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.

  2. Derivation of a melamine oral reference dose (RfD) and drinking-water total allowable concentration.

    PubMed

    Bhat, Virunya S; Ball, Gwen L; McLellan, Clifton J

    2010-01-01

    Due to its high nitrogen content, melamine has been used to adulterate food to increase apparent protein content. In 2008, thousands of Chinese infants consumed reconstituted formula derived from melamine-adulterated milk. Urinary-tract stones (comprised of melamine and uric acid) accumulated in some victims and lead to acute renal failure or death. Premature infants and children (<2 yr) have an increased susceptibility to ingested melamine. Due to incomplete reporting, the human data were inadequate to identify a no-observed-adverse-effect level (NOAEL) for melamine-induced pediatric urolithiasis. Urolithiasis, urinary bladder cystitis, and ulcerations were observed in F344 rats after subchronic or chronic ingestion of melamine at > or =72 mg/kg-d. Bladder epithelial damage was followed by epithelial hyperplasia that progressed to bladder papillomas and carcinomas in male but not female F344 rats or male or female B6C3F1 mice. Short-term assays suggest, at best, weak genotoxic activity, and kinetic data show that melamine is not metabolized. Since reliable exposure information was lacking from the clinical reports, an oral reference dose (RfD) based on urolithiasis in male rats after 13 wk of continuous melamine ingestion was calculated as a 10% benchmark dose (38 mg/kg-d). Incorporation of 10-fold interspecies and intraspecies (for the increased susceptibility of infants) uncertainty factors and a threefold database uncertainty factor (for the lack of immunological, neurological and reproduction toxicity data) yields an oral RfD of 0.13 mg/kg-d. Assuming the 70-kg adult consumes 2 L of drinking water daily, a total allowable concentration of 0.9 mg/L (900 microg/L) was calculated for melamine in drinking water.

  3. Reference doses for dental radiography.

    PubMed

    Napier, I D

    1999-04-24

    To establish reference doses for use within dental radiography. Retrospective analysis, single centre. UK General Dental Practice, 1995-1998. A statistical analysis was performed on the results from NRPB evaluations of dental x-ray equipment within general practice. The third quartile patient entrance dose was determined from 6,344 assessments of intra-oral x-ray equipment. The third quartile dose-width product was determined from 387 assessments of panoramic x-ray equipment. The third quartile patient entrance dose for an adult mandibular molar intra-oral radiograph is 3.9 mGy. The third quartile dose-width product for a standard adult panoramic radiograph is 66.7 mGy mm. NRPB recommends the adoption of reference doses of 4 mGy for an adult mandibular molar intra-oral radiograph and 65 mGy mm for a standard adult panoramic radiograph. These reference values can be used as a guide to accepted clinical practice. Where radiography is carried out using doses above these reference values, a thorough review of radiographic practice should be made to either improve techniques, or justify keeping the current techniques. However, attainment of doses at or below the reference values cannot be construed as achievement of optimum performance; further dose reductions below the reference value are still practicable.

  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. 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.

  6. 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

  7. National reference doses for dental cephalometric radiography.

    PubMed

    Holroyd, J R

    2011-12-01

    Diagnostic reference levels (DRLs) are an important tool in the optimisation of clinical radiography. Although national DRLs are provided for many diagnostic procedures including dental intra-oral radiography, there are currently no national DRLs set for cephalometric radiography. In the absence of formal national DRLs, the Health Protection Agency (HPA) has previously published National Reference Doses (NRDs) covering a wide range of diagnostic X-ray examinations. The aim of this study was to determine provisional NRDs for cephalometric radiography. Measurements made by the Dental X-ray Protection Service (DXPS) of the HPA, as part of the cephalometric X-ray equipment testing service provided to dentists and dental trade companies throughout the UK, were used to derive provisional NRDs. Dose-area product measurements were made on 42 X-ray sets. Third quartile dose-area product values for adult and child lateral cephalometric radiography were found to be 41 mGy cm² and 25 mGy cm², respectively, with individual measurements ranging from 3 mGy cm² to 108 mGy cm². This report proposes provisional NRDs of 40 mGy cm² and 25 mGy cm² for adult and child lateral cephalometric radiographs, respectively; these doses could be considered by employers when establishing their local DRLs.

  8. 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.

  9. 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.

  10. A CONCEPTUAL FRAMEWORK FOR MANAGING RADIATION DOSE TO PATIENTS IN DIAGNOSTIC RADIOLOGY USING REFERENCE DOSE LEVELS.

    PubMed

    Almén, Anja; Båth, Magnus

    2016-06-01

    The overall aim of the present work was to develop a conceptual framework for managing radiation dose in diagnostic radiology with the intention to support optimisation. An optimisation process was first derived. The framework for managing radiation dose, based on the derived optimisation process, was then outlined. The outset of the optimisation process is four stages: providing equipment, establishing methodology, performing examinations and ensuring quality. The optimisation process comprises a series of activities and actions at these stages. The current system of diagnostic reference levels is an activity in the last stage, ensuring quality. The system becomes a reactive activity only to a certain extent engaging the core activity in the radiology department, performing examinations. Three reference dose levels-possible, expected and established-were assigned to the three stages in the optimisation process, excluding ensuring quality. A reasonably achievable dose range is also derived, indicating an acceptable deviation from the established dose level. A reasonable radiation dose for a single patient is within this range. The suggested framework for managing radiation dose should be regarded as one part of the optimisation process. The optimisation process constitutes a variety of complementary activities, where managing radiation dose is only one part. This emphasises the need to take a holistic approach integrating the optimisation process in different clinical activities.

  11. Derivation of Human Lethal Doses

    DTIC Science & Technology

    2006-01-19

    extrapolate to human lethal doses. In this effort, Ekwall et al. (1998) collected data on human lethal doses in acute poisonings from handbooks on...emergency medicine, pharmacology, forensic medicine, and industrial chemical toxicology, in addition to a poison information center. The authors presented...lethal doses would be dose-response data in people. Estimates of doses from case reports of fatal poisonings provide information on what doses can be

  12. The US EPA reference dose for methylmercury: sources of uncertainty.

    PubMed

    Rice, Deborah C

    2004-07-01

    The US Environmental Protection Agency (EPA) derived a reference dose for methylmercury in 2001, based on an extensive analysis by the National Research Council (NRC) of the National Academy of Sciences. The NRC performed benchmark dose analysis on a number of endpoints from three longitudinal prospective studies: the Seychelles Islands, the Faroe Islands, and the New Zealand studies. Adverse effects were reported in the latter two studies, but not in the Seychelles study. The NRC also performed an integrative analysis of all three studies. Dose conversion from cord blood or maternal hair mercury concentration was performed by EPA using a one-compartment pharmacokinetic model. A total uncertainty factor of 10 was applied for intrahuman pharmacokinetic and pharmacodynamic variability. There are numerous decisions made by the NRC/EPA that could greatly affect the value of the reference dose (RfD). Some of these include the choice of a linear model for the relationship between mercury body burden and neuropsychological performance, the choice of values of P0 and the benchmark response, the use of the "critical study/critical endpoint" approach in the interpretation of the maternal body burden that corresponds to the RfD, the use of central tendencies in a one-compartment pharmacokinetic model rather than the inclusion of the distributions of variables for the population of reproductive-age women, the assumption of unity for the ratio of fetal cord blood to maternal blood methylmercury concentrations, the choice of a total of 10 as an uncertainty factor, and the lack of dose-response analysis for other health effects such as cardiovascular disease. In addition, it may be argued that derivation of a RfD for methylmercury is inappropriate, given that there does not appear to be a threshold for adverse neuropsychological effects based on available data.

  13. Review of the Reference Dose and Reference Concentration Processes Document

    EPA Pesticide Factsheets

    Summarizes the review and deliberations of the Risk Assessment Forum’s RfD/RfC Technical Panel and its recommendations for improvements in oral referencedose/inhalation reference concentration (RfD/RfC) process.

  14. 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.

  15. Diagnostic reference levels and effective dose in paediatric cardiac catheterization.

    PubMed

    Onnasch, D G W; Schröder, F K; Fischer, G; Kramer, H-H

    2007-03-01

    European states within the EEC are required to establish and use diagnostic reference levels (DRLs) in X-ray examinations. However, up to now there have been no DRLs for cardiac catheterization in children, nor as a rule is the effective dose estimated. We have evaluated the dose-area products (DAPs) for three different types of angiocardiography systems over a time span of 8 years. For each system DAP increased in proportion to the body weight (BW) over two orders of magnitude. The proportionality constant decreased over the years. To reduce the broad distribution of DAP the doses for cine acquisition (DAPA) and fluoroscopy (DAPF) were indexed with respect to the total numbers of acquired images (AN) and the total times of fluoroscopy (FT). DAPA/AN is directly proportional to BW with a high correlation (r = 0.896, n = 1346). Likewise, DAPF/FT is proportional to BW from 0.1 kg to 100 kg (r = 0.84, n = 2138). Therefore, by normalizing DAP to BW the growth dependent variation of DAP can be eliminated. There are numerous short examinations with very small total DAPs, which were separated from the group of diagnostic examinations. The mean DAP/BW of this group is 0.41 Gycm2 kg(-1) (90th percentile: 0.81 Gycm2 kg(-1), n = 1106). For interventional procedures in congenital heart diseases DAP/BW is significantly higher (p<0.001) (mean: 0.56 Gycm2 kg(-1), 90th percentile: 1.16 Gycm2 kg(-1), n = 883). There are significant differences between different types of interventional procedures, the mean values being between 0.35 Gycm2 kg(-1) (occlusion of patent ductus botalli, n = 165) and 1.30 Gycm2 kg(-1) (occlusion of ventricular septal defect, n = 32). For patients who are catheterized several times over the years, the cumulative effective dose (E) may reach high values, being especially high for patients with hypoplastic left heart syndrome (typically 11 mSv). E is derived from DAP/BW by use of a constant DAP/BW to E conversion factor, independent of the age of the patient

  16. Application of a physiologically based pharmacokinetic model for reference dose and reference concentration estimation for acetone.

    PubMed

    Gentry, P Robinan; Covington, Tammie R; Clewell, Harvey J; Anderson, Melvin E

    2003-12-12

    Recent health risk assessments to propose a Reference Dose (RfD) for acetone (Forsyth, 2001; U.S. EPA, 2001) have been based on the results of an oral subchronic study conducted in rats and mice (Dietz et al., 1991; NTP, 1991). These assessments have utilized the traditional concept of establishing the RfD by determining the lowest experimentally determined No-Observed-Adverse-Effect Level (NOAEL) and applying various Uncertainty Factors (UFs) (U.S. EPA, 1988). This article describes a risk assessment for acetone based on the systemic toxicity observed in subchronic and developmental toxicity studies to estimate an RfD and an inhalation reference concentration (RfC) for acetone. Specifically, this approach examined the subchronic study by Dietz et al. (1991), as well as an inhalation developmental toxicity study on acetone (Mast et al., 1988) and several toxicology studies of isopropanol (IPA). This was accomplished by applying a physiologically based pharmacokinetic (PBPK) model developed previously for IPA and its metabolite acetone (Clewell et al., 2001). The incorporation of the PBPK model into the derivation of an RfD and RfC for acetone allowed for a tissue-based approach rather than an external exposure-based approach, making it possible to derive an oral RfD from an inhalation study. In addition, the use of the PBPK model to analyze data from chronic and reproductive/developmental studies conducted with IPA enabled an assessment of the potential for acetone to produce any of the effects observed in the IPA studies. This analysis provided sufficient information to reduce the need for UFs in the adjustment of the NOAEL from the oral subchronic study for the determination of an RfD. Using the PBPK model in the acetone risk assessment supports a composite UF of 60 for the subchronic study, compared to composite factors of 300 to 3000 in the other recent risk assessments. This difference resulted in an RfD of 16 mg/kg/d, compared to the values of 0.3 to 3 that

  17. Derivation of an oral toxicity reference value for nickel.

    PubMed

    Haber, Lynne T; Bates, Hudson K; Allen, Bruce C; Vincent, Melissa J; Oller, Adriana R

    2017-06-15

    Nickel (Ni) is in the earth's crust and can be found in environmental compartments such as water, soil, and air, as well as food. This paper presents an assessment of the oral nickel toxicity data in support of non-cancer health-based oral exposure limits or toxicity reference values (TRVs). This paper derives TRVs for three populations of interest: adults, toddlers, and people who have been dermally sensitized to nickel. The adult/lifetime TRV of 20 μg Ni/kg-day is based on post-implantation loss/perinatal mortality in a 2-generation reproductive study in rats. Several recent assessments by regulatory agencies have used the same study and endpoint, but the dose-response modeling conducted here was more appropriate for the study design. Toxicokinetic data from rats and humans indicate that the applied uncertainty factors are very conservative. Because the endpoint relates to fetal exposure and is not relevant to toddlers, a toddler TRV was derived based on decreased body weight in young rats; this TRV was also 20 μg Ni/kg-day. A separate TRV of 4 μg Ni/kg in addition to Ni in food was derived for protection of nickel-sensitized populations from flare-up of dermatitis, based on studies of single exposures in humans under conditions that maximize oral absorption. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  18. Dose area product reference levels in dental panoramic radiology.

    PubMed

    Tierris, Christine E; Yakoumakis, Emmanuel N; Bramis, George N; Georgiou, Evangelos

    2004-01-01

    The purpose of this study was to measure DAP (Dose Area Product) values in panoramic radiology with the use of a DAP meter, to determine corresponding reference levels, and to compare DAP between panoramic and intraoral radiology. DAP was measured in 62 panoramic X-ray units for 3 types of exposure (male, female and child) and in 20 intraoral X-ray units of 50, 60 and 70 kVp. DAP reference levels were 117 mGy cm2, 97 mGy cm2 and 77 mGy cm2 for exposure of a male, female and child respectively. Results showed that DAP from a panoramic dental examination is approximately twice that from a single intraoral examination. DAP meter is a very convenient and easy to use tool for patient dosimetry and for the establishment of reference levels in dental panoramic radiology.

  19. Health assessment of phosgene: approaches for derivation of reference concentration.

    PubMed

    Gift, Jeffrey S; McGaughy, Robert; Singh, Dharm V; Sonawane, Babasaheb

    2008-06-01

    This paper describes the derivation of the chronic reference concentration (RfC) for human inhalation of phosgene that was recently added to the Environmental Protection Agency's (EPA) Integrated Risk Information System (IRIS) data base (U.S. EPA, 2005. Toxicological Review of Phosgene: In Support of Summary Information on the Integrated Risk Information System (IRIS). Available online at: ). The RfC is an estimate of daily phosgene exposure to the human population that is likely to be without appreciable risk of deleterious effects during a lifetime. [For this and other definitions relevant to EPA risk assessments refer to the glossary of terms in the US EPA IRIS website (http://www.epa.gov/IRIS).] Phosgene is a potential environmental pollutant that is primarily used as a catalyst in the polyurethane industry. It is a gas at room temperature, and in aqueous solution it rapidly hydrolyzes to CO2 and HCl. In the absence of chronic human health effects information and lifetime animal cancer bioassays, the RfC is based on two 12-week inhalation studies in F344 rats which measured immune response and pulmonary effects, respectively. The immune response study showed impaired clearance of bacteria that was administered into the lungs of rats immediately after exposure to phosgene at concentrations of 0.1, 0.2 and 0.5 ppm. It also showed that the immune response in uninfected rats was stimulated by phosgene exposure at all concentrations. The pulmonary effects study showed a progressive concentration-related thickening and inflammation in the bronchiolar regions of the lung that was mild at 0.1 ppm and severe at 1.0 ppm. An increase in collagen content, as observed with histological collagen stains, was observed at 0.2 ppm and above. Though there is considerable uncertainty associated with the species and exposure duration employed, this endpoint is considered an indication of chronic lung injury of potential relevance to humans. Three different

  20. 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.

  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. 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

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

    DOE PAGES

    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

  4. 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.

  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. Comparison of dose at an interventional reference point between the displayed estimated value and measured value.

    PubMed

    Chida, Koichi; Inaba, Yohei; Morishima, Yoshiaki; Taura, Masaaki; Ebata, Ayako; Yanagawa, Isao; Takeda, Ken; Zuguchi, Masayuki

    2011-07-01

    Today, interventional radiology (IR) X-ray units are required for display of doses at an interventional reference point (IRP) for the operator (IR physician). The dose displayed at the IRP (the reference dose) of an X-ray unit has been reported to be helpful for characterizing patient exposure in real time. However, no detailed report has evaluated the accuracy of the reference doses displayed on X-ray equipment. Thus, in this study, we compared the displayed reference dose to the actual measured value in many IR X-ray systems. Although the displayed reference doses of many IR X-ray systems agreed with the measured actual values within approximately 15%, the doses of a few IR units were not close. Furthermore, some X-ray units made in Japan displayed reference doses quite different from the actual measured value, probably because the reference point of these units differs from the International Electrotechnical Commission standard. Thus, IR physicians should pay attention to the location of the IRP of the displayed reference dose in Japan. Furthermore, physicians should be aware of the accuracy of the displayed reference dose of the X-ray system that they use for IR. Thus, regular checks of the displayed reference dose of the X-ray system are important.

  7. Radiation Dose Deposition in the Active Marrow of Reference Man.

    DTIC Science & Technology

    1977-10-31

    gamma ray-fission neutron exposure , the relative biological effec- tiveness (RBE) per unit marrow dose between neutrons and gamma rays in producing...calculations in terms of marrow dose (rad (marrow)) per unit incident fluence. The third presents in- tegral marrow doses calculated for exposure to...in the marrow than other devices. This is shown by the fact that the neutron dose deposited by a given total exposure from such a de- vice is as much

  8. 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

  9. Site-specific reference person parameters and derived concentration standards for the Savannah River Site.

    PubMed

    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 reference intake for air, water, meat, dairy, freshwater fish, saltwater invertebrates, produce (fruits and vegetables), and grains for the 95th percentile are 17.4 m d, 2.19 L d, 220.6 g d, 674 cm d, 66.4 g d, 23.0 g d, 633.4 g d (448.5 g dand 631.7 g d) and 251.3 g d, respectively. For the 50th percentile: 13.4 m d, 0.809 L d, 86.4 g d, 187 cm d, 8.97 g d, 3.04 g d, 169.5 g d (45.9 g d and 145.6 g d), 101.3 g d, respectively. These 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.

  10. 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.

  11. Dose coefficients for ICRP reference pediatric phantoms exposed to idealised external gamma fields.

    PubMed

    Chang, Lienard A; Simon, Steven L; Jorgensen, Timothy J; Schauer, David A; Lee, Choonsik

    2017-03-20

    Organ and effective dose coefficients have been calculated for the International Commission on Radiological Protection (ICRP) reference pediatric phantoms externally exposed to mono-energetic photon radiation (x- and gamma-rays) from 0.01 to 20 MeV. Calculations used Monte Carlo radiation transport techniques. Organ dose coefficients, i.e., organ absorbed dose per unit air kerma (Gy/Gy), were calculated for 28 organs and tissues including the active marrow (or red bone marrow) for 10 phantoms (newborn, 1 year, 5 year, 10 year, and 15 year old male and female). Radiation exposure was simulated for 33 photon mono-energies (0.01-20 MeV) in six irradiation geometries: antero-posterior (AP), postero-anterior, right lateral, left lateral, rotational, and isotropic. Organ dose coefficients for different ages closely agree in AP geometry as illustrated by a small coefficient of variation (COV) (the ratio of the standard deviation to the mean) of 4.4% for the lungs. The small COVs shown for the effective dose and AP irradiation geometry reflect that most of the radiosensitive organs are located in the front part of the human body. In contrast, we observed differences in organ dose coefficients across the ages of the phantoms for lateral irradiation geometries. We also observed variation in dose coefficients across different irradiation geometries, where the COV ranges from 18% (newborn male) to 38% (15 year old male) across idealised whole body irradiation geometries for the major organs (active marrow, colon, lung, stomach wall, and breast) at the energy of 0.1 MeV. Effective dose coefficients were also derived for applicable situations, e.g., radiation protection or risk projection. Our results are the first comprehensive set of organ and effective dose coefficients applicable to children and adolescents based on the newly adopted ICRP pediatric phantom series. Our tabulated organ and effective dose coefficients for these next-generation phantoms should provide more

  12. Deriving a unique reference frame for GPS measurements

    NASA Technical Reports Server (NTRS)

    Malla, Rajendra P.; Wu, Sien-Chong

    1988-01-01

    Two strategies for deriving a unique reference frame for GPS (Global Positioning System) measurements are discussed. The first strategy utilizes the precise relative positions which have been predetermined by VLBI (very long baseline interferometry) 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 second strategy establishes a reference frame by holding only the longitudinal 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's rotation in the GPS measurements. The coordinate system thus defined will be a geocentric earth fixed coordinate system. A covariance analysis shows that geometric positioning to an accuracy of a few centimeters can be achieved with just one day of precise GPS pseudorange and carrier phase data.

  13. 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. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Furthering the derivation of predictive wildlife toxicity reference values for use in soil cleanup decisions.

    PubMed

    Mayfield, David B; Johnson, Mark S; Burris, Janet A; Fairbrother, Anne

    2014-07-01

    The development of media-specific ecological values for risk assessment includes the derivation of acceptable levels of exposure for terrestrial wildlife (e.g., birds, mammals, reptiles, and amphibians). Although the derivation and subsequent application of these values can be used for screening purposes, there is a need to identify toxicological effects thresholds specifically for making remedial decisions at individual contaminated sites. A workshop was held in the fall of 2012 to evaluate existing methods and recent scientific developments for refining ecological soil screening levels (Eco-SSLs) and improving the derivation of site-specific ecological soil clean-up values for metals (Eco-SCVs). This included a focused session on the development and derivation of toxicity reference values (TRVs) for terrestrial wildlife. Topics that were examined included: methods for toxicological endpoint selection, techniques for dose-response assessment, approaches for cross-species extrapolation, and tools to incorporate environmental factors (e.g., metal bioavailability and chemistry) into a reference value. The workgroup also made recommendations to risk assessors and regulators on how to incorporate site-specific wildlife life history and toxicity information into the derivation of TRVs to be used in the further development of soil cleanup levels. © 2013 SETAC.

  16. Reference dose levels for patients undergoing common diagnostic X-ray examinations in Irish hospitals.

    PubMed

    Johnston, D A; Brennan, P C

    2000-04-01

    Wide variations in patient dose for the same type of X-ray examination have been evident from various international dose surveys. Reference dose levels provide a framework to reduce this variability and aid in the optimization of radiation protection. The aim of this study was to establish, for the first time, a baseline for national reference dose levels in Ireland for four of the most common X-ray examinations: chest, abdomen, pelvis and lumbar spine. Measurements of entrance surface dose using thermoluminescent dosemeters (TLDs) for these four X-ray examinations were performed on 10 patients in each of 16 randomly selected hospitals. This represented 42% of Irish hospitals applicable to this study. Results have shown wide variation of mean hospital doses, from a factor of 3 for an anteroposterior lumbar spine to a factor of 23 for the chest X-ray. The difference between maximum and minimum individual patient dose values varied up to a factor of 75. Reasons for these dose variations were complex but, in general, low tube potential, high mAs and low filtration were associated with high-dose hospitals. This study also demonstrated lower reference dose levels of up to 40% when compared with those established by the UK and the Commission of the European Communities for four out of six projections. Only the chest X-ray exhibited a similar reference level to those established elsewhere. This emphasizes the importance of each country establishing its own reference dose levels that are appropriate to their own radiographic techniques and practices in order to optimize patient protection.

  17. Definition of Local Diagnostic Reference Levels in a Radiology Department Using a Dose Tracking Software.

    PubMed

    Ghetti, C; Ortenzia, O; Palleri, F; Sireus, M

    2016-09-10

    Dose optimization in radiological examinations is a mandatory issue: in this study local Diagnostic Reference Levels (lDRLs) for Clinical Mammography (MG), Computed Tomography (CT) and Interventional Cardiac Procedures (ICP) performed in our Radiology Department were established. Using a dose tracking software, we have collected Average Glandular Dose (AGD) for two clinical mammographic units; CTDIvol, Size-Specific Dose Estimate (SSDE), Dose Length Product (DLP) and total DLP (DLPtot) for five CT scanners; Fluoro Time, Fluoro Dose Area Product (DAP) and total DAP (DAPtot) for two angiographic systems. Data have been compared with Italian Regulation and with the recent literature. The 75th percentiles of the different dosimetric indices have been calculated. Automated methods of radiation dose data collection allow a fast and detailed analysis of a great amount of data and an easy determination of lDRLs for different radiological procedures.

  18. 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

  19. A new reference point for patient dose estimation in neurovascular interventional radiology.

    PubMed

    Kawasaki, Kohei; Imazeki, Masaharu; Hasegawa, Ryota; Shiba, Shinichi; Takahashi, Hiroyuki; Sato, Kazuhiko; Ota, Jyoji; Suzuki, Hiroaki; Awai, Kazuo; Sakamoto, Hajime; Tajima, Osamu; Tsukamoto, Atsuko; Kikuchi, Tatsuya; Kageyama, Takahiro; Kato, Kyoichi

    2013-07-01

    In interventional radiology, dose estimation using the interventional reference point (IRP) is a practical method for obtaining the real-time skin dose of a patient. However, the IRP is defined in terms of adult cardiovascular radiology and is not suitable for dosimetry of the head. In the present study, we defined a new reference point (neuro-IRP) for neuro-interventional procedures. The neuro-IRP was located on the central ray of the X-ray beam, 9 cm from the isocenter, toward the focal spot. To verify whether the neuro-IRP was accurate in dose estimation, we compared calculated doses at the neuro-IRP and actual measured doses at the surface of the head phantom for various directions of the X-ray projection. The resulting calculated doses were fairly consistent with actual measured doses, with the error in this estimation within approximately 15%. These data suggest that dose estimation using the neuro-IRP for the head is valid.

  20. Reference dosimetry of proton pencil beams based on dose-area product: a proof of concept.

    PubMed

    Gomà, Carles; Safai, Sairos; Vörös, Sándor

    2017-06-21

    This paper describes a novel approach to the reference dosimetry of proton pencil beams based on dose-area product ([Formula: see text]). It depicts the calibration of a large-diameter plane-parallel ionization chamber in terms of dose-area product in a (60)Co beam, the Monte Carlo calculation of beam quality correction factors-in terms of dose-area product-in proton beams, the Monte Carlo calculation of nuclear halo correction factors, and the experimental determination of [Formula: see text] of a single proton pencil beam. This new approach to reference dosimetry proves to be feasible, as it yields [Formula: see text] values in agreement with the standard and well-established approach of determining the absorbed dose to water at the centre of a broad homogeneous field generated by the superposition of regularly-spaced proton pencil beams.

  1. Reference dosimetry of proton pencil beams based on dose-area product: a proof of concept

    NASA Astrophysics Data System (ADS)

    Gomà, Carles; Safai, Sairos; Vörös, Sándor

    2017-06-01

    This paper describes a novel approach to the reference dosimetry of proton pencil beams based on dose-area product (DAPw ). It depicts the calibration of a large-diameter plane-parallel ionization chamber in terms of dose-area product in a 60Co beam, the Monte Carlo calculation of beam quality correction factors—in terms of dose-area product—in proton beams, the Monte Carlo calculation of nuclear halo correction factors, and the experimental determination of DAPw of a single proton pencil beam. This new approach to reference dosimetry proves to be feasible, as it yields DAPw values in agreement with the standard and well-established approach of determining the absorbed dose to water at the centre of a broad homogeneous field generated by the superposition of regularly-spaced proton pencil beams.

  2. Evaluation of organ doses in brachytherapy treatment of uterus cancer using mathematical reference Indian adult phantom.

    PubMed

    Biju, K

    2012-01-01

    Quantifying organ dose to healthy organs during radiotherapy is essential to estimate the radiation risk. Dose factors are generated by simulating radiation transport through an anthropomorphic mathematical phantom representing a reference Indian adult using the Monte Carlo method. The mean organ dose factors (in mGy min(-1) GBq(-1)) are obtained considering the microselectron (192)Ir source and BEBIG (60)Co sources in the uterus of a reference Indian adult female phantom. The present study provides the factors for mean absorbed dose to organs applicable to the Indian female patient population undergoing brachytherapy treatment of uterus cancer. This study also includes a comparison of the dimension of organs in the phantom model with measured values of organs in the various investigated patients.

  3. Basis of the Massachusetts reference dose and drinking water standard for perchlorate.

    PubMed

    Zewdie, Tsedash; Smith, C Mark; Hutcheson, Michael; West, Carol Rowan

    2010-01-01

    Perchlorate inhibits the uptake of iodide in the thyroid. Iodide is required to synthesize hormones critical to fetal and neonatal development. Many water supplies and foods are contaminated with perchlorate. Exposure standards are needed but controversial. Here we summarize the basis of the Massachusetts (MA) perchlorate reference dose (RfD) and drinking water standard (DWS), which are considerably lower and more health protective than related values derived by several other agencies. We also review information regarding perchlorate risk assessment and policy. MA Department of Environmental Protection (DEP) scientists, with input from a science advisory committee, assessed a wide range of perchlorate risk and exposure information. Health outcomes associated with iodine insufficiency were considered, as were data on perchlorate in drinking water disinfectants. We used a weight-of-the-evidence approach to evaluate perchlorate risks, paying particular attention to sensitive life stages. A health protective RfD (0.07 microg/kg/day) was derived using an uncertainty factor approach with perchlorate-induced iodide uptake inhibition as the point of departure. The MA DWS (2 microg/L) was based on risk management decisions weighing information on perchlorate health risks and its presence in certain disinfectant solutions used to treat drinking water for pathogens. Current data indicate that perchlorate exposures attributable to drinking water in individuals at sensitive life stages should be minimized and support the MA DEP perchlorate RfD and DWS. Widespread exposure to perchlorate and other thyroid toxicants in drinking water and foods suggests that more comprehensive policies to reduce overall exposures and enhance iodine nutrition are needed.

  4. Basis of the Massachusetts Reference Dose and Drinking Water Standard for Perchlorate

    PubMed Central

    Zewdie, Tsedash; Smith, C. Mark; Hutcheson, Michael; West, Carol Rowan

    2010-01-01

    Objective Perchlorate inhibits the uptake of iodide in the thyroid. Iodide is required to synthesize hormones critical to fetal and neonatal development. Many water supplies and foods are contaminated with perchlorate. Exposure standards are needed but controversial. Here we summarize the basis of the Massachusetts (MA) perchlorate reference dose (RfD) and drinking water standard (DWS), which are considerably lower and more health protective than related values derived by several other agencies. We also review information regarding perchlorate risk assessment and policy. Data sources MA Department of Environmental Protection (DEP) scientists, with input from a science advisory committee, assessed a wide range of perchlorate risk and exposure information. Health outcomes associated with iodine insufficiency were considered, as were data on perchlorate in drinking water disinfectants. Data synthesis We used a weight-of-the-evidence approach to evaluate perchlorate risks, paying particular attention to sensitive life stages. A health protective RfD (0.07 μg/kg/day) was derived using an uncertainty factor approach with perchlorate-induced iodide uptake inhibition as the point of departure. The MA DWS (2 μg/L) was based on risk management decisions weighing information on perchlorate health risks and its presence in certain disinfectant solutions used to treat drinking water for pathogens. Conclusions Current data indicate that perchlorate exposures attributable to drinking water in individuals at sensitive life stages should be minimized and support the MA DEP perchlorate RfD and DWS. Widespread exposure to perchlorate and other thyroid toxicants in drinking water and foods suggests that more comprehensive policies to reduce overall exposures and enhance iodine nutrition are needed. PMID:20056583

  5. Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

    EPA Science Inventory

    This document is the final report from 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...

  6. Proposed Oral Reference Dose (RfD) for Barium and Compounds (Final Report, 2004)

    EPA Science Inventory

    This document is the final report from 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...

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry

    EPA Pesticide Factsheets

    EPA's methodology for estimation of inhalation reference concentrations (RfCs) as benchmark estimates of the quantitative dose-response assessment of chronic noncancer toxicity for individual inhaled chemicals.

  13. Identifying Institutional Diagnostic Reference Levels for CT with Radiation Dose Index Monitoring Software.

    PubMed

    MacGregor, Kate; Li, Iris; Dowdell, Timothy; Gray, Bruce G

    2015-08-01

    To retrospectively evaluate radiation optimization efforts over 4 years for three computed tomography (CT) protocols and to determine institutional (local) diagnostic reference levels for prospective tracking by using automated radiation dose index monitoring software. Approval for this retrospective observational study was obtained from the hospital research ethics board, and the need to obtain informed consent was waived. The study followed a 48-month radiation dose optimization effort in a large academic inner-city trauma and quaternary referral center. Exposure according to equipment, protocol, and year (2010-2013) for adult patients was determined for routine unenhanced head CT examinations, CT pulmonary angiography examinations, and CT examinations for renal colic. Mean exposure (as volume CT dose index [CTDIvol] and dose-length product [DLP]) was averaged to establish local diagnostic reference levels. Means and 75th percentiles for 2013 were compared with findings from surveys in Canada and diagnostic reference levels for similar protocol types internationally. Student t tests were performed to assess significance between annual means, and χ(2) tests were performed for changes in categoric variables. There were 36 996 examinations in 25 234 patients. There was an average exposure reduction of 22% for CTDIvol and 13% for DLP from 2010 to 2013. In 2013, mean CTDIvol for routine head examinations was 50.8 mGy ± 3.7 (standard deviation), 11.8 mGy ± 5.6 for CT pulmonary angiography examinations, and 10.2 mGy ± 4.2 for renal colic CT examinations, while mean DLP was 805.7 mGy · cm ± 124.3, 432.8 mGy-cm ± 219.9, and 469.4 mGy · cm ± 209.2, respectively. The mean CTDIvol and DLP in 2013 were at or close to identified reference values; however, additional optimization is required to reach "as low as reasonably achievable" values for all examinations. Automated methods of radiation dose data collection permit a detailed analysis of radiation dose according

  14. Allergen reference doses for precautionary labeling (VITAL 2.0): clinical implications.

    PubMed

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

    2014-01-01

    There has been a dramatic proliferation of precautionary labeling by manufacturers to mitigate the perceived risk from low-level contamination from allergens in food. This has resulted in a significant reduction in choice of potentially safe foods for allergic consumers. We aimed to establish reference doses for 11 commonly allergenic foods to guide a rational approach by manufacturers based on all publically available valid oral food challenge data. Reference doses were developed from statistical dose-distribution modeling of individual thresholds of patients in a dataset of more than 55 studies of clinical oral food challenges. Sufficient valid data were available for peanut, milk, egg, and hazelnut to allow assessment of the representativeness of the data used. The data were not significantly affected by the heterogeneity of the study methodology, including little effect of age on results for those foods for which sufficient numbers of adult challenge data were available (peanut and hazelnut). Thus by combining data from all studies, the eliciting dose for an allergic reaction in 1% of the population estimated for the following were 0.2 mg of protein for peanut, 0.1 mg for cow's milk, 0.03 mg for egg, and 0.1 mg for hazelnut. These reference doses will form the basis of the revised Voluntary Incidental Trace Allergen Labeling (VITAL) 2.0 thresholds now recommended in Australia. These new levels will enable manufacturers to apply credible precautionary labeling and provide increased consumer confidence in their validity and reliability, as well as improving consumer safety. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. 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.

  16. Provisional Reference Dose for the Aromatic Fraction of Jet Fuel: Insight into Complex Mixtures

    DTIC Science & Technology

    2005-04-01

    Petroleum Hydrocarbon Criteria Working Group UF uncertainty factor UV ultraviolet light wt% weight percent vi PROVISIONAL REFERENCE DOSE FOR THE AROMATIC...week) included. RBC = red blood cell. UF = total uncertainty factor , including modifying factors when applied. aU.S. EPA (2004). bThis unpublished...approach applied uncertainty factors to NOAELs or LOAELs from the critical 11 studies. The TPHCWG primarily accepted default values of 10 for

  17. Patient doses in paediatric CT: feasibility of setting diagnostic reference levels.

    PubMed

    Järvinen, H; Merimaa, K; Seuri, R; Tyrväinen, E; Perhomaa, M; Savikurki-Heikkilä, P; Svedström, E; Ziliukas, J; Lintrop, M

    2011-09-01

    Despite the fact that doses to paediatric patients from computed tomography (CT) examinations are of special concern, only few data or studies for setting of paediatric diagnostic reference levels (DRLs) have been published. In this study, doses to children were estimated from chest and head CT, in order to study the feasibility of DRLs for these examinations. It is shown that for the DRLs, patient dose data from different CT scanners should be collected in age or weight groups, possibly for different indications. For practical reasons, the DRLs for paediatric chest CT should be given as a continuous DRL curve as a function of patient weight. For paediatric head CT, DRLs for a few age groups could be given. The users of the DRLs should be aware of the calibration phantom applied in the console calibration for different paediatric scanning protocols. The feasibility of DRLs should be re-evaluated every 2-3 y.

  18. 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.

  19. Mean glandular dose in six digital mammography services in Santiago, Chile: preliminary reference levels.

    PubMed

    Leyton, Fernando; Nogueira, Maria Do Socorro; Dantas, Marcelino; Duran, Maria Paz; Ubeda, Carlos

    2015-07-01

    The purpose of this paper was to estimate mean glandular dose levels (DG) in six digital mammography systems in Santiago, Chile, and to propose preliminary reference levels to execute mammography in Chile. The study was carried out assessing two direct digital systems and four computer-based radiography (CR) systems. Estimates of DG were calculated for different thicknesses of polymethyl methacrylate according to the quality control protocol in digital mammography of the Spanish Society of Medical Physics and NHSBSP Equipment Report 0604 Version 3. DG values ranged between 0.64 and 7.26 mGy for a range of 20- to 70-mm thickness, respectively. Thirty-six per cent of DG was higher than the acceptable dose level and 100 % of DG was higher than the desirable level. It is therefore necessary to optimise doses. The initial proposal to establish dose reference levels for DG would range between 0.90 and 6.40 mGy for a thickness range of 20 to 70 mm.

  20. Evaluation of organ doses and effective dose according to the ICRP Publication 110 reference male/female phantom and the modified ImPACT CT patient dosimetry.

    PubMed

    Kobayashi, Masanao; Asada, Yasuki; Matsubara, Kosuke; Matsunaga, Yuta; Kawaguchi, Ai; Katada, Kazuhiro; Toyama, Hiroshi; Koshida, Kichiro; Suzuki, Shouichi

    2014-09-07

    We modified the Imaging Performance Assessment of CT scanners (ImPACT) to evaluate the organ doses and the effective dose based on the International Commission on Radiological Protection (ICRP) Publication 110 reference male/female phantom with the Aquilion ONE ViSION Edition scanner. To select the new CT scanner, the measurement results of the CTDI100,c and CTDI100,p for the 160 (head) and the 320 (body) mm polymethylmethacrylate phantoms, respectively, were entered on the Excel worksheet. To compute the organ doses and effective dose of the ICRP reference male/female phantom, the conversion factors obtained by comparison between the organ doses of different types of phantom were applied. The organ doses and the effective dose were almost identical for the ICRP reference male/female and modified ImPACT. The results of this study showed that, with the dose assessment of the ImPACT, the difference in sex influences only testes and ovaries. Because the MIRD-5 phantom represents a partially hermaphrodite adult, the phantom has the dimensions of the male reference man including testes, ovaries, and uterus but no female breasts, whereas the ICRP male/female phantom includes whole-body male and female anatomies based on high-resolution anatomical datasets. The conversion factors can be used to estimate the doses of a male and a female accurately, and efficient dose assessment can be performed with the modified ImPACT.

  1. 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.

