12

    This file contains a list of relevant references on the Biot theory (forward and inverse approaches), the double-porosity and dual-permeability theory, and seismic wave propagation in fracture porous media, in RIS format, to approach seismic monitoring in a complex fractured porous medium such as Brady?s Geothermal Field.

  2. Ready Reference.

    ERIC Educational Resources Information Center

    Koltay, Emery

    2001-01-01

    Includes four articles that relate to ready reference, including a list of publishers' toll-free telephone numbers and Web sites; how to obtain an ISBN (International Standard Book Number) and an ISSN (International Standard Serial Number); and how to obtain an SAN (Standard Address Number), for organizations that are involved in the book…

  3. Human respiratory tract cancer risks of inhaled formaldehyde: dose-response predictions derived from biologically-motivated computational modeling of a combined rodent and human dataset.

    PubMed

    Conolly, Rory B; Kimbell, Julia S; Janszen, Derek; Schlosser, Paul M; Kalisak, Darin; Preston, Julian; Miller, Frederick J

    2004-11-01

    Formaldehyde inhalation at 6 ppm and above causes nasal squamous cell carcinoma (SCC) in F344 rats. The quantitative implications of the rat tumors for human cancer risk are of interest, since epidemiological studies have provided only equivocal evidence that formaldehyde is a human carcinogen. Conolly et al. (Toxicol. Sci. 75, 432-447, 2003) analyzed the rat tumor dose-response assuming that both DNA-reactive and cytotoxic effects of formaldehyde contribute to SCC development. The key elements of their approach were: (1) use of a three-dimensional computer reconstruction of the rat nasal passages and computational fluid dynamics (CFD) modeling to predict regional dosimetry of formaldehyde; (2) association of the flux of formaldehyde into the nasal mucosa, as predicted by the CFD model, with formation of DNA-protein cross-links (DPX) and with cytolethality/regenerative cellular proliferation (CRCP); and (3) use of a two-stage clonal growth model to link DPX and CRCP with tumor formation. With this structure, the prediction of the tumor dose response was extremely sensitive to cell kinetics. The raw dose-response data for CRCP are J-shaped, and use of these data led to a predicted J-shaped dose response for tumors, notwithstanding a concurrent low-dose-linear, directly mutagenic effect of formaldehyde mediated by DPX. In the present work the modeling approach used by Conolly et al. (ibid.) was extended to humans. Regional dosimetry predictions for the entire respiratory tract were obtained by merging a three-dimensional CFD model for the human nose with a one-dimensional typical path model for the lower respiratory tract. In other respects, the human model was structurally identical to the rat model. The predicted human dose response for DPX was obtained by scale-up of a computational model for DPX calibrated against rat and rhesus monkey data. The rat dose response for CRCP was used "as is" for the human model, since no preferable alternative was identified. Three

  4. Numerical model for computation of effective and ambient dose equivalent at flight altitudes. Application for dose assessment during GLEs

    NASA Astrophysics Data System (ADS)

    Mishev, Alexander; Usoskin, Ilya

    2015-05-01

    A numerical model for assessment of the effective dose and ambient dose equivalent produced by secondary cosmic ray particles of galactic and solar origin at commercial aircraft altitudes is presented. The model represents a full chain analysis based on ground-based measurements of cosmic rays, from particle spectral and angular characteristics to dose estimation. The model is based on newly numerically computed yield functions and realistic propagation of cosmic ray in the Earth magnetosphere. The yield functions are computed using a straightforward full Monte Carlo simulation of the atmospheric cascade induced by primary protons and α-particles and subsequent conversion of secondary particle fluence (neutrons, protons, gammas, electrons, positrons, muons and charged pions) to effective dose or the ambient dose equivalent. The ambient dose equivalent is compared with reference data at various conditions such as rigidity cut-off and level of solar activity. The method is applied for computation of the effective dose rate at flight altitude during the ground level enhancement of 13 December 2006. The solar proton spectra are derived using neutron monitor data. The computation of the effective dose rate during the event explicitly considers the derived anisotropy i.e. the pitch angle distribution as well as the propagation of the solar protons in the magnetosphere of the Earth.

  5. Use of effective dose in medicine.

    PubMed

    Harrison, J; Lopez, P O

    2015-06-01

    This paper does not necessarily reflect the views of the International Commission on Radiological Protection. The protection quantity 'effective dose' was developed by the International Commission on Radiological Protection (ICRP) for use in the radiological protection of workers and the public. In this context, it is used as a risk-adjusted dosimetric quantity to optimise protection, comparing received or planned doses with constraints, reference levels, and limits expressed in the same quantity. Considering exposures incurred during medical procedures, effective dose can be of practical value for comparing: doses from different diagnostic examinations and interventional procedures; the use of similar technologies and procedures in different hospitals and countries; and the use of different technologies for the same medical examination, provided that the representative patients or patient populations for which the effective doses are derived are similar with regard to age and sex. However, as stated in ICRP Publication 103, '… risk assessment for medical diagnosis and treatment… is best evaluated using appropriate risk values for the individual tissues at risk and for the age and sex distribution of the individuals undergoing the medical procedures'. This topic was explored in a session of the First ICRP Symposium with arguments for and against the use of a new quantity referred to as 'effective risk', and examination of variations in estimated risk for different diagnostic procedures according to the age and sex of the exposed individuals. This paper restates the primary purposes of effective dose, and summarises estimates of variation in individual risk from medical procedures. The authors support the judicious use of effective dose as an indicator of possible risk, but caution against the use of effective risk as compared with the calculation of scientific best estimates of risk with consideration of associated uncertainties. PMID:25816282

  6. Systemic exposure to and disposition of catechols derived from Salvia miltiorrhiza roots (Danshen) after intravenous dosing DanHong injection in human subjects, rats, and dogs.