  2. Determination of a site-specific reference dose for methylmercury for fish-eating populations.

    PubMed

    Shipp, A M; Gentry, P R; Lawrence, G; Van Landingham, C; Covington, T; Clewell, H J; Gribben, K; Crump, K

    2000-11-01

    Environmental risk-management decisions in the U.S. involving potential exposures to methylmercury currently use a reference dose (RfD) developed by the U.S. Environmental Protection Agency (USEPA). This RfD is based on retrospective studies of an acute poisoning incident in Iraq in which grain contaminated with a methylmercury fungicide was inadvertently used in the baking of bread. The exposures, which were relatively high but lasted only a few months, were associated with neurological effects in both adults (primarily paresthesia) and infants (late walking, late talking, etc.). It is generally believed that the developing fetus represents a particularly sensitive subpopulation for the neurological effects of methylmercury. The USEPA derived an RfD of 0.1 microg/kg/day based on benchmark dose (BMD) modeling of the combined neurological endpoints reported for children exposed in utero. This RfD included an uncertainty factor of 10 to consider human pharmacokinetic variability and database limitations (lack of data on multigeneration effects or possible long-term sequelae of perinatal exposure). Alcoa signed an Administrative Order of Consent for the conduct of a remedial investigation/feasibility study (RI/FS) at their Point Comfort Operations and the adjacent Lavaca Bay in Texas to address the effects of historical discharges of mercury-containing wastewater. In cooperation with the Texas Natural Resource Conservation Commission and USEPA Region VI, Alcoa conducted a baseline risk assessment to assess potential risk to human health and the environment. As a part of this assessment. Alcoa pursued the development of a site-specific RfD for methylmercury to specifically address the potential human health effects associated with the ingestion of contaminated finfish and shellfish from Lavaca Bay. Application of the published USEPA RfD to this site is problematic; while the study underlying the RfD represented acute exposure to relatively high concentrations of

  3. Local-Reference Patient Dose Evaluation in Conventional Radiography Examinations in Mazandaran, Iran

    PubMed Central

    Khoshdel-Navi, D.; Shabestani-Monfared, A.; Deevband, M. R.; Abdi, R.; Nabahati, M.

    2016-01-01

    Background The most efficient application of ionizing radiation is serving medical purposes and using this radiation has caused people to learn that artificial sources of radiation exposure among these resources can be of highest exposure rate. Obiective The present study is aimed at initially establishing a baseline for local-reference dose level in Mazandaran, Iran in 12 projections of the most conventional x-ray examination. Methods In this study, 13 public hospitals in Mazandaran province were selected for review and required data collected for ten adult patients with mean weight of 70±10kg in each projection. Then, information of each center was separately analyzed. Next, in order to measure x-ray output tube, the dosimeter RTI model Barracuda calibrated has been applied for measuring air karma within energy rage of 40-150kvp. ESAK and ESD parameters, usually used for monitoring DRL in conventional radiography, were calculated. Results Mean ESDs in this study has been obtained to 1.47±0.98 for skull (PA/AP), 1.01±0.79 for skull (LAT), 0.67±0.38 for cervical spine (AP), 0.79±0.37 for cervical (LAT), 0.49±0.38 for chest (PA/AP), 1.06±0.44 for chest (LAT), 2.15±0.73 for thoracic spine (AP), 3±0.87 for thoracic spine (LAT), 2.81 ±0.82 for lumbar spine (AP), 4.28±0.78 for lumbar (LAT), 2.07±1.17 for abdomen and 1.90±0.99 for pelvis, respectively. The ESDs calculated for chest examination in both projections, PA and LAT are more than values recommended by the UK (2000), Brazil and Slovenia. Conclusion The present study has determined wide variations in radiation dose of x-ray examinations among hospitals in Mazandaran, Iran. In order to reduce skin dose, an optimization procedure should be considered. Application of a reference dose (DRL) could be a practical method for this purpose. The role of optimization of radiography parameters for reducing patient dose is a significant issue. Through optimizing parameters, it would be possible to preserve image

  4. U.S. Diagnostic Reference Levels and Achievable Doses for 10 Adult CT Examinations.

    PubMed

    Kanal, Kalpana M; Butler, Priscilla F; Sengupta, Debapriya; Bhargavan-Chatfield, Mythreyi; Coombs, Laura P; Morin, Richard L

    2017-02-21

    Purpose To develop diagnostic reference levels (DRLs) and achievable doses (ADs) for the 10 most common adult computed tomographic (CT) examinations in the United States as a function of patient size by using the CT Dose Index Registry. Materials and Methods Data from the 10 most commonly performed adult CT head, neck, and body examinations from 583 facilities were analyzed. For head examinations, the lateral thickness was used as an indicator of patient size; for neck and body examinations, water-equivalent diameter was used. Data from 1 310 727 examinations (analyzed by using SAS 9.3) provided median values, as well as means and 25th and 75th (DRL) percentiles for volume CT dose index (CTDIvol), dose-length product (DLP), and size-specific dose estimate (SSDE). Applicable results were compared with DRLs from eight countries. Results More than 46% of the facilities were community hospitals; 13% were academic facilities. More than 48% were in metropolitan areas, 39% were suburban, and 13% were rural. More than 50% of the facilities performed fewer than 500 examinations per month. The abdomen and pelvis was the most frequently performed examination in the study (45%). For body examinations, DRLs (75th percentile) and ADs (median) for CTDIvol, SSDE, and DLP increased consistently with the patient's size (water-equivalent diameter). The relationships between patient size and DRLs and ADs were not as strong for head and neck examinations. These results agree well with the data from other countries. Conclusion DRLs and ADs as a function of patient size were developed for the 10 most common adult CT examinations performed in the United States. (©) RSNA, 2017.

  5. A global multicenter study on reference values: 1. Assessment of methods for derivation and comparison of reference intervals.

    PubMed

    Ichihara, Kiyoshi; Ozarda, Yesim; Barth, Julian H; Klee, George; Qiu, Ling; Erasmus, Rajiv; Borai, Anwar; Evgina, Svetlana; Ashavaid, Tester; Khan, Dilshad; Schreier, Laura; Rolle, Reynan; Shimizu, Yoshihisa; Kimura, Shogo; Kawano, Reo; Armbruster, David; Mori, Kazuo; Yadav, Binod K

    2017-04-01

    The IFCC Committee on Reference Intervals and Decision Limits coordinated a global multicenter study on reference values (RVs) to explore rational and harmonizable procedures for derivation of reference intervals (RIs) and investigate the feasibility of sharing RIs through evaluation of sources of variation of RVs on a global scale. For the common protocol, rather lenient criteria for reference individuals were adopted to facilitate harmonized recruitment with planned use of the latent abnormal values exclusion (LAVE) method. As of July 2015, 12 countries had completed their study with total recruitment of 13,386 healthy adults. 25 analytes were measured chemically and 25 immunologically. A serum panel with assigned values was measured by all laboratories. RIs were derived by parametric and nonparametric methods. The effect of LAVE methods is prominent in analytes which reflect nutritional status, inflammation and muscular exertion, indicating that inappropriate results are frequent in any country. The validity of the parametric method was confirmed by the presence of analyte-specific distribution patterns and successful Gaussian transformation using the modified Box-Cox formula in all countries. After successful alignment of RVs based on the panel test results, nearly half the analytes showed variable degrees of between-country differences. This finding, however, requires confirmation after adjusting for BMI and other sources of variation. The results are reported in the second part of this paper. The collaborative study enabled us to evaluate rational methods for deriving RIs and comparing the RVs based on real-world datasets obtained in a harmonized manner. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  6. 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.

  7. Derivation of inhalation toxicity reference values for propylene oxide using mode of action analysis: example of a threshold carcinogen.

    PubMed

    Sweeney, Lisa M; Kirman, Christopher R; Albertini, Richard J; Tan, Yu-Mei; Clewell, Harvey J; Filser, Johannes G; Csanády, György; Pottenger, Lynn H; Banton, Marcy I; Graham, Cynthia J; Andrews, Larry S; Papciak, Raymond J; Gargas, Michael L

    2009-01-01

    Propylene oxide (PO) is an important industrial chemical used primarily in the synthesis of other compounds. Inhalation carcinogenesis studies in rodents, with no-observed-adverse-effect levels (NOAELs) of 100 and 200 ppm, have revealed that chronic, high exposure to PO can induce tumors at the site of contact. Despite these characteristics, there is no evidence that typical environmental or occupational exposures to PO constitute a health risk for humans. The nongenotoxic effects of PO (glutathione depletion and cell proliferation) that augment its DNA-reactive and non-DNA-reactive genotoxicity are expected to be similar in humans and rodents. Available evidence on mode-of-action suggests that cancer induction by PO at the site of contact in rodents is characterized by a practical threshold. Human toxicity reference values for potential carcinogenic effects of PO were derived based on nasal tumors identified in rodent studies and specified uncertainty factors. The 95% lower confidence limit on the dose producing a 10% increase in additional tumor risk (LED10) was calculated using the rat and mouse data sets. The human reference values derived from the rat and mouse LED10 values were 0.7 and 0.5 ppm PO, respectively. A similar noncancer reference value, 0.4 ppm, was derived on the basis of non-neoplastic nasal effects in rats.

  8. 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.

  9. Stimulating effect of adaptogens: an overview with particular reference to their efficacy following single dose administration.

    PubMed

    Panossian, A; Wagner, H

    2005-10-01

    Plant adaptogens are compounds that increase the ability of an organism to adapt to environmental factors and to avoid damage from such factors. The beneficial effects of multi-dose administration of adaptogens are mainly associated with the hypothalamic-pituitary-adrenal (HPA) axis, a part of the stress-system that is believed to play a primary role in the reactions of the body to repeated stress and adaptation. In contrast, the single dose application of adaptogens is important in situations that require a rapid response to tension or to a stressful situation. In this case, the effects of the adaptogens are associated with another part of the stress-system, namely, the sympatho-adrenal-system (SAS), that provides a rapid response mechanism mainly to control the acute reaction of the organism to a stressor. This review focuses primarily on the SAS-mediated stimulating effects of single doses of adaptogens derived from Rhodiola rosea, Schizandra chinensis and Eleutherococcus senticosus. The use of these drugs typically generates no side effects, unlike traditional stimulants that possess addiction, tolerance and abuse potential, produce a negative effect on sleep structure, and cause rebound hypersomnolence or 'come down' effects. Furthermore, single administration of these adaptogens effectively increases mental performance and physical working capacity in humans. R. rosea is the most active of the three plant adaptogens producing, within 30 min of administration, a stimulating effect that continues for at least 4-6 h. The active principles of the three plants that exhibit single dose stimulating effects are glycosides of phenylpropane- and phenylethane-based phenolic compounds such as salidroside, rosavin, syringin and triandrin, the latter being the most active. Copyright (c) 2005 John Wiley & Sons, Ltd.

  10. [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.

  11. 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.

  12. Normalized organ doses and effective doses to a reference Indian adult male in conventional medical diagnostic x-ray examinations.

    PubMed

    Biju, K; Nagarajan, P S

    2006-03-01

    This work discusses the dose computations of 80 kV diagnostic x-rays made on a mathematical phantom representing an average Indian adult, since it is felt that results based on MIRD adult phantom calculations are not strictly appropriate for the population in India. Normalized organ equivalent doses and effective doses for an Indian adult male have been estimated. Normalization is done with respect to the entrance skin dose of the patient. Twenty common diagnostic x-ray examinations have been considered in this study and the doses are presented. This study would enable estimation of radiation induced detriment to the patient subpopulation in India. Since the external dimensions of the phantom are nearly the same as that of 15-y-old NRPB pediatric phantom, our results are also compared with those of latter and the agreement was found to be satisfactory.

  13. Perchlorate exposure from infant formula and comparisons with the perchlorate reference dose.

    PubMed

    Schier, Joshua G; Wolkin, Amy F; Valentin-Blasini, Lisa; Belson, Martin G; Kieszak, Stephanie M; Rubin, Carol S; Blount, Benjamin C

    2010-05-01

    Perchlorate exposure may be higher in infants compared with older persons, due to diet (infant formula) and body weight versus intake considerations. Our primary objective was to quantitatively assess perchlorate concentrations in commercially available powdered infant formulas (PIFs). Secondary objectives were: (1) to estimate exposure in infants under different dosing scenarios and compare them with the perchlorate reference dose (RfD); (2) estimate the perchlorate concentration in water used for preparing PIFs that would result in a dose exceeding the RfD; and (3) estimate iodine intakes from PIFs. We quantified perchlorate levels in three samples (different lot numbers) of reconstituted PIF (using perchlorate-free water) from commercial brands of PIF in each of the following categories: bovine milk-based with lactose, soy-based, bovine milk-based but lactose-free, and elemental (typically consisting of synthetic amino acids). Exposure modeling was conducted to determine whether the RfD might be exceeded in 48 dosing scenarios that were dependent on age, centile energy intake per unit of body weight, body weight percentile, and PIF perchlorate concentration. We obtained three different samples in each of the five brands of bovine- and soy-based PIF, three different samples in each of the three brands of lactose-free PIF, and three different samples in two brands of elemental PIF. The results were as follows: bovine milk-based with lactose (1.72 microg/l, range: 0.68-5.05); soy-based (0.21 microg/l, range: 0.10-0.44); lactose-free (0.27 microg/l, range: 0.03-0.93); and elemental (0.18 microg/l, range: 0.08-0.4). Bovine milk-based PIFs with lactose had a significantly higher concentration of perchlorate (P<0.05) compared with all. Perchlorate was a contaminant of all commercially available PIFs tested. Bovine milk-based PIFs with lactose had a significantly higher perchlorate concentration perchlorate than soy, lactose-free, and elemental PIFs. The perchlorate Rf

  14. 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.

    PubMed

    Pelloski, Christopher E; Palmer, Matthew; Chronowski, Gregory M; Jhingran, Anuja; Horton, John; Eifel, Patricia J

    2005-05-01

    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). 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 137Cs 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 cm3 of bladder and rectum receiving the highest dose (DBV2 and DRV2, 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. 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 DRV2 (p = 0.561); the mean (+/- standard deviation) difference was 21 cGy (+/- 344 cGy). The median volume of the rectum that received at least the ICRU reference-point dose was 2.1 cm3. In 66 (71%) of 93 cases, <5 cm3

  15. 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

  16. Dose estimation for astronauts using dose conversion coefficients calculated with the PHITS code and the ICRP/ICRU adult reference computational phantoms.

    PubMed

    Sato, Tatsuhiko; Endo, Akira; Sihver, Lembit; Niita, Koji

    2011-03-01

    Absorbed-dose and dose-equivalent rates for astronauts were estimated by multiplying fluence-to-dose conversion coefficients in the units of Gy.cm(2) and Sv.cm(2), respectively, and cosmic-ray fluxes around spacecrafts in the unit of cm(-2) s(-1). The dose conversion coefficients employed in the calculation were evaluated using the general-purpose particle and heavy ion transport code system PHITS coupled to the male and female adult reference computational phantoms, which were released as a common ICRP/ICRU publication. The cosmic-ray fluxes inside and near to spacecrafts were also calculated by PHITS, using simplified geometries. The accuracy of the obtained absorbed-dose and dose-equivalent rates was verified by various experimental data measured both inside and outside spacecrafts. The calculations quantitatively show that the effective doses for astronauts are significantly greater than their corresponding effective dose equivalents, because of the numerical incompatibility between the radiation quality factors and the radiation weighting factors. These results demonstrate the usefulness of dose conversion coefficients in space dosimetry. © Springer-Verlag 2010

  17. Mouse micronucleus assay as a surrogate to assess genotoxic potential of arsenic at its human reference dose.

    PubMed

    Khan, Parimal K; Kesari, Vibudh P; Kumar, Amod

    2013-01-01

    Exposure to high contents of arsenic (a genotoxic carcinogen) in humans through drinking water is one of the most serious concerns in many parts of the world including India. The United States Environmental Protection Agency (USEPA) has recommended a permissible limit of daily exposure in humans to arsenic as its reference dose (0.3 μg kg(-1) d(-1)) with almost no likelihood of any adverse effect. The present work was a quantitative assessment of the genotoxic potential of arsenic at the exposure level of its human reference dose through micronucleus (MN) assay in mice. The animals were exposed to various doses of arsenic through oral gavaging for 15 consecutive days. Significant increases in the frequency of micronucleated erythrocytes were observed in mice upon exposure to arsenic which occurred even at its human reference dose and in a dose-dependent manner. The study of the genotoxic potential of arsenic in humans at lower exposure levels (including its human reference dose) is, therefore, highly desirable for risk assessment and hazard identification. Copyright © 2012 Elsevier Ltd. All rights reserved.

  18. Dose Conversion Coefficients Based on Taiwanese Reference Phantoms and Monte Carlo Simulations for Use in External Radiation Protection.

    PubMed

    Chang, Shu-Jun; Hsu, Jui-Ting; Hung, Shih-Yen; Liu, Yan-Lin; Jiang, Shiang-Huei; Wu, Jay

    2017-05-01

    Reference phantoms are widely applied to evaluate the radiation dose for external exposure. However, the frequently used reference phantoms are based on Caucasians. Dose estimation for Asians using a Caucasian phantom can result in significant errors. This study recruited 40 volunteers whose body sizes are close to the average Taiwanese population. Magnetic resonance imaging was performed to obtain the organ volume for construction of the Taiwanese reference man (TRM) and Taiwanese reference woman (TRW). The dose conversion coefficients (DCC) resulting from photo beams in anterior-posterior, posterior-anterior, right-lateral, left-lateral, and isotropic irradiation geometries were estimated. In the anterior-posterior geometry, the mean DCC differences among organs between the TRM and ORNL phantom at 0.1, 1, and 10 MeV were 7.3%, 5.8%, and 5.2%, respectively. For the TRW, the mean differences from the ORNL phantom at the three energies were 10.6%, 7.4%, and 8.3%. The DCCs of the Taiwanese reference phantoms and the ORNL phantom presented similar trends in other geometries. The torso size of the phantom and the mass and geometric location of the organ have a significant influence on the DCC. The Taiwanese reference phantoms can be used to establish dose guidelines and regulations for radiation protection from external exposure.

  19. Issues raised by the reference doses for perfluorooctane sulfonate and perfluorooctanoic acid.

    PubMed

    Dong, Zhaomin; Bahar, Md Mezbaul; Jit, Joytishna; Kennedy, Bruce; Priestly, Brian; Ng, Jack; Lamb, Dane; Liu, Yanju; Duan, Luchun; Naidu, Ravi

    2017-08-01

    On 25th May 2016, the U.S. EPA released reference doses (RfDs) for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA) of 20ng/kg/day, which were much more conservative than previous values. These RfDs rely on the choices of animal point of departure (PoD) and the toxicokinetics (TK) model. At this stage, considering that the human evidence is not strong enough for RfD determination, using animal data may be appropriate but with more uncertainties. In this article, the uncertainties concerning RfDs from the choices of PoD and TK models are addressed. Firstly, the candidate PoDs should include more critical endpoints (such as immunotoxicity), which may lead to lower RfDs. Secondly, the reliability of the adopted three-compartment TK model is compromised: the parameters are not non-biologically plausible; and this TK model was applied to simulate gestation and lactation exposures, while the two exposure scenarios were not actually included in the model structure. Copyright © 2017. Published by Elsevier Ltd.

  20. 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.

  1. Fluence-to-dose conversion coefficients for neutrons and protons calculated using the PHITS code and ICRP/ICRU adult reference computational phantoms.

    PubMed

    Sato, Tatsuhiko; Endo, Akira; Zankl, Maria; Petoussi-Henss, Nina; Niita, Koji

    2009-04-07

    The fluence to organ-dose and effective-dose conversion coefficients for neutrons and protons with energies up to 100 GeV was calculated using the PHITS code coupled to male and female adult reference computational phantoms, which are to be released as a common ICRP/ICRU publication. For the calculation, the radiation and tissue weighting factors, w(R) and w(T), respectively, as revised in ICRP Publication 103 were employed. The conversion coefficients for effective dose equivalents derived using the radiation quality factors of both Q(L) and Q(y) relationships were also estimated, utilizing the functions for calculating the probability densities of the absorbed dose in terms of LET (L) and lineal energy (y), respectively, implemented in PHITS. By comparing these data with the corresponding data for the effective dose, we found that the numerical compatibilities of the revised w(R) with the Q(L) and Q(y) relationships are fairly established. The calculated data of these dose conversion coefficients are indispensable for constructing the radiation protection systems based on the new recommendations given in ICRP103 for aircrews and astronauts, as well as for workers in accelerators and nuclear facilities.

  2. The relationship between anthropometric indices derived from the CDC/WHO international reference.

    PubMed

    Macfarlane, S B

    1996-01-01

    This paper examines the relationship between the standard deviation scores of weight-for-age (WAZ), height-for-age (HAZ) and weight-for-height (WHZ) calculated using the CDC/WHO reference. The pattern of WHZ with age is explored for CDC/WHO reference children following set paths for WAZ and HAZ, and the nature of the regression of WAZ on HAZ and WHZ is examined for the Ghana Demographic and Health Survey data (1988). Reference children with heights and weights at the lower end of the range for their population showed discrepancies in their WHZ indices. A marked discontinuity between 23 and 24 months reflected the junction between the two data sets from which the CDC/WHO reference was derived. There was also clear curvature in the values for WHZ between 3 and 23 months, particularly apparent for children with weights and heights well below the reference median. While the regression equation for the Ghanaian data was similar to that already described by Keller in 1983, marked curvature was observed in the residual plot for children under 2 years. Consistency with age is a prerequisite for a weight-for-height index. The peculiarities of this index as based on the CDC/WHO reference undermine the validity of its use in measuring malnutrition among young children in developing countries. It is suggested that serious consideration is given to the use of an alternative index of wasting and to the development of alternative reference figures.

  3. Reprint of "Update of the reference and HBM values derived by the German Human Biomonitoring Commission".

    PubMed

    Schulz, Christine; Wilhelm, Michael; Heudorf, Ursel; Kolossa-Gehring, Marike

    2012-02-01

    In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview. Copyright © 2011 Elsevier GmbH. All rights reserved.

  4. Update of the reference and HBM values derived by the German Human Biomonitoring Commission.

    PubMed

    Schulz, Christine; Wilhelm, Michael; Heudorf, Ursel; Kolossa-Gehring, Marike

    2011-12-01

    In 2007, we reviewed the working principles and working procedures of the German Human Biomonitoring Commission together with the reference values and human biomonitoring (HBM) values derived up to that time. Since then, the Commission has decided to derive additionally HBM I values on the basis of tolerable daily intakes and has used and evaluated this new approach on the metabolites of (2-ethylhexyl) phthalate (DEHP) in urine. Furthermore, the Commission has derived a HBM I value for thallium in urine, has recinded the HBM values for lead in blood, and has updated the HBM values for cadmium in urine. Based on the representative data of the German Environmental Survey on Children from 2003 to 2006 (GerES IV), the Commission has updated the reference values for a large number of environmental pollutants in urine and blood of children in Germany. Since 2007, the Commission has derived new and updated reference values for PFOS and PFOA in human plasma, for thallium in urine, for aromatic amines in urine, for a comprehensive number of phthalate metabolites in urine, and for organochlorine pesticides in human breast milk. Furthermore, the Commission has evaluated background exposure levels for two naphthalene metabolites and acrylamide (using acrylamide-haemoglobin adduct) for the general population. This paper reports the new values, including those already published, in order to provide an updated overview. Copyright © 2011 Elsevier GmbH. All rights reserved.

  5. Developing regional weight-for-age growth references for malaria-endemic countries to optimize age-based dosing of antimalarials

    PubMed Central

    van Buuren, Stef; ter Kuile, Feiko O; Stasinopoulos, D Mikis; Rigby, Robert A; Terlouw, Dianne J

    2015-01-01

    Abstract Objective To derive regional weight-for-age growth references to help optimize age-based dosing of antimalarials in Africa, the Americas, South-East Asia and the Western Pacific. Methods A weight-for-age database was constructed from pre-existing population-based anthropometric data obtained from household surveys and research groups. It contained data collected between 1995 and 2012 on 1 263 119 individuals (909 368 female, 353 751 male) older than 14 days and younger than 50 years in 64 malaria-endemic countries. Regional growth references were generated using a generalized additive model for location, scale and shape by combining data with varying distributions from a range of sources. Countries were weighted by their population at risk of malaria to enable references to be used in optimizing the dosing of antimalarials. Findings Large differences in weight-for-age distributions existed between the regions and between the regions and global growth standards. For example, the average adult male from the Americas weighed 68.1 kg – 6.0 kg more than males in South-East Asia and the Western Pacific (average: 62.1 kg). For adult women, the difference was over 10.4 kg: the average was 60.4 kg in the Americas and 50.0 kg in South-East Asia and the Western Pacific. Conclusion There were substantial variations in weight-for-age growth curves between malaria-endemic areas. The growth reference charts derived here can be used to guide the evidence-based optimization of aged-based dosing regimens for antimalarials and other drugs often prescribed by age. PMID:25883400

  6. 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%.

  7. Chernobyl Doses. Volume 2. Conifer Stress near Chernobyl Derived from Landsat Imagery

    DTIC Science & Technology

    1992-12-01

    Defense Nuclear Agency Alexandria, VA 22310-3398 AD-A259 085 S.... IiilII|IlH~l D.A-TR-92-3,,.v2 Chernobyl Doses Volume 2-Conifer Stress Near... Chernobyl Derived from Landsat Imagery Gene E. McClellan Terrence H. Hemmer Ronald N. DeWitt Pacific-Sierra Research Corporation 12340 Santa Monica Boulevard...870929 - 920228 4. TITLE AND SUBTITLE 5. FUNDING NUMBERS Chernobyl Doses C - DNA 001-87-C-0104 Volume 2- Conifer Stress Near Chernobyl Derived from

  8. [The comparison between dose rates at the interventional reference point of the angiography systems in many facilities].

    PubMed

    Ishibashi, Tooru; Imada, Naoyuki; Yamashita, Yukari; Asou, Hiroya; Matsumoto, Yoriaki; Inada, Satoshi; Okino, Mizuho; Nonaka, Haruki; Mizutani, Hiroshi

    2012-01-01

    The management of the radiation dose is very important in interventional radiology (IVR), especially in percutaneous coronary intervention (PCI). Therefore, we measured entrance surface doses at the interventional reference point of 27 cardiac intervention procedures in 22 cardiac catheterization laboratories around Hiroshima, and compared these doses. Recently, for cardiac interventional radiology, the X-ray machines using flat-panel detectors (FPD) instead of image intensifiers (I.I.) is increasing; 13 systems used FPD and 14 systems used I.I. For fluoroscopy rate, the difference between laboratories was 9 times. For cineangiography rate, the difference between laboratories was 7 times. In addition, between both devices, the I.I. group is bigger than the FPD group. When comparing by the same condition, for the dose at the interventional reference point, no significant difference was detected between the FPD group and the I.I. group. This study shows that FPD is not available for reducing the radiation dose simply. Therefore, it is necessary that we think of the balance with image quality and radiation dose. The optimization of the devices and cardiac intervention procedures becomes very important.

  9. 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

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

    PubMed Central

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

    2012-01-01

    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. 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.

  12. 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.

  13. The probability of correct target dosage: dose-population histograms for deriving treatment margins in radiotherapy.

    PubMed

    van Herk, M; Remeijer, P; Rasch, C; Lebesque, J V

    2000-07-01

    To provide an analytical description of the effect of random and systematic geometrical deviations on the target dose in radiotherapy and to derive margin rules. The cumulative dose distribution delivered to the clinical target volume (CTV) is expressed analytically. Geometrical deviations are separated into treatment execution (random) and treatment preparation (systematic) variations. The analysis relates each possible preparation (systematic) error to the dose distribution over the CTV and allows computation of the probability distribution of, for instance, the minimum dose delivered to the CTV. The probability distributions of the cumulative dose over a population of patients are called dose-population histograms in short. Large execution (random) variations lead to CTV underdosage for a large number of patients, while the same level of preparation (systematic) errors leads to a much larger underdosage for some of the patients. A single point on the histogram gives a simple "margin recipe." For example, to ensure a minimum dose to the CTV of 95% for 90% of the patients, a margin between CTV and planning target volume (PTV) is required of 2.5 times the total standard deviation (SD) of preparation (systematic) errors (Sigma) plus 1.64 times the total SD of execution (random) errors (sigma') combined with the penumbra width, minus 1.64 times the SD describing the penumbra width (sigma(p)). For a sigma(p) of 3.2 mm, this recipe can be simplified to 2.5 Sigma + 0.7 sigma'. Because this margin excludes rotational errors and shape deviations, it must be considered as a lower limit for safe radiotherapy. Dose-population histograms provide insight into the effects of geometrical deviations on a population of patients. Using a dose-probability based approach, simple algorithms for choosing margins were derived.

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

    PubMed

    Keshavkumar, Biju

    2012-07-01

    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 (192)Ir and (60)Co 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%.

  15. Survey of computed tomography doses and establishment of national diagnostic reference levels in the Republic of Belarus.

    PubMed

    Kharuzhyk, S A; Matskevich, S A; Filjustin, A E; Bogushevich, E V; Ugolkova, S A

    2010-01-01

    Computed tomography dose index (CTDI) was measured on eight CT scanners at seven public hospitals in the Republic of Belarus. The effective dose was calculated using normalised values of effective dose per dose-length product (DLP) over various body regions. Considerable variations of the dose values were observed. Mean effective doses amounted to 1.4 +/- 0.4 mSv for brain, 2.6 +/- 1.0 mSv for neck, 6.9 +/- 2.2 mSv for thorax, 7.0 +/- 2.3 mSv for abdomen and 8.8 +/- 3.2 mSv for pelvis. Diagnostic reference levels (DRLs) were proposed by calculating the third quartiles of dose value distributions (body region/volume CTDI, mGy/DLP, mGy cm): brain/60/730, neck/55/640, thorax/20/500, abdomen/25/600 and pelvis/25/490. It is evident that the protocols need to be optimised on some of the CT scanners, in view of the fact that these are the first formulated DRLs for the Republic of Belarus.

  16. ESTIMATION OF CARDIAC CT ANGIOGRAPHY RADIATION DOSE TOWARD THE ESTABLISHMENT OF NATIONAL DIAGNOSTIC REFERENCE LEVEL FOR CCTA IN IRAN.

    PubMed

    Hosseini Nasab, Seyed Mohammad Bagher; Shabestani-Monfared, Ali; Deevband, Mohammad Reza; Paydar, Reza; Nabahati, Mehrdad

    2016-08-29

    In recent years, with the introduction of 64-slice CT and dual-source CT technology, coronary CT angiography (CCTA) has emerged as a useful diagnostic imaging modality as a non-invasive assessment of coronary heart disease. CT produces a larger radiation dose than other imaging tests and cardiac CT involves higher radiation dose with the advances in the spatial and temporal resolution. The aims of this study are patient dose assessment and establishment of national diagnostic reference level for CCTA in Iran. A questionnaire was sent to CCTA centers. Data for patient and CT protocols were obtained. The volumetric CT dose index (CTDIvol), dose length product (DLP) and total DLP were considered in the 32 cm standard body phantom. Calculation of estimated effective dose (ED) was obtained by multiplying the DLP by a conversion factor [k = 0.014 mSv (mGy·cm)(-1)]. Mean value of CTDIvol and DLP for CCTA was 50 mGy and 825 mGy·cm. The third quartile (75th) of the distribution of mean CTDIvol (66.54 mGy) and DLP (1073 mGy·cm) values was expressed as the diagnostic reference level (DRL) for CCTA in Iran. The median of ED was 10.26 mSv and interquartile range of ED was 7.08-15.03 mSv. A large variety in CTDIvol and DLP among CT scanner and different sites due to variability in CT parameter is noted. It seems that training could help to reduce patient's dose.

  17. CLSI-Derived Hematology and Biochemistry Reference Intervals for Healthy Adults in Eastern and Southern Africa

    PubMed Central

    Karita, Etienne; Ketter, Nzeera; Price, Matt A.; Kayitenkore, Kayitesi; Kaleebu, Pontiano; Nanvubya, Annet; Anzala, Omu; Jaoko, Walter; Mutua, Gaudensia; Ruzagira, Eugene; Mulenga, Joseph; Sanders, Eduard J.; Mwangome, Mary; Allen, Susan; Bwanika, Agnes; Bahemuka, Ubaldo; Awuondo, Ken; Omosa, Gloria; Farah, Bashir; Amornkul, Pauli; Birungi, Josephine; Yates, Sarah; Stoll-Johnson, Lisa; Gilmour, Jill; Stevens, Gwynn; Shutes, Erin; Manigart, Olivier; Hughes, Peter; Dally, Len; Scott, Janet; Stevens, Wendy; Fast, Pat; Kamali, Anatoli

    2009-01-01

    Background Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. Methods and Findings Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S.-derived DAIDS AE grading criteria, we observed 774 (35

  18. CLSI-derived hematology and biochemistry reference intervals for healthy adults in eastern and southern Africa.

    PubMed

    Karita, Etienne; Ketter, Nzeera; Price, Matt A; Kayitenkore, Kayitesi; Kaleebu, Pontiano; Nanvubya, Annet; Anzala, Omu; Jaoko, Walter; Mutua, Gaudensia; Ruzagira, Eugene; Mulenga, Joseph; Sanders, Eduard J; Mwangome, Mary; Allen, Susan; Bwanika, Agnes; Bahemuka, Ubaldo; Awuondo, Ken; Omosa, Gloria; Farah, Bashir; Amornkul, Pauli; Birungi, Josephine; Yates, Sarah; Stoll-Johnson, Lisa; Gilmour, Jill; Stevens, Gwynn; Shutes, Erin; Manigart, Olivier; Hughes, Peter; Dally, Len; Scott, Janet; Stevens, Wendy; Fast, Pat; Kamali, Anatoli

    2009-01-01

    Clinical laboratory reference intervals have not been established in many African countries, and non-local intervals are commonly used in clinical trials to screen and monitor adverse events (AEs) among African participants. Using laboratory reference intervals derived from other populations excludes potential trial volunteers in Africa and makes AE assessment challenging. The objective of this study was to establish clinical laboratory reference intervals for 25 hematology, immunology and biochemistry values among healthy African adults typical of those who might join a clinical trial. Equal proportions of men and women were invited to participate in a cross sectional study at seven clinical centers (Kigali, Rwanda; Masaka and Entebbe, Uganda; two in Nairobi and one in Kilifi, Kenya; and Lusaka, Zambia). All laboratories used hematology, immunology and biochemistry analyzers validated by an independent clinical laboratory. Clinical and Laboratory Standards Institute guidelines were followed to create study consensus intervals. For comparison, AE grading criteria published by the U.S. National Institute of Allergy and Infectious Diseases Division of AIDS (DAIDS) and other U.S. reference intervals were used. 2,990 potential volunteers were screened, and 2,105 (1,083 men and 1,022 women) were included in the analysis. While some significant gender and regional differences were observed, creating consensus African study intervals from the complete data was possible for 18 of the 25 analytes. Compared to reference intervals from the U.S., we found lower hematocrit and hemoglobin levels, particularly among women, lower white blood cell and neutrophil counts, and lower amylase. Both genders had elevated eosinophil counts, immunoglobulin G, total and direct bilirubin, lactate dehydrogenase and creatine phosphokinase, the latter being more pronounced among women. When graded against U.S. -derived DAIDS AE grading criteria, we observed 774 (35.3%) volunteers with grade one

  19. Verification of absorbed dose rates in reference beta radiation fields: Measurements with an extrapolation chamber and radiochromic film.

    PubMed

    Reynaldo, S R; Benavente, J A; Da Silva, T A

    2016-11-01

    Beta Secondary Standard 2 (BSS 2) provides beta radiation fields with certified values of absorbed dose to tissue and the derived operational radiation protection quantities. As part of the quality assurance, the reliability of the CDTN BSS2 system was verified through measurements in the (90)Sr/(90)Y and (85)Kr beta radiation fields. Absorbed dose rates and their angular variation were measured with a 23392 model PTW extrapolation chamber and with Gafchromic radiochromic films on a PMMA slab phantom. The feasibility of using both methods was analyzed.

  20. Dose-Response Relationship between Alanine Aminotransferase Levels within the Reference Interval and Metabolic Syndrome in Chinese Adults

    PubMed Central

    Wu, Peipei; Chen, Qicai; Chen, Lili; Zhang, Pengpeng; Xiao, Juan; Chen, Xiaoxiao; Liu, Meng

    2017-01-01

    Purpose Elevation in serum alanine aminotransferase (ALT) levels is a biomarker for metabolic syndrome (MS); however, the relationship has not been fully investigated within the reference interval of ALT levels. Our objective was to explore the relationship between serum ALT levels within the reference interval and MS in Chinese adults. Materials and Methods This cross-sectional study included 16028 adults, who attended routine health check-ups at Shengli Oilfield Central Hospital from January 2006 to March 2012. The reference interval of serum ALT level was defined as less than 40 U/L. Logistic regression models and restricted cubic spline were used to evaluate the association of ALT with MS. Results The prevalence of MS in the total population was 13.7% (6.4% for females and 18.4% for males). Multiple logistic regression showed that ALT levels were positively associated with MS after adjustment for potential confounding factors. The odds ratio of MS in the top quartile was 4.830 [95% confidence interval (CI): 2.980–7.829] in females and 3.168 (95% CI: 2.649–3.790) in males, compared with the ALT levels in the bottom quartile. The restricted cubic spline models revealed a positive non-linear dose-response relationship between ALT levels and the risk of MS in women (p for nonlinearity was 0.0327), but a positive linear dose-response relationship in men (p for nonlinearity was 0.0659). Conclusion Serum ALT levels within the reference interval are positively associated with MS in a dose-response manner. Elevated ALT levels, even within the reference interval, may reflect early dysmetabolic changes. PMID:27873509

  1. Calculation of the absorbed dose distribution due to irregularly shaped photon beams using pencil beam kernels derived from basic beam data

    NASA Astrophysics Data System (ADS)

    Storchi, Pascal; Woudstra, Evert

    1996-04-01

    In radiotherapy, accurately calculated dose distributions of irregularly shaped photon beams are needed. In this paper, an algorithm is presented which enables the calculation of dose distributions due to irregular fields using pencil beam kernels derived from simple basic beam data usually measured on treatment units, i.e. central axis depth - dose curves and profiles. The only extra data that are needed, and are not currently measured, is the phantom scatter factor curve at the reference depth. The algorithm has been developed as an extension to a previously developed algorithm for rectangular fields which is based on the Milan - Bentley storage model. In the case of an irregular field, the depth dose and the boundary function are computed by convolution of a field intensity function with pencil beam kernels. The depth dose is computed by using a `scatter' kernel, which is derived from the stored depth - dose curves and from the phantom scatter factor curve. The boundary function is computed by using a `boundary' kernel, which is derived from the boundary profile of a number of large square fields. Because of the simplicity of the data used and the underlying concepts, which for instance do not separate the head scatter from the primary beam, this algorithm presents some shortcomings. On the other hand, this simplicity is also of great advantage and the inaccuracy is acceptable for most clinical situations.

  2. 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.

  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. 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.

  5. 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.

  6. 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.

  7. 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.

  8. DOSE REFERENCE LEVELS IN SPANISH INTRAORAL DENTAL RADIOLOGY: STABILISATION OF THE INCORPORATION OF DIGITAL SYSTEMS IN DENTAL CLINICAL PRACTICES.

    PubMed

    Alcaraz, M; Velasco, F; Olivares, A; Velasco, E; Canteras, M

    2016-12-01

    A total of 34 044 official quality assurance reports in dental radiodiagnostic surgery from 16 regions of Spain, compiled from 2002 to 2014, were studied in order to determine the progress of diagnostic reference levels (DRLs) for obtaining diagnostic images under normal conditions for clinical practice in Spanish dental clinics. A DRL of 2.8 mGy was set in 2014, which represents a 41.7 % decrease compared with that of 2002 (4.8 mGy). Over the same time period, the mean dose fell by 55.2 %. However, over the last 3 y, the stabilisation of the mean dose administered to patients has been observed with only a 6.7 % reduction in DRLs, which corresponds to the stabilisation of dental radiodiagnostic surgery on replacing the use of radiographic film with digital imaging systems. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  9. 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.

  10. Deriving dose limits for warnings in electronic prescribing systems: statistical analysis of prescription data at University Hospital Birmingham, UK.

    PubMed

    Coleman, Jamie J; Hodson, James; Ferner, Robin E

    2012-04-01

    : Electronic decision support can reduce medication errors, and dose-range checking is one element of that support. : The aim of this study was to design an approach to setting upper dose warning limits in electronic prescribing systems where there are historical data on dosing. : We used historical data on 56 drug-form combinations for which over 100 prescriptions had been issued between 1 June 2009 and 31 May 2010 in a bespoke electronic prescribing system at University Hospital Birmingham, UK. First, two experts derived dose limits for each drug-form combination, then the drugs were randomly divided into a training set and a test set. A variation of the 'Nearest Rank' approach to estimate statistical limits was used to derive the percentile with the optimal sensitivity and specificity. : For the 28 drug-form combinations in the test set, the 86th percentile of dose gave a mean sensitivity of 95.3% and a mean specificity of 97.9% for warning limits, representing the highest reasonable dose; the 96th percentile gave a mean sensitivity of 90.2% and mean specificity of 99.5% for disallow limits, beyond which no dose should be prescribed. : Dosing decision support within electronic prescribing systems can be derived by statistical analysis of historical prescription data. We advocate a combined theoretical and statistical derivation of dose checking rules in order to ensure that prescribers are alerted appropriately to potentially toxic doses.