    PubMed

    Li, Meijuan; Wang, Fengqing; Huang, Yühong; Du, Feifei; Zhong, Chenchun; Olaleye, Olajide E; Jia, Weiwei; Li, Yanfen; Xu, Fang; Dong, Jiajia; Li, Jian; Lim, Justin B R; Zhao, Buchang; Jia, Lifu; Li, Li; Li, Chuan

    2015-05-01

    DanHong injection is a Danshen (Salvia miltiorrhiza roots)-based injectable solution for treatment of coronary artery disease and ischemic stroke. Danshen catechols are believed to be responsible for the injection's therapeutic effects. This study aimed to characterize systemic exposure to and elimination of Danshen catechols in human subjects, rats, and dogs receiving intravenous DanHong injection. A total of 28 catechols were detected, with content levels of 0.002-7.066 mM in the injection, and the major compounds included tanshinol, protocatechuic aldehyde, salvianolic acid B, rosmarinic acid, salvianolic acids A and D, and lithospermic acid with their daily doses ≥10 μmol/subject. After dosing, tanshinol, salvianolic acid D, and lithospermic acid exhibited considerable exposure in human subjects and rats. However, only tanshinol had considerable exposure in dogs. The considerable exposure to tanshinol was due to its having the highest dose, whereas that to salvianolic acid D and lithospermic acid was due to their relatively long elimination half-lives in the human subjects and rats. Protocatechuic aldehyde and rosmarinic acid circulated in the bloodstream predominantly as metabolites; salvianolic acids A and B exhibited low plasma levels with their human plasma metabolites little or not detected. Tanshinol and salvianolic acid D were eliminated mainly via renal excretion. Elimination of other catechols involved hepatobiliary and/or renal excretion of their metabolites. Methylation was found to be the primary metabolism for most Danshen catechols and showed intercompound and interspecies differences in rate and degree in vitro. The information gained here is relevant to pharmacological and toxicological research on DanHong injection. PMID:25670806

  7. Are radiosensitivity data derived from natural field conditions consistent with data from controlled exposures? A case study of Chernobyl wildlife chronically exposed to low dose rates.

    PubMed

    Garnier-Laplace, J; Geras'kin, S; Della-Vedova, C; Beaugelin-Seiller, K; Hinton, T G; Real, A; Oudalova, A

    2013-07-01

    The discrepancy between laboratory or controlled conditions ecotoxicity tests and field data on wildlife chronically exposed to ionising radiation is presented for the first time. We reviewed the available chronic radiotoxicity data acquired in contaminated fields and used a statistical methodology to support the comparison with knowledge on inter-species variation of sensitivity to controlled external γ irradiation. We focus on the Chernobyl Exclusion Zone and effects data on terrestrial wildlife reported in the literature corresponding to chronic dose rate exposure situations (from background ~100 nGy/h up to ~10 mGy/h). When needed, we reconstructed the dose rate to organisms and obtained consistent unbiased data sets necessary to establish the dose rate-effect relationship for a number of different species and endpoints. Then, we compared the range of variation of radiosensitivity of species from the Chernobyl-Exclusion Zone with the statistical distribution established for terrestrial species chronically exposed to purely gamma external irradiation (or chronic Species radioSensitivity Distribution - SSD). We found that the best estimate of the median value (HDR50) of the distribution established for field conditions at Chernobyl (about 100 μGy/h) was eight times lower than the one from controlled experiments (about 850 μGy/h), suggesting that organisms in their natural environmental were more sensitive to radiation. This first comparison highlights the lack of mechanistic understanding and the potential confusion coming from sampling strategies in the field. To confirm the apparent higher sensitive of wildlife in the Chernobyl Exclusion Zone, we call for more a robust strategy in field, with adequate design to deal with confounding factors. PMID:22336569

  8. Derivation of the critical effect size/benchmark response for the dose-response analysis of the uptake of radioactive iodine in the human thyroid.

    PubMed

    Weterings, Peter J J M; Loftus, Christine; Lewandowski, Thomas A

    2016-08-22

    Potential adverse effects of chemical substances on thyroid function are usually examined by measuring serum levels of thyroid-related hormones. Instead, recent risk assessments for thyroid-active chemicals have focussed on iodine uptake inhibition, an upstream event that by itself is not necessarily adverse. Establishing the extent of uptake inhibition that can be considered de minimis, the chosen benchmark response (BMR), is therefore critical. The BMR values selected by two international advisory bodies were 5% and 50%, a difference that had correspondingly large impacts on the estimated risks and health-based guidance values that were established. Potential treatment-related inhibition of thyroidal iodine uptake is usually determined by comparing thyroidal uptake of radioactive iodine (RAIU) during treatment with a single pre-treatment RAIU value. In the present study it is demonstrated that the physiological intra-individual variation in iodine uptake is much larger than 5%. Consequently, in-treatment RAIU values, expressed as a percentage of the pre-treatment value, have an inherent variation, that needs to be considered when conducting dose-response analyses. Based on statistical and biological considerations, a BMR of 20% is proposed for benchmark dose analysis of human thyroidal iodine uptake data, to take the inherent variation in relative RAIU data into account. Implications for the tolerated daily intakes for perchlorate and chlorate, recently established by the European Food Safety Authority (EFSA), are discussed. PMID:27268963

  9. Real-time analysis of endogenous protoporphyrin IX fluorescence from δ-aminolevulinic acid and its derivatives reveals distinct time- and dose-dependent characteristics in vitro

    NASA Astrophysics Data System (ADS)

    Kiesslich, Tobias; Helander, Linda; Illig, Romana; Oberdanner, Christian; Wagner, Andrej; Lettner, Herbert; Jakab, Martin; Plaetzer, Kristjan

    2014-08-01

    Photodynamic therapy (PDT) and photodiagnosis based on the intracellular production of the photosensitizer protoporphyrin IX (PPIX) by administration of its metabolic precursor δ-aminolevulinic acid (ALA) achieved their breakthrough upon the clinical approval of MAL (ALA methyl ester) and HAL (ALA hexyl ester). For newly developed ALA derivatives or application in new tumor types, in vitro determination of PPIX formation involves multiparametric experiments covering variable pro-drug concentrations, medium composition, time points of analysis, and cell type(s). This study uses a fluorescence microplate reader with a built-in temperature and atmosphere control to investigate the high-resolution long-term kinetics (72 h) of cellular PPIX fueled by administration of either ALA, MAL, or HAL for each 10 different concentrations. For simultaneous proliferation correction, A431 cells were stably transfected with green fluorescent protein. The results indicate that the peak PPIX level is a function of both, incubation concentration and period: maximal PPIX is generated with 1 to 2-mM ALA/MAL or 0.125-mM HAL; also, the PPIX peak shifts to longer incubation periods with increasing pro-drug concentrations. The results underline the need for detailed temporal analysis of PPIX formation to optimize ALA (derivative)-based PDT or photodiagnosis and highlight the value of environment-controlled microplate readers for automated in vitro analysis.

  10. Emergence of Hyper-Resistant Escherichia coli MG1655 Derivative Strains after Applying Sub-Inhibitory Doses of Individual Constituents of Essential Oils.

    PubMed

    Chueca, Beatriz; Berdejo, Daniel; Gomes-Neto, Nelson J; Pagán, Rafael; García-Gonzalo, Diego

    2016-01-01

    The improvement of food preservation by using essential oils (EOs) and their individual constituents (ICs) is attracting enormous interest worldwide. Until now, researchers considered that treatments with such antimicrobial compounds did not induce bacterial resistance via a phenotypic (i.e., transient) response. Nevertheless, the emergence of genotypic (i.e., stable) resistance after treatment with these compounds had not been previously tested. Our results confirm that growth of Escherichia coli MG1655 in presence of sub-inhibitory concentrations of the ICs carvacrol, citral, and (+)-limonene oxide do not increase resistance to further treatments with either the same IC (direct resistance) or with other preservation treatments (cross-resistance) such as heat or pulsed electric fields (PEF). Bacterial mutation frequency was likewise lower when those IC's were applied; however, after 10 days of re-culturing cells in presence of sub-inhibitory concentrations of the ICs, we were able to isolate several derivative strains (i.e., mutants) displaying an increased minimum inhibitory concentration to those ICs. Furthermore, when compared to the wild type (WT) strain, they also displayed direct resistance and cross-resistance. Derivative strains selected with carvacrol and citral also displayed morphological changes involving filamentation along with cell counts at late-stationary growth phase that were lower than the WT strain. In addition, co-cultures of each derivative strain with the WT strain resulted in a predominance of the original strain in absence of ICs, indicating that mutants would not out-compete WT cells under optimal growth conditions. Nevertheless, growth in the presence of ICs facilitated the selection of these resistant mutants. Thus, as a result, subsequent food preservation treatments of these bacterial cultures might be less effective than expected for WT cultures. In conclusion, this study recommends that treatment with ICs at sub

  11. Emergence of Hyper-Resistant Escherichia coli MG1655 Derivative Strains after Applying Sub-Inhibitory Doses of Individual Constituents of Essential Oils

    PubMed Central

    Chueca, Beatriz; Berdejo, Daniel; Gomes-Neto, Nelson J.; Pagán, Rafael; García-Gonzalo, Diego