  11. Derivation of reference distribution functions for Tokamak-plasmas by statistical thermodynamics

    NASA Astrophysics Data System (ADS)

    Sonnino, Giorgio; Cardinali, Alessandro; Peeters, Philippe; Steinbrecher, György; Sonnino, Alberto; Nardone, Pasquale

    2014-03-01

    A general approach for deriving the expression of reference distribution functions by statistical thermodynamics is illustrated, and applied to the case of a magnetically confined plasma. The local equilibrium is defined by imposing the minimum entropy production, which applies only to the linear regime near a stationary thermodynamically non-equilibrium state and the maximum entropy principle under the scale invariance restrictions. This procedure may be adopted for a system subject to an arbitrary number of thermodynamic forces, however, for concreteness, we analyze, afterwords, a magnetically confined plasma subject to three thermodynamic forces, and three energy sources: (i) the total Ohmic heat, supplied by the transformer coil; (ii) the energy supplied by neutral beam injection (NBI); and (iii) the RF energy supplied by ion cyclotron resonant heating (ICRH) system which heats the minority population. In this limit case, we show that the derived expression of the distribution function is more general than that one, which is currently used for fitting the numerical steady-state solutions obtained by simulating the plasma by gyro-kinetic codes. An application to a simple model of fully ionized plasmas submitted to an external source is discussed. Through kinetic theory, we fixed the values of the free parameters linking them with the external power supplies. The singularity at low energy in the proposed distribution function is related to the intermittency in the turbulent plasma.

  12. Derivation of Australian diagnostic reference levels for paediatric multi detector computed tomography.

    PubMed

    Hayton, Anna; Wallace, Anthony

    2016-09-01

    Australian National Diagnostic Reference Levels for paediatric multi detector computed tomography were established for three protocols, Head, Chest and AbdoPelvis, across two age groups, Baby/Infant 0-4 years and Child 5-14 years by the Australian Radiation Protection and Nuclear Safety Agency in 2012. The establishment of Australian paediatric DRLs is an important step towards lowering patient CT doses on a national scale. While Adult DRLs were calculated with data collected from the web based Australian National Diagnostic Reference Level Service, no paediatric data was submitted in the first year of service operation. Data from an independent Royal Australian and New Zealand College of Radiologists Quality Use of Diagnostic Imaging paediatric optimisation survey was used. The paediatric DRLs were defined for CTDIvol (mGy) and DLP (mGy·cm) values that referenced the 16 cm PMMA phantom for the Head protocol and the 32 cm PMMA phantom for body protocols for both paediatric age groups. The Australian paediatric DRLs for multi detector computed tomography are for the Head, Chest and AbdoPelvis protocols respectively, 470, 60 and 170 mGy·cm for the Baby/Infant age group, and 600, 110 and 390 mGy·cm for the Child age group. A comparison with published international paediatric DRLs for computed tomography reveal the Australian paediatric DRLs to be lower on average. However, the comparison is complicated by misalignment of defined age ranges. It is the intention of ARPANSA to review the paediatric DRLs in conjunction with a review of the adult DRLs, which should occur within 5 years of their publication.

  13. 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

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

    PubMed

    Ubeda, Carlos; Miranda, Patricia; Vano, Eliseo

    2015-02-01

    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. 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. 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(2) for <1 yr; 1.74 and 1.90 Gy cm(2) for 1 to <5 yr; 2.83 and 3.22 Gy cm(2) for 5 to <10 yr; and 7.34 and 8.68 Gy cm(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(2) /kg) for diagnostic and therapeutic procedures. 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 may be large differences in child size. These DRLs were

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

    PubMed

    Ubeda, Carlos; Miranda, Patricia; Vano, Eliseo

    2015-02-01

    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. 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. 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 cm2 for <1 yr; 1.74 and 1.90 Gy cm2 for 1 to <5 yr; 2.83 and 3.22 Gy cm2 for 5 to <10 yr; and 7.34 and 8.68 Gy cm2 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 cm2/kg) for diagnostic and therapeutic procedures. 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 may be large differences in child size. These DRLs were obtained at the

  16. Development of a reference dose for the persistent congeners of weathered toxaphene based on in vivo and in vitro effects related to tumor promotion.

    PubMed

    Simon, Ted; Manning, Randall

    2006-04-01

    Toxaphene is a mixture of chlorinated camphenes and bornanes that was produced and used in the United States until 1982. 1.3 million tons of toxaphene have been released worldwide. "Technical" toxaphene (TT) consists of a mixture of up to 800 different chemicals, known as congeners. TT weathers in the environment by both biotic and abiotic processes. The human body burden of toxaphene consists of only five persistent congeners that are not metabolized; three of these occur in considerably greater amounts than the other two. Because of the rapid metabolism and excretion of the non-persistent congeners, the persistent congeners that make up the human body burden most likely play a role in eliciting any potential adverse effects. EPA's toxicity assessment for TT is based on the occurrence of liver cancer in rodents, and considerable doubt exists whether this assessment is applicable to weathered toxaphene (WT). Using experimental results from European Union scientists, a reference dose (RfD) was developed for WT based on the three most persistent congeners that comprise the human body burden. The critical effect chosen was tumor promotion and this endpoint is considered protective for other endpoints as well. Although RfDs are typically derived for non-carcinogenic effects, the endpoint of tumor promotion is appropriate for RfD development because the experimental data suggest a dose threshold. The RfD for weathered toxaphene represented by the sum of the three major persistent congeners ( summation 3PC) is 2E-05 mg/kg-day. To apply this reference dose to a particular WT mixture, information is needed regarding the percentage of summation 3PC in the mixture.

  17. 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

    2016-01-07

    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

  18. 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

  19. 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.

  20. 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

  1. The point of transition on the dose-effect curve as a reference point in the evaluation of in vitro toxicity data.

    PubMed

    Sand, Salomon; Ringblom, Joakim; Håkansson, Helen; Öberg, Mattias

    2012-10-01

    Dose-effect evaluation is an increasingly important step of health risk assessment. The foreseen increase of in vitro methods argues for the development and evaluation of a clearly defined reference points for dose-effect modelling of in vitro data. In the present study, the traditional use of a concentration corresponding to 10% or 50% of the maximal effect (EC₁₀ or EC₅₀) is compared with a strategy, under which, a reference point (Benchmark dose, BMD(T) ) is calculated that represents the dose where the slope of the dose-effect curve changes the most (per unit log-dose) in the low dose region. To illustrate the importance of the reference point, dose-effect data on CYP1A1 enzyme activity for 30 polychlorinated biphenyl (PCB) congeners were evaluated in order to calculate relative potencies, in relation to 2,3,7,8-TCDD, with confidence intervals (CIs). The present study shows that the interpretation of the results as potency and rank orders potentially depends on the choice and definition of the reference point (BMD(T) , EC₁₀ or EC₅₀). This is important as potency ranking may be used as a method for screening and prioritization, in research, in policy development or in pharmaceutical development. The use of the BMD(T) implies a focus on the change of structure in the parameter's dose-response rather than a particular percentage change in the response in such a parameter. In conclusion, the BMD(T) may be used as an alternative base for evaluation of dose-effect relationships in vitro. It offers an objective geometrical definition of a reference point in the low-dose region of the dose-effect curve.

  2. Comparing measurement-derived (3DVH) and machine log file-derived dose reconstruction methods for VMAT QA in patient geometries.

    PubMed

    Tyagi, Neelam; Yang, Kai; Yan, Di

    2014-07-08

    The purpose of this study was to compare the measurement-derived (3DVH) dose reconstruction method with machine log file-derived dose reconstruction method in patient geometries for VMAT delivery. A total of ten patient plans were selected from a regular fractionation plan to complex SBRT plans. Treatment sites in the lung and abdomen were chosen to explore the effects of tissue heterogeneity on the respective dose reconstruction algorithms. Single- and multiple-arc VMAT plans were generated to achieve the desired target objectives. Delivered plan in the patient geometry was reconstructed by using ArcCHECK Planned Dose Perturbation (ACPDP) within 3DVH software, and by converting the machine log file to Pinnacle3 9.0 treatment plan format and recalculating dose with CVSP algorithm. In addition, delivered gantry angles between machine log file and 3DVH 4D measurement were also compared to evaluate the accuracy of the virtual inclinometer within the 3DVH. Measured ion chamber and 3DVH-derived isocenter dose agreed with planned dose within 0.4% ± 1.2% and -1.0% ± 1.6%, respectively. 3D gamma analysis showed greater than 98% between log files and 3DVH reconstructed dose. Machine log file reconstructed doses and TPS dose agreed to within 2% in PTV and OARs over the entire treatment. 3DVH reconstructed dose showed an average maximum dose difference of 3% ± 1.2% in PTV, and an average mean difference of -4.5% ± 10.5% in OAR doses. The average virtual inclinometer error (VIE) was -0.65° ± 1.6° for all patients, with a maximum error of -5.16° ± 4.54° for an SRS case. The time averaged VIE was within 1°-2°, and did not have a large impact on the overall accuracy of the estimated patient dose from ACPDP algorithm. In this study, we have compared two independent dose reconstruction methods for VMAT QA. Both methods are capable of taking into account the measurement and delivery parameter discrepancy, and display the delivered dose in CT patient geometry rather than

  3. Diagnostic reference level: an important tool for reducing radiation doses in adult and pediatric nuclear medicine procedures in Brazil.

    PubMed

    Willegaignon, José; Braga, Luis F E F; Sapienza, Marcelo T; Coura-Filho, George B; Cardona, Marissa A R; Alves, Carlos E R; Gutterres, Ricardo F; Buchpiguel, Carlos A

    2016-05-01

    This study aimed to establish a concise method for determining a diagnostic reference level (DRL) for adult and pediatric nuclear medicine patients on the basis of diagnostic procedures and administered radioisotope as a means of controlling medical exposure. A screening was carried out in all Brazilian Nuclear Medicine Service (NMS) establishments to support this study by collecting the average activities administered during adult diagnostic procedures and the rules applied to adjust these according to the patient's age and body mass. Percentile 75 was used in all the activities administered as a means of establishing DRL for adult patients, with additional correction factors for pediatric patients. Radiation doses from nuclear medicine procedures on the basis of average administered activity were calculated for all diagnostic exams. A total of 107 NMSs in Brazil agreed to participate in the project. From the 64 nuclear medicine procedures studied, bone, kidney, and parathyroid scans were found to be used in more than 85% of all the NMSs analyzed. There was a large disparity among the activities administered, when applying the same procedures, this reaching, in some cases, more than 20 times between the lowest and the highest. Diagnostic exams based on Ga, Tl, and I radioisotopes proved to be the major exams administering radiation doses to patients. On introducing the DRL concept into clinical routine, the minimum reduction in radiation doses received by patients was about 15%, the maximum was 95%, and the average was 50% compared with the previously reported administered activities. Variability in the available diagnostic procedures as well as in the amount of activities administered within the same procedure was appreciable not only in Brazil, but worldwide. Global efforts are needed to establish a concise DRL that can be applied in adult and pediatric nuclear medicine procedures as the application of DRL in clinical routine has been proven to be an important

  4. A national reference for inactivated polio vaccine derived from Sabin strains in Japan.

    PubMed

    Shirato, Haruko; Someya, Yuichi; Ochiai, Masaki; Horiuchi, Yoshinobu; Takahashi, Motohide; Takeda, Naokazu; Wakabayashi, Kengo; Ouchi, Yasumitsu; Ota, Yoshihiro; Tano, Yoshio; Abe, Shinobu; Yamazaki, Shudo; Wakita, Takaji

    2014-09-08

    As one aspect of its campaign to eradicate poliomyelitis, the World Health Organization (WHO) has encouraged development of the inactivated polio vaccine (IPV) derived from the Sabin strains (sIPV) as an option for an affordable polio vaccine, especially in low-income countries. The Japan Poliomyelitis Research Institute (JPRI) inactivated three serotypes of the Sabin strains and made sIPV preparations, including serotypes 1, 2 and 3 D-antigens in the ratio of 3:100:100. The National Institute of Infectious Diseases, Japan, assessed the immunogenic stability of these sIPV preparations in a rat potency test, according to an evaluation method recommended by the WHO. The immunogenicity of the three serotypes was maintained for at least 4 years when properly stored under -70°C. Based on these data, the sIPV preparations made by JPRI have been approved as national reference vaccines by the Japanese national control authority and used for the quality control of the tetracomponent sIPV-containing diphtheria-tetanus-acellular pertussis combination vaccines that were licensed for a routine polio immunization in Japan. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Using total beta-activity measurements in milk to derive thyroid doses from Chernobyl fallout.

    PubMed

    Drozdovitch, V; Germenchuk, M; Bouville, A

    2006-01-01

    Following the Chernobyl accident, more than 200 childhood thyroid cancer cases have been observed in Brest Oblast of Belarus in territories slightly contaminated with 137Cs, but with suspected relatively high 131I fallout. The most helpful measurements available that can be used to estimate thyroid doses for the population of Brest Oblast are the total beta-activity measurements in cow's milk performed using DP-100 device within a few weeks after the accident. The 131I concentrations in milk were derived from the total beta-activity measurements on the basis of (1) a radioecological model used to estimate the variation with time of the radionuclide composition in milk and (2) the determination of the calibration factors of the DP-100 device for the most important radionuclides present in milk. As a result, 131I concentrations in milk were reconstructed for territories with different levels of 137Cs deposition. A non-linear dependence of the 131I concentration in milk on the 137Cs deposition density was obtained; it was used to estimate the thyroid doses from the consumption of 131I-contaminated cow's milk by the population of Brest Oblast. The average individual thyroid doses have been estimated to be 0.15, 0.18, 0.12, 0.06, 0.04 and 0.03 Gy for newborn, children aged 1, 5, 10 and 15 y and adults, respectively. The collective thyroid dose for the entire population of Brest Oblast is estimated to be 64,500 man Gy, the contribution from the adult population being about one half of the total. The methodology that is described could be applied in the framework of epidemiological studies of the relationship between radiation exposure to the thyroid gland and thyroid cancer in areas where numerous total beta-activity measurements in cow's milk were performed within a few weeks after the accident.

  6. 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).

  7. 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.

  8. 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.

  9. 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

  10. Immunogenicity of single-dose Vero cell-derived Japanese encephalitis vaccine in Japanese adults.

    PubMed

    Takeshita, Nozomi; Lim, Chang-Kweng; Mizuno, Yasutaka; Shimbo, Takuro; Kotaki, Akira; Ujiie, Mugen; Hayakawa, Kayoko; Kato, Yasuyuki; Kanagawa, Shuzo; Kaku, Mitsuo; Takasaki, Tomohiko

    2014-04-01

    In Japan, intensive immunization against Japanese encephalitis (JE) was performed from 1967 to 1976, and regular JE immunization was performed thereafter. However, for Japanese adults facing JE risk, dates of vaccination with new inactivated Vero cell-derived JE vaccine are unavailable. This study investigated how a single dose of Vero cell-derived JE vaccine affects Japanese adults. Neutralizing antibodies were measured pre- and post-JE vaccination in 79 participants (age 40.7 ± 9.4 years), enrolled between October 2009 and March 2011, whose JE-vaccination data were gathered from vaccination records and history taking. Before vaccination, the participants' seroprotection rate (SPR) was 51.9%, whereas SPR after vaccination was 93.7%. The seroconversion rate (SCR), which measures seronegative cases that turn seropositive after vaccination, was 86.8%. The geometric mean titer (GMT) was 14.7 before vaccination and 70.1 after vaccination. Age was a significant difference between seroprotected (42.8 years) and non-seroprotected (38.7 years) groups before vaccination. Then the difference of age, SCR, pre-vaccination GMT, post-vaccination GMT and sex ratio were also significant in participants aged 25-39 years and ≥40 years, who represent generations born when Japan's JE-vaccination policy changed. SCR was 100% in participants aged 25-39 years with a vaccination recorded 55.6% in participants aged 25-39 without a vaccination record, and 96.0% in participants aged ≥40 years. Thus, more participants aged 25-39 years were seroprotected before vaccination, but SCR was higher in those aged ≥40 years. Most Japanese adults can be protected after one-dose vaccination, but this may be insufficient for people aged 25-39 years without recorded JE vaccination.

  11. Phototoxic Risk Assessments on Benzophenone Derivatives: Photobiochemical Assessments and Dermal Cassette-Dosing Pharmacokinetic Study.

    PubMed

    Seto, Yoshiki; Ohtake, Hiroto; Kato, Masashi; Onoue, Satomi

    2015-08-01

    This study aimed to qualify photosafety screening on the basis of photochemical and pharmacokinetic (PK) data on dermally applied chemicals. Six benzophenone derivatives (BZPs) were selected as model compounds, and in vitro photochemical/phototoxic characterization and dermal cassette-dosing PK study were carried out. For comparison, an in vivo phototoxicity test was also conducted. All of the BZPs exhibited strong UVA/UVB absorption with molar extinction coefficients of over 2000 M(-1) × cm(-1), and benzophenone and ketoprofen exhibited significant reactive oxygen species (ROS) generation upon exposure to simulated sunlight (about 2.0 mW/cm(2)); however, ROS generation from sulisobenzone and dioxybenzone was negligible. To verify in vitro phototoxicity, a 3T3 neutral red uptake phototoxicity test was carried out, and benzophenone and ketoprofen were categorized to be phototoxic chemicals. The dermal PK parameters of ketoprofen were indicative of the highest dermal distribution of all BZPs tested. On the basis of its in vitro photochemical/phototoxic and PK data, ketoprofen was deduced to be highly phototoxic. The rank of predicted phototoxic risk of BZPs on the basis of the proposed screening strategy was almost in agreement with the results from the in vivo phototoxicity test. The combined use of photochemical and cassette-dosing PK data would provide reliable predictions of phototoxic risk for candidates with high productivity.

  12. Duration of effects on clinical parameters and referred hyperalgesia in rats after abdominal surgery and multiple doses of analgesic.

    PubMed

    Cooper, Dale M; Hoffman, Wherly; Wheat, Nathan; Lee, Hsiu-Yung

    2005-08-01

    This study evaluated the duration of clinical effects and referred hyperalgesia in rats (n = 10 per group) undergo ing abdominal surgery with analgesics (ketoprofen at 3 mg/kg and buprenorphine at 0.01 or 0.1 mg/kg) administered intramuscularly twice daily for 72 h beginning prior to surgery; no-surgery and no-analgesia control groups were included. Food and water consumption and body weight were monitored daily. As a measure of referred hyperalgesia, tail-flick latency was measured daily, before and 4 h after analgesia administration. Compared with those of the no-surgery controls, significant decreases in food consumption and body weight occurred 24 h after surgery without analgesics. There were nonsignificant reductions in these effects by analgesics, but the benefits were not significantly different than those of saline. These parameters continued to be decreased with variable significance in the buprenorphine groups at 48 and 72 h after surgery. In both buprenorphine-treated groups, water consumption was significantly increased at 24 h after surgery but not at 48 or 72 h. Tail-flick latency was not significantly different between the no-surgery and no-analgesia groups but was significantly increased 4 h after high-dose buprenorphine administration and declined nonsignificantly over time in the other groups. We conclude that painful effects from surgery are present primarily during the first 24 h after surgery. The analgesic regimens tested did not completely reduce these effects. Buprenorphine was associated with adverse effects for as long as 72 h after surgery. Referred hyperalgesia from this abdominal surgery could not be measured using the tail-flick assay.

  13. 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.

  14. 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.

  15. 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)

    Yang, L.; Yu, J.; Wang, G.

    2016-12-01

    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.

  16. 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

  17. Evaluation of dose-area product of common radiographic examinations towards establishing a preliminary diagnostic reference levels (PDRLs) in Southwestern Nigeria.

    PubMed

    Jibiri, Nnamdi N; Olowookere, Christopher J

    2016-11-08

    In Nigeria, a large number of radiographic examinations are conducted yearly for various diagnostic purposes. However, most examinations carried out do not have records of doses received by the patients, and the employed exposure parameters used are not documented; therefore, adequate radiation dose management is hin-dered. The aim of the present study was to estimate the dose-area product (DAP) of patients examined in Nigeria, and to propose regional reference dose levels for nine common examinations (chest PA, abdomen AP, pelvis AP, lumbar AP, skull AP, leg AP, knee AP, hand AP, and thigh AP) undertaken in Nigeria. Measurement of entrance surface dose (ESD) was carried out using thermoluminescent dosimeter (TLD). Measured ESDS were converted into DAP using the beam area of patients in 12 purposely selected hospitals. Results of the study show that the maximum/ minimum ratio ranged from 3 for thigh AP to 57 in abdomen AP. The range of determined mean and 75th percentile DAPs were 0.18-17.16, and 0.25-28.59 Gy cm2, respectively. Data available for comparison show that 75th percentile DAPs in this study (in chest PA, abdomen AP, pelvis AP, lumbar AP) are higher than NRPB-HPE reference values. The DAP in this study is higher by factor of 31.4 (chest PA), 9.9 (abdomen AP), 2.2 (pelvis AP), and 2.1 (lumbar AP) than NRPB-HPE values. The relative higher dose found in this study shows nonoptimization of practice in Nigeria. It is expected that regular dose auditing and dose optimization implementation in Nigeria would lead to lower DAP value, especially in abdomen AP. The 75th percentile DAP distribution reported in this study could be taken as regional diagnostic reference level in the Southwestern Nigeria; however, a more extensive nationwide dose survey is required to establish national reference dose. © 2016 The Authors.

  18. FMA-RadLex: An Application Ontology of Radiological Anatomy derived from the Foundational Model of Anatomy Reference Ontology

    PubMed Central

    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

  19. 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

  20. Deriving adaptive MRF coefficients from previous normal-dose CT scan for low-dose image reconstruction via penalized weighted least-squares minimization

    PubMed Central

    Zhang, Hao; Han, Hao; Wang, Jing; Ma, Jianhua; Liu, Yan; Moore, William; Liang, Zhengrong

    2014-01-01

    Purpose: Repeated computed tomography (CT) scans are required for some clinical applications such as image-guided interventions. To optimize radiation dose utility, a normal-dose scan is often first performed to set up reference, followed by a series of low-dose scans for intervention. One common strategy to achieve the low-dose scan is to lower the x-ray tube current and exposure time (mAs) or tube voltage (kVp) setting in the scanning protocol, but the resulted image quality by the conventional filtered back-projection (FBP) method may be severely degraded due to the excessive noise. Penalized weighted least-squares (PWLS) image reconstruction has shown the potential to significantly improve the image quality from low-mAs acquisitions, where the penalty plays an important role. In this work, the authors' explore an adaptive Markov random field (MRF)-based penalty term by utilizing previous normal-dose scan to improve the subsequent low-dose scans image reconstruction. Methods: In this work, the authors employ the widely-used quadratic-form MRF as the penalty model and explore a novel idea of using the previous normal-dose scan to obtain the MRF coefficients for adaptive reconstruction of the low-dose images. In the coefficients determination, the authors further explore another novel idea of using the normal-dose scan to obtain a scale map, which describes an optimal neighborhood for the coefficients determination such that a local uniform region has a small spread of frequency spectrum and, therefore, a small MRF window, and vice versa. The proposed penalty term is incorporated into the PWLS image reconstruction framework, and the low-dose images are reconstructed via the PWLS minimization. Results: The presented adaptive MRF based PWLS algorithm was validated by physical phantom and patient data. The experimental results demonstrated that the presented algorithm is superior to the PWLS reconstruction using the conventional Gaussian MRF penalty or the edge

  1. Derivation of no-effect and reference-level sediment quality values for application at Saskatchewan uranium operations.

    PubMed

    Burnett-Seidel, Charlene; Liber, Karsten

    2013-11-01

    To date, the majority of empirical approaches used to derive sediment quality values (SQVs) have focused on metal concentrations in sediment associated with adverse effects on benthic invertebrate communities. Here, we propose the no-effect (NE) approach. This SQV derivation methodology uses metal concentrations in sediment associated with unaffected benthic communities (i.e., from reference sites and lightly contaminated no-effect sites) and accounts for local benthic invertebrate tolerance and potential chemical interactions at no-effect exposure sites. This NE approach was used to propose alternative regional SQVs for uranium operations in northern Saskatchewan. Three different sets of NE values were derived using different combinations of benthic invertebrate community effects criteria (abundance, richness, evenness, Bray-Curtis index). Additionally, reference values were derived based solely on sediment metal concentrations from reference sites. In general, NE values derived using abundance, richness, and evenness (NE1 and NE2 values) were found to be higher than the NE values derived using all four metrics (NE3 values). Derived NE values for Cr, Cu, Pb, and V did not change with the incorporation of additional effects criteria due to a lack of influence from the uranium operations on the concentrations of these metals in sediment. However, a gradient of exposure concentrations was apparent for As, Mo, Ni, Se, and U in sediment which allowed for tolerable exposure levels of these metals in sediment to be defined. The findings from this assessment have suggested a range of new, alternate metal SQVs for use at uranium operations in northern Saskatchewan.

  2. 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.

  3. Reference intervals for C-peptide and insulin derived from a general adult Danish population.

    PubMed

    Larsen, Pia Bükmann; Linneberg, Allan; Hansen, Torben; Friis-Hansen, Lennart

    2017-05-01

    Despite international efforts to standardize C-peptide and insulin calibrators and immunoassays, platform dependent differences still exist, and platform specific reference intervals are hence needed for correct interpretation. We therefore wanted to establish traceable reference intervals for C-peptide and insulin. In 623 consecutively recruited participants, insulin and C-peptide were measured using the Cobas e411 (Roche Diagnostics, Switzerland). Participants with diabetes were excluded (fasting Glucose ≥7.0mmol/L or HbA1c≥6.5%/≥48mmol/L) and reference intervals were calculated with and without the inclusion of persons who were prediabetic, according to two definitions (The World Health Organization (WHO) and American Diabetes Association (ADA)). To ensure the correctness of calibration, the control pools were analyzed by a reference laboratory. The reference intervals were calculated according to the IFCC guidelines, using the RefVal software (Solberg, Oslo, Norway). Comparison of our results with those from the reference laboratory revealed equivalence for C-peptide results whereas the insulin determined on the Cobas e411 assay were 15-20% higher. The difference is attributed to an incorrect conversion factor for converting from activity to metric units. The Cobas e411 assay uses the factor 6.945 for converting from U/mL to pmol/L. This is in disagreement with the biological activity of insulin which is 166.8×10(6)IU/mol or 6.00nmol/IU. We successfully established reference intervals for C-peptide and insulin for non-diabetic and prediabetic participants. The reference intervals for fasting C-peptide and fasting insulin are ready for implementation. A recertification of the insulin standards is needed. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. 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.

  5. Reference ranges for the clinical laboratory derived from a rural population in Kericho, Kenya.

    PubMed

    Kibaya, Rukia S; Bautista, Christian T; Sawe, Frederick K; Shaffer, Douglas N; Sateren, Warren B; Scott, Paul T; Michael, Nelson L; Robb, Merlin L; Birx, Deborah L; de Souza, Mark S

    2008-10-03

    The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrollment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9:1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/microl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7-11.1) and neutrophil counts (1850 cells/microl; range 914-4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment.

  6. Reference Ranges for the Clinical Laboratory Derived from a Rural Population in Kericho, Kenya

    PubMed Central

    Kibaya, Rukia S.; Bautista, Christian T.; Sawe, Frederick K.; Shaffer, Douglas N.; Sateren, Warren B.; Scott, Paul T.; Michael, Nelson L.; Robb, Merlin L.; Birx, Deborah L.; de Souza, Mark S.

    2008-01-01

    The conduct of Phase I/II HIV vaccine trials internationally necessitates the development of region-specific clinical reference ranges for trial enrolment and participant monitoring. A population based cohort of adults in Kericho, Kenya, a potential vaccine trial site, allowed development of clinical laboratory reference ranges. Lymphocyte immunophenotyping was performed on 1293 HIV seronegative study participants. Hematology and clinical chemistry were performed on up to 1541 cohort enrollees. The ratio of males to females was 1.9∶1. Means, medians and 95% reference ranges were calculated and compared with those from other nations. The median CD4+ T cell count for the group was 810 cells/µl. There were significant gender differences for both red and white blood cell parameters. Kenyan subjects had lower median hemoglobin concentrations (9.5 g/dL; range 6.7–11.1) and neutrophil counts (1850 cells/µl; range 914–4715) compared to North Americans. Kenyan clinical chemistry reference ranges were comparable to those from the USA, with the exception of the upper limits for bilirubin and blood urea nitrogen, which were 2.3-fold higher and 1.5-fold lower, respectively. This study is the first to assess clinical reference ranges for a highland community in Kenya and highlights the need to define clinical laboratory ranges from the national community not only for clinical research but also care and treatment. PMID:18833329

  7. Environmentally relevant dose of arsenic interferes in functions of human monocytes derived dendritic cells.

    PubMed

    Bahari, Abbas; Salmani, Vahid

    2017-06-05

    Arsenic is a major environmental pollutant and highly hazardous toxin to human health, which well established as carcinogen and immune deregulatory properties. Dendritic cells (DCs) have a pivotal role in cell-mediated immunity for T-cell activation and antigen presentation. In this study, T cell activation, some key functional genes expression, cell stability and phagocytosis capacity of human monocytes derived DCs (MDDCs) were analyzed after in vitro exposure to very low dose of arsenic for 12 and 24h. Arsenic decreased continually phagocytosis capacity of MDDCs. Furthermore, down-regulation of the cell-surface expression of the co-stimulatory molecule CD40 after 24h post treatment with arsenic, confirmed arsenic interferers in the phagocytosis process. Pro inflammatory cytokines, IL1β and TNFα were more expressed in arsenic-treated MDDCs while IL6 transiently was down regulated. In general, our novel findings here strongly suggest that low level of arsenic dysregulates four fundamental immune processes of DCs. Mechanistically; this could explain the observed immunodeficiency activity of Arsenic, and give direction for comprehension the pathogenesis of Arsenic-induced diseases. Copyright © 2017. Published by Elsevier B.V.

  8. Determination of dose rate from Chernobyl-derived radiocaesium in Estonian soil.

    PubMed

    Lust, M; Realo, E

    2012-10-01

    The deposition and vertical depth distribution of 134Cs and 137Cs in the natural undisturbed soil profiles down to 20-25 cm were studied at locations in the North Eastern Estonia, which were most strongly affected by the Chernobyl fallout in 1986. The total depositions were estimated based on summing the sampled and measured activities of 134Cs and 137Cs in all sections of soil profiles. The Chernobyl 137Cs deposition values varied considerably from site to site and the range was from 3.9 kBq m(-2) to 50.2 kBq m(-2), with the average of 22.8 kBq m(-2) for the region (reference data May 1, 1986). The ratio of total activities, A(134Cs)/A(137Cs), varied in the range from 0.47 to 0.55. Using a compartment model and the observed data on the 134Cs and 137Cs activity concentrations (Bq m(-2)) in four compartments, 0-1 cm, 1-5 cm, 5-15 cm and 15-30 cm, of soil collected in 1991-2003, the approximate residence half-times of radiocaesium in soil were determined. The latter increased from 3.7 y in the top-most compartment to 8.6 y and 36.4 y in the deeper compartments, respectively. The time dependence of the external gamma-dose rate at the height of 1 m above a flat ground area arising from the deposited and migrating radiocaesium was calculated using the modeled data on the 134Cs and 137Cs activity in soil compartments. Considering the total depositions of radiocaesium in soil from the Chernobyl 1986 accident, the 50 year effective doses caused by external gamma exposure varied in the range from 0.13 mSv to 1.74 mSv, with the mean of 0.79 mSv in the region. Copyright © 2012 Elsevier Ltd. All rights reserved.

  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. 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

  11. Recurrent miscarriage associated with antiphospholipid antibodies: prophylactic treatment with low-dose aspirin and fish oil derivates.

    PubMed

    Carta, G; Iovenitti, P; Falciglia, K

    2005-01-01

    The aim of this study was to evaluate the effects of two different prophylactic protocols, low-dose aspirin and fish oil derivates, in the treatment of patients with recurrent pregnancy loss associated with antiphospholipid antibodies (APA) syndrome. A prospective study included 30 patients who were alternately assigned to treatment. Each patient had had at least two consecutive spontaneous abortions, positive antiphospholipid antibodies on two occasions, and a complete evaluation. Among patients treated with low-dose aspirin, 12 out of the 15 (80%) pregnancies ended in live births. In the fish oil derivate group 11 out of the 15 (73.3%) ended in live births (p > 0.05). There were no significant differences between the low-dose aspirin and the fish oil derivates groups with respect to gestational age at delivery (39.9 +/- 0.4 vs 39 +/- 1.5 weeks), fetal birth weight (3290 +/- 200g vs 3560 +/- 100 g), number of cesarean sections (25% vs 18%), or complications. There were no significant differences in terms of pregnancy outcome between women with recurrent pregnancy loss associated with APA syndrome treated with low-dose aspirin or fish oil derivates.

  12. 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…

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

    PubMed

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

    2016-04-01

    The developmental effects of NMP are well studied in Sprague-Dawley rats following oral, inhalation, and dermal routes of exposure. Short-term and chronic occupational exposure limit (OEL) values were derived using an updated physiologically based pharmacokinetic (PBPK) model for NMP, along with benchmark dose modeling. Two suitable developmental endpoints were evaluated for human health risk assessment: (1) for acute exposures, the increased incidence of skeletal malformations, an effect noted only at oral doses that were toxic to the dam and fetus; and (2) for repeated exposures to NMP, changes in fetal/pup body weight. Where possible, data from multiple studies were pooled to increase the predictive power of the dose-response data sets. For the purposes of internal dose estimation, the window of susceptibility was estimated for each endpoint, and was used in the dose-response modeling. A point of departure value of 390 mg/L (in terms of peak NMP in blood) was calculated for skeletal malformations based on pooled data from oral and inhalation studies. Acceptable dose-response model fits were not obtained using the pooled data for fetal/pup body weight changes. These data sets were also assessed individually, from which the geometric mean value obtained from the inhalation studies (470 mg*hr/L), was used to derive the chronic OEL. A PBPK model for NMP in humans was used to calculate human equivalent concentrations corresponding to the internal dose point of departure values. Application of a net uncertainty factor of 20-21, which incorporates data-derived extrapolation factors, to the point of departure values yields short-term and chronic occupational exposure limit values of 86 and 24 ppm, respectively. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  14. 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

  15. 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

  16. 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

  17. 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. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. CLSI-Based Validation of Manufacturer-Derived Reference Intervals on the Cobas 8000 Platform.

    PubMed

    Leitner-Ferenc, Veronika; Atamaniuk, Johanna; Jansen-Skoupy, Sonja; Stöckelmeier, Brigitta; Grohs, Katharina; Födinger, Manuela

    2017-05-01

    Reference intervals provided by diagnostic test manufacturers should be transferred to clinical laboratories after validation. Although protocols exist, laboratories rarely perform and report on results of validation studies. We validated reference intervals (RIs) of 87 analytes on a Cobas 8000 platform according to standards published by the Clinical and Laboratory Standards Institute (CLSI). For 8 analytes, decision limits were provided in the package inserts. Among the 79 RIs subjected to transference validation, 8 were found not valid for transference, including lactate dehydrogenase (LDH) among women, and the following among both sexes: potassium, homocysteine, immunoglobulin E (IgE), free lambda light chain (FLC λ), C3 complement (C3c), folate, and 25-hydroxy vitamin D (25[(OH]D). For LDH, potassium, homocysteine, C3c, folate, and 25(OH)D, RIs or thresholds suitable for transference were available in the literature; however, this was not the case for IgE and FLC λ. The present study demonstrates that validation of RIs provided in the manufacturer provided package inserts is indispensable.

  19. 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

  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. P Wave Indices: Derivation of Reference Values from the Framingham Heart Study

    PubMed Central

    Magnani, Jared W.; Johnson, Victor M.; Sullivan, Lisa M.; Lubitz, Steven A.; Schnabel, Renate B.; Ellinor, Patrick T.; Benjamin, Emelia J.

    2012-01-01

    Background P wave indices, an electrocardiographic phenotype reflecting atrial electrophysiology and morphology, may be altered in multiple disease states or by cardiovascular risk factors. Reference values for P wave indices, providing cut points for their classification and interpretation, have not yet been established and are essential towards facilitating clinical application and comparison between studies. Methods We randomly selected 20 men and 20 women from 10-year age intervals between <25 years to 76–85 years from the Framingham Heart Study Original and Offspring Cohorts, excluding subjects with prevalent cardiovascular disease, hypertension, diabetes or obesity. The total included 295 subjects; eligibility in women >75 years was limited by exclusion criteria. We used a digital measurement technique with demonstrated intrarater reproducibility to determine P wave indices. P wave indices examined included the maximum, mean, lead II and PR durations, dispersion, and the standard deviation of duration. Results All P wave indices were significantly (P<0.0001) correlated with advancing age. Means of all P wave indices were lower in women as compared to men. PR interval duration was strongly correlated with maximum, mean, and lead II mean P wave durations. In multivariable models adjusting for significant anthropometric and clinical associations risk factors, significant differences persisted by age and sex in P wave indices. Conclusions In our healthy sample without cardiovascular disease, hypertension, diabetes or obesity, men and older subjects had longer mean P wave indices. Our description of P wave indices establishes reference values for future comparative studies and facilitates the classification of P wave indices. PMID:20946557

  2. 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.

  3. (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.

  4. Derivation of gender and age-specific reference intervals from fully normal Japanese individuals and the implications for health screening.

    PubMed

    Yamakado, Minoru; Ichihara, Kiyoshi; Matsumoto, Yoshiyuki; Ishikawa, Yoshiki; Kato, Kiminori; Komatsubara, Yusuke; Takaya, Norihide; Tomita, Shohken; Kawano, Reo; Takada, Keisuke; Watanabe, Kiyoaki

    2015-07-20

    With nationwide standardization of laboratory tests among institutions for health screening in Japan, common reference intervals (RIs) were derived from records of 1,500,000 health check attendees. Targets were 20 basic laboratory tests including body mass index (BMI) and systolic and diastolic blood pressures (SBP, DBP). Individuals fulfilling the following strict criteria were chosen: SBP<130, DBP<85mmHg, BMI<25kg/m(2), non-smoking, ethanol consumption<20g/day and under no mediation with no remarkable current/past illnesses. The latent abnormal values exclusion (LAVE) method was applied to ensure fully normal results. RIs were derived by parametric method using modified Box-Cox power transformation. Among all attendees, 23% fulfilled the criteria. Application of the LAVE method further reduced the dataset by 40%-50%. Age-related charts of test results differed greatly between genders in almost all tests. Comparison of derived RIs with clinical decision limits (CDLs) revealed that the upper limits of RIs differed from CDLs according to gender and age. Implementation of gender and age-specific RIs derived from individuals with fully normal health attributes will (1) enable appropriate interpretation of test results in health screening and (2) promote judicious application of CDLs for therapeutic intervention, taking into account gender, age and other health attributes. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. SUDOQU: a new dose model to derive criteria for surface contamination of non-food (consumer) goods, containers and conveyances.

    PubMed

    van Dillen, Teun

    2015-04-01

    The Fukushima nuclear accident (Japan, 11 March 2011) revealed the need for well-founded criteria for surface contamination and associated screening levels related to the import of non-food (consumer) goods, containers and conveyances. The only available European-harmonised criteria are those laid down in the IAEA transport regulations, but these criteria date back from the early 1960s and only apply to the safe transport of radioactive materials. The main problem is that a generic dose-assessment model for consumer products is missing. Therefore, RIVM (National Institute for Public Health and the Environment) developed a new methodology entitled SUDOQU (SUrface DOse QUantification) to calculate the annual effective dose for both consumers and non-radiological workers, addressing issues of removability of surface contamination. The methodology can be used to derive criteria and screening levels for surface contamination and could serve as a useful tool for policy-makers and radiation-protection specialists.

  6. 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.