    2016-01-01

    The improvement of food preservation by using essential oils (EOs) and their individual constituents (ICs) is attracting enormous interest worldwide. Until now, researchers considered that treatments with such antimicrobial compounds did not induce bacterial resistance via a phenotypic (i.e., transient) response. Nevertheless, the emergence of genotypic (i.e., stable) resistance after treatment with these compounds had not been previously tested. Our results confirm that growth of Escherichia coli MG1655 in presence of sub-inhibitory concentrations of the ICs carvacrol, citral, and (+)-limonene oxide do not increase resistance to further treatments with either the same IC (direct resistance) or with other preservation treatments (cross-resistance) such as heat or pulsed electric fields (PEF). Bacterial mutation frequency was likewise lower when those IC's were applied; however, after 10 days of re-culturing cells in presence of sub-inhibitory concentrations of the ICs, we were able to isolate several derivative strains (i.e., mutants) displaying an increased minimum inhibitory concentration to those ICs. Furthermore, when compared to the wild type (WT) strain, they also displayed direct resistance and cross-resistance. Derivative strains selected with carvacrol and citral also displayed morphological changes involving filamentation along with cell counts at late-stationary growth phase that were lower than the WT strain. In addition, co-cultures of each derivative strain with the WT strain resulted in a predominance of the original strain in absence of ICs, indicating that mutants would not out-compete WT cells under optimal growth conditions. Nevertheless, growth in the presence of ICs facilitated the selection of these resistant mutants. Thus, as a result, subsequent food preservation treatments of these bacterial cultures might be less effective than expected for WT cultures. In conclusion, this study recommends that treatment with ICs at sub

  12. Analysis of cell cycle regulated and regulating proteins following exposure of lung derived cells to sub-lethal doses of a-rays

    NASA Astrophysics Data System (ADS)

    Trani, D.; Claudio, P. P.; Cassone, M.; Lucchetti, C.; D'Agostino, L.; Caputi, M.; Giordano, A.

    Introduction Since the last century mankind had to face an increased exposure to man made and natural sources of radiation Radiation represents a therapeutic instrument for radiosensitive cancers as well as a cytotoxic agent for normal human tissues The effects of prolonged exposure to low doses of high energy radiation are still not well-known at the molecular and clinical level Understanding their molecular effects will aid in developing more tailored therapeutic strategies as well as implementing radio-protective measures essential prerequisite for the long-time permanence of men in space Objective of the study The general aim of this study was to evaluate the susceptibility and the response of lung epithelial cells to DNA damage induced by ionizing radiations We decided to study a panel of epithelial bronchial cell lines because of their fast-growth rate and their prominent exposure to both environmental and medical radiations The specific objective of our study was to qualitatively and semi-quantitatively assess the involvement and behaviour of selected genes in DNA damage DNA-repair mechanisms and apoptosis which follow radiation exposure with the aim to determine the involvement of the most promising targets for the early detection of radiation-mediated lung damage before chronic disease develops Methods Four epithelial cell lines one normal and three neoplastic were selected in order to detect and compare survival cell cycle and protein expression differences related to their different genetic asset

  13. Dose rate constant and energy spectrum of interstitial brachytherapy sources.

    PubMed

    Chen, Z; Nath, R

    2001-01-01

    In the past two years, several new manufacturers have begun to market low-energy interstitial brachytherapy seeds containing 125I and 103Pd. Parallel to this development, the National Institute of Standards and Technology (NIST) has implemented a modification to the air-kerma strength (S(K)) standard for 125I seeds and has also established an S(K) standard for 103Pd seeds. These events have generated a considerable number of investigations on the determination of the dose rate constants (inverted V) of interstitial brachytherapy seeds. The aim of this work is to study the general properties underlying the determination of dose rate constant and to develop a simple method for a quick and accurate estimation of dose rate constant. As the dose rate constant of clinical seeds is defined at a fixed reference point, we postulated that dose rate constant may be calculated by treating the seed as an effective point source when the seed's source strength is specified in S(K) and its source characteristics are specified by the photon energy spectrum measured in air at the reference point. Using a semi-analytic approach, an analytic expression for dose rate constant was derived for point sources with known photon energy spectra. This approach enabled a systematic study of dose rate constant as a function of energy. Using the measured energy spectra, the calculated dose rate constant for 125I model 6711 and 6702 seeds and for 192Ir seed agreed with the AAPM recommended values within +/-1%. For the 103Pd model 200 seed, the agreement was 5% with a recently measured value (within the +/-7% experimental uncertainty) and was within 1% with the Monte Carlo simulations. The analytic expression for dose rate constant proposed here can be evaluated using a programmable calculator or a simple spreadsheet and it provides an efficient method for checking the measured dose rate constant for any interstitial brachytherapy seed once the energy spectrum of the seed is known. PMID:11213926