  7. A brain region-specific predictive gene map for autism derived by profiling a reference gene set.

    PubMed

    Kumar, Ajay; Swanwick, Catherine Croft; Johnson, Nicole; Menashe, Idan; Basu, Saumyendra N; Bales, Michael E; Banerjee-Basu, Sharmila

    2011-01-01

    Molecular underpinnings of complex psychiatric disorders such as autism spectrum disorders (ASD) remain largely unresolved. Increasingly, structural variations in discrete chromosomal loci are implicated in ASD, expanding the search space for its disease etiology. We exploited the high genetic heterogeneity of ASD to derive a predictive map of candidate genes by an integrated bioinformatics approach. Using a reference set of 84 Rare and Syndromic candidate ASD genes (AutRef84), we built a composite reference profile based on both functional and expression analyses. First, we created a functional profile of AutRef84 by performing Gene Ontology (GO) enrichment analysis which encompassed three main areas: 1) neurogenesis/projection, 2) cell adhesion, and 3) ion channel activity. Second, we constructed an expression profile of AutRef84 by conducting DAVID analysis which found enrichment in brain regions critical for sensory information processing (olfactory bulb, occipital lobe), executive function (prefrontal cortex), and hormone secretion (pituitary). Disease specificity of this dual AutRef84 profile was demonstrated by comparative analysis with control, diabetes, and non-specific gene sets. We then screened the human genome with the dual AutRef84 profile to derive a set of 460 potential ASD candidate genes. Importantly, the power of our predictive gene map was demonstrated by capturing 18 existing ASD-associated genes which were not part of the AutRef84 input dataset. The remaining 442 genes are entirely novel putative ASD risk genes. Together, we used a composite ASD reference profile to generate a predictive map of novel ASD candidate genes which should be prioritized for future research.

  8. Pre-operative CT coronary angiography in patients with mitral valve prolapse referred for surgical repair: comparison of accuracy, radiation dose and cost versus invasive coronary angiography.

    PubMed

    Pontone, Gianluca; Andreini, Daniele; Bertella, Erika; Cortinovis, Sarah; Mushtaq, Saima; Foti, Claudia; Annoni, Andrea; Formenti, Alberto; Baggiano, Andrea; Conte, Edoardo; Ballerini, Giovanni; Fiorentini, Cesare; Bartorelli, Antonio L; Pepi, Mauro

    2013-09-10

    The aims of this study are to evaluate the accuracy of low dose multidetector computed tomography coronary angiography (MDCT) versus invasive coronary angiography (ICA) in ruling out CAD in patients with mitral valve prolapse and severe mitral regurgitation (MVP) before cardiac surgery and to compare the overall effective radiation dose (ED) and cost of a diagnostic approach in which conventional ICA should be performed only in patients with significant CAD as detected by MDCT. Eighty patients with MVP and without history of CAD were randomized to MDCT (Group 1) or ICA (Group 2) to rule out CAD before surgery. However, ICA was also performed as gold standard reference in Group 1 to test the diagnostic accuracy of MDCT. A diagnostic work-up A in whom all patients underwent low-dose MDCT as initial diagnostic test and those with positive findings were referred for ICA was compared with work-up B in which all patients were referred for ICA according to the standard of care in terms of ED and cost. The two groups were homogeneous in terms of gender, age and body mass index. The overall feasibility and accuracy in a patient-based model were 99% and 93%, respectively. The overall ED and costs were significantly lower in diagnostic work-up A compared to diagnostic work-up B. The accuracy of low dose MDCT for ruling out the presence of significant CAD in patients undergoing elective valve surgery for mitral valve prolapse is excellent with a reduction of overall radiation dose exposure and costs. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  9. 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

  10. The dose-dependence biological effect of laser fluence on rabbit fibroblasts derived from urethral scar.

    PubMed

    Yang, Yong; Yu, Bo; Sun, Dongchong; Wu, Yuanyi; Xiao, Yi

    2015-04-01

    Two-micrometer laser vaporization resection has been used in clinic for years, but some patients received the treatment are still faced with excessive and abnormal wound repair which leads to the recurrent of urethral stricture eventually. Fibroblasts play a key role in the processes of "narrow-expansion/operation-restenosis" recurring problems. Here, we investigated the effect of laser fluence biomodulation on urethral scar fibroblasts as well as the underlying mechanism. Urethral scar fibroblasts were isolated and cultured, and laser irradiation (2 μm) was applied at different laser fluence or doses (0, 0.125, 0.5, 2, 8, 32 J/cm(2)) with a single exposure in 1 day. The effect of 2-μm laser irradiation on cell proliferation, viability, and expression of scar formation related genes were investigated. Two-micrometer laser irradiation with intermediate dose (8 J/cm(2)) promoted scar fibroblasts proliferation and reactive oxygen species (ROS) production, while higher doses of 32 J/cm(2) are suppressive as it decreased the survival rate, viability, and proliferation of fibroblasts. In addition, qRT-PCR and Western blotting results both proven that collagen type I, collagen IV, MMP9, and CTGF display significant increase, yet the TGF-β1 expression was severely reduced at intermediate dose (8 J/cm(2)) group when compared with the others groups. Our findings suggest the scar formation-related genes are sensitive to intermediate laser irradiation dose, the most in scar fibroblasts. We revealed the bioeffect and molecular mechanism of 2-μm laser irradiation on rabbit urethral scar fibroblasts. Our study provides new insights into the mechanisms which involved in the excessive and abnormal wound repair of 2-μm laser vaporization resection. These results could potentially contribute to further study on biological effects and application of 2-μm laser irradiation in urethral stricture therapy.

  11. Comparative molecular field analysis to derive pharmacophore maps for induction doses of intravenous anaesthetic agents.

    PubMed

    Sear, J W

    2011-03-01

    The present study examines the molecular basis of induction of anaesthesia by i.v. hypnotic agents using comparative molecular field analysis (CoMFA). ED(50) induction doses for 14 i.v. anaesthetics in human subjects (expressed as molar dose per kilogram body weight) were obtained from the literature. Immobilizing potency data for the same 14 agents (expressed as the EC(50) plasma free drug concentrations that abolish movement in response to a noxious stimulus in 50% patients) were taken from our previous publication. These data were used to form CoMFA models for the two aspects of anaesthetic activity. Molecular alignment was achieved by field-fit minimization techniques. The lead structure for both models was eltanolone. The final CoMFA model for the ED(50) induction dose was based on two latent variables, and explained 99.3% of the variance in observed activities. It showed good intrinsic predictability (cross-validated q(2)=0.849). The equivalent model for immobilizing activity was also based on two latent variables, with r(2)=0.988 and q(2)=0.852. Although there was a correlation between -log ED(50) and -log EC(50) (r(2)=0.779), comparison of the pharmacophore maps showed poor correlation for both electrostatic and steric regions when isocontours were constructed by linking lattice grid points, making the greatest 40% contributions; the relative contributions of electrostatic and steric interactions differing between the models (induction dose: 2.5:1; immobilizing activity 1.8:1). Comparison of two CoMFA activity models shows only small elements of commonality, suggesting that different molecular features may be responsible for these two properties of i.v. anaesthetics.

  12. Bayesian fitting of a logistic dose-response curve with numerically derived priors.

    PubMed

    Huson, L W; Kinnersley, N

    2009-01-01

    In this report we describe the Bayesian analysis of a logistic dose-response curve in a Phase I study, and we present two simple and intuitive numerical approaches to construction of prior probability distributions for the model parameters. We combine these priors with the expert prior opinion and compare the results of the analyses with those obtained from the use of alternative prior formulations.

  13. A nitroimidazole derivative, PR-350, enhances the killing of pancreatic cancer cells exposed to high-dose irradiation under hypoxia.

    PubMed

    Mizumoto, Kazuhiro; Qian, Li-Wu; Zhang, Li; Nagai, Eishi; Kura, Shinobu; Tanaka, Masao

    2002-03-01

    The radiosensitizing effects of PR-350, a nitroimidazole derivative, were examined concerning the cell killing of human pancreatic cancer cell lines exposed to high doses of gamma-ray irradiation in vitro. The percentages of dead cells were analyzed with a multiwell plate reader to measure the fluorescence intensity of propidium iodide before and after a digitonin treatment. The sensitizing effect of PR-350 on cell killing by high-dose irradiation was confirmed by time-course, dose-dependency, and microscopic observations. In five of seven pancreatic cancer cell lines in which the number of dead cells was determined 5 days after 30 Gy irradiation in the presence of PR-350, the number was significantly increased under hypoxic conditions, but not under aerobic conditions. The selective radiosensitive effect of PR-350 on hypoxic cells was also confirmed by flow cytometry. The results indicate that PR-350 can enhance the killing of pancreatic cancer cells by high-dose irradiation under hypoxia, which supports its clinical radiosensitizing effects when administered during intraoperative irradiation to pancreatic cancer.

  14. 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.

  15. Air kerma calculation in Monte Carlo simulations for deriving normalized glandular dose coefficients in mammography

    NASA Astrophysics Data System (ADS)

    Sarno, Antonio; Mettivier, Giovanni; Russo, Paolo

    2017-07-01

    The estimation of the mean glandular dose in mammography using Monte Carlo simulations requires the calculation of the incident air kerma evaluated on the breast surface. In such a calculation, caution should be applied in considering explicitly the presence of the top compression paddle, since Compton scattering in this slab may produce a large spread of the incidence angles of x-ray photons on the scoring surface. Then, the calculation of the incident air kerma should contain the ‘effective’ area of the scoring surface, which takes into account the angle of incidence of photons on such a surface. Using Geant4 Monte Carlo simulations with a code previously validated according to the Task Group 195 of the American Association of Physicists in Medicine, we show that for typical x-ray spectra and energy range adopted in mammography, the resulting discrepancy in the calculation of the incident air kerma may lead to an overestimation from a minimum of 10% up to 12% of normalized dose coefficients and, hence, of the corresponding mean glandular dose if this contribution is not considered.

  16. A Single Dose of Vero Cell–Derived Japanese Encephalitis (JE) Vaccine (Ixiaro) Effectively Boosts Immunity in Travelers Primed With Mouse Brain–Derived JE Vaccines

    PubMed Central

    Erra, Elina O.; Askling, Helena Hervius; Rombo, Lars; Riutta, Jukka; Vene, Sirkka; Yoksan, Sutee; Lindquist, Lars; Pakkanen, Sari H.; Huhtamo, Eili; Vapalahti, Olli; Kantele, Anu

    2012-01-01

    Background. A significant part of the world population lives in areas with endemic Japanese encephalitis (JE). For travelers from nonendemic countries, Vero cell–derived vaccine (JE-VC; Ixiaro) has replaced traditional mouse brain–derived vaccines (JE-MB) associated with safety concerns. The 2 vaccines are derived from different viral strains: JE-VC from the SA14-14-2 strain and JE-MB from the Nakayama strain. No data exist regarding whether JE-VC can be used to boost immunity after a primary series of JE-MB; therefore, a primary series of JE-VC has been recommended to all travelers regardless of previous vaccination history. Methods. One hundred twenty travelers were divided into 4 groups: Volunteers with no prior JE vaccination received primary immunization with (group 1) JE-MB or (group 2) JE-VC, and those primed with JE-MB received a single booster dose of (group 3) JE-MB or (group 4) JE-VC. Immune responses were tested before and 4–8 weeks after vaccination using plaque reduction neutralization test (PRNT) against both vaccine strains. Results. In vaccine-naive travelers, the vaccination response rate for test strains Nakayama and SA14-14-2 was 100% and 87% after primary vaccination with JE-MB and 87% and 94% after JE-VC, respectively. Antibody levels depended on the target virus, with higher titers against homologous than heterologous PRNT50 target strain (P < .001). In travelers primed with JE-MB, vaccination response rates were 91% and 91%, and 98% and 95% after a booster dose of JE-MB or JE-VC, respectively. Subgroup analysis revealed that a higher proportion of primed (98%/95%) than nonprimed (39%/42%) volunteers responded to a single dose of JE-VC (P < .001). Conclusions. A single dose of JE-VC effectively boosted immunity in JE-MB–primed travelers. Current recommendations should be reevaluated. Clinical Trials Registration. NCT01386827. PMID:22696017

  17. Effects of Different Containers on Radioactivity Measurements using a Dose Calibrator with Special Reference to (111)In and (123)I.

    PubMed

    Inoue, Yusuke; Abe, Yutaka; Kikuchi, Kei; Miyatake, Hiroki; Watanabe, Atsushi

    2017-01-01

    Low-energy characteristic x-rays emitted by (111)In and (123)I sources are easily absorbed by the containers of the sources, affecting radioactivity measurements using a dose calibrator. We examined the effects of different containers on the estimated activities. The radioactivities of (111)In, (123)I, (201)Tl, and (99m)Tc were measured in containers frequently employed in clinical practice in Japan. The (111)In measurements were performed in the vials A and B of the (111)In-pentetreotide preparation kit and in the plastic syringe. The activities of (123)I-metaiodobenzylguanidine and (201)Tl chloride were measured in the prefilled glass syringes and plastic syringes. The milking vial, vial A, vial B, and plastic syringe were used to assay (99m)Tc. For (111)In and (123)I, measurements were performed with and without a copper filter. The filter was inserted into the well of the dose calibrator to absorb low-energy x-rays. The relative estimate was defined as the ratio of the activity estimated with the dose calibrator to the standard activity. The estimated activities varied greatly depending on the container when (111)In and (123)I sources were assayed without the copper filter. The relative estimates of (111)In were 0.908, 1.072, and 1.373 in the vial A, vial B, and plastic syringe, respectively. The relative estimates of (123)I were 1.052 and 1.352 in the glass syringe and plastic syringe, respectively. Use of the copper filter eliminated the container-dependence in (111)In and (123)I measurements. Container-dependence was demonstrated in neither (201)Tl nor (99m)Tc measurements. The activities of (111)In and (123)I estimated with a dose calibrator differ greatly among the containers. Accurate estimation may be attained using the container-specific correction factor or using the copper filter.

  18. Hippocampal brain-derived neurotrophic factor mediates recovery from chronic stress-induced spatial reference memory deficits.

    PubMed

    Ortiz, J Bryce; Mathewson, Coy M; Hoffman, Ann N; Hanavan, Paul D; Terwilliger, Ernest F; Conrad, Cheryl D

    2014-11-01

    Chronic restraint stress impairs hippocampal-mediated spatial learning and memory, which improves following a post-stress recovery period. Here, we investigated whether brain-derived neurotrophic factor (BDNF), a protein important for hippocampal function, would alter the recovery from chronic stress-induced spatial memory deficits. Adult male Sprague-Dawley rats were infused into the dorsal hippocampal cornu ammonis (CA)3 region with an adeno-associated viral vector containing the sequence for a short hairpin RNA (shRNA) directed against BDNF or a scrambled sequence (Scr). Rats were then chronically restrained (wire mesh, 6 h/day for 21 days) and assessed for spatial learning and memory using a radial arm water maze (RAWM) either immediately after stressor cessation (Str-Imm) or following a 21-day post-stress recovery period (Str-Rec). All groups learned the RAWM task similarly, but differed on the memory retention trials. Rats in the Str-Imm group, regardless of adeno-associated viral contents, committed more errors in the spatial reference memory domain on the single retention trial during day 3 than did the non-stressed controls. Importantly, the typical improvement in spatial memory following the recovery from chronic stress was blocked with the shRNA against BDNF, as Str-Rec-shRNA performed worse on the RAWM compared with the non-stressed controls or Str-Rec-Scr. The stress effects were specific for the reference memory domain, but knockdown of hippocampal BDNF in unstressed controls briefly disrupted spatial working memory as measured by repeated entry errors on day 2 of training. These results demonstrated that hippocampal BDNF was necessary for the recovery from stress-induced hippocampal-dependent spatial memory deficits in the reference memory domain.

  19. 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.

  20. The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats.

    PubMed

    Hamlyn, Eugene; Brand, Linda; Shahid, Mohammed; Harvey, Brian H

    2009-10-01

    Ampakines have shown beneficial effects on cognition in selected animal models of learning. However, their ability to modify long-term spatial memory tasks has not been studied yet. This would lend credence to their possible value in treating disorders of cognition. We evaluated the actions of subchronic Org 26576 administration on spatial reference memory performance in the 5-day Morris water maze task in male Sprague-Dawley rats, at doses of 1, 3 and 10 mg/kg twice daily through intraperitoneal injection over 12 days. Org 26576 exerted a dose and time-dependent effect on spatial learning, with dosages of 3 and 10 mg/kg significantly enhancing acquisition on day 1. Globally, escape latency decreased significantly as the training days progressed in the saline and Org 26576-treated groups, indicating that significant and equal learning had taken place over the learning period. However, at the end of the learning period, all doses of Org 26576 significantly improved spatial memory storage/retrieval without confounding effects in the cued version of the task. Org 26576 offers early phase spatial memory benefits in rats, but particularly enhances search accuracy during reference memory retrieval. These results support its possible utility in treating disorders characterized by deficits in cognitive performance.

  1. 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

  2. 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.

  3. 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.

  4. Accuracy of Acuros XB and AAA dose calculation for small fields with reference to RapidArc(®) stereotactic treatments.

    PubMed

    Fogliata, Antonella; Nicolini, Giorgia; Clivio, Alessandro; Vanetti, Eugenio; Cozzi, Luca

    2011-11-01

    To assess the accuracy against measurements of two photon dose calculation algorithms (Acuros XB and the Anisotropic Analytical algorithm AAA) for small fields usable in stereotactic treatments with particular focus on RapidArc(®). Acuros XB and AAA were configured for stereotactic use. Baseline accuracy was assessed on small jaw-collimated open fields for different values for the spot sizes parameter in the beam data: 0.0, 0.5, 1, and 2 mm. Data were calculated with a grid of 1 × 1 mm(2). Investigated fields were: 3 × 3, 2 × 2, 1 × 1, and 0.8 × 0.8 cm(2) with a 6 MV photon beam generated from a Clinac2100iX (Varian, Palo Alto, CA). Profiles, PDD, and output factors were measured in water with a PTW diamond detector (detector size: 4 mm(2), thickness 0.4 mm) and compared to calculations. Four RapidArc test plans were optimized, calculated and delivered with jaw settings J3 × 3, J2 × 2, and J1 × 1 cm(2), the last was optimized twice to generate high (H) and low (L) modulation patterns. Each plan consisted of one partial arc (gantry 110° to 250°), and collimator 45°. Dose to isocenter was measured in a PTW Octavius phantom and compared to calculations. 2D measurements were performed by means of portal dosimetry with the GLAaS method developed at authors' institute. Analysis was performed with gamma pass-fail test with 3% dose difference and 2 mm distance to agreement thresholds. Open square fields: penumbrae from open field profiles were in good agreement with diamond measurements for 1 mm spot size setting for Acuros XB, and between 0.5 and 1 mm for AAA. Maximum MU difference between calculations and measurements was 1.7% for Acuros XB (0.2% for fields greater than 1 × 1 cm(2)) with 0.5 or 1 mm spot size. Agreement for AAA was within 0.7% (2.8%) for 0.5 (1 mm) spot size. RapidArc plans: doses were evaluated in a 4 mm diameter structure at isocenter and computed values differed from measurements by 0.0, -0.2, 5.5, and

  5. Patient and staff doses in paediatric interventional cardiology derived from experimental measurements with phantoms.

    PubMed

    Ubeda, Carlos; Vano, Eliseo; Miranda, Patricia; Aguirre, Daniel; Riquelme, Nemorino; Dalmazzo, Dandaro; Galaz, Sergio

    2016-01-01

    The aim of this paper was to determine experimentally the entrance surface air kerma (ESAK) and kerma-area product (KAP) levels to patients and scatter doses at the cardiologist's eyes during paediatric interventional cardiology (IC) procedures for Chile, on the basis of measurements taken from X-ray systems characterization for different thicknesses of polymethyl methacrylate, together with the average values of fluoroscopy time and number of cine frames for ten paediatric IC procedures. The range of cumulative ESAK values when the different clinical procedures were simulated was from 2 to 1100 mGy. KAP values ranged from 0.30 to 150 Gy cm(2). Scatter doses at cardiologist's eyes for the simulated procedures ranged from 0.20 to 116 µSv per procedure. Large differences between the X-ray systems were found in our study. Standardized guidelines in terms of X-ray system setting and protocols should be developed for hospitals that perform paediatric IC procedures in Chile.

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

    PubMed

    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.

  7. Three-dimensional dose distribution of proton beams derived from luminescence images of water

    NASA Astrophysics Data System (ADS)

    Yamamoto, S.; Watabe, H.; Toshito, T.; Komori, M.

    2017-05-01

    We recently found that luminescence was emitted from water during proton irradiation at lower energy than the Cerenkov-light threshold and imaging was possible by using a CCD camera. However, since the measured distributions were projection images of the luminescence, precise dose estimations from the images were not possible. If the 3 dimensional images can be formed from the projection images, more precise dose information could be obtained. For this purpose, we calculate the 3-dimensional distribution of the proton beams from the luminescence images and use them for beam width estimations. We assumed that the proton beams have circular shape and the transverse images were reconstructed from the projection images using the filtered backprojection (FBP) algorithm for positron emission tomography (PET). The reconstructed images were compared to estimate the proton-beam widths with those obtained from the projection images and simulation results. We obtained 3-dimensional distributions of the proton beams from the projection images and also the reconstructed sagittal, coronal, and transverse images as well as volume rendering images. The estimated beam widths from the reconstructed images, which were slightly smaller than those obtained from the projection images, were identical to those calculated with the simulation. The 3-dimensional distributions of the luminescence images of water of proton beams could be reconstructed from the projection images and showed improved accuracy in estimating the beam widths of the proton beams.

  8. 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.

  9. A system for protecting the environment from ionising radiation: selecting reference fauna and flora, and the possible dose models and environmental geometries that could be applied to them.

    PubMed

    Pentreath, R J; Woodhead, D S

    2001-09-28

    In order to demonstrate, explicitly, that the environment can be protected with respect to controlled sources of ionising radiation, it is essential to have a systematic framework within which dosimetry models for fauna and flora can be used. And because of the practical limitations on what could reasonably be modelled and the amount of information that could reasonably be obtained, it is also necessary to limit the application of such models to a 'set' of fauna and flora within a reference' context. This paper, therefore, outlines the factors that will need to be considered to select such 'reference' fauna and flora, and describes some of the factors and constraints necessary to develop the associated dosimetry models. It also describes some of the most basic environmental geometrics within which the dose models could be set in order to make comparisons amongst different radiation sources.

  10. 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).

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

    NASA Astrophysics Data System (ADS)

    Alvarez, J. T.; Sander, T.; de Pooter, J. A.; Allisy-Roberts, P. J.; Kessler, C.

    2014-01-01

    An indirect comparison of the standards for reference air kerma rate for 192Ir high dose rate brachytherapy sources of the National Physical Laboratory (NPL), United Kingdom, and of the Bureau International des Poids et Mesures (BIPM) was carried out at the NPL in June 2010. The comparison result, based on the calibration coefficients for a transfer standard and expressed as a ratio of the NPL and the BIPM standards for reference air kerma rate, is 0.9989 with a combined standard uncertainty of 0.0057. 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).

  12. 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

  13. Determination of absorbed dose in water at the reference point d(r0, theta0) for an 192Ir HDR brachytherapy source using a Fricke system.

    PubMed

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

    2008-12-01

    A ring-shaped Fricke device was developed to measure the absolute dose on the transverse bisector of a 192Ir high dose rate (HDR) source at 1 cm from its center in water, D(r0, theta0). It consists of a polymethylmethacrylate (PMMA) rod (axial axis) with a cylindrical cavity at its center to insert the 192Ir 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(r0, theta0). Irradiations were performed with a Nucletron microselectron HDR unit loaded with an 192Ir 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 192Ir 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(r0, theta0) by 2.0%. Applying the corresponding correction factor, the D(r0, theta0) 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 method towards calibration of brachytherapy radiation sources in terms of D(r0

  14. Dose-dependent induction of IL-6 by plant-derived proteases in vitro

    PubMed Central

    Rose, B; Herder, C; Löffler, H; Meierhoff, G; Schloot, N C; Walz, M; Martin, S

    2006-01-01

    Oral administration of proteases such as bromelain and papain is commonly used in patients with a wide range of inflammatory conditions, but their molecular and cellular mechanisms of action are still poorly understood. The aim of our study was to investigate the impact of these proteases on the release of interleukin-6 (IL-6) and other cytokines in the recently described modified mixed lymphocyte culture (MMLC) test system which is based on the mutual interaction of cells of the innate and adaptive immunity. Bromelain and papain enhanced IL-6 production dose-dependently up to 400-fold in MMLC before and up to 30-fold after neutralization of LPS content of proteases using polymyxin B, indicating that IL-6 induction by protease treatment was attributable to both protease action and LPS content of enzyme preparations. The production of IFNγ and IL-10 was not altered by bromelain or papain, indicating a selective and differential immune activation. Both proteases impaired cytokine stability, cell proliferation and expression of cell surface molecules like CD14 only marginally, suggesting no impact of these mechanisms on protease-mediated cytokine release. These findings might provide the mechanistic rationale for the current use of proteases in wound healing and tissue regeneration since these processes depend on IL-6 induction. PMID:16367938

  15. Effect of single dose of diuretics on renal magnesium excretion in man, with special reference to their site of action.

    PubMed

    Sotorník, I; Schück, O

    1976-01-01

    The administration of a single dose of furosemide, ethacrynic acid and polythiazide to healthy individuals under conditions of maximum water diuresis produces a significant increase in renal magnesium excretion. Elevated Mg excretion displayed a direct correlation to renal sodium excretion after furosemide (r=0.689, p less than 0.001), ethacrynic acid (r=0.869, p less than 0.001) and polythiazide (r=0.586, p less than 0.01). The slopes of the various regression lines did not differe significantly from each other or from the slope of the regression line characterizing this correlation for mannitol (r= 0.603, p less than 0.01). A significant linear correlation was likewise found between the excretion of Mg and total osmotically active substances after furosemide (r=0.783, p less than 0.001), ethacrynic acid (r=0.88, p less than 0.001) and polythiazide (r=0.646, p less than 0.01). The regression lines of the given correlations did not differ significantlyfrom each other, but their slopes were significantly higher than that of the regression line for the correlation after mannitol (r=0.454, p less than 0.01). The findings indicate that tubular Mg transport is influenced both by a decrease in tubular Na resorption in the diluting segment (polythiazide) and by an effect on Na resorption in the parts of the nephron proximal to the diluting segment of the nephron (furosemide, ethacrynic acid).

  16. Longitudinal studies of cardiac troponin-I concentrations in serum from male Sprague Dawley rats: baseline reference ranges and effects of handling and placebo dosing on biological variability.

    PubMed

    Schultze, A Eric; Carpenter, Kent H; Wians, Frank H; Agee, Sara J; Minyard, Jennifer; Lu, Quynh Anh; Todd, John; Konrad, Robert J

    2009-10-01

    Serum cardiac troponin-I has been validated as a biomarker for cardiotoxicity in numerous animal models; however, baseline reference ranges for cTnI concentration in a healthy population of laboratory rats, as well as an investigation of biological cTnI variability in rats with respect to time, handling, and placebo dosing methods, have not been reported. In this study, we used an ultrasensitive cTnI immunoassay to quantify hourly concentrations of cTnI in live rats handled under standard laboratory conditions using 15 microL of serum per determination. The baseline reference range (mean 4.94 pg/mL, range 1-15 pg/mL, 99% confidence interval [CI]) of cTnI concentration in rats was consistent with previously reported reference ranges for cTnI in humans (1-12 pg/mL) and with preliminary studies in dogs (1-4 pg/mL) and monkeys (4-5 pg/mL) using the same cTnI assay method. In addition, cTnI concentrations in individual rat serum samples show minimal biological variability over a twenty-four-hour interval when compared to a meaningful reference change value of 193% to 206%. Furthermore, measurements of cTnI concentration were consistent within the reference limits in individual rats over long periods and under three different standard laboratory handling conditions. Thus, using this new method, rats can be followed longitudinally at hourly intervals, and a doubling of cTnI concentration would be significant above biological variability. This is a new paradigm for preclinical testing, which allows transient changes in cTnI concentration to be accurately quantified. This understanding of baseline and biological variability in rats will be fundamental for designing and analyzing future studies that assess potential cardiotoxicity in drug development.

  17. Endothelial-derived hyperpolarization contributes to acetylcholine-mediated vasodilation in human skin in a dose-dependent manner.

    PubMed

    Brunt, Vienna E; Fujii, Naoto; Minson, Christopher T

    2015-11-01

    Cutaneous acetylcholine (ACh)-mediated dilation is commonly used to assess microvascular function, but the mechanisms of dilation are poorly understood. Depending on dose and method of administration, nitric oxide (NO) and prostanoids are involved to varying extents and the roles of endothelial-derived hyperpolarizing factors (EDHFs) are unclear. In the present study, five incremental doses of ACh (0.01-100 mM) were delivered either as a 1-min bolus (protocol 1, n = 12) or as a ≥20-min continuous infusion (protocol 2, n = 10) via microdialysis fibers infused with 1) lactated Ringer, 2) tetraethylammonium (TEA) [a calcium-activated potassium channel (KCa) and EDHF inhibitor], 3) L-NNA+ketorolac [NO synthase (NOS) and cyclooxygenase (COX) inhibitors], and 4) TEA+L-NNA+Ketorolac. The hyperemic response was characterized as peak and area under the curve (AUC) cutaneous vascular conductance (CVC) for bolus infusions or plateau CVC for continuous infusions, and reported as %maximal CVC. In protocol 1, TEA, alone and combined with NOS+COX inhibition, attenuated peak CVC (100 mM Ringer 59 ± 6% vs. TEA 43 ± 5%, P < 0.05; L-NNA+ketorolac 35 ± 4% vs. TEA+L-NNA+ketorolac 25 ± 4%, P < 0.05) and AUC (Ringer 25,414 ± 3,528 vs. TEA 21,403 ± 3,416%·s, P < 0.05; L-NNA+ketorolac 25,628 ± 3,828%(.)s vs. TEA+L-NNA+ketorolac 20,772 ± 3,711%·s, P < 0.05), although these effects were only significant at the highest dose of ACh. At lower doses, TEA lengthened the total time of the hyperemic response (10 mM Ringer 609 ± 78 s vs. TEA 860 ± 67 s, P < 0.05). In protocol 2, TEA alone did not affect plateau CVC, but attenuated plateau in combination with NOS+COX inhibition (100 mM 50.4 ± 6.6% vs. 30.9 ± 6.3%, P < 0.05). Therefore, EDHFs contribute to cutaneous ACh-mediated dilation, but their relative contribution is altered by the dose and infusion procedure.

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

    PubMed Central

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

    2014-01-01

    Introduction 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. Methods 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 (PKA), skin surface entrance dose (KAR), fluoroscopy time (FT), and patient height and weight were collected for 3 months. The DRL was set from the 75th percentile of the PKA. Results 2590 patients were included in the CA group where the median FT was 3.5 min (inter-quartile range = 2.3–6.1). Median KAR = 581 mGy (374–876). Median PKA = 3908 uGym2 (2489–5865) DRL = 5865 uGym2. 947 patients were included in the PCI group where median FT was 11.2 min (7.7–17.4). Median KAR = 1501 mGy (928–2224). Median PKA = 8736 uGym2 (5449–12,900) DRL = 12,900 uGym2. Conclusion This study established a benchmark for radiation dose for diagnostic and interventional coronary angiography in Queensland public facilities. PMID:26229649

  19. Monte Carlo simulated correction factors for machine specific reference field dose calibration and output factor measurement using fixed and iris collimators on the CyberKnife system

    NASA Astrophysics Data System (ADS)

    Francescon, P.; Kilby, W.; Satariano, N.; Cora, S.

    2012-06-01

    Monte Carlo (MC) simulation of dose to water and dose to detector has been used to calculate the correction factors needed for dose calibration and output factor measurements on the CyberKnife system. Reference field ionization chambers simulated were the PTW 30006, Exradin A12, and NE 2571 Farmer chambers, and small volume chambers PTW 31014 and 31010. Correction factors for Farmer chambers were found to be 0.7%-0.9% larger than those determined from TRS-398 due mainly to the dose gradient across the chamber cavity. For one microchamber where comparison was possible, the factor was 0.5% lower than TRS-398 which is consistent with previous MC simulations of flattening filter free Linacs. Output factor detectors simulated were diode models PTW 60008, 60012, 60017, 60018, Sun Nuclear edge detector, air-filled microchambers Exradin A16 and PTW 31014, and liquid-filled microchamber PTW 31018 microLion. Factors were generated for both fixed and iris collimators. The resulting correction factors differ from unity by up to +11% for air-filled microchambers and -6% for diodes at the smallest field size (5 mm), and tend towards unity with increasing field size (correction factor magnitude <1% for all detectors at field sizes >15 mm). Output factor measurements performed using these detectors with fixed and iris collimators on two different CyberKnife systems showed initial differences between detectors of >15% at 5 mm field size. After correction the measurements on each unit agreed within ˜1.5% at the smallest field size. This paper provides a complete set of correction factors needed to apply a new small field dosimetry formalism to both collimator types on the CyberKnife system using a range of commonly used detectors.

  20. 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

  1. Enrichment increases hippocampal neurogenesis independent of blood monocyte-derived microglia presence following high-dose total body irradiation.

    PubMed

    Ruitenberg, Marc J; Wells, Julia; Bartlett, Perry F; Harvey, Alan R; Vukovic, Jana

    2017-06-01

    Birth of new neurons in the hippocampus persists in the brain of adult mammals and critically underpins optimal learning and memory. The process of adult neurogenesis is significantly reduced following brain irradiation and this correlates with impaired cognitive function. In this study, we aimed to compare the long-term effects of two environmental paradigms (i.e. enriched environment and exercise) on adult neurogenesis following high-dose (10Gy) total body irradiation. When housed in standard (sedentary) conditions, irradiated mice revealed a long-lasting (up to 4 months) deficit in neurogenesis in the granule cell layer of the dentate gyrus, the region that harbors the neurogenic niche. This depressive effect of total body irradiation on adult neurogenesis was partially alleviated by exposure to enriched environment but not voluntary exercise, where mice were single-housed with unlimited access to a running wheel. Exposure to voluntary exercise, but not enriched environment, did lead to significant increases in microglia density in the granule cell layer of the hippocampus; our study shows that these changes result from local microglia proliferation rather than recruitment and infiltration of circulating Cx3cr1(+/gfp) blood monocytes that subsequently differentiate into microglia-like cells. In summary, latent neural precursor cells remain present in the neurogenic niche of the adult hippocampus up to 8 weeks following high-dose total body irradiation. Environmental enrichment can partially restore the adult neurogenic process in this part of the brain following high-dose irradiation, and this was found to be independent of blood monocyte-derived microglia presence. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

  2. 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). © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology.

  3. 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.

  4. 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.

  5. 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

  6. Improving thermal dose accuracy in magnetic resonance-guided focused ultrasound surgery: Long-term thermometry using a prior baseline as a reference.

    PubMed

    Bitton, Rachel R; Webb, Taylor D; Pauly, Kim Butts; Ghanouni, Pejman

    2016-01-01

    To investigate thermal dose volume (TDV) and non-perfused volume (NPV) of magnetic resonance-guided focused ultrasound (MRgFUS) treatments in patients with soft tissue tumors, and describe a method for MR thermal dosimetry using a baseline reference. Agreement between TDV and immediate post treatment NPV was evaluated from MRgFUS treatments of five patients with biopsy-proven desmoid tumors. Thermometry data (gradient echo, 3T) were analyzed over the entire course of the treatments to discern temperature errors in the standard approach. The technique searches previously acquired baseline images for a match using 2D normalized cross-correlation and a weighted mean of phase difference images. Thermal dose maps and TDVs were recalculated using the matched baseline and compared to NPV. TDV and NPV showed between 47%-91% disagreement, using the standard immediate baseline method for calculating TDV. Long-term thermometry showed a nonlinear local temperature accrual, where peak additional temperature varied between 4-13°C (mean = 7.8°C) across patients. The prior baseline method could be implemented by finding a previously acquired matching baseline 61% ± 8% (mean ± SD) of the time. We found 7%-42% of the disagreement between TDV and NPV was due to errors in thermometry caused by heat accrual. For all patients, the prior baseline method increased the estimated treatment volume and reduced the discrepancies between TDV and NPV (P = 0.023). This study presents a mismatch between in-treatment and post treatment efficacy measures. The prior baseline approach accounts for local heating and improves the accuracy of thermal dose-predicted volume. © 2015 Wiley Periodicals, Inc.

  7. Improving Thermal Dose Accuracy in Magnetic Resonance-Guided Focused Ultrasound Surgery: Long-Term Thermometry Using a Prior Baseline as a Reference

    PubMed Central

    Bitton, Rachel R.; Webb, Taylor D.; Pauly, Kim Butts; Ghanouni, Pejman

    2015-01-01

    Purpose To investigate thermal dose volume (TDV) and non-perfused volume (NPV) of magnetic resonance-guided focused ultrasound (MRgFUS) treatments in patients with soft tissue tumors, and describe a method for MR thermal dosimetry using a baseline reference. Materials and Methods Agreement between TDV and immediate post treatment NPV was evaluated from MRgFUS treatments of five patients with biopsy-proven desmoid tumors. Thermometry data (gradient echo, 3T) were analyzed over the entire course of the treatments to discern temperature errors in the standard approach. The technique searches previously acquired baseline images for a match using 2D normalized cross-correlation and a weighted mean of phase difference images. Thermal dose maps and TDVs were recalculated using the matched baseline and compared to NPV. Results TDV and NPV showed between 47%–91% disagreement, using the standard immediate baseline method for calculating TDV. Long-term thermometry showed a nonlinear local temperature accrual, where peak additional temperature varied between 4–13°C (mean = 7.8°C) across patients. The prior baseline method could be implemented by finding a previously acquired matching baseline 61% ± 8% (mean ± SD) of the time. We found 7%–42% of the disagreement between TDV and NPV was due to errors in thermometry caused by heat accrual. For all patients, the prior baseline method increased the estimated treatment volume and reduced the discrepancies between TDV and NPV (P = 0.023). Conclusion This study presents a mismatch between in-treatment and post treatment efficacy measures. The prior baseline approach accounts for local heating and improves the accuracy of thermal dose-predicted volume. PMID:26119129

  8. 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.

  9. Novel Application of Stem Cell-Derived Neurons to Evaluate the Time- and Dose-Dependent Progression of Excitotoxic Injury

    PubMed Central

    Gut, Ian M.; Beske, Phillip H.; Hubbard, Kyle S.; Lyman, Megan E.; Hamilton, Tracey A.; McNutt, Patrick M.

    2013-01-01

    Glutamate receptor (GluR)-mediated neurotoxicity is implicated in a variety of disorders ranging from ischemia to neural degeneration. Under conditions of elevated glutamate, the excessive activation of GluRs causes internalization of pathologic levels of Ca2+, culminating in bioenergetic failure, organelle degradation, and cell death. Efforts to characterize cellular and molecular aspects of excitotoxicity and conduct therapeutic screening for pharmacologic inhibitors of excitogenic progression have been hindered by limitations associated with primary neuron culture. To address this, we evaluated glutamate-induced neurotoxicity in highly enriched glutamatergic neurons (ESNs) derived from murine embryonic stem cells. As of 18 days in vitro (DIV 18), ESNs were synaptically coupled, exhibited spontaneous network activity with neurotypic mEPSCs and expressed NMDARs and AMPARs with physiological current:voltage behaviors. Addition of 0.78–200 μM glutamate evoked reproducible time- and dose-dependent metabolic failure in 6 h, with a calculated EC50 value of 0.44 μM at 24 h. Using a combination of cell viability assays and electrophysiology, we determined that glutamate-induced toxicity was specifically mediated by NMDARs and could be inhibited by addition of NMDAR antagonists, increased extracellular Mg2+ or substitution of Ba2+ for Ca2+. Glutamate treatment evoked neurite fragmentation and focal swelling by both immunocytochemistry and scanning electron microscopy. Presentation of morphological markers of cell death was dose-dependent, with 0.78–200 μM glutamate resulting in apoptosis and 3000 μM glutamate generating a mixture of necrosis and apoptosis. Addition of neuroprotective small molecules reduced glutamate-induced neurotoxicity in a dose-dependent fashion. These data indicate that ESNs replicate many of the excitogenic mechanisms observed in primary neuron culture, offering a moderate-throughput model of excitotoxicity that combines the verisimilitude

  10. 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.

  11. 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.

  12. Experimental derivation of wall correction factors for ionization chambers used in high dose rate 192Ir source calibration.