  14. Equianalgesic dose ratios for opioids. a critical review and proposals for long-term dosing.

    PubMed

    Pereira, J; Lawlor, P; Vigano, A; Dorgan, M; Bruera, E

    2001-08-01

    Clinicians involved in the opioid pharmacotherapy of cancer-related pain should be acquainted with a variety of opioids and be skilled in the selection of doses when the type of opioid or route of administration needs changing. The optimal dose should avoid under-dosing or overdosing, both associated with negative outcomes for the patient. Although equianalgesic dose tables are generally used to determine the new doses in these circumstances, the evidence to support the ratios indicated in these tables largely refers to the context of single dose administration. The applicability of these ratios to the setting of chronic opioid administration has been questioned. A systematic search of published literature from 1966 to September 1999 was conducted to critically appraise the emerging evidence on equianalgesic dose ratios derived from studies of chronic opioid administration. There were six major findings: 1) there exists a general paucity of data related to long-term dosing and studies are heterogeneous in nature; 2) the ratios exhibit extremely wide ranges; 3) methadone is more potent than previously appreciated; 4) the ratios related to methadone are highly correlated with the dose of the previous opioid; 5) the ratio may change according to the direction the opioid switch; and 6) discrepancies exist with respect to both oxycodone and fentanyl. Overall, these findings have important clinical implications for clinicians and warrant consideration in the potential revision of current tables. The complexity of the clinical context in which many switches occur must be recognized and also appreciated in the design of future studies. PMID:11495714

  15. A comparative study on the anti-inflammatory effects of single oral doses of naproxen and its hydrogen sulfide (H2S)-releasing derivative ATB-346 in rats with carrageenan-induced synovitis

    PubMed Central

    2013-01-01

    Background Non-steroidal antiinflammatory drugs (NSAIDs) are the most commonly prescribed agents for arthritic patients, although gastric effects limit their long-term use. Considering the reported gastric safety of hydrogen sulfide (H2S)-releasing NSAIDs, in addition to the anti-inflammatory effects of H2S administration to rats with synovitis, we decided to evaluate the effects of the H2S-releasing naproxen derivative ATB-346 in this animal model. Methods Male Wistar rats were anesthetized with inhalatory halothane and pre-treated with equimolar oral doses of either naproxen (0.3, 1, 3 or 10 mg/kg) or ATB-346 (0.48, 1.6, 4.8, or 16 mg/kg) 30 min before the i.art. injection of 7.5 mg of carrageenan (CGN) into the right knee joint cavity. Joint swelling and pain score were assessed after 1, 3 and 5 h, and tactile allodynia after 2 and 4 h. After the last measurement, the joint cavity lavages were performed for counting of the recruited leukocytes. The drugs (at the highest doses) were also tested for their gastric effects by evaluating macroscopical damage score and neutrophil recruitment (measured as myeloperoxidase – MPO activity) in the stomachs 5 h after administration of the drugs. In addition, the serum naproxen pharmacokinetic profiles of both compounds, administered at the highest equimolar doses, were obtained during the first 6 h after dosing. Results At the two highest tested doses, both naproxen and ATB-346 reduced edema and pain score (measured 3 and 5 h after CGN; P < 0.001). Tactile allodynia was similarly inhibited by ~45% 4 h after CGN by both naproxen (at 1, 3 and 10 mg/kg) and ATB-346 (at 1.6 and 4.8 mg/kg; P < 0.001), as well as leukocyte infiltration. Naproxen (but not ATB-346) induced significant gastric damage and, despite the increased gastric MPO activity by ~130% in the naproxen-, but not in the ATB-346-treated rats, this effect was of no statistical significance. Conclusion The presence of a H2S-releasing moiety in

  16. [STUDYING SOME PHARMACOLOGICAL EFFECTS OF NEW 3-HYDROXYPYRIDINE DERIVATIVE].

    PubMed

    Yasnetsov, V V; Tsublova, E G; Yasnetsov, Vic V; Skachilova, S Ya; Karsanova, S K; Ivanov, Yu V

    2016-01-01

    It was established that a new 3-hydroxypyridine (3-HP) derivative, 2-ethyl-6-methyl-3-hydroxypyridine L-aspartate (3-HP), in small doses (1 and 5 mg/kg) increased physical performance in treadmill and swimming tests on rats. The new substance showed greater or equal effects compared to the reference actoprotector drugs metaprot and ladasten in much higher doses. The gluconeogenesis inhibitor tryptophan significantly (74 ± 5%, p < 0.01) prevented this stimulatory effect of 3-HPA in the treadmill test on rats. 3-HPA at a higher dose (30 mg/kg) had marked antiamnesic effect on various models of amnesia in mice. It was more effective than reference drugs mexidol (another 3-HP derivative) in a dose of 30 mg/kg and nootropic drug piracetam in a dose of 200 mg/kg, but had equal effect with these drugs in doses of 50 and 800 mg/kg, respectively. 3-HPA (30 mg/kg per day) had neuroprotective effect in rats with brain ischemia and decreased the neurologic deficiency more effectively than mexidol (50 mg/kg per day). PMID:27416675

  17. A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.

    PubMed

    Hindmarch, I

    1977-11-01

    Repeated doses of 5 mg nitrazepam, 15 mg flurazepam, and 1 mg flunitrazepam improved subjective assessments of the ease of getting to sleep and the perceived quality of induced sleep in a population of 30 healthy volunteers. The subjective reports of improved sleep inducement were related to a perceived difficulty in awakening from sleep the morning following medication. This subjectively reported "hangover" is also shown in the impairment of mental arithmetic abilities as measured on the serial subtraction of sevens technique. However, complex psychomotor performance is unaffected by repeated administration of these three benzodiazepine derivatives, although these later results are somewhat equivocal. Evidence of a "rebound phenomenon" following 4 nights' withdrawal of active medication is shown in both subjective and objective measures of sleep and early morning behaviour. PMID:22990

  18. Selection of appropriate tumour data sets for Benchmark Dose Modelling (BMD) and derivation of a Margin of Exposure (MoE) for substances that are genotoxic and carcinogenic: considerations of biological relevance of tumour type, data quality and uncertainty assessment.