    PubMed

    Maréchal, M H; de Almeida, C E; Ferreira, I H; Sibata, C H

    2002-01-01

    At present there are no specific primary standards for 192Ir high dose rate sources used in brachytherapy. Traceability to primary standards is guaranteed through the method recommended by the AAPM that derives the air kerma calibration factor for the 192Ir gamma rays as the average of the air kerma calibration factors for x-rays and 137Cs gamma-rays or the Maréchal et al. method that uses the energy-weighted air kerma calibration factors for 250 kV x rays and 60Co gamma rays as the air kerma calibration factor for the 192Ir gamma rays. In order to use these methods, it is necessary to use the same buildup cap for all energies and the appropriate wall correction factor for each chamber. This work describes experimental work used to derive the A(W) for four different ionization chambers and different buildup cap materials for the three energies involved in the Maréchal et al. method. The A(W) for the two most common ionization chambers used in hospitals, the Farmer NE 2571 and PTW N30001 is 0.995 and 0.997, respectively, for 250 kV x rays, 0.982 and 0.985 for 192Ir gamma rays, and 0.979 and 0.991 for 60Co gamma rays, all for a PMMA build-up cap of 0.550 gm cm(-2). A comparison between the experimental values and Monte Carlo calculations shows an agreement better than 0.9%. Availability of the A(W) correction factors for all commercial chambers allows users of the in-air calibration jig, provided by the manufacturer, to alternatively use the Maréchal et al. method. Calibration laboratories may also used this method for calibration of a well-type ionization chamber with a comparable accuracy to the AAPM method.

  13. Dose dependent effects of platelet derived chondroitinsulfate A on the binding of CCL5 to endothelial cells

    PubMed Central

    Weingart, Christian; Nelson, Peter J; Krämer, Bernhard K; Mack, Matthias

    2008-01-01

    Background Chemokines immobilized on endothelial cells play a central role in the induced firm adhesion and transendothelial migration of leukocytes. Activation of platelets at sites of vascular injury is considered to support leukocyte adhesion and extravasation. However, activated platelets also secrete soluble glycosaminoglycans that can interfere with immobilization of chemokines. We therefore analyzed the impact of platelet derived glycosaminoglycans on the immobilization of the chemokine CCL5 (RANTES) on human microvascular endothelial cells and their influence on CCL5-CCR5 interactions. Results We confirm that undiluted serum in contrast to plasma decreases binding of CCL5 to endothelial cells. However, when lower concentrations of serum were used, CCL5-presentation on endothelial cells was markedly enhanced. This enhancement was neutralized if serum was digested with chondroinitase ABC. Using different chondroitinsulfate-subtypes we demonstrate that chondroitinsulfate A mediates the enhanced presentation of CCL5 on endothelial cells, whereas chondroitinsulfate B/C even at low concentrations block CCL5 binding. CCR5 downregulation on CCR5-transfected CHO cells or human monocytes is increased by preincubation of CCL5 with serum or chondroitinsulfate A. Conclusion We show that chondroitinsulfate A released from platelets increases the binding of chemokines to endothelial cells and supports receptor internalization in a dose dependent manner. These data help to understand the proinflammatory effects of activated platelets. PMID:19068144

  14. Dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells of mice

    PubMed Central

    Luo, Lan; Yan, Chen; Urata, Yoshishige; Hasan, Al Shaimaa; Goto, Shinji; Guo, Chang-Ying; Zhang, Shouhua; Li, Tao-Sheng

    2017-01-01

    We evaluated the dose-dependency and reversibility of radiation-induced injury in cardiac explant-derived cells (CDCs), a mixed cell population grown from heart tissues. Adult C57BL/6 mice were exposed to 0, 10, 50 and 250 mGy γ-rays for 7 days and atrial tissues were collected for experiments 24 hours after last exposure. The number of CDCs was significantly decreased by daily exposure to over 250 mGy. Interestingly, daily exposure to over 50 mGy significantly decreased the c-kit expression and telomerase activity, increased 53BP1 foci in the nuclei of CDCs. However, CD90 expression and growth factors production in CDCs were not significantly changed even after daily exposure to 250 mGy. We further evaluated the reversibility of radiation-induced injury in CDCs at 1 week and 3 weeks after a single exposure to 3 Gy γ-rays. The number and growth factors production of CDCs were soon recovered at 1 week. However, the increased expression of CD90 were retained at 1 week, but recovered at 3 weeks. Moreover, the decreased expression of c-kit, impaired telomerase activity, and increased 53BP1 foci were poorly recovered even at 3 weeks. These data may help us to find the most sensitive and reliable bio-parameter(s) for evaluating radiation-induced injury in CDCs. PMID:28098222

  15. Modeling the long-term transport and accumulation of radionuclides in the landscape for derivation of dose conversion factors.

    PubMed

    Avila, Rodolfo Moreno; Kautsky, Ulrik; Ekström, Per-Anders

    2006-12-01

    To evaluate the radiological impact of potential releases to the biosphere from a geological repository for spent nuclear fuel, it is necessary to assess the long-term dynamics of the distribution of radionuclides in the environment. In this paper, we propose an approach for making prognoses of the distribution and fluxes of radionuclides released from the geosphere, in discharges of contaminated groundwater, to an evolving landscape. The biosphere changes during the temperate part (spanning approximately 20,000 years) of an interglacial period are handled by building biosphere models for the projected succession of situations. Radionuclide transport in the landscape is modeled dynamically with a series of interconnected radioecological models of those ecosystem types (sea, lake, running water, mire, agricultural land and forest) that occur at present, and are projected to occur in the future, in a candidate area for a geological repository in Sweden. The transformation between ecosystems is modeled as discrete events occurring every thousand years by substituting one model by another. Examples of predictions of the radionuclide distribution in the landscape are presented for several scenarios with discharge locations varying in time and space. The article also outlines an approach for estimating the exposure of man resulting from all possible reasonable uses of a potentially contaminated landscape, which was used for derivation of Landscape Dose Factors.

  16. 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.

  17. Embryotoxic effects of thalidomide derivatives in the non-human primate callithrix jacchus. IV. Teratogenicity of micrograms/kg doses of the EM12 enantiomers.

    PubMed

    Heger, W; Schmahl, H J; Klug, S; Felies, A; Nau, H; Merker, H J; Neubert, D

    1994-01-01

    The dose-response of the teratogenic potency of the thalidomide (Thd) derivative EM12 was evaluated in the common marmoset (Callithrix jacchus). The smallest daily dose found to be effective was 30 micrograms EM12/kg body wt. This is the lowest dose of a Thd derivative ever reported to induce severe skeletal abnormalities. Ten micrograms EM12/kg body wt may be considered the no-observed-adverse-effect-level (NOAEL) under the experimental conditions chosen. The teratogenic potencies of the two EM12 enantiomers were tested at 100 micrograms/kg body wt, the dose which just induces an almost 100% effect in the case of the racemate. The S(-)-EM12 was found to induce typical severe limb abnormalities such as amelia, phocomelia, and radius aplasia, and none of the exposed fetuses were devoid of skeletal defects. In contrast, only few and minor skeletal defects were observed after application of the R(+) enantiomer. Although a pronounced teratogenic potency of the R(+)-EM12 can now largely be excluded, these low-dose studies are not sufficient to completely rule out any teratogenic potential of this enantiomer, since racemisation to small amounts of the S(-) form may occur in vivo. Further studies with Thd derivatives which are unable to racemise are necessary to prove the assumed complete ineffectiveness of the R(+) enantiomers.

  18. Human biomonitoring reference values for metals and trace elements in blood and urine derived from the Canadian Health Measures Survey 2007-2013.

    PubMed

    Saravanabhavan, Gurusankar; Werry, Kate; Walker, Mike; Haines, Douglas; Malowany, Morie; Khoury, Cheryl

    2017-03-01

    Human biomonitoring reference values are statistical estimates that indicate the upper margin of background exposure to a given chemical at a given time. Nationally representative human biomonitoring data on 176 chemicals, including several metals and trace elements, are available in Canada from 2007 to 2013 through the Canadian Health Measures Survey (CHMS). In this work, we used a systematic approach based on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry to derive reference values (RV95s) for metals and trace elements. These RV95s were derived for blood and urine matrices in the general Canadian population based on the latest biomonitoring data from the CHMS. Biomarkers were chosen based on specific selection criteria, including widespread detection in Canadians (≥66% detection rate). Reference populations were created for each biomarker by applying appropriate exclusion criteria. Age and sex were evaluated as possible partitioning criteria and separate RV95s were derived for the sub-populations in cases where partitioning was deemed necessary. The RV95s for metals and trace elements in blood ranged from 0.18μg/L for cadmium in young children aged 3-5 years to 7900μg/L for zinc in males aged 20-79 years. In the case of urinary biomarkers, the RV95s ranged from 0.17μg/L for antimony in the total population aged 3-79 years to 1400mg/L for fluoride in adults aged 20-79 years. These RV95s represent the first set of reference values for metals and trace elements in the general Canadian population. We compare the RV95s from other countries where available and discuss factors that could influence such comparisons. Copyright © 2016 The Authors. Published by Elsevier GmbH.. All rights reserved.

  19. 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.

  20. The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies

    PubMed Central

    Miller, Robert; Stalder, Tobias; Jarczok, Marc; Almeida, David M.; Badrick, Ellena; Bartels, Meike; Boomsma, Dorret I.; Coe, Christopher L.; Dekker, Marieke C. J.; Donzella, Bonny; Fischer, Joachim E.; Gunnar, Megan R.; Kumari, Meena; Lederbogen, Florian; Oldehinkel, Albertine J.; Power, Christine; Rosmalen, Judith G.; Ryff, Carol D.; Subramanian, S V; Tiemeier, Henning; Watamura, Sarah E.; Kirschbaum, Clemens

    2016-01-01

    Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5 to 98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1 to 16 hours after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle. PMID:27448524

  1. The CIRCORT database: Reference ranges and seasonal changes in diurnal salivary cortisol derived from a meta-dataset comprised of 15 field studies.

    PubMed

    Miller, Robert; Stalder, Tobias; Jarczok, Marc; Almeida, David M; Badrick, Ellena; Bartels, Meike; Boomsma, Dorret I; Coe, Christopher L; Dekker, Marieke C J; Donzella, Bonny; Fischer, Joachim E; Gunnar, Megan R; Kumari, Meena; Lederbogen, Florian; Power, Christine; Ryff, Carol D; Subramanian, S V; Tiemeier, Henning; Watamura, Sarah E; Kirschbaum, Clemens

    2016-11-01

    Diurnal salivary cortisol profiles are valuable indicators of adrenocortical functioning in epidemiological research and clinical practice. However, normative reference values derived from a large number of participants and across a wide age range are still missing. To fill this gap, data were compiled from 15 independently conducted field studies with a total of 104,623 salivary cortisol samples obtained from 18,698 unselected individuals (mean age: 48.3 years, age range: 0.5-98.5 years, 39% females). Besides providing a descriptive analysis of the complete dataset, we also performed mixed-effects growth curve modeling of diurnal salivary cortisol (i.e., 1-16h after awakening). Cortisol decreased significantly across the day and was influenced by both, age and sex. Intriguingly, we also found a pronounced impact of sampling season with elevated diurnal cortisol in spring and decreased levels in autumn. However, the majority of variance was accounted for by between-participant and between-study variance components. Based on these analyses, reference ranges (LC/MS-MS calibrated) for cortisol concentrations in saliva were derived for different times across the day, with more specific reference ranges generated for males and females in different age categories. This integrative summary provides important reference values on salivary cortisol to aid basic scientists and clinicians in interpreting deviations from the normal diurnal cycle. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Platelet-Rich Plasma Influences Expansion and Paracrine Function of Adipose-Derived Stromal Cells in a Dose-Dependent Fashion.

    PubMed

    Willemsen, Joep C N; Spiekman, Maroesjka; Stevens, H P Jeroen; van der Lei, Berend; Harmsen, Martin C

    2016-03-01

    Lipofilling is a treatment modality to restore tissue volume. Both platelet-rich plasma and adipose-derived stromal cells have been reported to augment the efficacy of lipofilling, yet results are not conclusive. The authors hypothesized that the variation reported in literature is caused by a dose-dependent influence of platelet-rich plasma on adipose-derived stromal cells. Whole blood (n = 3) was used to generate platelet-rich plasma, which was diluted with Dulbecco's Modified Eagle Medium to 15%, 5%, and 1.7%, with 15% platelet-poor plasma and 10% fetal calf serum as controls. Pooled adipose-derived stromal cells (n = 3) were cultured in these media. Gene expression was assessed, along with angiogenic sprouting of endothelial cells by conditioned medium and platelet-rich plasma. platelet-rich plasma in culture medium affected the expression of genes in a dose-dependent manner. The 15% concentration stimulated proliferation almost eightfold. Mesenchymal markers were unaffected. Interestingly, expression of collagens type 1 and 3 increased at lower concentrations, whereas transforming growth factor-β showed reduced expression in lower concentrations. Proangiogenic gene expression was unaltered or strongly reduced in a dose-dependent manner. platelet-rich plasma promoted endothelial sprouting and survival in a dose-dependent manner; however, conditioned medium from adipose-derived stromal cells exposed to platelet-rich plasma blocked endothelial sprouting capabilities. The dose-dependent influence of platelet-rich plasma on the therapeutic capacity of adipose-derived stromal cells conditioned medium in vitro warrants caution in clinical trials.

  3. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia.

    PubMed

    Hou, Yu; Feng, Qi; Xu, Miao; Li, Guo-Sheng; Liu, Xue-Na; Sheng, Zi; Zhou, Hai; Ma, Ji; Wei, Yu; Sun, Yuan-Xin; Yu, Ying-Yi; Qiu, Ji-Hua; Shao, Lin-Lin; Liu, Xin-Guang; Hou, Ming; Peng, Jun

    2016-03-24

    Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor β was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1.

  4. Optimal gadolinium dose level for magnetic resonance imaging (MRI) contrast enhancement of U87-derived tumors in athymic nude rats for the assessment of photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Cross, Nathan; Varghai, Davood; Flask, Chris A.; Feyes, Denise K.; Oleinick, Nancy L.; Dean, David

    2009-02-01

    This study aims to determine the effect of varying gadopentetate dimeglumine (Gd-DTPA) dose on Dynamic Contrast Enhanced-Magnetic Resonance Imaging (DCE-MRI) tracking of brain tumor photodynamic therapy (PDT) outcome. Methods: We injected 2.5 x 105 U87 cells (derived from human malignant glioma) into the brains of six athymic nude rats. After 9, 12, and 13 days DCE-MRI images were acquired on a 9.4 T micro-MRI scanner before and after administration of 100, 150, or 200 μL of Gd-DTPA. Results: Tumor region normalized DCE-MRI scan enhancement at peak was: 1.217 over baseline (0.018 Standard Error [SE]) at the 100 μL dose, 1.339 (0.013 SE) at the 150 μL dose, and 1.287 (0.014 SE) at the 200 μL dose. DCE-MRI peak tumor enhancement at the 150 μL dose was significantly greater than both the 100 μL dose (p < 3.323E-08) and 200 μL dose (p < 0.0007396). Discussion: In this preliminary study, the 150 μL Gd-DTPA dose provided the greatest T1 weighted contrast enhancement, while minimizing negative T2* effects, in DCE-MRI scans of U87-derived tumors. Maximizing Gd-DTPA enhancement in DCE-MRI scans may assist development of a clinically robust (i.e., unambiguous) technique for PDT outcome assessment.

  5. The Asian project for collaborative derivation of reference intervals: (2) results of non-standardized analytes and transference of reference intervals to the participating laboratories on the basis of cross-comparison of test results.

    PubMed

    Ichihara, Kiyoshi; Ceriotti, Ferruccio; Kazuo, Mori; Huang, Yang-Yang; Shimizu, Yoshihisa; Suzuki, Haruki; Kitagawa, Masami; Yamauchi, Kazuyoshi; Hayashi, Sadao; Tsou, Chia-Chun; Yamamoto, Yoshikazu; Ishida, Shigeo; Leong, Linda; Sano, Michitaka; Lim, Hwan Sub; Suwabe, Akira; Woo, Hee-Yeon; Kojima, Keiya; Okubo, Yoshio

    2013-07-01

    The 2009 Asian multicenter study for derivation of reference intervals (RIs) featured: 1) centralized measurements to exclude reagent-dependent variations; 2) inclusion of non-standardized analytes (hormones, tumor makers, etc.) in the target; and 3) cross-check of test results between the central and local laboratories. Transferability of centrally derived RIs for non-standardized analytes based on the cross-check was examined. Forty non-standardized analytes were centrally measured in sera from 3541 reference individuals recruited by 63 laboratories. Forty-four laboratories collaborated in the cross-check study by locally measuring aliquots of sera from 9 to 73 volunteers (average 22.2). Linear relationships were obtained by the major-axis regression. Error in converting RIs using the regression line was expressed by the coefficient of variation of slope b [CV(b)]. CV(b) <10% was set as the cut-off value allowing the conversion. The significance of factors for partitioning RIs was determined similarly as in the first report. Significant sex-, age-, and region-related changes in test results were observed in 17, 15, and 11 of the 40 analytes, respectively. In the cross-comparison study, test results were not harmonized in the majority of immunologically measured analytes, but their average CV(b)s were <10% except for total protein, cystatin C, CA19-9, free thyroxine, and triiodothyronine. After conversion, 74% of centrally derived RIs were transferred to each local laboratory. Our results point to the feasibility of: 1) harmonizing test results across different laboratories; and 2) sharing centrally derived RIs of non-standardized analytes by means of comparative measurement of a set of commutable specimens.

  6. Derivation of acoustoelastic Lamb wave dispersion curves in anisotropic plates at the initial and natural frames of reference.

    PubMed

    C Kubrusly, Alan; M B Braga, Arthur; von der Weid, Jean Pierre

    2016-10-01

    The propagation speed of ultrasonic waves in pre-stressed media can be evaluated either at the natural or initial frames of reference. In this paper general equations that can be applied to the partial wave technique are presented in order to obtain the dispersion spectra of acoustoelastic Lamb waves in anisotropic plates in either frame of reference. Employing these equations, dispersion curves for the fundamental modes in a pre-stressed transversely isotropic aluminum plate were numerically obtained in both reference frames under longitudinal and transverse loading with the material transverse axis along each of the Cartesian directions, as well as the propagation along a non-principal direction. Results confirm that due to the material natural anisotropy, the speed variation depends not only on the pre-stress direction but also on the material orientation as well as on the polarization of the propagating mode. Similar to bulk waves, the relationship between the speed at the natural and initial frames is a function of the load direction.

  7. Human biomonitoring reference values derived for persistent organic pollutants in blood plasma from the Canadian Health Measures Survey 2007-2011.

    PubMed

    Haines, Douglas A; Khoury, Cheryl; Saravanabhavan, Gurusankar; Werry, Kate; Walker, Mike; Malowany, Morie

    2017-06-01

    Nationally representative human biomonitoring data on persistent organic pollutants (POPs) including organochlorine pesticides (OCs), polychlorinated biphenyls (PCBs) brominated flame retardants (BFRs) and perfluoroalkyl substances (PFASs) are available through the Canadian Health Measures Survey (CHMS). We have used a systematic approach building on the reference interval concept proposed by the International Federation of Clinical Chemistry and Laboratory Medicine and the International Union of Pure and Applied Chemistry to derive human biomonitoring reference values (RV95s) for selected POPs in blood plasma in the general Canadian population. Biomarkers were chosen based on specific selection criteria including their detection in most Canadians (>66% detection rate). Age and sex were evaluated as possible partitioning criteria and separate RV95s were derived for the sub-populations in cases where partitioning was deemed necessary. RV95s for OCs, PCBs, and BFRs were derived both on a whole weight of blood plasma and on a lipid weight adjusted basis whereas they were derived only on a whole weight basis for PFASs. RV95s ranged from 0.018μg/L (PCB 201) to 21μg/L (perfluorooctane sulfonate) and from 3.1μg/kg lipid (PCB 201) to 1400μg/kg lipid (p,p'-DDE). The 22 RV95s reported in this paper represent the first set of reference values for POPs in the Canadian general population against which individual and population human biomonitoring data may be compared. Crown Copyright © 2017. Published by Elsevier GmbH. All rights reserved.

  8. 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.

  9. A global reference database from very high resolution commercial satellite data and methodology for application to Landsat derived 30 m continuous field tree cover data

    USGS Publications Warehouse

    Pengra, Bruce; Long, Jordan; Dahal, Devendra; Stehman, Stephen V.; Loveland, Thomas R.

    2015-01-01

    The methodology for selection, creation, and application of a global remote sensing validation dataset using high resolution commercial satellite data is presented. High resolution data are obtained for a stratified random sample of 500 primary sampling units (5 km  ×  5 km sample blocks), where the stratification based on Köppen climate classes is used to distribute the sample globally among biomes. The high resolution data are classified to categorical land cover maps using an analyst mediated classification workflow. Our initial application of these data is to evaluate a global 30 m Landsat-derived, continuous field tree cover product. For this application, the categorical reference classification produced at 2 m resolution is converted to percent tree cover per 30 m pixel (secondary sampling unit)for comparison to Landsat-derived estimates of tree cover. We provide example results (based on a subsample of 25 sample blocks in South America) illustrating basic analyses of agreement that can be produced from these reference data. Commercial high resolution data availability and data quality are shown to provide a viable means of validating continuous field tree cover. When completed, the reference classifications for the full sample of 500 blocks will be released for public use.

  10. 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.

  11. SU-E-T-773: Use of a Commercial TPS for Deriving Exit Dose Distribution for Patient Specific QA with An EPID

    SciTech Connect

    Haering, P; Lang, C; Splinter, M

    2015-06-15

    Purpose: A method to derive exit dose distributions with a commercial treatment planning system for comparison to Epid measured doses. Methods: In contrast to published methods, we present an approach that uses a treatment planning system (Raystation, Raysearch) to calculate exit dose patterns based on a modified patient CT dataset. The EPID is assumed as water equivalent and therefore is represented as water filled ring in the images. This is done by: -Export a renamed copy of the patient CT and plan data set. —Manipulate the CT-data to a field of view of 1000 mm. — Insert the water filled cylinder ring, centered to the target point. — Manipulate plan file with the new target and dose prescription point. — Import and recalculate dose on the manipulated data set. — Export and extract exit field dose matrix from the cylinder (optional entrance dose). — Calibrate matrix to size and rebin data from the cylinder to EPID equivalent data. — Correct Epid measurement for scatter, position and field size. -Evaluate and compare data in Verisoft (PTW). Data manipulation and extraction is done by a simple tool (IDL, Exelis). Results: This method was tested on a Siemens Artiste 6MV for field sizes up to 27×27cm2 limited by used geometry and EPID size. First phantom measurements show good results for fields up to 20×20cm (pass rate > 95% for 3%, 3mm Gamma index) while larger fields have higher discrepancies towards the field edges. This might Result from off axis softening of the beam and the higher sensitivity of the detector to beam scatter. Conclusion: This method might simplify the use of exit dosimetry with the EPID for patient specific QA as it uses the dose calculation of a commercial treatment planning system. The concept was proven by phantom data sets, giving acceptable results.

  12. 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

  13. 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.

  14. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic‐derived dose justification for phase 3 studies in patients with nosocomial pneumonia

    PubMed Central

    Miller, Benjamin W.; Huntington, Jennifer A.; Nicolau, David P.

    2016-01-01

    Abstract Ceftolozane/tazobactam is an antipseudomonal antibacterial approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intra‐abdominal infections (cIAIs) and in phase 3 clinical development for treatment of nosocomial pneumonia. A population pharmacokinetic (PK) model with the plasma‐to‐epithelial lining fluid (ELF) kinetics of ceftolozane/tazobactam was used to justify dosing regimens for patients with nosocomial pneumonia in phase 3 studies. Monte Carlo simulations were performed to determine ceftolozane/tazobactam dosing regimens with a >90% probability of target attainment (PTA) for a range of pharmacokinetic/pharmacodynamic targets at relevant minimum inhibitory concentrations (MICs) for key pathogens in nosocomial pneumonia. With a plasma‐to‐ELF penetration ratio of approximately 50%, as observed from an ELF PK study, a doubling of the current dose regimens for different renal functions that are approved for cUTIs and cIAIs is needed to achieve >90% PTA for nosocomial pneumonia. For example, a 3‐g dose of ceftolozane/tazobactam for nosocomial pneumonia patients with normal renal function is needed to achieve a >90% PTA (actual 98%) for the 1‐log kill target against pathogens with an MIC of ≤8 mg/L in ELF, compared with the 1.5‐g dose approved for cIAIs and cUTIs. PMID:26096377

  15. Ceftolozane/tazobactam pharmacokinetic/pharmacodynamic-derived dose justification for phase 3 studies in patients with nosocomial pneumonia.

    PubMed

    Xiao, Alan J; Miller, Benjamin W; Huntington, Jennifer A; Nicolau, David P

    2016-01-01

    Ceftolozane/tazobactam is an antipseudomonal antibacterial approved for the treatment of complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections (cIAIs) and in phase 3 clinical development for treatment of nosocomial pneumonia. A population pharmacokinetic (PK) model with the plasma-to-epithelial lining fluid (ELF) kinetics of ceftolozane/tazobactam was used to justify dosing regimens for patients with nosocomial pneumonia in phase 3 studies. Monte Carlo simulations were performed to determine ceftolozane/tazobactam dosing regimens with a > 90% probability of target attainment (PTA) for a range of pharmacokinetic/pharmacodynamic targets at relevant minimum inhibitory concentrations (MICs) for key pathogens in nosocomial pneumonia. With a plasma-to-ELF penetration ratio of approximately 50%, as observed from an ELF PK study, a doubling of the current dose regimens for different renal functions that are approved for cUTIs and cIAIs is needed to achieve > 90% PTA for nosocomial pneumonia. For example, a 3-g dose of ceftolozane/tazobactam for nosocomial pneumonia patients with normal renal function is needed to achieve a > 90% PTA (actual 98%) for the 1-log kill target against pathogens with an MIC of ≤ 8 mg/L in ELF, compared with the 1.5-g dose approved for cIAIs and cUTIs.

  16. Lyophilized bovine hemoglobin as a possible reference material for the determination of hemoglobin derivatives in human blood.

    PubMed

    Maas, B H; Buursma, A; Ernst, R A; Maas, A H; Zijlstra, W G

    1998-11-01

    We investigated the suitability of a lyophilized bovine hemoglobin (LBH) preparation containing various fractions of oxyhemoglobin (O2Hb), carboxyhemoglobin (COHb), and methemoglobin (MetHb) for quality assessment in multicomponent analysis (MCA) of hemoglobin derivatives. It was demonstrated that a stable preparation of these components after reconstitution yields a hemoglobin solution that is spectrophotometrically equivalent with a fresh bovine hemoglobin solution. The preparation was found to be stable for at least 1 year when it is kept at 2-8 degrees C and for 1 h after reconstitution. We determined the fractions of O2Hb, COHb, and MetHb of several LBH preparations, using the complete spectra of 480-650 nm with 2-nm intervals and absorptivities as determined for pure LBH solutions. A field trial involving various types of multiwavelength hemoglobin photometers showed the suitability of LBH as a quality-control material. Computer models of the various common multiwavelength hemoglobin photometers may be useful for establishing more accurate target values of LBH preparations for each type of photometer and for studying the importance of the influence of specific factors such as wavelength selection, absorptivity values, and interfering dyes.

  17. 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. Copyright © 2011. Published by Elsevier B.V.

  18. 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

  19. 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.

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

    PubMed

    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

    2015-03-01

    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. 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. 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. 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 in Hieracium and should also assist with

  1. Bioaccessibility of Fukushima-Accident-Derived Cs in Soils and the Contribution of Soil Ingestion to Radiation Doses in Children.

    PubMed

    Takahara, Shogo; Ikegami, Maiko; Yoneda, Minoru; Kondo, Hitoshi; Ishizaki, Azusa; Iijima, Masashi; Shimada, Yoko; Matsui, Yasuto

    2016-09-30

    Ingestion of contaminated soil is one potential internal exposure pathway in areas contaminated by the Fukushima Daiichi Nuclear Power Plant accident. Doses from this pathway can be overestimated if the availability of radioactive nuclides in soils for the gastrointestinal tract is not considered. The concept of bioaccessibility has been adopted to evaluate this availability based on in vitro tests. This study evaluated the bioaccessibility of radioactive cesium from soils via the physiologically-based extraction test (PBET) and the extractability of those via an extraction test with 1 mol/L of hydrochloric acid (HCl). The bioaccessibility obtained in the PBET was 5.3% ± 1%, and the extractability in the tests with HCl was 16% ± 3%. The bioaccessibility was strongly correlated with the extractability. This result indicates the possibility that the extractability in HCl can be used as a good predictor of the bioaccessibility with PBET. In addition, we assessed the doses to children from the ingestion of soil via hand-to-mouth activity based on our PBET results using a probabilistic approach considering the spatial distribution of radioactive cesium in Date City in Fukushima Prefecture and the interindividual differences in the surveyed amounts of soil ingestion in Japan. The results of this assessment indicate that even if children were to routinely ingest a large amount of soil with relatively high contamination, the radiation doses from this pathway are negligible compared with doses from external exposure owing to deposited radionuclides in Fukushima Prefecture.

  2. A traceable reference for direct comparative assessment of total naphthenic acid concentrations in commercial and acid extractable organic mixtures derived from oil sands process water.

    PubMed

    Brunswick, Pamela; Hewitt, L Mark; Frank, Richard A; Kim, Marcus; van Aggelen, Graham; Shang, Dayue

    2017-02-23

    The advantage of using naphthenic acid (NA) mixtures for the determination of total NA lies in their chemical characteristics and identification of retention times distinct from isobaric interferences. However, the differing homolog profiles and unknown chemical structures of NA mixtures do not allow them to be considered a traceable reference material. The current study provides a new tool for the comparative assessment of different NA mixtures by direct reference to a single, well-defined and traceable compound, decanoic-d19 acid. The method employed an established liquid chromatography time-of-flight mass spectrometry (LC/QToF) procedure that was applicable both to the classic O2 NA species dominating commercial mixtures and additionally to the O4 species known to be present in acid extractable organics (AEOs) derived from oil sands process water (OSPW). Four different commercial NA mixtures and one OSPW-derived AEOs mixture were comparatively assessed. Results showed significant difference among Merichem Technical, Aldrich, Acros, and Kodak commercial NA mixtures with respect to "equivalent to decanoic-d19 acid" concentration ratios to nominal. Furthermore, different lot numbers of single commercial NA mixtures were found to be inconsistent with respect to their homolog content by percent response. Differences in the observed homolog content varied significantly, particularly at the lower (n = 9-14) and higher (n = 20-23) carbon number ranges. Results highlighted the problem between using NA mixtures from different sources and different lot numbers but offered a solution to the problem from a concentration perspective. It is anticipated that this tool may be utilized in review of historical data in addition to future studies, such as the study of OSPW derived acid extractable organics (AEOs) and fractions employed during toxicological studies.

  3. Safety and Immunogenicity of Cell Culture-Derived A/H3N2 Variant Influenza Vaccines: A Phase I Randomized, Observer-Blind, Dose-Ranging Study

    PubMed Central

    Johnson, Casey; Hohenboken, Matthew; Poling, Terry; Jaehnig, Peter; Kanesa-thasan, Niranjan

    2015-01-01

    Background. A/H3N2 variant (H3N2v) influenza may sustain human-to-human transmission, and an available candidate vaccine would be important. Methods. In this phase I, randomized, observer-blind, dose-ranging study, 627 healthy subjects ≥3 years of age were randomized to receive 2 vaccinations with H3N2c cell-culture-derived vaccine doses containing 3.75 µg, 7.5 µg, or 15 µg hemagglutinin antigen of H3N2v with or without MF59 (registered trademark of Novartis AG) adjuvant (an oil-in-water emulsion). This paper reports Day 43 planned interim data. Results. Single MF59-adjuvanted H3N2c doses elicited immune responses in almost all subjects regardless of antigen and adjuvant dose; the Center for Biologics Evaluation Research and Review (CBER) licensure criteria were met for all groups. Subjects with prevaccination hemagglutination inhibition titers <10 and children 3–<9 years achieve CBER criteria only after receiving 2 doses of nonadjuvanted H3N2c vaccine. Highest antibody titers were observed in the 7.5 µg + 0.25 mL MF59 groups in all age cohorts. MF59-adjuvanted H3N2c vaccines showed the highest rates of solicited local and systemic events, predominately mild or moderate. Conclusions. A single dose of H3N2c vaccine may be immunogenic and supports further development of MF59-adjuvanted H3N2c vaccines, especially for pediatric populations. Clinical Trials Registration. ClinicalTrials.gov identifier NCT01855945 (http://clinicaltrials.gov/ct2/show/NCT01855945). PMID:25538277

  4. 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

  5. Global transport of Fukushima-derived radionuclides from Japan to Asia, North America and Europe. Estimated doses and expected health effects

    NASA Astrophysics Data System (ADS)

    Evangeliou, Nikolaos; Stohl, Andreas; Balkanski, Yves

    2017-04-01

    The earthquake and the subsequent tsunami that occurred offshore of Japan resulted in a serious accident at the nuclear facility of Fukushima. A large number of fission products were released and transported worldwide. We estimate that around 23% of the released 137Cs remained into Japan, while 76% deposited in the oceans. Around 163 TBq deposited over North America, among which 95 TBq over USA, 40 TBq over Canada and 5 TBq over Greenland). About 14 TBq deposited over Europe (mostly in the European part of Russia, Sweden and Norway) and 47 TBq over Asia (mostly in the Asian part of Russia, Philippines and South Korea), while traces were observed over Africa, Oceania and Antarctica. Since the radioactive plume followed a northward direction before its arrival to USA and then to Europe, a significant amount of about 69 TBq deposited in the Arctic, as well. An attempt to assess exposure of the population and the environment showed that the effective dose from gamma irradiation during the first 3 months was estimated between 1-5 mSv in Fukushima and the neighbouring prefectures. In the rest of Japan, the respective doses were found to be less than 0.5 mSv, whereas in the rest of the world it was less than 0.1 mSv. Such doses are equivalent with the obtained dose from a simple X-ray; for the highly contaminated regions, they are close to the dose limit for exposure due to radon inhalation (10 mSv). The calculated dose rates from radiocesium exposure on reference organisms ranged from 0.03 to 0.18 μGy h-1, which are 2 orders of magnitude below the screening dose limit (10 μGy h-1) that could result in obvious effects on the population. However, monitoring data have shown that much higher dose rates were committed to organisms raising ecological risk for small mammals and reptiles in terms of cytogenetic damage and reproduction.

  6. 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.

  7. Dose-response studies with nitrosoheptamethyleneimine and its alpha-deuterium-labeled derivative in F344 rats

    SciTech Connect

    Lijinsky, W.; Reuber, M.D.; Davies, T.S.; Riggs, C.W.

    1982-11-01

    A dose-response study of the carcinogenicity of nitrosoheptamethyleneimine (N-HEP) in inbred F344 male and female rats was performed by administration of the nitrosamine at several concentrations in drinking water to groups of 20 rats. The concentrations differed by a factor of nearly 2.5 and ranged from 1.0 to 100 mg/liter. The duration of treatment was 13, 25, 50, or 100 weeks, after which the animals were allowed to die naturally of tumors induced. In most treated groups the incidence of tumors of the upper gastrointestinal tract approached 100%. However, at the higher doses there was an inverse relationship between total dose and survival time of the rats. Matched treatment of groups of rat with N-HEP labeled with deuterium in the alpha positions resulted in longer survival. The slower action of the deuterium-labeled compound, as measured by a lower rate of death from tumors, suggests that cleavage of a carbon-hydrogen bond at an alpha position is a rate-limiting step in carcinogenesis by N-HEP in rats.

  8. Reliable measurement of 3D foot bone angles based on the frame-of-reference derived from a sole of the foot

    NASA Astrophysics Data System (ADS)

    Kim, Taeho; Lee, Dong Yeon; Park, Jinah

    2016-03-01

    Clinical management of foot pathology requires accurate and robust measurement of the anatomical angles. In order to measure a 3D angle, recent approaches have adopted a landmark-based local coordinate system to establish bone angles used in orthopedics. These measurement methods mainly assess the relative angle between bones using a representative axis derived from the morphological feature of the bone and therefore, the results can be affected by bone deformities. In this study, we propose a method of deriving a global frame-of-reference to acquire consistent direction of the foot by extracting the undersurface of the foot from the CT image data. The two lowest positions of the foot skin are identified from the surface to define the base plane, and the direction from the hallux to the fourth toe is defined together to construct the global coordinate system. We performed the experiment on 10 volumes of foot CT images of healthy subjects to verify that the proposed method provides reliable measurements. We measured 3D angles for talus-calcaneus and talus-navicular using facing articular surfaces of paired bones. The angle was reported in 3 projection angles based on both coordinate systems defined by proposed global frame-of-reference and by CT image planes (saggital, frontal, and transverse). The result shows that the quantified angle using the proposed method considerably reduced the standard deviation (SD) against the angle using the conventional projection planes, and it was also comparable with the measured angles obtained from local coordinate systems of the bones. Since our method is independent from any individual local shape of a bone, unlike the measurement method using the local coordinate system, it is suitable for inter-subject comparison studies.

  9. A general method to derive tissue parameters for Monte Carlo dose calculation with multi-energy CT.

    PubMed

    Lalonde, Arthur; Bouchard, Hugo

    2016-11-21

    To develop a general method for human tissue characterization with dual- and multi-energy CT and evaluate its performance in determining elemental compositions and quantities relevant to radiotherapy Monte Carlo dose calculation. Ideal materials to describe human tissue are obtained applying principal component analysis on elemental weight and density data available in literature. The theory is adapted to elemental composition for solving tissue information from CT data. A novel stoichiometric calibration method is integrated to the technique to make it suitable for a clinical environment. The performance of the method is compared with two techniques known in literature using theoretical CT data. In determining elemental weights with dual-energy CT, the method is shown to be systematically superior to the water-lipid-protein material decomposition and comparable to the parameterization technique. In determining proton stopping powers and energy absorption coefficients with dual-energy CT, the method generally shows better accuracy and unbiased results. The generality of the method is demonstrated simulating multi-energy CT data to show the potential to extract more information with multiple energies. The method proposed in this paper shows good performance to determine elemental compositions from dual-energy CT data and physical quantities relevant to radiotherapy dose calculation. The method is particularly suitable for Monte Carlo calculations and shows promise in using more than two energies to characterize human tissue with CT.

  10. 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

  11. 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

  12. The susceptibility of IMRT dose distributions to intrafraction organ motion: An investigation into smoothing filters derived from four dimensional computed tomography data

    SciTech Connect

    Coolens, Catherine; Evans, Phil M.; Seco, Joao; Webb, Steve; Blackall, Jane M.; Rietzel, Eike; Chen, George T. Y.

    2006-08-15

    This study investigated the sensitivity of static planning of intensity-modulated beams (IMBs) to intrafraction deformable organ motion and assessed whether smoothing of the IMBs at the treatment-planning stage can reduce this sensitivity. The study was performed with a 4D computed tomography (CT) data set for an IMRT treatment of a patient with liver cancer. Fluence profiles obtained from inverse-planning calculations on a standard reference CT scan were redelivered on a CT scan from the 4D data set at a different part of the breathing cycle. The use of a nonrigid registration model on the 4D data set additionally enabled detailed analysis of the overall intrafraction motion effects on the IMRT delivery during free breathing. Smoothing filters were then applied to the beam profiles within the optimization process to investigate whether this could reduce the sensitivity of IMBs to intrafraction organ motion. In addition, optimal fluence profiles from calculations on each individual phase of the breathing cycle were averaged to mimic the convolution of a static dose distribution with a motion probability kernel and assess its usefulness. Results from nonrigid registrations of the CT scan data showed a maximum liver motion of 7 mm in superior-inferior direction for this patient. Dose-volume histogram (DVH) comparison indicated a systematic shift when planning treatment on a motion-frozen, standard CT scan but delivering over a full breathing cycle. The ratio of the dose to 50% of the normal liver to 50% of the planning target volume (PTV) changed up to 28% between different phases. Smoothing beam profiles with a median-window filter did not overcome the substantial shift in dose due to a difference in breathing phase between planning and delivery of treatment. Averaging of optimal beam profiles at different phases of the breathing cycle mainly resulted in an increase in dose to the organs at risk (OAR) and did not seem beneficial to compensate for organ motion

  13. Prediction of the vertebral strength using a finite element model derived from low-dose biplanar imaging: benefits of subject-specific material properties.