    PubMed

    Edler, Lutz; Hart, Andy; Greaves, Peter; Carthew, Philip; Coulet, Myriam; Boobis, Alan; Williams, Gary M; Smith, Benjamin

    2014-08-01

    This article addresses a number of concepts related to the selection and modelling of carcinogenicity data for the calculation of a Margin of Exposure. It follows up on the recommendations put forward by the International Life Sciences Institute - European branch in 2010 on the application of the Margin of Exposure (MoE) approach to substances in food that are genotoxic and carcinogenic. The aims are to provide practical guidance on the relevance of animal tumour data for human carcinogenic hazard assessment, appropriate selection of tumour data for Benchmark Dose Modelling, and approaches for dealing with the uncertainty associated with the selection of data for modelling and, consequently, the derived Point of Departure (PoD) used to calculate the MoE. Although the concepts outlined in this article are interrelated, the background expertise needed to address each topic varies. For instance, the expertise needed to make a judgement on biological relevance of a specific tumour type is clearly different to that needed to determine the statistical uncertainty around the data used for modelling a benchmark dose. As such, each topic is dealt with separately to allow those with specialised knowledge to target key areas of guidance and provide a more in-depth discussion on each subject for those new to the concept of the Margin of Exposure approach. PMID:24176677

  19. Patient dose measurements in diagnostic radiology procedures in Korea.

    PubMed

    Kim, You-hyun; Choi, Jong-hak; Kim, Chang-kyun; Kim, Jung-min; Kim, Sung-soo; Oh, Yu-whan; Lee, Chang-yeap; Kang, Dae-hyun; Lee, Young-bae; Cho, Pyong-kon; Kim, Hyung-chul; Kim, Chel-min

    2007-01-01

    This study is the first nationwide investigation aimed at estimating the patient dose for radiographic examinations in Korea including gastrointestinal studies, computed tomography and mammography. The survey data from 161 hospitals and the dose data from 32 hospitals were analysed. The third quartile entrance surface dose, dose area product (DAP), weighted CT dose index (CTDIw) and mean glandular dose (MGD) were reported. All the estimated doses were less than the stated International Atomic Energy Agency (IAEA) reference levels for radiographic examinations. However, DAPs for the fluoroscopic examinations had higher dose values than the IAEA reference levels. In addition, the CTDIw and MGD were lower than the IAEA reference levels. PMID:17223642

  20. Comparative analysis of the anxiolytic effects of 3-hydroxypyridine and succinic acid derivatives.

    PubMed

    Volchegorskii, I A; Miroshnichenko, I Yu; Rassokhina, L M; Faizullin, R M; Malkin, M P; Pryakhina, K E; Kalugina, A V

    2015-04-01

    Threefold administration of 3-hydroxypyridine derivatives emoxipine and mexidol in optimal doses corresponding to the therapeutic dose range for humans produced an anxiolytic effect and stimulated risk behavior in the elevated plus maze test in rats. These effects were most pronounced after injection of 3-hydroxypyridine derivative emoxipine. Combination of 3-hydroxypyridine cation and succinate anion in the mexidol structure led to attenuation of the anxiolytic effect and less pronounced stimulation of the risk behavior. By the anxiolytic effect and induction of risk behavior, emoxipine and mexidol were close to the reference substance amitriptyline. Reamberin, a succinic acid derivative, had no pronounced tranquilizing properties, but risk behavior induction was similar to that produced by mexidol. In contrast to other test agents, the reference substance α-lipoic acid produced anxiogenic effects and suppressed risk behavior. The obtained results suggest that Russian-made 3-hydroxypyridine derivatives emoxipine and mexidol are promising preparations for the treatment of anxiety disorders. PMID:25894772

  1. Library Reference Services.

    ERIC Educational Resources Information Center

    Miller, Constance; And Others

    1985-01-01

    Seven articles on library reference services highlight reference obsolescence in academic libraries, major studies of unobtrusive reference tests, methods for evaluating reference desk performance, reference interview evaluation, problems of reference desk control, online searching by end users, and reference collection development in…

  2. Determination of absorbed dose to water in reference conditions for radiotherapy kilovoltage x-rays between 10 and 300 kV: a comparison of the data in the IAEA, IPEMB, DIN and NCS dosimetry protocols

    NASA Astrophysics Data System (ADS)

    Peixoto, J. G. P.; Andreo, P.

    2000-03-01

    A comparison of four of the most commonly used dosimetry protocols for the determination of absorbed dose to water in therapeutic kilovoltage x-rays using an ionization chamber (IAEA TRS-277, IPEMB, DIN and NCS) has been carried out. Owing to the different energy ranges and HVLs recommended by each protocol, backscatter factors, water-to-air mass energy absorption coefficient ratios and perturbation correction factors have been recast to a common quality range that all protocols satisfy individually to make a comparison possible. The results of the comparison show that in the sometimes reduced quality range originally included by the different protocols, determinations of absorbed dose to water at all beam qualities agree to within ±1.0% with that obtained using the second edition of the IAEA TRS-277 code of practice (1997). The extrapolation of data to a common beam quality range practically preserves the agreement for all the protocols except for that issued by the NCS at the extremes of the range, where differences of up to 1.8% and 1.4% have been found for low and medium energies respectively. In all cases the DIN protocol yields very good agreement with TRS-277.

  3. Health physics research reactor reference dosimetry

    SciTech Connect

    Sims, C.S.; Ragan, G.E.

    1987-06-01

    Reference neutron dosimetry is developed for the Health Physics Research Reactor (HPRR) in the new operational configuration directly above its storage pit. This operational change was physically made early in CY 1985. The new reference dosimetry considered in this document is referred to as the 1986 HPRR reference dosimetry and it replaces any and all HPRR reference documents or papers issued prior to 1986. Reference dosimetry is developed for the unshielded HPRR as well as for the reactor with each of five different shield types and configurations. The reference dosimetry is presented in terms of three different dose and six different dose equivalent reporting conventions. These reporting conventions cover most of those in current use by dosimetrists worldwide. In addition to the reference neutron dosimetry, this document contains other useful dosimetry-related data for the HPRR in its new configuration. These data include dose-distance measurements and calculations, gamma dose measurements, neutron-to-gamma ratios, ''9-to-3 inch'' ratios, threshold detector unit measurements, 56-group neutron energy spectra, sulfur fluence measurements, and details concerning HPRR shields. 26 refs., 11 figs., 31 tabs.

  4. Organ doses can be estimated from the computed tomography (CT) dose index for cone-beam CT on radiotherapy equipment.

    PubMed

    Martin, Colin J; Abuhaimed, Abdullah; Sankaralingam, Marimuthu; Metwaly, Mohamed; Gentle, David J

    2016-06-01

    Cone beam computed tomography (CBCT) systems are fitted to radiotherapy linear accelerators and used for patient positioning prior to treatment by image guided radiotherapy (IGRT). Radiotherapists' and radiographers' knowledge of doses to organs from CBCT imaging is limited. The weighted CT dose index for a reference beam of width 20 mm (CTDIw,ref) is displayed on Varian CBCT imaging equipment known as an On-Board Imager (OBI) linked to the Truebeam linear accelerator. This has the potential to provide an indication of organ doses. This knowledge would be helpful for guidance of radiotherapy clinicians preparing treatments. Monte Carlo simulations of imaging protocols for head, thorax and pelvic scans have been performed using EGSnrc/BEAMnrc, EGSnrc/DOSXYZnrc, and ICRP reference computational male and female phantoms to derive the mean absorbed doses to organs and tissues, which have been compared with values for the CTDIw,ref displayed on the CBCT scanner console. Substantial variations in dose were observed between male and female phantoms. Nevertheless, the CTDIw,ref gave doses within  ±21% for the stomach and liver in thorax scans and 2  ×  CTDIw,ref can be used as a measure of doses to breast, lung and oesophagus. The CTDIw,ref could provide indications of doses to the brain for head scans, and the colon for pelvic scans. It is proposed that knowledge of the link between CTDIw for CBCT should be promoted and included in the training of radiotherapy staff. PMID:26975735

  5. Reference Frames and Relativity.

    ERIC Educational Resources Information Center

    Swartz, Clifford

    1989-01-01

    Stresses the importance of a reference frame in mechanics. Shows the Galilean transformation in terms of relativity theory. Discusses accelerated reference frames and noninertial reference frames. Provides examples of reference frames with diagrams. (YP)

  6. Range reference atmosphere Shemya, Alaska

    NASA Astrophysics Data System (ADS)

    1991-08-01

    A reference atmosphere is a statistical model of the earth's atmosphere, derived from upper air observations over a specific location. The individual RRA is the authoritative source for upper atmosphere climatology over the launch and recovery site for which it has been prepared. The RRA's are used to plan, evaluate, and establish environmental launch constraints for aerospace vehicles launched from a particular location.

  7. The induction of human myeloid derived suppressor cells through hepatic stellate cells is dose-dependently inhibited by the tyrosine kinase inhibitors nilotinib, dasatinib and sorafenib, but not sunitinib.