    PubMed

    Sapin-de Brosses, Emilie; Jolivet, Erwan; Travert, Christophe; Mitton, David; Skalli, Wafa

    2012-02-01

    A finite element analysis on osteoporotic vertebrae. This study aims to validate subject-specific finite element models (FEMs) derived from a low-dose imaging system (EOS, Biospace Med, France) for the prediction of vertebral strength. The vertebrae are submitted to an eccentric compression force leading to compression and anterior bending. Given the aging population, osteoporosis and vertebral fractures are a major public health issue. A low bone mineral density (BMD) does not always explain incident fractures, and multifactorial analyses are required. In this context, FEMs based on quantitative computed tomography (QCT) have been proposed to predict vertebral strength in vitro or quantify effects of treatments. However, the clinical use of such a model for the in vivo follow-up of the whole spine is limited by the high-radiation dose induced by QCT and the lying position, which does not allow postural assessment with the same modality. Fourteen vertebrae were modeled using a parametric meshing method. The mesh was subject-specific using geometric parameters computed on the 3-dimensional (3D) reconstructions obtained from the EOS biplanar radiographs. The contribution of cortical bone was taken into account by modeling a cortico-cancellous shell whose properties were derived from experimental data. The effect of subject-specific bone Young's moduli derived from EOS vertebral areal BMD was quantified. The 3D position of the point-of-load application and the 3D orientation of the force was faithfully reproduced in the model to compare the predicted strength and experimental strength under the same loading conditions. The relative error of prediction decreased from 43% to 16% (2.5 times) when subject-specific mechanical properties, derived from EOS areal BMD, were implemented in the FEM compared with averaged material properties. The resulting subject-specific FEMs predicted vertebral strength with a level of significance close to the QCT-based models (r adjusted = 0

  14. Low dose inflammatory potential of silica particles in human-derived THP-1 macrophage cell culture studies - Mechanism and effects of particle size and iron.

    PubMed

    Premshekharan, Gayatri; Nguyen, Kennedy; Zhang, Hongqiao; Forman, Henry Jay; Leppert, Valerie Jean

    2017-06-25

    Silica and iron are major constituents in ambient particulate matter, and iron is a common impurity in many engineered nanomaterials. The purpose of this work was to determine the pro-inflammatory and other biological effects and mechanism of particle size and iron presence under low dose, non-cytotoxic conditions that are likely to approximate actual exposure levels, in contrast with higher dose studies in which cytotoxicity occurs. Specifically, human-derived THP-1 macrophages were exposed to 1 μg/ml of pristine and iron-coated 50 nm and 2 μm engineered silica nanoparticles. Particles were first characterized for size, size distribution, surface area, iron concentration, phase and aggregation in cell culture media. Then, biological assays were conducted to determine a non-lethal dose used in subsequent experiments. Superoxide production, lipid peroxidation, and increased pro-inflammatory cytokine (TNF-α and IL-1β) mRNA expression were measured as a function of particle size and iron presence. Smaller particle size and the presence of iron increased superoxide production, lipid peroxidation, and the induction of pro-inflammatory cytokine mRNA expression. Separate addition of an iron-chelator, a scavenger of superoxide and hydrogen peroxide, and an inhibitor of phosphatidylcholine specific phospholipase C (PC-PLC), suppressed the increase in cytokine mRNA expression. Furthermore, free iron itself showed none of the aforementioned effects. The results highlight the importance of particle size and iron in lung inflammation for both natural and engineered nanomaterials, under low dose, non-toxic conditions, and support the role of an oxidant, lipid peroxidation and PC-PLC dependent inflammatory mechanism. Copyright © 2017 Elsevier B.V. All rights reserved.

  15. Low-dose azithromycin improves phagocytosis of bacteria by both alveolar and monocyte-derived macrophages in chronic obstructive pulmonary disease subjects.

    PubMed

    Hodge, Sandra; Reynolds, Paul N

    2012-07-01

    Chronic inflammation and reduced airways integrity in chronic obstructive pulmonary disease (COPD) potentially results from secondary necrosis as a result of impaired phagocytosis of apoptotic material by airway macrophages, and increased bacterial colonization. We have previously shown that administration of low-dose azithromycin to subjects with COPD improved macrophage phagocytosis of apoptotic airway epithelial cells, reduced inflammation and increased expression of macrophage mannose receptor. We firstly investigated whether there were defects in the ability of both alveolar (AM) and monocyte-derived macrophages (MDM) to phagocytose bacteria in COPD, as we have previously reported for phagocytosis of apoptotic cells. We then assessed the effects of administration of low-dose azithromycin to COPD patients on the ability of AM and MDM to phagocytose bacteria. Azithromycin (250 mg orally daily for 5 days then 2× weekly (total 12 weeks)) was administered to 11 COPD subjects and phagocytosis of fluorescein isothiocyanate-labelled Escherichia coli assessed by flow cytometry. COPD subjects had a significant defect in the ability of both AM and MDM to phagocytose bacteria that was significantly improved by administration of low-dose azithromycin The data provide further support for the long-term use of low dose azithromycin as an attractive adjunct treatment option for COPD. Improved clearance of both apoptotic cells and bacteria in the airway may have a dual effect; reducing the risk of secondary necrosis and release of toxic cell contents that perpetuate inflammation as well as contributing to a reduction in the rate of exacerbations in COPD. © 2012 The Authors. Respirology © 2012 Asian Pacific Society of Respirology.

  16. Calculation of singlet oxygen dose using explicit and implicit dose metrics during benzoporphyrin derivative monoacid ring A (BPD-MA)-PDT in vitro and correlation with MLL cell survival.

    PubMed

    Weston, Mark A; Patterson, Michael S

    2011-01-01

    Photodynamic therapy (PDT) oxygen consumption, clonogenic cell survival, fluorescence photobleaching and photoproduct formation were investigated during benzoporphyrin derivative monoacid (BPD-MA)-PDT of MAT-LyLu cells in vitro. Cells were incubated with BPD-MA concentrations of 0.1, 0.5 or 2.5 μg mL(-1) for 2 h and then treated with 405 nm light under oxygenated and hypoxic conditions. Fluorescence spectra were acquired during treatment, and photobleaching and photoproduct generation were quantified using singular value decomposition of the spectra. Cell survival was measured at set times during the treatment using a colony-forming assay. The amount of oxygen consumed by PDT per photon absorbed decreased with BPD-MA intracellular concentration. Survival was correlated with the total amount of oxygen consumed by PDT per unit volume, which is assumed to be equivalent to the amount of singlet oxygen that reacted. A photobleaching-based singlet oxygen dose metric was also found to predict survival independent of intracellular BPD-MA concentration. The BPD-MA photoproduct was bleached during the treatment. Two singlet oxygen dose metrics based on photoproduct kinetics could not be correlated with cell survival over the full range of intracellular BPD-MA concentrations used. © 2011 The Authors. Photochemistry and Photobiology © 2011 The American Society of Photobiology.

  17. 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

  18. 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

    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

    2011-02-01

    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(•U+2212)) 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.

  19. 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

  20. An optimization protocol for Swiss 3T3 feeder cell growth-arrest by Mitomycin C dose-to-volume derivation strategy.

    PubMed

    Chugh, Rishi Man; Chaturvedi, Madhusudan; Yerneni, Lakshmana Kumar

    2017-04-01

    Feeder cell functionality following growth-arrest with the cost-effective Mitomycin C vis-à-vis irradiation is controversial due to several methodological variables reported. Earlier, we demonstrated variability in growth arrested Swiss 3T3 feeder cell life-span following titration of feeder cell densities with Mitomycin C concentrations which led to the derivation of doses per cell. Alternatively, to counter the unexpected feeder regrowth at high exposure cell density, we proposed titration of a fixed density with arithmetically derived volumes of Mitomycin C solution that corresponded to permutations of specific concentrations and doses per cell. We now describe an experimental procedure of inducing differential feeder cell growth-arrest by titrating with such volumes and validating the best feeder batch through target cell growth assessment. A safe cell density of Swiss 3T3 tested for the exclusion of Mitomycin C resistant variants was titrated with a range of volumes of a Mitomycin C solution. The differentially growth-arrested feeder batches generated were tested for short-term and long-term viability and human epidermal keratinocyte growth supporting ability. The feeder cell extinction rate was directly proportional to the volume of Mitomycin C solution within a given concentration per se. The keratinocyte colony forming efficiency and the overall growth in mass cultures were maximal with a median extinction rate produced by an intermediate volume, while the faster and slower extinction rates by high and low volumes, respectively, were suboptimal. The described method could counter the inadequacies of growth-arrest with Mitomycin C.

  1. 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

  2. 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.

  3. Identification of stable reference genes for gene expression analysis of three-dimensional cultivated human bone marrow-derived mesenchymal stromal cells for bone tissue engineering.

    PubMed

    Rauh, Juliane; Jacobi, Angela; Stiehler, Maik

    2015-02-01

    The principles of tissue engineering (TE) are widely used for bone regeneration concepts. Three-dimensional (3D) cultivation of autologous human mesenchymal stromal cells (MSCs) on porous scaffolds is the basic prerequisite to generate newly formed bone tissue. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a specific and sensitive analytical tool for the measurement of mRNA-levels in cells or tissues. For an accurate quantification of gene expression levels, stably expressed reference genes (RGs) are essential to obtain reliable results. Since the 3D environment can affect a cell's morphology, proliferation, and gene expression profile compared with two-dimensional (2D) cultivation, there is a need to identify robust RGs for the quantification of gene expression. So far, this issue has not been adequately investigated. The aim of this study was to identify the most stably expressed RGs for gene expression analysis of 3D-cultivated human bone marrow-derived MSCs (BM-MSCs). For this, we analyzed the gene expression levels of n=31 RGs in 3D-cultivated human BM-MSCs from six different donors compared with conventional 2D cultivation using qRT-PCR. MSCs isolated from bone marrow aspirates were cultivated on human cancellous bone cube scaffolds for 14 days. Osteogenic differentiation was assessed by cell-specific alkaline phosphatase (ALP) activity and expression of osteogenic marker genes. Expression levels of potential reference and target genes were quantified using commercially available TaqMan(®) assays. mRNA expression stability of RGs was determined by calculating the coefficient of variation (CV) and using the algorithms of geNorm and NormFinder. Using both algorithms, we identified TATA box binding protein (TBP), transferrin receptor (p90, CD71) (TFRC), and hypoxanthine phosphoribosyltransferase 1 (HPRT1) as the most stably expressed RGs in 3D-cultivated BM-MSCs. Notably, genes that are routinely used as RGs, for example, beta actin

  4. 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

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

    PubMed Central

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

    2017-01-01

    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 R2 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: R2 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: R2 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: (R2 0·70 – 0·82). Estimated TATFM correlated well with published prediction equations for total body fat based on underwater weighing (R2 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

  6. Coronary angiography and percutaneous transluminal coronary angioplasty procedures: Evaluation of patients' maximum skin dose using Gafchromic films and a comparison of local levels with reference levels proposed in the literature.

    PubMed

    Giordano, C; D'Ercole, L; Gobbi, R; Bocchiola, M; Passerini, F

    2010-10-01

    The aim of this study was to evaluate the maximum skin dose (MSD) in patients undergoing interventional cardiology procedures, obtaining local reference levels and comparing these with the reference levels proposed in the literature. The patients' MSD was measured using Gafchromic XR type R films. In order to evaluate reference levels, the number of images acquired, the fluoroscopy times and the KAP(TOTAL) were recorded for each procedure. For the evaluation of the MSD, 8 coronary angiography (CA) and 16 percutaneous transluminal coronary angioplasty (PTCA) procedures, carried out in the period from May to June 2008, were analyzed. For the CA procedures the MSD values were below 0.5 Gy. For the PTCA procedures, we found a fairly good correlation between fluoroscopy time and MSD (r = 0.80, p = 0.0002) and between MSD and WFP (r = 0.863, p < 0.0001); there was a strong correlation between KAP(TOTAL) and MSD (r = 0.904, p <0.0001). Since the correlation between KAP(TOTAL) and MSD is more striking than that with fluoroscopic time and the WFP, KAP measurements are suitable for online skin dosimetry and may, therefore, be used to avoid radiation-induced skin injuries. A MSD greater than 3 Gy occurred in only one procedure. For calculus of the local reference levels, we extended the data-gathering to 30 procedure CA and to 40 PTCA: we compared local practice with that in other centers using the guidance levels proposed by Balter et al. Our median KAP values were below these proposed guidance levels; our mean KAP values were above these proposed action levels. From a first application of the proposed reference levels, it appears that, according to the recommendations of Balter et al. an investigation into local practice is not necessary. Copyright © 2010 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  7. Usual Dose of Simvastatin Does Not Inhibit Plaque Progression and Lumen Loss at the Peri-Stent Reference Segments after Bare-Metal Stent Implantation: A Serial Intravascular Ultrasound Analysis

    PubMed Central

    Hong, Young Joon; Choi, Yun Ha; Ma, Eun Hye; Ko, Jum Suk; Lee, Min Goo; Park, Keun Ho; Sim, Doo Sun; Yoon, Nam Sik; Youn, Hyun Ju; Kim, Kye Hun; Park, Hyung Wook; Kim, Ju Han; Ahn, Youngkeun; Cho, Jeong Gwan; Park, Jong Chun; Kang, Jung Chaee

    2010-01-01

    Background/Aims The aim of this study was to assess the effects of a usual dose of simvastatin (20 mg/day) on plaque regression and vascular remodeling at the peri-stent reference segments after bare-metal stent implantation. Methods We retrospectively investigated serial intravascular ultrasound (IVUS) findings in 380 peri-stent reference segments (184 proximal and 196 distal to the stent) in 196 patients (simvastatin group, n = 132 vs. non-statin group, n = 64). Quantitative volumetric IVUS analysis was performed in 5-mm vessel segments proximal and distal to the stent. Results IVUS follow-up was performed at a mean of 9.4 months after stenting (range, 5 to 19 months). No significant differences were observed in the changes in mean plaque plus media (P&M) area, mean lumen area, and mean external elastic membrane (EEM) area from post-stenting to follow-up at both proximal and distal edges between the simvastatin and non-statin group. Although lumen loss within the first 3 mm from each stent edge was primarily due to an increase in P&M area rather than a change in EEM area, and lumen loss beyond 3 mm from each stent edge was due to a combination of increased P&M area and decreased EEM area, no significant differences in changes were observed in P&M, EEM, and lumen area at every 1-mm subsegment between the simvastatin and non-statin group. Conclusions A usual dose of simvastatin does not inhibit plaque progression and lumen loss and does not affect vascular remodeling in peri-stent reference segments in patients undergoing bare-metal stent implantation. PMID:21179272

  8. 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...

  9. 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...

  10. 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

  11. Sorghum bran in the diet dose dependently increased the excretion of catechins and microbial-derived phenolic acids in female rats.

    PubMed

    Gu, Liwei; House, Suzanne E; Rooney, Lloyd; Prior, Ronald L

    2007-06-27

    Sorghum bran is concentrated with procyanidins (predominately polymers), which may be beneficial for health in humans; however, the bioavailability of procyanidins is not well-understood. Female Sprague-Dawley rats were fed an AIN93G diet containing 0, 5, 10, 20, or 40% Hi-tannin sorghum bran (n = 5-7 for each group) for 50 days. Sorghum bran contained 23.3 mg/g of procyanidins. The urinary excretions of catechin, epicatechin, methylated catechins, and phenolic acids were analyzed using liquid chromatography-tandem mass spectrometry. Sorghum bran dose dependently increased the urinary excretion of catechin (0-2.2 nmol/day) and 3'-O-methylcatechin (0-9.5 nmol/day). Their serum concentrations also increased with dose (range of 0-14 nM for 3'-O-methylcatechin). Among the 14 phenolic acids analyzed, 3,4-dihydroxybenzoic acid, 3-methoxy-4-hydroxybenzoic acid, and 4-hydroxyphenylacetic acid dominated in the serum (1.8-8 micromol/L). In the urine, 3-methoxy-4-hydroxyphenylacetic acid, 3-hydroxyphenylacetic acid, and 3-hydroxyphenylpropionic acid dominated and their excretion increased significantly with the level of sorghum bran in the diet. The summed phenolic acid excretion was 0.8 micromol/day in the control group and increased to 23 micromol/day for 40% sorghum bran group. The hippuric acid excretion ranged from 2.2 to 16.2 micromol/day and peaked in the 10% sorghum bran group. On the basis of chromic oxide, a nonabsorbable marker, total procyanidins and polymers disappeared progressively, and significant degradation occurred in the cecum and colon. Catechins and procyanidins in sorghum were bioavailable; however, bacteria-derived phenolic acids were the predominant metabolites of procyanidins. Procyanidins degraded in the gastrointestinal tract. Depolymerization was not observed.

  12. LbCML38 and LbRH52, two reference genes derived from RNA-Seq data suitable for assessing gene expression in Lycium barbarum L.

    PubMed Central

    Gong, Lei; Yang, Yajun; Chen, Yuchao; Shi, Jing; Song, Yuxia; Zhang, Hongxia

    2016-01-01

    For quantitative real-time PCR (qRT-PCR) analysis, the key prerequisite that determines result accuracy is the selection of appropriate reference gene(s). Goji (Lycium barbarum L.) is a multi-branched shrub belonging to the Solanaceae family. To date, no systematic screening or evaluation of reference gene(s) in Goji has been performed. In this work, we identified 18 candidate reference genes from the transcriptomic sequencing data of 14 samples of Goji at different developmental stages and under drought stress condition. The expression stability of these candidate genes was rigorously analyzed using qRT-PCR and four different statistical algorithms: geNorm, BestKeeper, NormFinder and RefFinder. Two novel reference genes LbCML38 and LbRH52 showed the most stable expression, whereas the traditionally used reference genes such as LbGAPDH, LbHSP90 and LbTUB showed unstable expression in the tested samples. Expression of a target gene LbMYB1 was also tested and compared using optimal reference genes LbCML38 and LbRH52, mediocre reference gene LbActin7, and poor reference gene LbHSP90 as normalization standards, respectively. As expected, calculation of the target gene expression by normalization against LbCML38, LbActin7 or LbHSP90 showed significant differences. Our findings suggest that LbCML38 and LbRH52 can be used as reference genes for gene expression analysis in Goji. PMID:27841319

  13. Low-dose oral immunization with lyophilized tissue of herbicide-resistant lettuce expressing hepatitis B surface antigen for prototype plant-derived vaccine tablet formulation.

    PubMed

    Pniewski, Tomasz; Kapusta, Józef; Bociąg, Piotr; Wojciechowicz, Jacek; Kostrzak, Anna; Gdula, Michał; Fedorowicz-Strońska, Olga; Wójcik, Piotr; Otta, Halina; Samardakiewicz, Sławomir; Wolko, Bogdan; Płucienniczak, Andrzej

    2011-05-01

    Efficient immunization against hepatitis B virus (HBV) and other pathogens with plant-based oral vaccines requires appropriate plant expressors and the optimization of vaccine compositions and administration protocols. Previous immunization studies were mainly based on a combination of the injection of a small surface antigen of HBV (S-HBsAg) and the feeding with raw tissue containing the antigen, supplemented with an adjuvant, and coming from plants conferring resistance to kanamycin. The objective of this study was to develop a prototype oral vaccine formula suitable for human immunization. Herbicide-resistant lettuce was engineered, stably expressing through progeny generation micrograms of S-HBsAg per g of fresh weight and formed into virus-like particles (VLPs). Lyophilized tissue containing a relatively low, 100-ng VLP-assembled antigen dose, administered only orally to mice with a long, 60-day interval between prime and boost immunizations and without exogenous adjuvant, elicited mucosal and systemic humoral anti-HBs responses at the nominally protective level. Lyophilized tissue was converted into tablets, which preserved S-HBsAg content for at least one year of room temperature storage. The results of the study provide indications on immunization methodology using a durable, efficacious, and convenient plant-derived prototype oral vaccine against hepatitis B.

  14. 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.

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

    PubMed

    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

  16. 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

  17. Low-dose benzo(a)pyrene and its epoxide metabolite inhibit myogenic differentiation in human skeletal muscle-derived progenitor cells.

    PubMed

    Chiu, Chen-Yuan; Yen, Yuan-Peng; Tsai, Keh-Sung; Yang, Rong-Sen; Liu, Shing-Hwa

    2014-04-01

    The risk of low birth weights is elevated in prenatal exposure to polycyclic aromatic hydrocarbons (PAHs), which are ubiquitous environmental pollutants generated from combustion of organic compounds, including cigarette smoke. We hypothesized that benzo(a)pyrene (BaP), a member of PAHs existing in cigarette smoke, may affect the myogenesis to cause low birth weights. We investigated the effects of BaP and its main metabolite, benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), on the myogenic differentiation of human skeletal muscle-derived progenitor cells (HSMPCs). HSMPCs were isolated by a modified preplate technique and cultured in myogenic differentiation media with or without BaP and BPDE (0.25 and 0.5 μM) for 4 days. The multinucleated myotube formation was morphologically analyzed by hematoxylin and eosin staining. The expressions of myogenic differentiation markers and related signaling proteins were determined by Western blotting. Both BaP and BPDE at the submicromolar concentrations (0.25 and 0.5 μM) dose-dependently repressed HSMPCs myogenic differentiation without obvious cell toxicity. Both BaP and BPDE inhibited the muscle-specific protein expressions (myogenin and myosin heavy chain) and phosphorylation of Akt (a known modulator in myogenesis), which could be significantly reversed by the inhibitors for aryl hydrocarbon receptor (AhR), estrogen receptor (ER), and nuclear factor (NF)-κB. BaP- and BPDE-activated NF-κB-p65 protein phosphorylation could also be attenuated by both AhR and ER inhibitors. The inhibitory effects of BaP and BPDE on myogenesis were reversed after withdrawing BaP exposure, but not after BPDE withdrawal. These results suggest that both BaP and BPDE are capable of inhibiting myogenesis via an AhR- or/and ER-regulated NF-κB/Akt signaling pathway.

  18. 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.

  19. 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

  20. 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

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

    2010-11-01

    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. 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. 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. 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. Copyright © 2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  1. 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.

  2. A comparison of three methods of setting prescribing budgets, using data derived from defined daily dose analyses of historic patterns of use.

    PubMed Central

    Maxwell, M; Howie, J G; Pryde, C J

    1998-01-01

    BACKGROUND: Prescribing matters (particularly budget setting and research into prescribing variation between doctors) have been handicapped by the absence of credible measures of the volume of drugs prescribed. AIM: To use the defined daily dose (DDD) method to study variation in the volume and cost of drugs prescribed across the seven main British National Formulary (BNF) chapters with a view to comparing different methods of setting prescribing budgets. METHOD: Study of one year of prescribing statistics from all 129 general practices in Lothian, covering 808,059 patients: analyses of prescribing statistics for 1995 to define volume and cost/volume of prescribing for one year for 10 groups of practices defined by the age and deprivation status of their patients, for seven BNF chapters; creation of prescribing budgets for 1996 for each individual practice based on the use of target volume and cost statistics; comparison of 1996 DDD-based budgets with those set using the conventional historical approach; and comparison of DDD-based budgets with budgets set using a capitation-based formula derived from local cost/patient information. RESULTS: The volume of drugs prescribed was affected by the age structure of the practices in BNF Chapters 1 (gastrointestinal), 2 (cardiovascular), and 6 (endocrine), and by deprivation structure for BNF Chapters 3 (respiratory) and 4 (central nervous system). Costs per DDD in the major BNF chapters were largely independent of age, deprivation structure, or fundholding status. Capitation and DDD-based budgets were similar to each other, but both differed substantially from historic budgets. One practice in seven gained or lost more than 100,000 Pounds per annum using DDD or capitation budgets compared with historic budgets. The DDD-based budget, but not the capitation-based budget, can be used to set volume-specific prescribing targets. CONCLUSIONS: DDD-based and capitation-based prescribing budgets can be set using a simple

  3. 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.

  4. Functional Entropy Variables: A New Methodology for Deriving Thermodynamically Consistent Algorithms for Complex Fluids, with Particular Reference to the Isothermal Navier-Stokes-Korteweg Equations

    DTIC Science & Technology

    2012-11-01

    and Computer Aided Design ( CAD ) [37]. Invoking the isoparametric paradigm, isogeometric analysis utilizes the same basis functions that are used in CAD ...a2b λ T0t ∗ = L0 √ a λ t∗ = We 1 2 t∗. (42) The relation (42) will be useful when we design our numerical algorithm in Section 3.3. We will...ICES REPORT 12-43 November 2012 Functional Entropy Variables: A New Methodology for Deriving Thermodynamically Consistent Algorithms for Complex

  5. The effect of flaxseed dose on circulating concentrations of alpha-linolenic acid and secoisolariciresinol diglucoside derived enterolignans in young, healthy adults.

    PubMed

    Edel, Andrea L; Patenaude, Amanda F; Richard, Melanie N; Dibrov, Elena; Austria, J Alejandro; Aukema, Harold M; Pierce, Grant N; Aliani, Michel

    2016-03-01

    The primary endpoint was to determine the plasma concentration of alpha-linolenic acid (ALA), and its metabolites, following milled flaxseed consumption at four doses. Secondary outcomes focused on plasma enterolignan concentrations and the effects on tolerability, platelet aggregation, plasma lipids and urinary thromboxane levels. Healthy, younger adults (n = 34; 18-49 years old) were randomized into four groups consuming one muffin daily for 30 days fortified with 10, 20, 30 or 40 g of milled flaxseed. Blood and urine were collected at baseline and 4 weeks. Plasma ALA concentrations increased with all flaxseed doses (P < 0.01), except the 20 g/day dose (P = 0.10), yet there was no significant dose-dependent response (P = 0.81). Only with the 30 g/day diet were n-3 polyunsaturated fatty acids (P = 0.007), and eicosapentaenoic acid (EPA) (P = 0.047) increased from baseline values. Docosapentaenoic acid and docosahexaenoic acid were not detected at any dose. Plasma total enterolignan concentrations significantly increased over time in all treatment groups, yet despite a dose-dependent tendency, no between-group differences were detected (P = 0.22). Flaxseed was well tolerated, even at the highest dose, as there were no reported adverse events, changes in cholesterol, platelet aggregation or urinary 11-dehydro-thromboxane B2. In healthy, younger adults, 10 g/day of milled flaxseed consumption is sufficient to significantly increase circulating ALA and total enterolignan concentrations; however, 30 g/day is required to convert ALA to EPA. Although all doses were well tolerated, 40 g/day is too low to attenuate cholesterol in this population.

  6. 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.

  7. Temporal development of total chlorine in the high-latitude stratosphere based on reference distributions of mean age derived from CO2 and SF6

    NASA Astrophysics Data System (ADS)

    Engel, Andreas; Strunk, Martin; Müller, Melanie; Haase, Hans-Peter; Poss, Christian; Levin, Ingeborg; Schmidt, Ulrich

    2002-06-01

    We present balloon-borne observations of CO2 and SF6 and derived vertical profiles of mean age for polar winter (inside vortex) and for midlatitude (nonwinter) conditions. For SF6-derived mean ages above 5 years a mesospheric SF6 sink may lead to an overestimation of mean age, while for younger mean ages (below 2 years) the seasonal cycle of CO2 may influence the mean age determination based on CO2. We suggest that SF6 be used as an age tracer in the lower part of the stratosphere (i.e., for low mean age), whereas CO2 will be the better age tracer for older air. The mean age distributions together with an estimate of the width of the age spectrum are used to estimate the stratospheric chlorine loading. On the basis of an emission scenario and the lifetimes of chlorine-containing compounds we estimate the future stratospheric chlorine loading. Inside the polar vortex, at an altitude of 20 km, we expect total chlorine to return to the values present in this region in 1980, when the ozone hole first appeared, around the year 2060. This estimate is based on the assumption that the general transport characteristics will not change over the period of the analysis and can thus be regarded as a best estimate based on stationary transport, the assumed set of lifetimes and emissions, and the mean age distribution derived from our measurements. As other factors influencing ozone may undergo temporal changes, this does not mean that ozone will necessarily recover at this time. While total chlorine is probably a good proxy for inorganic chlorine at altitudes above 20 km inside the polar vortex, the changing halocarbon mix may actually lead to an earlier return of inorganic chlorine to pre-ozone-hole values at lower altitudes.

  8. 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.

  9. Long-term effectiveness of plasma-derived hepatitis B vaccine 22-28 years after immunization in a hepatitis B virus endemic rural area: is an adult booster dose needed?

    PubMed

    Li, H; Li, G J; Chen, Q Y; Fang, Z L; Wang, X Y; Tan, C; Yang, Q L; Wang, F Z; Wang, F; Zhang, S; Bi, S L; Shen, L P

    2017-01-09

    Longan County is considered a highly endemic area for hepatitis B virus (HBV). The plasma-derived vaccine has been used in newborns in this area since 1987. A cross-sectional survey was conducted to evaluate the long-term effectiveness of this vaccine. In total, 1634 participants born during 1987-1993 and who had received a series of plasma-derived HB vaccinations at ages 0, 1, and 6 months were enrolled. Serological HBV markers were detected and compared with previous survey data. Overall the prevalence of hepatitis B surface antigen (HBsAg) in all participants was 3·79%; 3·47% of subjects who had received the first dose within 24 h were HBsAg positive, and 8·41% of subjects who had received a delayed first dose were also HBsAg positive. There were 1527 subjects identified who had received the first dose within 24 h and whose HBsAg and anti-HBc prevalence increased yearly after immunization, while the anti-HBs-positive rate and vaccine effectiveness declined. The geometric mean concentration of antibody in the anti-HB-positive participants was 55·13 mIU/ml and this declined after immunization. Fewer than 2·0% of participants had anti-HB levels ⩾1000 mIU/ml. The data show that the protective efficacy of the plasma-derived vaccinations declined and administration of HB vaccine within 24 h of birth was very important. To reduce the risk of HBV infection in this highly endemic area, a booster dose might be necessary if anti-HBs levels fall below 10 mIU/ml after age 18 years. Furthermore, studies on the immune memory induced by plasma-derived HB vaccine are needed.

  10. Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry

    PubMed Central

    Kucharski, Robert; Sołtysiak, Marta; Taszarek, Aleksandra; Miazgowski, Bartosz; Widecka, Krystyna

    2017-01-01

    Dual energy X-ray absorptiometry (DXA) is an established technique used in clinical and research settings to evaluate total and regional fat. Additionally, recently developed software allow to quantify visceral adipose tissue (VAT). Currently, there are no reference values available for GE Healthcare DXA systems for VAT. The aim of this study was to develop reference values for VAT in healthy European adults aged 20–30 years using a GE Healthcare Prodigy densitometer along with the dedicated CoreScan application. We also assessed the associations of VAT with traditional cardiometabolic risk factors. In 421 participants (207 men; 214 women), we performed DXA whole-body scans and calculated total body fat (BF) and VAT (in gender-specific percentiles). We also measured blood pressure and fasting glucose, insulin, and blood lipids. Males, in comparison with females, had 2-fold greater VAT both in units of mass (542 ± 451 g; 95% CI: 479.6‒605.1 g vs. 258 ± 226 g; 95% CI: 226.9‒288.6 g) and volume (570 ± 468 cm3; 95% CI: 505.1‒635.2 cm3 vs. 273 ± 237 cm3; 95% CI: 240.6‒305.3 cm3). They also had significantly higher the VAT/BF ratio. VAT showed a stronger positive correlation than BF with blood pressure, triglycerides, LDL-cholesterol, glucose, insulin, and homeostasis model assessment-insulin resistance index and a stronger negative correlation with HDL-cholesterol. Among these variables, VAT had the highest area under the curve for triglycerides ≥150 mg/dL (0.727 in males and 0.712 in females). In conclusion, we provide reference values for VAT obtained from healthy adults using the GE Healthcare DXA. These values may be useful in the diagnosis of visceral obesity, for identifying subjects with high obesity-related risks, in epidemiological studies, as a target for therapies, and in physically trained individuals. In both genders, VAT was associated with traditional cardiometabolic risk factors, particularly hypertriglyceridemia. PMID:28683146

  11. Visceral fat reference values derived from healthy European men and women aged 20-30 years using GE Healthcare dual-energy x-ray absorptiometry.

    PubMed

    Miazgowski, Tomasz; Kucharski, Robert; Sołtysiak, Marta; Taszarek, Aleksandra; Miazgowski, Bartosz; Widecka, Krystyna

    2017-01-01

    Dual energy X-ray absorptiometry (DXA) is an established technique used in clinical and research settings to evaluate total and regional fat. Additionally, recently developed software allow to quantify visceral adipose tissue (VAT). Currently, there are no reference values available for GE Healthcare DXA systems for VAT. The aim of this study was to develop reference values for VAT in healthy European adults aged 20-30 years using a GE Healthcare Prodigy densitometer along with the dedicated CoreScan application. We also assessed the associations of VAT with traditional cardiometabolic risk factors. In 421 participants (207 men; 214 women), we performed DXA whole-body scans and calculated total body fat (BF) and VAT (in gender-specific percentiles). We also measured blood pressure and fasting glucose, insulin, and blood lipids. Males, in comparison with females, had 2-fold greater VAT both in units of mass (542 ± 451 g; 95% CI: 479.6‒605.1 g vs. 258 ± 226 g; 95% CI: 226.9‒288.6 g) and volume (570 ± 468 cm3; 95% CI: 505.1‒635.2 cm3 vs. 273 ± 237 cm3; 95% CI: 240.6‒305.3 cm3). They also had significantly higher the VAT/BF ratio. VAT showed a stronger positive correlation than BF with blood pressure, triglycerides, LDL-cholesterol, glucose, insulin, and homeostasis model assessment-insulin resistance index and a stronger negative correlation with HDL-cholesterol. Among these variables, VAT had the highest area under the curve for triglycerides ≥150 mg/dL (0.727 in males and 0.712 in females). In conclusion, we provide reference values for VAT obtained from healthy adults using the GE Healthcare DXA. These values may be useful in the diagnosis of visceral obesity, for identifying subjects with high obesity-related risks, in epidemiological studies, as a target for therapies, and in physically trained individuals. In both genders, VAT was associated with traditional cardiometabolic risk factors, particularly hypertriglyceridemia.

  12. 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…

  13. 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"…

  14. 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"…

  15. 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…

  16. Reference Revolutions.

    ERIC Educational Resources Information Center

    Mason, Marilyn Gell

    1998-01-01

    Describes developments in Online Computer Library Center (OCLC) electronic reference services. Presents a background on networked cataloging and the initial implementation of reference services by OCLC. Discusses the introduction of OCLC FirstSearch service, which today offers access to over 65 databases, future developments in integrated…

  17. Deriving the reference value from the circadian motor active patterns in the "non-dementia" population, compared to the "dementia" population: What is the amount of physical activity conducive to the good circadian rhythm.

    PubMed

    Kodama, Ayuto; Kume, Yu; Tsugaruya, Megumi; Ishikawa, Takashi

    2016-01-01

    The circadian rhythm in older adults is commonly known to change with a decrease in physical activity. However, the association between circadian rhythm metrics and physical activity remains unclear. The objective of this study was to examine circadian activity patterns in older people with and without dementia and to determine the amount of physical activity conducive to a good circadian measurement. Circadian parameters were collected from 117 older community-dwelling people (66 subjects without dementia and 52 subjects with dementia); the parameters were measured continuously using actigraphy for 7 days. A receiver operating characteristic (ROC) curve was applied to determine reference values for the circadian rhythm parameters, consisting of interdaily stability (IS), intradaily variability (IV), and relative amplitude (RA), in older subjects. The ROC curve revealed reference values of 0.55 for IS, 1.10 for IV, and 0.82 for RA. In addition, as a result of the ROC curve in the moderate-to-vigorous physical Activity (MVPA) conducive to the reference value of the Non-parametric Circadian Rhythm Analysis per day, the optimal reference values were 51 minutes for IV and 55 minutes for RA. However, the IS had no classification accuracy. Our results demonstrated the reference values derived from the circadian parameters of older Japanese population with or without dementia. Also, we determined the MVPA conducive to a good circadian rest-active pattern. This reference value for physical activity conducive to a good circadian rhythm might be useful for developing a new index for health promotion in the older community-dwelling population.

  18. Associated factors for higher lead and cadmium blood levels, and reference values derived from general population of São Paulo, Brazil.

    PubMed

    Kira, Carmen Silvia; Sakuma, Alice Momoyo; De Capitani, Eduardo Mello; de Freitas, Clarice Umbelino; Cardoso, Maria Regina Alves; Gouveia, Nelson

    2016-02-01

    Human activities are associated with emissions of various metals into the environment, among which the heavy metals lead and cadmium stand out, as they pose a risk to human life even at low concentrations. Thus, accurate knowledge of the levels of these metals exhibited by the overall population, including children, is important. The aim of this study was to estimate the concentrations of lead and cadmium in the blood of adults, adolescents and children residing in the city of São Paulo, assess factors associated with higher lead and cadmium blood levels, and to establish reference values for this population. The study sample consisted of 669 adults over 20 years old, 264 adolescents aged 12 to 19 years old and 391 children under 11 years old from both genders. The samples were collected at the end of 2007 and during 2008 in different city zones. Higher blood lead concentration was significantly associated with gender, smoking, offal intake, area of residence and age. The blood cadmium concentration was significantly associated with gender, smoking, consumption of distilled beverages and age. The reference values of lead and cadmium established for adults above 20 years old were 33 μg/L and 0.6 μg/L, respectively, for adolescents (12 to 19 years old) were 31 μg/L and 0.6 μg/L, respectively and for children under 11 years old were 29 μg/L and 0.2 μg/L, respectively. The results of this study indicate that the exposure levels of the investigated population to lead and cadmium are low.

  19. 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).

  20. Evaluation of Safety and Pharmacokinetics of Sodium 2,2 Dimethylbutyrate, a Novel Short Chain Fatty Acid Derivative, in a Phase 1, Double-Blind, Placebo-Controlled, Single- and Repeat-Dose Studies in Healthy Volunteers

    PubMed Central

    Perrine, Susan P.; Wargin, William A.; Boosalis, Michael S.; Wallis, Wayne J.; Case, Sally; Keefer, Jeffrey R.; Faller, Douglas V.; Welch, William C.; Berenson, Ronald J.

    2013-01-01

    Pharmacologic induction of fetal globin synthesis is an accepted therapeutic strategy for treatment of the beta hemoglobinopathies and thalassemias, as even small increases in hemoglobin F (HbF) levels reduce clinical severity in sickle cell disease and reduce anemia in beta thalassemia. Prior generation short chain fatty acid therapeutics, arginine butyrate and phenylbutyrate, increased fetal and total hemoglobin levels in patients, but were limited by high doses or intravenous infusion. A fetal globin-inducing therapeutic with convenient oral dosing would be an advance for these classic molecular diseases. Healthy adult human subjects were treated with a novel SCFA derivative, sodium 2,2 dimethylbutyrate (SDMB), or placebo, with one of four single dose levels (2, 5, 10 and 20 mg/kg) or daily doses (5, 10, or 15 mg/kg) over 14 days, and monitored for adverse clinical and laboratory events, drug levels, reticulocytes, and HbF assays. SDMB was well-tolerated with no clinically significant adverse events related to study medication. The terminal half-life ranged from 9–15 hours. Increases in mean absolute reticulocytes were observed at all dose levels in the 14-day study. The favorable PK profiles and safety findings indicate that SDMB warrants further investigation for treatment of anemic subjects with beta hemoglobinopathies. PMID:21422239

  1. Metabolism of glyphosate in Sprague-Dawley rats: tissue distribution, identification, and quantitation of glyphosate-derived materials following a single oral dose.

    PubMed

    Brewster, D W; Warren, J; Hopkins, W E

    1991-07-01

    Five groups of male Sprague-Dawley rats were orally administered a mixture of [14C]- and [12C]-glyphosate (N-phosphonomethylglycine) at a dose level of 10 mg/kg body weight. The majority of radioactivity 2 hr after administration was associated with the gastrointestinal contents and small intestinal tissue. Approximately 35-40% of the administered dose was absorbed from the gastrointestinal tract, and urine and feces were equally important routes of elimination. The total body burden 7 days after administration was approximately 1% of the administered dose and was primarily associated with the bone. Total recovery for this study ranged from 95 to 102% of the administered dose. Metabolic profiles of tissues containing greater than 1% of the administered dose at various times after administration indicated that nearly 100% of the body burden of radioactivity was present as unmetabolized parent glyphosate. A minor component constituting less than 0.1% of the administered dose (less than 0.4 ppm) was observed in colon tissue from animals 2 hr after the administration of glyphosate and was also present in the GI contents of one animal 28 hr after administration of the radiolabel. The retention time for this metabolite was similar, but not identical, to the retention time for AMPA (aminomethylphosphonic acid), the major bacterial metabolite of glyphosate found in soil. Tissue extraction efficiency was always greater than 90% and stability assays indicated no significant effect of storage on either parent glyphosate or AMPA. The results from this study indicate that virtually no toxic metabolites of glyphosate were produced since there was little evidence of metabolism and essentially 100% of the body burden was parent compound with no significant persistence of material.

  2. [Estimation of effective doses derived from radon in selected SPA centers that use geothermal waters based on the information of radon concentrations].

    PubMed

    Walczak, Katarzyna; Zmyślony, Marek

    2013-01-01

    Geothermal waters contain, among other components, soluble radon gas. Alpha radioactive radon is a health hazard to humans, especially when it gets into the respiratory tract. SPA facilities that use geothermal water can be a source of an increased radiation dose to people who stay there. Based on the available literature concerning radon concentrations, we assessed exposure to radon among people - workers and visitors of Spa centers that use geothermal waters. Radon concentrations were analyzed in 17 geothermal centers: in Greece (3 centers), Iran (5), China (4) and India (5). Doses recived by people in the SPA were estimated using the formula that 1 hour exposure to 1 Bq/m3 of radon concentration and equilibrium factor F = 0.4 corresponds to an effective dose of 3.2 nSv. We have found that radon levels in SPAs are from a few to several times higher than those in confined spaces, where geothermal waters are not used (e.g., residential buildings). In 82% of the analyzed SPAs, workers may receive doses above 1 mSv/year. According to the relevant Polish regulations, people receiving doses higher than 1 mSv/year are included in category B of radiation exposure and require regular dosimetric monitoring. Doses received by SPA visitors are much lower because the time of their exposure to radon released from geothermal water is rather short. The analysis of radon concentration in SPA facilities shows that the radiological protection of people working with geothermal waters plays an important role. It seems reasonable to include SPA workers staying close to geotermal waters into a dosimetric monitoring program.

  3. 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)

  4. IERS Reference System.

    NASA Astrophysics Data System (ADS)

    Yokoyama, K.

    Present circumstances related to IERS activities are described from various points of view. The NASA Dynamics of Solid Earth (DOSE) program and the IERS intensive campaign proposed by J. Dickey of JPL are particularly interesting. It is important to implement international cooperation to establish a fundamental radio reference frame by carrying out global solution based on all geodetic observations, past and future. A precession and nutation model may be determined observationally with an accuracy of 0.2 - 0.3 mas in a few years. Then it will become possible to establish the radio reference frame with this accuracy.

  5. Uncertainty Quantification in Internal Dose Calculations for Seven Selected Radiopharmaceuticals.

    PubMed

    Spielmann, Vladimir; Li, Wei Bo; Zankl, Maria; Oeh, Uwe; Hoeschen, Christoph

    2016-01-01

    Dose coefficients of radiopharmaceuticals have been published by the International Commission on Radiological Protection (ICRP) and the MIRD Committee but without information concerning uncertainties. The uncertainty information of dose coefficients is important, for example, to compare alternative diagnostic methods and choose the method that causes the lowest patient exposure with appropriate and comparable diagnostic quality. For the study presented here, an uncertainty analysis method was developed and used to calculate the uncertainty of the internal doses of 7 common radiopharmaceuticals. On the basis of the generalized schema of dose calculation recommended by the ICRP and MIRD Committee, an analysis based on propagation of uncertainty was developed and applied for 7 radiopharmaceuticals. The method takes into account the uncertainties contributed from pharmacokinetic models and the so-called S values derived from several voxel computational phantoms previously developed at Helmholtz Zentrum München. Random and Latin hypercube sampling techniques were used to sample parameters of pharmacokinetic models and S values, and the uncertainties of absorbed doses and effective doses were calculated. The uncertainty factors (square root of the ratio between 97.5th and 2.5th percentiles) for organ-absorbed doses are in the range of 1.1-3.3. Uncertainty values of effective doses are lower in comparison to absorbed doses, the maximum value being approximately 1.4. The ICRP reference values showed a deviation comparable to the effective dose calculated in this study. A general statistical method was developed for calculating the uncertainty of absorbed doses and effective doses for 7 radiopharmaceuticals. The dose uncertainties can be used to further identify the most important parameters in the dose calculation and provide reliable dose coefficients for risk analysis of the patients in nuclear medicine. © 2016 by the Society of Nuclear Medicine and Molecular Imaging

  6. A SHORTCUT FORMULA FOR THE 230-MeV PROTON-INDUCED NEUTRON DOSE EQUIVALENT IN CONCRETE AFTER A METAL SHIELD, DERIVED FROM MONTE CARLO SIMULATIONS WITH MCNPX.

    PubMed

    Taal, A; van der Kooij, A; Okx, W J C

    2016-11-01

    Monte Carlo simulations were performed with MCNPX to determine the neutron dose equivalent in thick concrete after a metal shield, a double-layered shielding configuration. In the simulations, a 230-MeV proton beam impinging on a copper target was used to produce the neutrons. For forward angles up to 30° with respect to the proton beam, it is found that the neutron dose equivalent in thick concrete after a metal layer can be expressed in a single formula. This single formula being the neutron dose equivalent formula for a single thick concrete shield enhanced with an additional exponential term. The exponent of this additional exponential term is related to the relative macroscopic neutron removal cross section of the metal with respect to the concrete. The single formula found fits MCNPX data for the neutron dose equivalent in thick concrete after layers of metal ranging from beryllium to lead. First attempts were made to make this shortcut formula applicable to alloys and compounds of metals.

  7. A specific dose of grape seed-derived proanthocyanidins to inhibit body weight gain limits food intake and increases energy expenditure in rats.

    PubMed

    Serrano, Joan; Casanova-Martí, Àngela; Gual, Andreu; Pérez-Vendrell, Anna Maria; Blay, M Teresa; Terra, Ximena; Ardévol, Anna; Pinent, Montserrat

    2017-06-01

    Several studies have suggested that flavanols may have antiobesity effects; however, those effects clearly depend on the experimental conditions. In a previous study, we found that a single acute dose of grape seed proanthocyanidin extract (GSPE) has satiating effects. We therefore hypothesise that satiating doses of GSPE could be used to reduce body weight gain, and our present objective was to define the most effective dose. We assayed two GSPE doses in aged male Wistar rats. First we performed a subchronic (8-day) treatment by intragastric administration, which was repeated after a washout period. We measured body weight, energy intake and faeces composition; we performed indirect calorimetry; and we analysed the mRNA expression of genes involved in lipid metabolism to determine the target tissue for the GSPE. We observed that 0.5 g GSPE/kg BW significantly reduced food intake and thus the amount of energy absorbed. This dosage also increased lipid oxidation in subcutaneous adipose tissue, thus causing a higher total energy expenditure. These combined effects caused a decrease in body weight. Conversely, 1 g GSPE/kg BW, which also reduced energy absorption after the first treatment, had a rebound effect on body weight gain which resulted in a lower response to the proanthocyanidin extract. That is, after the second treatment, the GSPE did not reduce the energy absorbed or modify energy expenditure and body weight. GSPE at a dose of 0.5 g/kg can reduce body weight by limiting food intake and activating energy expenditure in subcutaneous adipose tissue.

  8. Measurement of dose in panoramic dental radiology.

    PubMed

    Williams, J R; Montgomery, A

    2000-09-01

    The National Radiological Protection Board (NRPB) has recommended the introduction of dose-width product (DWP) for the measurement of patient dose in panoramic dental radiology and has proposed a reference level of 65 mGy mm for adult exposures. This paper describes a method for measuring DWP and dose-area product (DAP) using thermoluminescent dosemeters (TLDs). The technique was used on 16 sets with a range of exposure settings. The mean value of DWP was 14% higher than the mean value reported from a survey by the NRPB. This difference is most likely to be caused by systematic variations due to measurement method. The average DAP for a standard adult examination was shown to be 11.3 cGy cm2. Data are presented so that the DAP can be derived from the exposure factors (tube current and operating potential) and beam area. Based on published data for effective dose, it is estimated that the DAP to effective dose conversion factor is approximately 0.06 mSv(Gy cm2)-1. The average DAP value (11.3 cGy cm2) can be compared with the average value for intraoral radiography (9.3 cGy cm2) based on the NRPB survey of entrance surface doses assuming 6 cm circular collimation.

  9. 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

  10. 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

  11. Pharmacokinetics and tolerability (Study 1) with particular reference to ocular safety (Study 2) of tiotropium Respimat soft mist inhaler: findings from two dose-ranging studies in healthy men.

    PubMed

    Feifel, Ulrich; Wallenstein, Gudrun; Rominger, Karl-Ludwig; Trommeshauser, Dirk; Platz, Juliane

    2008-01-01

    Data are presented from two randomized, double-blind, placebo-controlled studies in which the tolerability of tiotropium Respimat Soft MistTM Inhaler (SMI), a new-generation, propellant-free device for use in COPD, and the ocular safety oftiotropium were examined. In Study 1, 36 healthy males received tiotropium 8, 16, or 32 microg (n = 9/dose) or placebo (n = 3/dose level), administered once daily via Respimat SMI for 14 days. Safety and pharmacokinetics were evaluated. In Study 2, 48 healthy males received tiotropium 0.02, 0.04, 0.08, 0.16, 0.28, or 0.40 microg (n = 6/dose) or placebo (n = 2/dose level), applied as two drops to one eye (the highest dose was a significant multiple of a percentage of the proposed Respimat SMI clinical dose that could be inadvertently deposited in the eye). Ocular parameters were measured over 24 hours. Tiotropium Respimat SMI at doses up to 32 microg was well tolerated in Study 1; typical dose-dependent anticholinergic adverse events of mild-to-moderate intensity were observed. In Study 2, ocular tiotropium administration did not affect pupil diameter, pupillary reflex, intraocular pressure, or accommodation. Tiotropium Respimat SMI was well tolerated. Inadvertent ocular exposure to tiotropium up to 0.40 g is unlikely to result in ocular adverse effects.

  12. 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.

  13. Reference Roundup.

    ERIC Educational Resources Information Center

    Silver, Linda; And Others

    1982-01-01

    Briefly describes the nature and availability of reference books for children and adolescents and then reviews some recent publications of this type, including works of a general nature and works on social science, science, the arts, language, history and geography, and biography. (JL)

  14. 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…

  15. Assessment of the immunogenicity and safety of varying doses of an MF59®-adjuvanted cell culture-derived A/H1N1 pandemic influenza vaccine in Japanese paediatric, adult and elderly subjects.

    PubMed

    Fukase, Hiroyuki; Furuie, Hidetoshi; Yasuda, Yuji; Komatsu, Ryoya; Matsushita, Kenji; Minami, Taketsugu; Suehiro, Yutaka; Yotsuyanagi, Hiroshi; Kusadokoro, Haruko; Sawata, Hiroshi; Nakura, Noriko; Lattanzi, Maria

    2012-07-13

    Effective vaccination strategies are required to combat future influenza pandemics. Here we report the results of three independent clinical trials performed in Japan to assess the immunogenicity, tolerability and safety of varying doses of a cell culture-derived MF59(®)-adjuvanted A/H1N1 pandemic vaccine in healthy Japanese paediatric, adult and elderly subjects. One hundred and twenty-three children (6 months-18 years), and 200 adults (19-60 years) were randomly assigned in a 1:1 ratio to receive two doses of vaccine containing either 7.5 μg antigen with a full (9.75 mg) adjuvant dose, or 3.75 μg antigen with a half (4.875 mg) adjuvant dose. One hundred elderly (≥ 61 years) subjects received only the low antigen/adjuvant vaccine formulation. Immunogenicity was assessed by haemagglutination inhibition assay at baseline and three weeks after the first and second vaccine doses on Days 22 and 43, respectively. Solicited and unsolicited adverse reactions were recorded for seven and 21 days post-immunization, respectively. In adult and elderly subjects, a single low antigen/adjuvant dose vaccination was sufficient to meet all of the three European licensure criteria established for influenza vaccines. One high, or two low antigen/adjuvant dose vaccinations were required to meet the licensure criteria in paediatric subjects. Both vaccine formulations were well tolerated, with the majority of adverse reactions mild to moderate in severity. None of the five serious adverse events reported throughout the three trials were considered to be vaccine-related by the investigators. The use of MF59 adjuvant allows for much reduced vaccine antigen content, and a single dose administration schedule in adults and the elderly. The production of pandemic vaccine using modern cell culture techniques is highly advantageous in terms of the quantity, quality, and rapidity of antigen production; these benefits, in combination with the use of MF59, maximize manufacturing capacity and

  16. Body Size-Specific Organ and Effective Doses of Chest CT Screening Examinations of the National Lung Screening Trial.

    PubMed

    Lee, Choonsik; Flynn, Michael J; Judy, Phillip F; Cody, Dianna D; Bolch, Wesley E; Kruger, Randell L

    2017-05-01

    We calculated body size-specific organ and effective doses for 23,734 participants in the National Lung Screening Trial (NLST) using a CT dose calculator. We collected participant-specific technical parameters of 23,734 participants who underwent CT in the clinical trial. For each participant, we calculated two sets of organ doses using two methods. First, we computed body size-specific organ and effective doses using the National Cancer Institute CT (NCICT) dosimetry program, which is based on dose coefficients derived from a library of body size-dependent adult male and female computational phantoms. We then recalculated organ and effective doses using dose coefficients from reference size phantoms for all examinations to investigate potential errors caused by the lack of body size consideration in the dose calculations. The underweight participants (body mass index [BMI; weight in kilograms divided by the square of height in meters] < 18.5) received 1.3-fold greater lung dose (median, 4.93 mGy) than the obese participants (BMI > 30) (3.90 mGy). Thyroid doses were approximately 1.3- to 1.6-fold greater than the lung doses (6.3-6.5 mGy). The reference phantom-based dose calculation underestimates the body size-specific lung dose by up to 50% for the underweight participants and overestimates that value by up to 200% for the overweight participants. The median effective dose ranges from 2.01 mSv in obese participants to 2.80 mSv in underweight participants. Body size-specific organ and effective doses were computed for 23,734 NLST participants who underwent low-dose CT screening. The use of reference size phantoms can lead to significant errors in organ dose estimates when body size is not considered in the dose assessment.

  17. Productive vs non-productive infection by cell-free Varicella zoster virus of human neurons derived from embryonic stem cells is dependent upon infectious viral dose

    PubMed Central

    Sloutskin, Anna; Kinchington, Paul R.; Goldstein, Ronald S.

    2013-01-01

    Varicella Zoster virus (VZV) productively infects humans causing varicella upon primary infection and herpes zoster upon reactivation from latency in neurons. In-vitro studies using cell-associated VZV infection have demonstrated productive VZV-infection, while a few recent studies of human neurons derived from stem cells incubated with cell-free, vaccine-derived VZV did not result in generation of infectious virus. In the present study, 90%-pure human embryonic stem cell-derived neurons were incubated with recombinant cell-free pOka-derived made with an improved method or with VZV vaccine. We found that cell-free pOka and vOka at higher multiplicities of infection elicited productive infection in neurons followed by spread of infection, cytopathic effect and release of infectious virus into the medium. These results further validate the use of this unlimited source of human neurons for studying unexplored aspects of VZV interaction with neurons such as entry, latency and reactivation. PMID:23769240

  18. 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.

  19. Sex-specific 99th percentiles derived from the AACC Universal Sample Bank for the Roche Gen 5 cTnT assay: Comorbidities and statistical methods influence derivation of reference limits.

    PubMed

    Gunsolus, Ian L; Jaffe, Allan S; Sexter, Anne; Schulz, Karen; Ler, Ranka; Lindgren, Brittany; Saenger, Amy K; Love, Sara A; Apple, Fred S

    2017-09-13

    Our purpose was to determine a) overall and sex-specific 99th percentile upper reference limits (URL) and b) influences of statistical methods and comorbidities on the URLs. Heparin plasma from 838 normal subjects (423 men, 415 women) were obtained from the AACC (Universal Sample Bank). The cobas e602 measured cTnT (Roche Gen 5 assay); limit of detection (LoD), 3ng/L. Hemoglobin A1c (URL 6.5%), NT-proBNP (URL 125ng/L) and eGFR (60mL/min/1.73m(2)) were measured, along with identification of statin use, to better define normality. 99th percentile URLs were determined by the non-parametric (NP), Harrell-Davis Estimator (HDE) and Robust (R) methods. 355 men and 339 women remained after exclusions. Overall<50% of subjects had measureable concentrations ≥ LoD: 45.6% no exclusion, 43.5% after exclusion; compared to men: 68.1% no exclusion, 65.1% post exclusion; women: 22.7% no exclusion, 20.9% post exclusion. The statistical method used influenced URLs as follows: pre/post exclusion overall, NP 16/16ng/L, HDE 17/17ng/L, R not available; men NP 18/16ng/L, HDE 21/19ng/L, R 16/11ng/L; women NP 13/10ng/L, HDE 14/14ng/L, R not available. We demonstrated that a) the Gen 5 cTnT assay does not meet the IFCC guideline for high-sensitivity assays, b) surrogate biomarkers significantly lowers the URLs and c) statistical methods used impact URLs. Our data suggest lower sex-specific cTnT 99th percentiles than reported in the FDA approved package insert. We emphasize the importance of detailing the criteria used to include and exclude subjects for defining a healthy population and the statistical method used to calculate 99th percentiles and identify outliers. Copyright © 2017. Published by Elsevier Inc.

  20. 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. Copyright © 2016 The Author(s). Published by Elsevier Ireland Ltd.. All rights reserved.

  1. Dose Assessment of Los Alamos National Laboratory-Derived Residual Radionuclides in Soils within C Tracts (C-2, C-3, and C-4) for Land Transfer Decisions

    SciTech Connect

    Gillis, Jessica M.; Whicker, Jeffrey J.

    2016-01-26

    Three separate Sampling and Analysis Plans (SAPs) were prepared for tracts C-2, C-3, and C-4. The objective of sampling was to confirm, within the stated statistical confidence limits, that the mean levels of potential radioactive residual contamination in soils in the C Tracts are documented, in appropriate units, and are below the 15 mrem/y (150 μSv/y) Screening Action Levels (SALs). Results show that radionuclide concentration upper-bound 95% confidence levels were close to background levels, with the exception of Pu-239 and Cs-137 being slightly elevated above background, and all measurements were below the ALs and meet the real property release criteria for future construction or recreational use. A follow-up ALARA analysis showed that the costs of cleanup of the soil in areas of elevated concentration and confirmatory sampling would far exceed any benefit from dose reduction.

  2. Pharmacokinetics and derivation of an anticancer dosing regimen for PAC-1, a preferential small molecule activator of procaspase-3, in healthy dogs.

    PubMed

    Lucas, Pamela W; Schmit, Joanna M; Peterson, Quinn P; West, Diana C; Hsu, Danny C; Novotny, Chris J; Dirikolu, Levent; Churchwell, Mona I; Doerge, Daniel R; Garrett, Laura D; Hergenrother, Paul J; Fan, Timothy M

    2011-10-01

    PAC-1 is a preferential small molecule activator of procaspase-3 and has potential to become a novel and effective anticancer agent. The rational development of PAC-1 for translational oncologic applications would be advanced by coupling relevant in vitro cytotoxicity studies with pharmacokinetic investigations conducted in large mammalian models possessing similar metabolism and physiology as people. In the present study, we investigated whether concentrations and exposure durations of PAC-1 that induce cytotoxicity in lymphoma cell lines in vitro can be achievable in healthy dogs through a constant rate infusion (CRI) intravenous delivery strategy. Time- and dose-dependent procaspase-3 activation by PAC-1 with subsequent cytotoxicity was determined in a panel of B-cell lymphoma cells in vitro. The pharmacokinetics of PAC-1 administered orally or intravenously was studied in 6 healthy dogs using a crossover design. The feasibility of maintaining steady state plasma concentration of PAC-1 for 24 or 48 h that paralleled in vitro cytotoxic concentrations was investigated in 4 healthy dogs. In vitro, PAC-1 induced apoptosis in lymphoma cell lines in a time- and dose-dependent manner. The oral bioavailability of PAC-1 was relatively low and highly variable (17.8 ± 9.5%). The achievement and maintenance of predicted PAC-1 cytotoxic concentrations in normal dogs was safely attained via intravenous CRI lasting for 24 or 48 h in duration. Using the dog as a large mammalian model, PAC-1 can be safely administered as an intravenous CRI while achieving predicted in vitro cytotoxic concentrations.

  3. A questionnaire study to derive information on the working environment, clinical training, use of ancillary staff and optimization of patient radiation dose within UK dental practice.

    PubMed

    Orafi, I; Rushton, V E

    2012-08-01

    To evaluate the working environment of GDPs and Endodontists and the methods used to optimize patient radiation dose. A total of 857 GDPs and 170 specialist Endodontists were contacted. The responders, 603 of the former and 132 of the latter, completed a questionnaire covering practitioner demographics, pattern of practice, the use of radiographic techniques and the optimization of dose. Chi-squared tests were used to compare groups at the P=0.05 level of significance. For nonparametric data, the Mann-Whitney U-test was employed. A response rate of 73% was achieved. Overall, 79.5% of endodontic specialists used film holders compared with 65.9% of GDPs (P=0.001). One hundred and thirty (98.5%) endodontists and 581 (96.3%) GDPs reported that they were well prepared or adequately prepared in radiographically assessing the presence of apical pathosis. The study found significant differences (P<0.001) between the use of digital radiography by specialist endodontists 93 (70.5%) compared with general dental practitioners 167 (27.7%). Significant differences (P=0.004) were also observed in the use of rectangular collimation between endodontic specialists 55 (42%) and GDPs 223 (37%). With regard to the use of film holders in diagnostic radiography, 105 (79.5%) of endodontic specialists employed these devices compared with 396 (65.7%) GDPs; this finding was significant (P=0.005). For working length estimation, significant differences (P=0.001) were noted in the use of a film holder between endodontic specialists 105 (79.5%) and GDPs 386 (64%). Both Endodontists and GDPs demonstrated compliance with guidelines relating to radiation protection being more significant amongst those clinicians working within specialist clinical practice. © 2012 International Endodontic Journal.

  4. Biota Modeling in EPA's Preliminary Remediation Goal and Dose Compliance Concentration Calculators for Use in EPA Superfund Risk Assessment: Explanation of Intake Rate Derivation, Transfer Factor Compilation, and Mass Loading Factor Sources

    SciTech Connect

    Manning, Karessa L.; Dolislager, Fredrick G.; Bellamy, Michael B.

    2016-11-01

    The Preliminary Remediation Goal (PRG) and Dose Compliance Concentration (DCC) calculators are screening level tools that set forth Environmental Protection Agency's (EPA) recommended approaches, based upon currently available information with respect to risk assessment, for response actions at Comprehensive Environmental Response, Compensation, and Liability Act (CERCLA) sites, commonly known as Superfund. The screening levels derived by the PRG and DCC calculators are used to identify isotopes contributing the highest risk and dose as well as establish preliminary remediation goals. Each calculator has a residential gardening scenario and subsistence farmer exposure scenarios that require modeling of the transfer of contaminants from soil and water into various types of biota (crops and animal products). New publications of human intake rates of biota; farm animal intakes of water, soil, and fodder; and soil to plant interactions require updates be implemented into the PRG and DCC exposure scenarios. Recent improvements have been made in the biota modeling for these calculators, including newly derived biota intake rates, more comprehensive soil mass loading factors (MLFs), and more comprehensive soil to tissue transfer factors (TFs) for animals and soil to plant transfer factors (BV's). New biota have been added in both the produce and animal products categories that greatly improve the accuracy and utility of the PRG and DCC calculators and encompass greater geographic diversity on a national and international scale.

  5. An open-label dosing study to evaluate the safety and effects of a dietary plant-derived polysaccharide supplement on the N-glycosylation status of serum glycoproteins in healthy subjects

    PubMed Central

    Alavi, A; Fraser, O; Tarelli, E; Bland, M; Axford, J

    2011-01-01

    Background: The functional role of dietary carbohydrates in nutrition is one of the most complex and at times controversial areas in nutritional science. In-vitro and in-vivo studies suggest that certain dietary saccharide biopolymers can have bifidogenic and or immunomodulatory effects, and that some could represent preferential substrates or precursors that can impact cellular glycosylation. Objective: Examine the impact of oral ingestion of a standardized dietary plant-derived polydisperse polysaccharide supplement (Advanced Ambrotose powder (AA)) on the N-glycosylation status of serum glycoproteins in a cohort of healthy individuals. Design: An open-label study was carried out. This study was in two phases: pilot study (n=6 individuals) to assess safety and dose, and a larger study (n=12) to evaluate specific glycosylation changes. Serum N-glycosylation profiles, using mass spectrometry, were monitored at weekly intervals, for 7 weeks, to evaluate baseline levels and normal fluctuations. The individuals were then monitored for a further 7 weeks, during which time increasing doses of AA were ingested (1.3–5.2 g/day). Results: No adverse events were encountered. AA supplementation resulted in distinct changes in the relative intensities of seven biantennary N-glycans (P<0.001), and a significant overall shift towards increased sialylation. Regression analysis revealed a dose-dependent decrease in mono- and di-galactosylated structures (coefficient −0.130 decrease/week: P=0.02 and −0.690: P=0.005), and a concomitant increase in disialylated glycans ( × 1.083: P<0.05). Conclusions: Supplementation with the dietary plant-derived polysaccharides in AA resulted in significant changes in serum protein N-glycosylation in healthy individuals. How this occurs and whether it has biological significance remains to be evaluated. PMID:21224866

  6. Phase space determination from measured dose data for intraoperative electron radiation therapy.

    PubMed

    Herranz, E; Herraiz, J L; Ibáñez, P; Pérez-Liva, M; Puebla, R; Cal-González, J; Guerra, P; Rodríguez, R; Illana, C; Udías, J M

    2015-01-07

    A procedure to characterize beams of a medical linear accelerator for their use in Monte Carlo (MC) dose calculations for intraoperative electron radiation therapy (IOERT) is presented. The procedure relies on dose measurements in homogeneous media as input, avoiding the need for detailed simulations of the accelerator head. An iterative algorithm (EM-ML) has been employed to extract the relevant details of the phase space (PHSP) of the particles coming from the accelerator, such as energy spectra, spatial distribution and angle of emission of particles. The algorithm can use pre-computed dose volumes in water and/or air, so that the machine-specific tuning with actual data can be performed in a few minutes. To test the procedure, MC simulations of a linear accelerator with typical IOERT applicators and energies, have been performed and taken as reference. A solution PHSP derived from the dose produced by the simulated accelerator has been compared to the reference PHSP. Further, dose delivered by the simulated accelerator for setups not included in the fit of the PHSP were compared to the ones derived from the solution PHSP. The results show that it is possible to derive from dose measurements PHSP accurate for IOERT MC dose estimations.

  7. Fluence-to-dose confusion regarding external stochastic dose determination within the DOE complex.

    SciTech Connect

    Shores, E. F.; Brown, T. H.

    2002-01-01

    The Department of Energy's (DOE) occupational radiation protection dose limits are specified in 10 CFR 835 (hereafter referred to as 'regulation'). Ambiguity in the regulation regarding designation of dose and fluence-to-dose conversion factors leads to confusion and disagreement regarding the appropriate choice of conversion factors. Three primary dose quantities of relevance are absorbed dose, D, quality factor, Q, and the product of those, called dose equivalent, H. The modifier Q is intended to express the long-term fatal cancer causing potential of different radiation types and generally increases with energy for neutrons. For photons, Q is close to unity regardless of energy. In principle, H could be estimated by incorporating a phantom and relevant Q values in a radiation-transport model. In practice, this would entail too much model complexity and computer time. The evaluator of H instead relies on pre-calculated energy-dependent fluence-to-dose conversion factors. Three primary sets of fluence-to-dose conversion factors are commonly used to determine stochastic dose for neutrons and photons: (1) ANSI/ANS-6.1.1-1977 that incorporates the NCRP-38 data for neutrons and sets based on Claiborne and Wells for photons, (2) ANSI/ANS -6.1.1-1991 that are based on and nearly identical to the neutron and photon sets in ICRP -51, and (3) neutron and photon sets in ICRP-74. The first set is maximum H values in a 30-cm diameter cylinder phantom for neutrons and in a 30-cm thick slab phantom for photons. The second set is effective dose equivalent, HE, derived from an anthropomorphic phantom by summing the products of tissue dose equivalents, HT, and tissue weighting factors, w{sub T}. The third set is effective dose, E, also derived from an anthropomorphic phantom by summing the products of H{sub T} and w{sub T}. E is functionally identical to H{sub E} except H{sub T} is the product of D and the radiation weighting factor, w{sub R}, which is similar in meaning to Q.

  8. 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.

  9. 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

  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. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study.

    PubMed

    Tsubokura, Masaharu; Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)-4.29 mSv), 0.37 mSv (range: ND-3.61 mSv), 0.22 mSv (range: ND-1.44 mSv), 0.20 mSv (range: ND-1.87 mSv), and 0.17 mSv (range: ND-0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04-0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only limited and

  13. Individual external doses below the lowest reference level of 1 mSv per year five years after the 2011 Fukushima nuclear accident among all children in Soma City, Fukushima: A retrospective observational study

    PubMed Central

    Murakami, Michio; Nomura, Shuhei; Morita, Tomohiro; Nishikawa, Yoshitaka; Leppold, Claire; Kato, Shigeaki; Kami, Masahiro

    2017-01-01

    After the 2011 Fukushima Daiichi nuclear power plant accident, little information has been available on individual doses from external exposure among residents living in radioactively contaminated areas near the nuclear plant; in the present study we evaluated yearly changes in the doses from external exposure after the accident and the effects of decontamination on external exposure. This study considered all children less than 16 years of age in Soma City, Fukushima who participated in annual voluntary external exposure screening programs during the five years after the accident (n = 5,363). In total, 14,405 screening results were collected. The median participant age was eight years. The geometric mean levels of annual additional doses from external exposure attributable to the Fukushima accident, decreased each year: 0.60 mSv (range: not detectable (ND)–4.29 mSv), 0.37 mSv (range: ND–3.61 mSv), 0.22 mSv (range: ND–1.44 mSv), 0.20 mSv (range: ND–1.87 mSv), and 0.17 mSv (range: ND–0.85 mSv) in 2011, 2012, 2013, 2014, and 2015, respectively. The proportion of residents with annual additional doses from external exposure of more than 1 mSv dropped from 15.6% in 2011 to zero in 2015. Doses from external exposure decreased more rapidly than those estimated from only physical decay, even in areas without decontamination (which were halved in 395 days from November 15, 2011), presumably due to the weathering effects. While the ratios of geometric mean doses immediately after decontamination to before were slightly lower than those during the same time in areas without decontamination, annual additional doses reduced by decontamination were small (0.04–0.24 mSv in the year of immediately after decontamination was completed). The results of this study showed that the levels of external exposure among Soma residents less than 16 years of age decreased during the five years after the Fukushima Daiichi nuclear power plant accident. Decontamination had only

  14. Effect of high-dose nano-selenium and selenium-yeast on feed digestibility, rumen fermentation, and purine derivatives in sheep.

    PubMed

    Xun, Wenjuan; Shi, Liguang; Yue, Wenbin; Zhang, Chunxiang; Ren, Youshe; Liu, Qiang

    2012-12-01

    The aim of this study was to evaluate the effect of nano-selenium (NS) and yeast-selenium (YS) supplementation on feed digestibility, rumen fermentation, and urinary purine derivatives in sheep. Six male ruminally cannulated sheep, average 43.32 ± 4.8 kg of BW, were used in a replicated 3 × 3 Latin square experiment. The treatments were control (without NS and YS), NS with 4 g nano-Se (provide 4 mg Se), and YS with 4 g Se-yeast (provide 4 mg Se) per kilogram of diet dry matter (DM), respectively. Experimental periods were 25 days with 15 days of adaptation and 10 days of sampling. Ruminal pH, ammonia N concentration, molar proportion of propionate, and ratio of acetate to propionate were decreased (P < 0.01), and total ruminal VFA concentration was increased with NS and YS supplementation (P < 0.01). In situ ruminal neutral detergent fiber (aNDF) degradation of Leymus chinensis (P < 0.01) and crude protein (CP) of soybean meal (P < 0.01) were significantly improved by Se supplementation. Digestibilities of DM, organic matter, crude protein, ether extract, aNDF, and ADF in the total tract and urinary excretion of purine derivatives were also affected by feeding Se supplementation diets (P < 0.01). Ruminal fermentation was improved by feeding NS, and feed conversion efficiency was also increased compared with YS (P < 0.01). We concluded that nano-Se can be used as a preferentially available selenium source in ruminant nutrition.

  15. Effective dose analysis of three-dimensional rotational angiography during catheter ablation procedures

    NASA Astrophysics Data System (ADS)

    Wielandts, J.-Y.; Smans, K.; Ector, J.; De Buck, S.; Heidbüchel, H.; Bosmans, H.

    2010-02-01

    There is increasing use of three-dimensional rotational angiography (3DRA) during cardiac ablation procedures. As compared with 2D angiography, a large series of images are acquired, creating the potential for high radiation doses. The aim of the present study was to quantify patient-specific effective doses. In this study, we developed a computer model to accurately calculate organ doses and the effective dose incurred during 3DRA image acquisition. The computer model simulates the exposure geometry and uses the actual exposure parameters, including the variation in tube voltage and current that is realized through the automatic exposure control (AEC). We performed 3DRA dose calculations in 42 patients referred for ablation on the Siemens Axiom Artis DynaCT system (Erlangen, Germany). Organ doses and effective dose were calculated separately for all projections in the course of the C-arm rotation. The influence of patient body mass index (BMI), dose-area product (DAP), collimation and dose per frame (DPF) rate setting on the calculated doses was also analysed. The effective dose was found to be 5.5 ± 1.4 mSv according to ICRP 60 and 6.6 ± 1.8 mSv according to ICRP 103. Effective dose showed an inversely proportional relationship to BMI, while DAP was nearly BMI independent. No simple conversion coefficient between DAP and effective dose could be derived. DPF reduction did not result in a proportional effective dose decrease. These paradoxical findings were explained by the settings of the AEC and the limitations of the x-ray tube. Collimation reduced the effective dose by more than 20%. Three-dimensional rotational angiography is associated with a definite but acceptable radiation dose that can be calculated for all patients separately. Their BMI is a predictor of the effective dose. The dose reduction achieved with collimation suggests that its use is imperative during the 3DRA procedure.

  16. Maltese CT doses for commonly performed examinations demonstrate alignment with published DRLs across Europe.

    PubMed

    Zarb, Francis; McEntee, Mark; Rainford, Louise

    2012-06-01

    This work recommends dose reference levels (DRLs) for abdomen, chest and head computerised tomography (CT) examinations in Malta as the first step towards national CT dose optimisation. Third quartiles volume CT dose index  values for abdomen: 12.1 mGy, chest: 13.1 mGy and head: 41 mGy and third quartile dose-length product values for abdomen: 539.4, chest: 492 and head: 736 mGy cm(-1) are recommended as Maltese DRLs derived from this first Maltese CT dose survey. These values compare well with DRLs of other European countries indicating that CT scanning in Malta is consistent with standards of good practice. Further work to minimise dose without affecting image quality and extending the establishment of DRLs for other CT examinations is recommended.

  17. 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

    ... A (with a default value of 3) in lieu of a default of 10 for the reference dose (RfD) calculation. The quantitative significance of this procedure with regard to the magnitude of an RfD will depend on... derivation of the human equivalent dose is recommended as the default approach for RfDs for remote, as...

  18. Effect of deformable registration uncertainty on lung SBRT dose accumulation

    PubMed Central

    Samavati, Navid; Velec, Michael; Brock, Kristy K.

    2016-01-01

    Purpose: Deformable image registration (DIR) plays an important role in dose accumulation, such as incorporating breathing motion into the accumulation of the delivered dose based on daily 4DCBCT images. However, it is not yet well understood how the uncertainties associated with DIR methods affect the dose calculations and resulting clinical metrics. The purpose of this study is to evaluate the impact of DIR uncertainty on the clinical metrics derived from its use in dose accumulation. Methods: A biomechanical model based DIR method and a biomechanical-intensity-based hybrid method, which reduced the average registration error by 1.6 mm, were applied to ten lung cancer patients. A clinically relevant dose parameter [minimum dose to 0.5 cm3 (Dmin)] was calculated for three dose scenarios using both algorithms. Dose scenarios included static (no breathing motion), predicted (breathing motion at the time of planning), and total accumulated (interfraction breathing motion). The relationship between the dose parameter and a combination of DIR uncertainty metrics, tumor volume, and dose heterogeneity of the plan was investigated. Results: Depending on the dose heterogeneity, tumor volume, and DIR uncertainty, in over 50% of the patients, differences greater than 1.0 Gy were observed in the Dmin of the tumor in the static dose calculation on exhale phase of the 4DCT. Such differences were due to the errors in propagating the tumor contours from the reference planning 4DCT phase onto a subsequent 4DCT phase using each DIR algorithm and calculating the dose on that phase. The differences in predicted dose were more subtle when breathing motion was modeled explicitly at the time of planning with only one patient exhibiting a greater than 1.0 Gy difference in Dmin. Dmin differences of up to 2.5 Gy were found in the total accumulated delivered dose due to difference in quantifying the interfraction variations. Such dose uncertainties could potentially be clinically

  19. CSAHi study: Evaluation of multi-electrode array in combination with human iPS cell-derived cardiomyocytes to predict drug-induced QT prolongation and arrhythmia--effects of 7 reference compounds at 10 facilities.

    PubMed

    Kitaguchi, Takashi; Moriyama, Yuta; Taniguchi, Tomohiko; Ojima, Atsuko; Ando, Hiroyuki; Uda, Takaaki; Otabe, Koji; Oguchi, Masao; Shimizu, Shigekazu; Saito, Hiroyuki; Morita, Maya; Toratani, Atsushi; Asayama, Mahoko; Yamamoto, Wataru; Matsumoto, Emi; Saji, Daisuke; Ohnaka, Hiroki; Tanaka, Kohji; Washio, Ikumi; Miyamoto, Norimasa

    2016-01-01

    Drug-induced QT prolongation is a major safety issue during drug development because it may lead to lethal ventricular arrhythmias. In this study, we evaluated the utility of multi-electrode arrays (MEA) with human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) to predict drug-induced QT prolongation and arrhythmia. Ten facilities evaluated the effects of 7 reference drugs (E-4031, moxifloxacin, flecainide, terfenadine, chromanol 293B, verapamil, and aspirin) using a MED64 MEA system with commercially available hiPS-CMs. Field potential duration (FPD), beat rate, FPD corrected by Fridericia's formula (FPDc), concentration inducing FPDc prolongation by 10% (FPDc10), and incidence of arrhythmia-like waveform were evaluated. The inter-facility variability of absolute values before drug application was similar to the intra-facility variability for FPD, beat rate, and FPDc. The inter-facility variability of FPDc10 for 5 reference drugs ranged from 1.8- to 5.8-fold. At all 10 facilities, E-4031, moxifloxacin, and flecainide prolonged FPDc and induced arrhythmia-like waveforms at concentrations 1.8- to 6.1-fold higher than their FPDc10. Terfenadine prolonged FPDc and induced beating arrest at 8.0 times the FPDc10. The average FPDc10 values for E-4031, moxifloxacin, and terfenadine were comparable to reported plasma concentrations that caused QT prolongation or Torsade de Pointes in humans. Chromanol 293B, a IKs blocker, also prolonged FPDc but did not induce arrhythmia-like waveforms, even at 7.4 times the FPDc10. In contrast, verapamil shortened FPDc and aspirin did not affect FPDc or FP waveforms. MEA with hiPS-CMs can be a generalizable method for accurately predicting both QT prolongation and arrhythmogenic liability in humans. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Immunization of cattle using varying infective doses of Theileria parva lawrencei sporozoites derived from an African buffalo (Syncerus caffer) and treatment with buparvaquone.