    PubMed

    Heine, Annkristin; Schilling, Judith; Grünwald, Barbara; Krüger, Achim; Gevensleben, Heidrun; Held, Stefanie Andrea Erika; Garbi, Natalio; Kurts, Christian; Brossart, Peter; Knolle, Percy; Diehl, Linda; Höchst, Bastian

    2016-03-01

    Increased numbers of immunosuppressive myeloid derived suppressor cells (MDSCs) correlate with a poor prognosis in cancer patients. Tyrosine kinase inhibitors (TKIs) are used as standard therapy for the treatment of several neoplastic diseases. However, TKIs not only exert effects on the malignant cell clone itself but also affect immune cells. Here, we investigate the effect of TKIs on the induction of MDSCs that differentiate from mature human monocytes using a new in vitro model of MDSC induction through activated hepatic stellate cells (HSCs). We show that frequencies of monocytic CD14(+)HLA-DR(-/low) MDSCs derived from mature monocytes were significantly and dose-dependently reduced in the presence of dasatinib, nilotinib and sorafenib, whereas sunitinib had no effect. These regulatory effects were only observed when TKIs were present during the early induction phase of MDSCs through activated HSCs, whereas already differentiated MDSCs were not further influenced by TKIs. Neither the MAPK nor the NFκB pathway was modulated in MDSCs when any of the TKIs was applied. When functional analyses were performed, we found that myeloid cells treated with sorafenib, nilotinib or dasatinib, but not sunitinib, displayed decreased suppressive capacity with regard to CD8+ T cell proliferation. Our results indicate that sorafenib, nilotinib and dasatinib, but not sunitinib, decrease the HSC-mediated differentiation of monocytes into functional MDSCs. Therefore, treatment of cancer patients with these TKIs may in addition to having a direct effect on cancer cells also prevent the differentiation of monocytes into MDSCs and thereby differentially modulate the success of immunotherapeutic or other anti-cancer approaches. PMID:26786874

  8. Interim methods for development of inhalation reference concentrations. Draft report

    SciTech Connect

    Blackburn, K.; Dourson, M.; Erdreich, L.; DeRose, C.; Graham, J.A.

    1990-08-01

    An inhalation reference concentration (RfC) is an estimate of continuous inhalation exposure over a human lifetime that is unlikely to pose significant risk of adverse noncancer health effects and serves as a benchmark value for assisting in risk management decisions. Derivation of an RfC involves dose-response assessment of animal data to determine the exposure levels at which no significant increase in the frequency or severity of adverse effects between the exposed population and its appropriate control exists. The assessment requires an interspecies dose extrapolation from a no-observed-adverse-effect level (NOAEL) exposure concentration of an animal to a human equivalent NOAEL (NOAEL(HBC)). The RfC is derived from the NOAEL(HBC) by the application of generally order-of-magnitude uncertainty factors. Intermittent exposure scenarios in animals are extrapolated to chronic continuous human exposures. Relationships between external exposures and internal doses depend upon complex simultaneous and consecutive processes of absorption, distribution, metabolism, storage, detoxification, and elimination. To estimate NOAEL(HBC)s when chemical-specific physiologically-based pharmacokinetic models are not available, a dosimetric extrapolation procedure based on anatomical and physiological parameters of the exposed human and animal and the physical parameters of the toxic chemical has been developed which gives equivalent or more conservative exposure concentrations values than those that would be obtained with a PB-PK model.

  9. Evaluation of radiation dose to anthropomorphic paediatric models from positron-emitting labelled tracers

    NASA Astrophysics Data System (ADS)

    Xie, Tianwu; Zaidi, Habib

    2014-03-01

    PET uses specific molecules labelled with positron-emitting radionuclides to provide valuable biochemical and physiological information. However, the administration of radiotracers to patients exposes them to low-dose ionizing radiation, which is a concern in the paediatric population since children are at a higher cancer risk from radiation exposure than adults. Therefore, radiation dosimety calculations for commonly used positron-emitting radiotracers in the paediatric population are highly desired. We evaluate the absorbed dose and effective dose for 19 positron-emitting labelled radiotracers in anthropomorphic paediatric models including the newborn, 1-, 5-, 10- and 15-year-old male and female. This is achieved using pre-calculated S-values of positron-emitting radionuclides of UF-NCI paediatric phantoms and published biokinetic data for various radiotracers. The influence of the type of anthropomorphic model, tissue weight factors and direct human- versus mouse-derived biokinetic data on the effective dose for paediatric phantoms was also evaluated. In the case of 18F-FDG, dosimetry calculations of reference paediatric patients from various dose regimens were also calculated. Among the considered radiotracers, 18F-FBPA and 15O-water resulted in the highest and lowest effective dose in the paediatric phantoms, respectively. The ICRP 103 updated tissue-weighting factors decrease the effective dose in most cases. Substantial differences of radiation dose were observed between direct human- versus mouse-derived biokinetic data. Moreover, the effect of using voxel- versus MIRD-type models on the calculation of the effective dose was also studied. The generated database of absorbed organ dose and effective dose for various positron-emitting labelled radiotracers using new generation computational models and the new ICRP tissue-weighting factors can be used for the assessment of radiation risks to paediatric patients in clinical practice. This work also contributes

  10. 10 CFR Appendix B to Part 20 - Annual Limits on Intake (ALIs) and Derived Air Concentrations (DACs) of Radionuclides for...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... radioactive material, which refer to their retention (approximately days, weeks or years) in the pulmonary...,” “Inhalation ALI,” and “DAC,” are applicable to occupational exposure to radioactive material. The ALIs in this... internal committed dose equivalents resulting from inhalation of radioactive materials. Derived...