    PubMed

    Mutugi, J J; Young, A S; Maritim, A C; Linyonyi, A; Mbogo, S K; Leitch, B L

    1988-04-01

    A Theileria parva lawrencei isolate in the form of a sporozoite stabilate, derived by feeding clean Rhipicephalus appendiculatus nymphal ticks on an African buffalo (Syncerus caffer) captured in the Laikipia District, Kenya, was inoculated into groups of cattle at dilutions between 10(0) and 10(-3). Groups of 3 cattle infected with 1 ml inocula at 10(0), 10(-1) and 10(-2) dilutions were treated with 2.5 mg/kg body weight of buparvaquone on day 0 and similar groups were left untreated to act as controls. An additional group, given 10(0) dilution of the stabilate, was treated with buparvaquone on day 8 post-inoculation. It was found that all control cattle inoculated with the stabilate at dilutions between 10(0) and 10(-2) became infected, but only 2 out of 3 cattle developed patent infections at 10(-3) dilution. All 3 control cattle receiving 10(0) dilution died of theileriosis, 2 at 10(-1) and 10(-2) dilutions, and 1 at 10(-3) dilution died. Buparvaquone treatment on day 0 at 10(0) dilution resulted in the survival of 2 of 3 cattle and all the cattle at 10(-1) and 10(-2) dilutions. All the surviving cattle eventually developed a significant serological response against T. parva in the indirect fluorescent antibody test, except 1 in the 10(-3) dilution group, and were immune to homologous challenge when tested 3 months later with a lethal inoculum of stabilate, except 2 cattle in the 10(-3) dilution group. As a result of a theileriosis problem at about day 60 after inoculation in 2 cattle given 10(-2) dilution of stabilate and buparvaquone treatment on day 0, an additional 5 cattle were given 10(-2) dilution of stabilate and developed a good immunity after buparaquone treatment. None was shown to develop the carrier state. Treatment with buparvaquone on day 8 after infection with 10(0) dilution of stabilate was not successful since 2 died. The stabilate used was shown to produce reproducible infection in cattle at different dilutions.

  1. Dose response study of conjugated fatty acid derived from safflower oil on mammary and colon carcinogenesis pretreated with 7,12-dimethylbenz[a]anthracene (DMBA) and 1,2-dimethylhydrazine (DMH) in female Sprague-Dawley rats.

    PubMed

    Cheng, Jing Lei; Futakuchi, Mitsuru; Ogawa, Kumiko; Iwata, Toshio; Kasai, Masaaki; Tokudome, Shinkan; Hirose, Masao; Shirai, Tomoyuki

    2003-07-10

    To clarify the chemopreventive effects of conjugated fatty acid derived from safflower oil (CFA-S), rich in conjugated linoleic acid (CLA), on mammary and colon carcinogenesis, 6 week old female Sprague-Dawley (SD) rats received diet containing 0.01, 0.05, 0.1, 1, or 2% CFA-S subsequent to five times subcutaneous injections of 1,2-dimethyl-hydrazine (DMH) at a dose of 40 mg/kg b.w. and a single 50 mg/kg b.w. intragastric application of 7,12-dimethylbenz[a]anthracene (DMBA) during the first 11 days. The experiment was terminated at week 36. Numbers of mammary tumors, colon aberrant crypt foci (ACF), and proliferative indices of mammary tumors, and colon epithelium were analyzed. The 1% dose was found to be optimal for suppression of carcinogenesis in both target organs, a good correlation being noted with between data for cell proliferation. These results suggest that a diet containing appropriate levels of CFA-S may be useful for prevention of mammary and colon cancer.

  2. One-shot vaccination with an insect cell-derived low-dose influenza A H7 virus-like particle preparation protects mice against H7N9 challenge☆

    PubMed Central

    Klausberger, Miriam; Wilde, Monika; Palmberger, Dieter; Hai, Rong; Albrecht, Randy A.; Margine, Irina; Hirsh, Ariana; García-Sastre, Adolfo; Grabherr, Reingard; Krammer, Florian

    2014-01-01

    Human infections with a novel influenza A H7N9 subtype virus were reported in China recently. The virus caused severe disease with high mortality rates and it raised concerns over its pandemic potential. Here, we assessed in the mouse model protective efficacy of single immunisations with low vaccine doses of insect cell-derived H7 virus-like particles, consisting of hemagglutinin and matrix protein. Vaccinated mice were fully protected and survived a stringent lethal challenge (100 mLD50) with H7N9, even after a single, unadjuvanted, low vaccine dose (0.03 μg). Serum analysis revealed broad reactivity and hemagglutination inhibition activity across a panel of divergent H7 strains. Moreover, we detected significant levels of cross-reactivity to related group 2 hemagglutinins. These data demonstrate that virus-like particle vaccines have the potential to induce broadly protective immunity against the novel H7N9 virus and a variety of other H7 strains. PMID:24262313

  3. 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.

  4. Prescription n-3 fatty acids, but not eicosapentaenoic acid alone, improve reference memory-related learning ability by increasing brain-derived neurotrophic factor levels in SHR.Cg-Lepr(cp)/NDmcr rats, a metabolic syndrome model.

    PubMed

    Hashimoto, Michio; Inoue, Takayuki; Katakura, Masanori; Tanabe, Yoko; Hossain, Shahdat; Tsuchikura, Satoru; Shido, Osamu

    2013-10-01

    Metabolic syndrome is implicated in the decline of cognitive ability. We investigated whether the prescription n-3 fatty acid administration improves cognitive learning ability in SHR.Cg-Lepr(cp)/NDmcr (SHR-cp) rats, a metabolic syndrome model, in comparison with administration of eicosapentaenoic acid (EPA, C20:5, n-3) alone. Administration of TAK-085 [highly purified and concentrated n-3 fatty acid formulation containing EPA ethyl ester and docosahexaenoic acid (DHA, C22:6, n-3) ethyl ester] at 300 mg/kg body weight per day for 13 weeks reduced the number of reference memory-related errors in SHR-cp rats, but EPA alone had no effect, suggesting that long-term TAK-085 administration improves cognitive learning ability in a rat model of metabolic syndrome. However, the working memory-related errors were not affected in either of the rat groups. TAK-085 and EPA administration increased plasma EPA and DHA levels of SHR-cp rats, associating with an increase in EPA and DHA in the cerebral cortex. The TAK-085 administration decreased the lipid peroxide levels and reactive oxygen species in the cerebral cortex and hippocampus of SHR-cp rats, suggesting that TAK-085 increases antioxidative defenses. Its administration also increased the brain-derived neurotrophic factor levels in the cortical and hippocampal tissues of TAK-085-administered rats. The present study suggests that long-term TAK-085 administration is a possible therapeutic strategy for protecting against metabolic syndrome-induced learning decline.

  5. Calculation of effective dose.

    PubMed

    McCollough, C H; Schueler, B A

    2000-05-01

    The concept of "effective dose" was introduced in 1975 to provide a mechanism for assessing the radiation detriment from partial body irradiations in terms of data derived from whole body irradiations. The effective dose is the mean absorbed dose from a uniform whole-body irradiation that results in the same total radiation detriment as from the nonuniform, partial-body irradiation in question. The effective dose is calculated as the weighted average of the mean absorbed dose to the various body organs and tissues, where the weighting factor is the radiation detriment for a given organ (from a whole-body irradiation) as a fraction of the total radiation detriment. In this review, effective dose equivalent and effective dose, as established by the International Commission on Radiological Protection in 1977 and 1990, respectively, are defined and various methods of calculating these quantities are presented for radionuclides, radiography, fluoroscopy, computed tomography and mammography. In order to calculate either quantity, it is first necessary to estimate the radiation dose to individual organs. One common method of determining organ doses is through Monte Carlo simulations of photon interactions within a simplified mathematical model of the human body. Several groups have performed these calculations and published their results in the form of data tables of organ dose per unit activity or exposure. These data tables are specified according to particular examination parameters, such as radiopharmaceutical, x-ray projection, x-ray beam energy spectra or patient size. Sources of these organ dose conversion coefficients are presented and differences between them are examined. The estimates of effective dose equivalent or effective dose calculated using these data, although not intended to describe the dose to an individual, can be used as a relative measure of stochastic radiation detriment. The calculated values, in units of sievert (or rem), indicate the amount of

  6. [Consideration of the newly standardized interventional reference point].

    PubMed

    Sakamoto, Hajime; Aikawa, Yoshihito; Ikegawa, Hiroaki; Sano, Yoshitomo; Araki, Tsutomu

    2004-04-01

    The interventional reference point is standardized by the International Electrotechnical Commission (IEC), and is adapted to adult cardiovascular studies. We examined the precision of the indicated incident dose at the interventional reference point. As a fundamental examination, we compared entrance phantom dose and incident dose at the interventional reference point. We also compared the entrance skin dose of patients with incident dose at the interventional reference point and evaluated the possibility of clinical application. Results showed that the incident dose at the interventional reference point indicated an underestimation of 0.77 times to an overestimation of 2.2 times when representing entrance surface dose. In clinical application, the incident dose at the interventional reference point calculated from the dose area product tended to overestimate by about 1.17 times the entrance skin dose measured by thermoluminescence dosimeter (TLD). Furthermore, the evaluation varied according to the angles of the C-arm of the x-ray system. A interventional reference point is a useful standard for simple, real-time dose measurement by the indirect method. It is important to understand the characteristics of the indicated incident dose at the interventional reference point in clinical use.

  7. [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).

  8. Dose-area product measurements in panoramic dental radiology.

    PubMed

    Poppe, B; Looe, H K; Pfaffenberger, A; Chofor, N; Eenboom, F; Sering, M; Rühmann, A; Poplawski, A; Willborn, K

    2007-01-01

    In this study, dose-area product (DAP) measurements in panoramic dental radiology have been performed in Germany. The results obtained in this study were proposed as diagnostic reference levels (DRLs). A representative number of dental panoramic units, both with digital and conventional image receptors, have been chosen. Common statistical parameters such as mean, standard deviation and 3rd quartile have been calculated. For four different standard programmes, 'large adult', 'adult male', 'adult female' and 'child', the proposed DRLs are 101, 87, 84 and 75 mGy cm(2), respectively. No clear tendency to a generalised dose reduction from the transition to digital techniques has been observed. Effective doses have been calculated from E/DAP conversion factors published in literature. Even though these values differ by a factor of approximately 3, upper limits of 15.8-21.2 microSv for the four different exposure settings were derived from the data.

  9. The photon-isoeffective dose in boron neutron capture therapy.

    PubMed

    González, Sara J; Santa Cruz, Gustavo A

    2012-12-01

    With the aim to relate the effects observed in a clinical boron neutron capture therapy protocol to the corresponding outcomes in a standard photon radiation therapy, "RBE-weighted" doses are customarily calculated by adding the contributions of the different radiations, each one weighted by a fixed (dose and dose rate independent) relative biological effectiveness factor. In this study, the use of fixed factors is shown to have a formal inconsistency, which in practice leads to unrealistically high tumor doses. We then introduce a more realistic approach that essentially exploits all the experimental information available from survival experiments. The proposed formalism also includes first-order repair of sublethal lesions by means of the generalized Lea-Catcheside factor in the modified linear-quadratic model, and considers synergistic interactions between different radiations. This formalism is of sufficient simplicity therefore to be directly included in all BNCT treatment planning systems. In light of this formalism, the photon-isoeffective doses for two BNCT clinical targets were computed and compared with the standard dose calculation procedure. For the case of brain tumors and clinically relevant absorbed doses, the proposed approach derives isoeffective doses that are much lower than the fixed RBE method, regardless of considering synergism. Thus, for a tumor that receives a mean total absorbed dose of 15 Gy (value achievable with 50 ppm of boron concentration and typical beams used in the clinic), the photon-isoeffective doses are 28 Gy (IsoE) and 30 Gy (IsoE) (without and with synergism, respectively), in contrast to 51 Gy (RBE) for the fixed RBE method. When the clinical outcome of the Argentine cutaneous melanoma treatments is assessed with regard to the doses derived from the standard procedure, it follows that the fixed RBE approach is not suitable to understand the observed clinical results in terms of the photon radiotherapy data. Moreover, even

  10. 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…

  11. Survey of computed tomography scanners in Taiwan: Dose descriptors, dose guidance levels, and effective doses

    SciTech Connect

    Tsai, H. Y.; Tung, C. J.; Yu, C. C.; Tyan, Y. S.

    2007-04-15

    The IAEA and the ICRP recommended dose guidance levels for the most frequent computed tomography (CT) examinations to promote strategies for the optimization of radiation dose to CT patients. A national survey, including on-site measurements and questionnaires, was conducted in Taiwan in order to establish dose guidance levels and evaluate effective doses for CT. The beam quality and output and the phantom doses were measured for nine representative CT scanners. Questionnaire forms were completed by respondents from facilities of 146 CT scanners out of 285 total scanners. Information on patient, procedure, scanner, and technique for the head and body examinations was provided. The weighted computed tomography dose index (CTDI{sub w}), the dose length product (DLP), organ doses and effective dose were calculated using measured data, questionnaire information and Monte Carlo simulation results. A cost-effective analysis was applied to derive the dose guidance levels on CTDI{sub w} and DLP for several CT examinations. The mean effective dose{+-}standard deviation distributes from 1.6{+-}0.9 mSv for the routine head examination to 13{+-}11 mSv for the examination of liver, spleen, and pancreas. The surveyed results and the dose guidance levels were provided to the national authorities to develop quality control standards and protocols for CT examinations.

  12. In defence of collective dose.

    PubMed

    Fairlie, I; Sumner, D

    2000-03-01

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

  13. 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.

  14. 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.

  15. 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)

  16. 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)

  17. A comparative clinical trial evaluating efficacy and safety of fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe) versus reference drug (nimesulide) and other NSAIDs in the treatment of osteoarthritis.

    PubMed

    Prabhu, V V

    2008-06-01

    Sixty consecutive patients of either sex, above the age of 18 years with symptoms of osteo-arthritis participated in this open, randomised, comparative clinical trial carried out over 3 months. Patients were randomised into 5 groups: Group A (paracetamol 500 mg), group B (ibuprofen 400 mg), group C (nimesulide 100 mg), group D (diclofenac 50 mg), and group E [fixed dose combination of nimesulide (100 mg) and racemethionine (50 mg) (namsafe)]. The efficacy parameters were pain intensity, pain on movement, tenderness and swelling. The liver function tests were carried out to estimate the effect of the drugs on the hepatic profile. The Wilcoxon signed rank test and the Kruskal Wallis (one way ANOVA) test were utilised to evaluate the significance of the change from baseline to the final visit. The treatment with combination of nimesulide and racemethionine gave the best relief from tenderness. With respect to pain intensity and pain movement, combination of nimesulide and racemethionine with nimesulide efficacy was comparable. Theliver function test data at the end of 6 months show that combination of nimesulide and racemethionine treated group showed the least rise in the serum asparatate aminotransferase and alanine aminotransferase levels, whereas in the other treatment groups it was very pronounced. Thereby, combination of nimesulide and racemethionine is found to be better for the long-term treatment of osteo-arthritis in patients. The combination of the two agents, namely nimesulide and racemethionine is expected to augment the safety profile of nimesulide, without influencing the effectiveness of the analgesic agent, i.e., nimesulide.

  18. 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

  19. Derivative based sensitivity analysis of gamma index

    PubMed Central

    Sarkar, Biplab; Pradhan, Anirudh; Ganesh, T.

    2015-01-01

    Originally developed as a tool for patient-specific quality assurance in advanced treatment delivery methods to compare between measured and calculated dose distributions, the gamma index (γ) concept was later extended to compare between any two dose distributions. It takes into effect both the dose difference (DD) and distance-to-agreement (DTA) measurements in the comparison. Its strength lies in its capability to give a quantitative value for the analysis, unlike other methods. For every point on the reference curve, if there is at least one point in the evaluated curve that satisfies the pass criteria (e.g., δDD = 1%, δDTA = 1 mm), the point is included in the quantitative score as “pass.” Gamma analysis does not account for the gradient of the evaluated curve - it looks at only the minimum gamma value, and if it is <1, then the point passes, no matter what the gradient of evaluated curve is. In this work, an attempt has been made to present a derivative-based method for the identification of dose gradient. A mathematically derived reference profile (RP) representing the penumbral region of 6 MV 10 cm × 10 cm field was generated from an error function. A general test profile (GTP) was created from this RP by introducing 1 mm distance error and 1% dose error at each point. This was considered as the first of the two evaluated curves. By its nature, this curve is a smooth curve and would satisfy the pass criteria for all points in it. The second evaluated profile was generated as a sawtooth test profile (STTP) which again would satisfy the pass criteria for every point on the RP. However, being a sawtooth curve, it is not a smooth one and would be obviously poor when compared with the smooth profile. Considering the smooth GTP as an acceptable profile when it passed the gamma pass criteria (1% DD and 1 mm DTA) against the RP, the first and second order derivatives of the DDs (δD’, δD”) between these two curves were derived and used as the boundary

  20. Computational assessment of effective dose and patient specific doses for kilovoltage stereotactic radiosurgery of wet age-related macular degeneration

    NASA Astrophysics Data System (ADS)

    Hanlon, Justin Mitchell

    Age-related macular degeneration (AMD) is a leading cause of vision loss and a major health problem for people over the age of 50 in industrialized nations. The current standard of care, ranibizumab, is used to help slow and in some cases stabilize the process of AMD, but requires frequent invasive injections into the eye. Interest continues for stereotactic radiosurgery (SRS), an option that provides a non-invasive treatment for the wet form of AMD, through the development of the IRay(TM) (Oraya Therapeutics, Inc., Newark, CA). The goal of this modality is to destroy choroidal neovascularization beneath the pigment epithelium via delivery of three 100 kVp photon beams entering through the sclera and overlapping on the macula delivering up to 24 Gy of therapeutic dose over a span of approximately 5 minutes. The divergent x-ray beams targeting the fovea are robotically positioned and the eye is gently immobilized by a suction-enabled contact lens. Device development requires assessment of patient effective dose, reference patient mean absorbed doses to radiosensitive tissues, and patient specific doses to the lens and optic nerve. A series of head phantoms, including both reference and patient specific, was derived from CT data and employed in conjunction with the MCNPX 2.5.0 radiation transport code to simulate treatment and evaluate absorbed doses to potential tissues-at-risk. The reference phantoms were used to evaluate effective dose and mean absorbed doses to several radiosensitive tissues. The optic nerve was modeled with changeable positions based on individual patient variability seen in a review of head CT scans gathered. Patient specific phantoms were used to determine the effect of varying anatomy and gaze. The results showed that absorbed doses to the non-targeted tissues were below the threshold levels for serious complications; specifically the development of radiogenic cataracts and radiation induced optic neuropathy (RON). The effective dose

  1. Dose-area product measurements and determination of conversion coefficients for the estimation of effective dose in dental lateral cephalometric radiology.

    PubMed

    Looe, H K; Eenboom, F; Chofor, N; Pfaffenberger, A; Sering, M; Rühmann, A; Poplawski, A; Willborn, K; Poppe, B

    2007-01-01

    A study has been carried out to propose diagnostic reference levels (DRLs) for lateral cephalometric radiology in Germany based on the dose-area product (DAP). DRLs were proposed separately for child and adult exposure settings which are 26.4 and 32.6 mGy cm2, respectively. Organ absorbed doses from lateral cephalometric radiology were also measured using thermoluminescence detectors (TLDs) and an adult anthropomorphic phantom specially design for dosimetric study in dental radiology. Effective doses were then calculated using three different techniques where the salivary gland and brain tissue were given different weighting factors. Conversion coefficients for estimating effective dose from DAP value derived in this study range from 0.042 to 0.149 microSv/mGy cm2.

  2. The limitations of using vertical cutoff rigidities determined from the IGRF magnetic field models for computing aircraft radiation dose.

    PubMed

    Smart, D F; Shea, M A

    2003-01-01

    Vertical cutoff rigidities derived from the International Geomagnetic Reference Fields (IGRF) are normally used to compute the radiation dose at a specific location and to organize the radiation dose measurements acquired at aircraft altitudes. This paper presents some of the usually ignored limits on the accuracy of the vertical cutoff rigidity models and describes some of the computational artifacts present in these models. It is noted that recent aircraft surveys of the radiation dose experienced along specific flight paths is sufficiently precise that the secular variation of the geomagnetic field is observable.

  3. TEPC performance for a reference standard.

    PubMed

    Zhang, Weihua; Wang, Zhiqiang; Liu, Yina; Li, Chunjuan; Xiao, Xuefu; Luo, Hailong; Chen, Jun; Li, Wei

    2014-01-01

    A portable tissue-equivalent proportional counter (TEPC)-based system was developed, which will be used as a reference standard in the neutron mixed field for radiation protection. In this paper, microdosimetry of the TEPC system was studied both in neutron ((252)Cf and (241)Am-Be sources) and gamma ((137)Cs and (60)Co sources) reference radiation fields. The measured neutron and gamma-dose equivalent rates were, respectively, compared with those of the reference ambient dose equivalent rate H(*)(10). And the measured microdosimetric spectra were compared with the Monte Carlo code FLUKA simulated results. All of the comparisons primarily agreed well.

  4. A review of a priori regression models for warfarin maintenance dose prediction.

    PubMed

    Francis, Ben; Lane, Steven; Pirmohamed, Munir; Jorgensen, Andrea

    2014-01-01

    A number of a priori warfarin dosing algorithms, derived using linear regression methods, have been proposed. Although these dosing algorithms may have been validated using patients derived from the same centre, rarely have they been validated using a patient cohort recruited from another centre. In order to undertake external validation, two cohorts were utilised. One cohort formed by patients from a prospective trial and the second formed by patients in the control arm of the EU-PACT trial. Of these, 641 patients were identified as having attained stable dosing and formed the dataset used for validation. Predicted maintenance doses from six criterion fulfilling regression models were then compared to individual patient stable warfarin dose. Predictive ability was assessed with reference to several statistics including the R-square and mean absolute error. The six regression models explained different amounts of variability in the stable maintenance warfarin dose requirements of the patients in the two validation cohorts; adjusted R-squared values ranged from 24.2% to 68.6%. An overview of the summary statistics demonstrated that no one dosing algorithm could be considered optimal. The larger validation cohort from the prospective trial produced more consistent statistics across the six dosing algorithms. The study found that all the regression models performed worse in the validation cohort when compared to the derivation cohort. Further, there was little difference between regression models that contained pharmacogenetic coefficients and algorithms containing just non-pharmacogenetic coefficients. The inconsistency of results between the validation cohorts suggests that unaccounted population specific factors cause variability in dosing algorithm performance. Better methods for dosing that take into account inter- and intra-individual variability, at the initiation and maintenance phases of warfarin treatment, are needed.

  5. Appropriate Use of Effective Dose in Radiation Protection and Risk Assessment.

    PubMed

    Fisher, Darrell R; Fahey, Frederic H

    2017-08-01

    Effective dose was introduced by the ICRP for the single, over-arching purpose of setting limits for radiation protection. Effective dose is a derived quantity or mathematical construct and not a physical, measurable quantity. The formula for calculating effective dose to a reference model incorporates terms to account for all radiation types, organ and tissue radiosensitivities, population groups, and multiple biological endpoints. The properties and appropriate applications of effective dose are not well understood by many within and outside the health physics profession; no other quantity in radiation protection has been more confusing or misunderstood. According to ICRP Publication 103, effective dose is to be used for "prospective dose assessment for planning and optimization in radiological protection, and retrospective demonstration of compliance for regulatory purposes." In practice, effective dose has been applied incorrectly to predict cancer risk among exposed persons. The concept of effective dose applies generally to reference models only and not to individual subjects. While conceived to represent a measure of cancer risk or heritable detrimental effects, effective dose is not predictive of future cancer risk. The formula for calculating effective dose incorporates committee-selected weighting factors for radiation quality and organ sensitivity; however, the organ weighting factors are averaged across all ages and both genders and thus do not apply to any specific individual or radiosensitive subpopulations such as children and young women. Further, it is not appropriate to apply effective dose to individual medical patients because patient-specific parameters may vary substantially from the assumptions used in generalized models. Also, effective dose is not applicable to therapeutic uses of radiation, as its mathematical underpinnings pertain only to observed late (stochastic) effects of radiation exposure and do not account for short-term adverse

  6. Fusion performance of low-dose recombinant human bone morphogenetic protein 2 and bone marrow-derived multipotent stromal cells in biodegradable scaffolds: a comparative study in a large animal model of anterior lumbar interbody fusion.

    PubMed

    Abbah, Sunny A; Lam, Christopher X F; Ramruttun, Amit K; Goh, James C H; Wong, Hee-Kit

    2011-10-01

    A large animal study comparing interbody fusion of a bioresorbable scaffold loaded with either low-dose recombinant human bone morphogenetic protein 2 (rhBMP-2) or bone marrow-derived multipotent stromal cells (BMSCs). To compare the quality of fusion resulting from implantation of medical grade poly (ε-caprolactone)-20% tricalcium phosphate (mPCL/TCP) scaffolds and two different bone growth stimulating agents. Nondegradable cages have been used for interbody fusion with good results. However, the overall advantage of lifelong implantation of a nondegradable device remains a subject of ongoing debate. The use of bioresorbable scaffolds might offer superior alternatives. In this study, we evaluated the quality of fusion obtained with two potential bone graft substitutes. Eleven Yorkshire pigs underwent a bisegmental (L2/L3; L4/L5) anterior lumbar interbody fusion (ALIF) in four groups, namely: (1) mPCL/TCP + 0.6 mg rhBMP-2; (2) mPCL/TCP + BMSCs; (3) mPCL/TCP (negative control); and (4) autologous bone grafts (positive control). RESULTS. The mean radiographic scores at 9 months were 3.0, 1.7, 1.0, and 1.8 for groups 1 to 4, respectively. The bone volume fraction of group 1 was two-folds higher than group 2. Histology, micro-computed tomographic scanning and biomechanical evaluation demonstrated solid and comparable fusion between groups 1 and 4. However, group 2 showed inferior quality of fusion when compared with groups 1 and 4 while group 3 showed no fusion even at 9 months. In addition, there was no evidence of implant rejection, chronic inflammation or any other complications. mPCL/TCP scaffolds loaded with low-dose rhBMP-2 is comparable to autograft bone as a bone graft substitute in this large animal ALIF model. Although BMSCs lagged behind autograft bone and rhBMP-2, evidence of bone ingrowth in this group warrants further investigation. Our results suggest that mPCL/TCP scaffolds loaded with rhBMP-2 or BMSCs may be a viable alternative to conventional cages

  7. Short-Term, High-Dose Fish Oil Supplementation Increases the Production of Omega-3 Fatty Acid-Derived Mediators in Patients With Peripheral Artery Disease (the OMEGA-PAD I Trial).

    PubMed

    Grenon, S Marlene; Owens, Christopher D; Nosova, Emily V; Hughes-Fulford, Millie; Alley, Hugh F; Chong, Karen; Perez, Sandra; Yen, Priscilla K; Boscardin, John; Hellmann, Jason; Spite, Matthew; Conte, Michael S

    2015-08-21

    Patients with peripheral artery disease (PAD) experience significant morbidity and mortality. The OMEGA-PAD I Trial, a randomized, double-blinded, placebo-controlled trial, addressed the hypothesis that short-duration, high-dose n-3 polyunsaturated fatty acids (n-3 PUFA) oral supplementation improves endothelial function and inflammation in PAD. Eighty patients with stable claudication received 4.4 g of fish oil or placebo for 1 month. The primary end point was endothelial function as measured by brachial artery flow-mediated vasodilation. Secondary end points included biomarkers of inflammation, n-3 polyunsaturated fatty acids metabolome changes, lipid profile, and walking impairment questionnaires. Although there was a significant increase in FMD in the fish oil group following treatment (0.7±1.8% increase from baseline, P=0.04), this response was not different then the placebo group (0.6±2.5% increase from baseline, P=0.18; between-group P=0.86) leading to a negative finding for the primary endpoint. There was, however, a significant reduction in triglycerides (fish oil: -34±46 mg/dL, P<0.001; placebo -10±43 mg/dL, P=0.20; between-group differential P-value: 0.02), and an increase in the omega-3 index of 4±1% (P<0.001) in the fish oil group (placebo 0.1±0.9%, P=0.49; between-group P<0.0001). We observed a significant increase in the production of pathway markers of specialized pro-resolving mediators generated from n-3 polyunsaturated fatty acids in the fish oil group. High-dose, short-duration fish oil supplementation did not lead to a different response in the primary end point of endothelial function between the treatment and placebo group, but improved serum triglycerides and increased the production of downstream n-3 polyunsaturated fatty acids-derived products and mediators in patients with PAD. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01310270. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by

  8. International reference standards: antibody standards for the indirect enzyme-linked immunosorbent assay.

    PubMed

    Wright, P F; Tounkara, K; Lelenta, M; Jeggo, M H

    1997-12-01

    Reference standards are used to calibrate similar assay systems against an international reference protocol and to provide a template for the preparation of secondary and/or working standards. Three reference standards are recommended for the indirect enzyme-linked immunosorbent assay: a strong positive standard, a weak positive standard and a negative serum standard. The negative standard should be derived from a single serum or from a serum pool which exhibits typical background activity in the reference protocol. The strong and weak positive standards should be derived from a single serum or from a serum pool which typifies the humoral response (antibody) to natural infection. Suitable candidates for the positive reference standards should exhibit dose/response curves in the mid-range of antibody activity. The strong and weak positive standards should each be prepared from a one-time dilution in the negative standard, to yield antibody activities which are defined by specific points on the linear portion of the dose/response curve. The strong positive standard should represent an antibody activity (absorbance value) midway between the upper and central points and the weak positive standard should represent an antibody activity midway between the central and lower points of the linear portion of the curve. Owing to inherent differences among assay systems, antibody activities should be expressed in relative rather than in absolute terms. It is recommended that the antibody activity of the strong positive standard should denote 100% positivity. The activities of the weak positive and negative standards should then be expressed as relative percentages. Every set of international reference standards should be accompanied by an information sheet which includes, among other things, a plot of the dose/response curve and an indication of the dilutions used to prepare the standards.

  9. Patient-Specific Thresholds and Doses of Intracranial Hypertension in Severe Traumatic Brain Injury.

    PubMed

    Lazaridis, Christos; Smielewski, Peter; Menon, David K; Hutchinson, Peter; Pickard, John D; Czosnyka, Marek

    2016-01-01

    Based on continuous monitoring of the pressure reactivity index (PRx), we defined individualized intracranial pressure (ICP) thresholds by graphing the relationship between ICP and PRx. We hypothesized that an "ICP dose" based on individually assessed ICP thresholds might correlate more closely with 6-month outcome compared with ICP doses derived from the recommended universal thresholds of 20 and 25 mmHg. Data from 327 patients with severe traumatic brain injury (TBI) were analyzed. ICP doses were computed as the cumulative area under the curve above the defined thresholds in graphing ICP versus time. The term Dose 20 (D20) was used to refer to an ICP threshold of 20 mm Hg. The markers D25 and DPRx were calculated similarly. The discriminative ability of each dose with regard to mortality was assessed by receiver operating characteristics analysis using fivefold cross-validation (CV). DPRx was found to be the best discriminator of mortality, despite the fact that D20 was twice as large as DPRx. Individualized doses of intracranial hypertension were stronger predictors of mortality than doses derived from the universal thresholds of 20 and 25 mm Hg. The PRx could offer a method of individualizing the ICP threshold.

  10. Reference Service Policy Statement.

    ERIC Educational Resources Information Center

    Young, William F.

    This reference service policy manual provides general guidelines to encourage reference service of the highest possible quality and to insure uniform practice. The policy refers only to reference service in the University Libraries and is intended for use in conjunction with other policies and procedures issued by the Reference Services Division.…

  11. Reference Service Policy Statement.

    ERIC Educational Resources Information Center

    Young, William F.

    This reference service policy manual provides general guidelines to encourage reference service of the highest possible quality and to insure uniform practice. The policy refers only to reference service in the University Libraries and is intended for use in conjunction with other policies and procedures issued by the Reference Services Division.…

  12. [Diagnostic reference levels in interventional radiology].

    PubMed

    Vañó Carruana, E; Fernández Soto, J M; Sánchez Casanueva, R M; Ten Morón, J I

    2013-12-01

    This article discusses the diagnostic reference levels for radiation exposure proposed by the International Commission on Radiological Protection (ICRP) to facilitate the application of the optimization criteria in diagnostic imaging and interventional procedures. These levels are normally established as the third quartile of the dose distributions to patients in an ample sample of centers and are supposed to be representative of good practice regarding patient exposure. In determining these levels, it is important to evaluate image quality as well to ensure that it is sufficient for diagnostic purposes. When the values for the dose received by patients are systematically higher or much lower than the reference levels, an investigation should determine whether corrective measures need to be applied. The European and Spanish regulations require the use of these reference values in quality assurance programs. For interventional procedures, the dose area product (or kerma area product) values are usually used as reference values together with the time under fluoroscopy and the total number of images acquired. The most modern imaging devices allow the value of the accumulated dose at the entrance to the patient to be calculated to optimize the distribution of the dose on the skin. The ICRP recommends that the complexity of interventional procedures be taken into account when establishing reference levels. In the future, diagnostic imaging departments will have automatic systems to manage patient dosimetric data; these systems will enable continuous dosage auditing and alerts about individual procedures that might involve doses several times above the reference values. This article also discusses aspects that need to be clarified to take better advantage of the reference levels in interventional procedures. Copyright © 2013 SERAM. Published by Elsevier Espana. All rights reserved.

  13. Considerations on a de minimis dose and disposal of exempt concentrations of radioactive wastes

    SciTech Connect

    Kocher, D.C.; O'Donnell, F.R.

    1987-05-01

    We propose as a generally applicable de minimis dose for members of the general public (1) a principal limit on annual committed effectie dose equivalent averaged over a lifetime of 0.01 mSv (1 mrem) and (2) a subsidiary limit on committed effective dose equivalent in any year of 0.05 mSv (5 mrem). Existing methodologies for using a de minimis dose are reviewed to derive exempt concentrations of radionuclides in solid wastes for purposes of disposal, and a methodology for application to disposal on the Oak Ridge Reservation is presented. Difficulties in application are discussed with reference to a proposal for an exemption level for uranium in solid wastes of 30 pCi/g. Finally, we discuss existing methods for measuring the uranium content in bulk solid wastes, because such measurements probably will be required in exempting uranium-bearing wastes for disposal.

  14. Bayesian estimation of dose thresholds

    NASA Technical Reports Server (NTRS)

    Groer, P. G.; Carnes, B. A.

    2003-01-01

    An example is described of Bayesian estimation of radiation absorbed dose thresholds (subsequently simply referred to as dose thresholds) using a specific parametric model applied to a data set on mice exposed to 60Co gamma rays and fission neutrons. A Weibull based relative risk model with a dose threshold parameter was used to analyse, as an example, lung cancer mortality and determine the posterior density for the threshold dose after single exposures to 60Co gamma rays or fission neutrons from the JANUS reactor at Argonne National Laboratory. The data consisted of survival, censoring times and cause of death information for male B6CF1 unexposed and exposed mice. The 60Co gamma whole-body doses for the two exposed groups were 0.86 and 1.37 Gy. The neutron whole-body doses were 0.19 and 0.38 Gy. Marginal posterior densities for the dose thresholds for neutron and gamma radiation were calculated with numerical integration and found to have quite different shapes. The density of the threshold for 60Co is unimodal with a mode at about 0.50 Gy. The threshold density for fission neutrons declines monotonically from a maximum value at zero with increasing doses. The posterior densities for all other parameters were similar for the two radiation types.

  15. Single daily dosing of aminoglycosides.

    PubMed

    Preston, S L; Briceland, L L

    1995-01-01

    To evaluate the rationale behind dosing aminoglycosides as a single daily dose versus traditional dosing approaches, we conducted a MEDLINE search to identify all pertinent articles, and also reviewed the references of all articles. Single daily dosing of aminoglycosides is not a new concept, having been examined since 1974. The advantages of this regimen include optimum concentration-dependent bactericidal activity, longer dosing intervals due to the postantibiotic effect (PAE), and prevention of bacterial adaptive resistance. Because of longer dosing intervals, toxicity may also be delayed or reduced. Costs may be reduced due to decreased monitoring and administration. Clinically, the regimen has been implemented in various patient populations with reported success. Questions remain, however, about optimum dose, peak and trough serum concentrations, and dose adjustment in patients with renal impairment or neutropenia. More clinical experience with this method in large numbers of patients has to be published. Pharmacists can be instrumental in monitoring patients receiving once-daily therapy and by educating health care professionals as to the rationale behind the therapy.

  16. Dosimetry of a cone beam CT device for oral and maxillofacial radiology using Monte Carlo techniques and ICRP adult reference computational phantoms.

    PubMed

    Morant, J J; Salvadó, M; Hernández-Girón, I; Casanovas, R; Ortega, R; Calzado, A

    2013-01-01

    The aim of this study was to calculate organ and effective doses for a range of available protocols in a particular cone beam CT (CBCT) scanner dedicated to dentistry and to derive effective dose conversion factors. Monte Carlo simulations were used to calculate organ and effective doses using the International Commission on Radiological Protection voxel adult male and female reference phantoms (AM and AF) in an i-CAT CBCT. Nine different fields of view (FOVs) were simulated considering full- and half-rotation modes, and also a high-resolution acquisition for a particular protocol. Dose-area product (DAP) was measured. Dose to organs varied for the different FOVs, usually being higher in the AF phantom. For 360°, effective doses were in the range of 25-66 μSv, and 46 μSv for full head. Higher contributions to the effective dose corresponded to the remainder (31%; 27-36 range), salivary glands (23%; 20-29%), thyroid (13%; 8-17%), red bone marrow (10%; 9-11%) and oesophagus (7%; 4-10%). The high-resolution protocol doubled the standard resolution doses. DAP values were between 181 mGy cm(2) and 556 mGy cm(2) for 360°. For 180° protocols, dose to organs, effective dose and DAP were approximately 40% lower. A conversion factor (DAP to effective dose) of 0.130 ± 0.006 μSv mGy(-1) cm(-2) was derived for all the protocols, excluding full head. A wide variation in dose to eye lens and thyroid was found when shifting the FOV in the AF phantom. Organ and effective doses varied according to field size, acquisition angle and positioning of the beam relative to radiosensitive organs. Good positive correlation between calculated effective dose and measured DAP was found.

  17. Application of Bayes theorem to aminoglycoside-associated nephrotoxicity: comparison of extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing.

    PubMed

    Kim, Myong-Jin; Bertino, Joseph S; Erb, Tara A; Jenkins, Paul L; Nafziger, Anne N

    2004-07-01

    The objective of this study was to examine the incidence of aminoglycoside-associated nephrotoxicity related to extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing by applying Bayes theorem. An electronic literature search of MEDLINE (1966-2003) and a manual search of references from published meta-analyses and review articles were performed. Studies using extended-interval dosing, individualized pharmacokinetic monitoring, or multiple-daily dosing and reported aminoglycoside-associated nephrotoxicity for patients > or = 16 years of age were included. Quality scores were assigned based on the rigor of definition of aminoglycoside-associated nephrotoxicity, duration of therapy, and length of follow-up of renal function after completion of therapy. Inclusion criteria were then based on these quality scores. Quantitative data on the incidence of aminoglycoside-associated nephrotoxicity were abstracted. Twelve extended-interval dosing studies (n = 916), 10 individualized pharmacokinetic monitoring studies (n = 2066), and 27 multiple-daily dosing studies (n = 4251) met the inclusion criteria. Prior probabilities of aminoglycoside-associated nephrotoxicity were derived from a combination of a review of published studies and expert judgment. The maximum densities for the final posterior probabilities of aminoglycoside-associated nephrotoxicity for extended-interval dosing, individualized pharmacokinetic monitoring, and multiple-daily dosing were located at 12% to 13%, 10% to 11%, and 13% to 14%, respectively. Application of Bayes theorem demonstrates that aminoglycoside dosing by individualized pharmacokinetic monitoring results in less aminoglycoside-associated nephrotoxicity than extended-interval dosing or multiple-daily dosing.

  18. Reach for Reference. Four Recent Reference Books

    ERIC Educational Resources Information Center

    Safford, Barbara Ripp

    2004-01-01

    This article provides descriptions of four new science and technology encyclopedias that are appropriate for inclusion in upper elementary and/or middle school reference collections. "The Macmillan Encyclopedia of Weather" (Stern, Macmillan Reference/Gale), a one-volume encyclopedia for upper elementary and middle level students, is a…

  19. Reach for Reference. Four Recent Reference Books

    ERIC Educational Resources Information Center

    Safford, Barbara Ripp

    2004-01-01

    This article provides descriptions of four new science and technology encyclopedias that are appropriate for inclusion in upper elementary and/or middle school reference collections. "The Macmillan Encyclopedia of Weather" (Stern, Macmillan Reference/Gale), a one-volume encyclopedia for upper elementary and middle level students, is a…

  20. Verification of IMRT dose distributions using a water beam imaging system.

    PubMed

    Li, J S; Boyer, A L; Ma, C M

    2001-12-01

    A water beam imaging system (WBIS) has been developed and used to verify dose distributions for intensity modulated radiotherapy using dynamic multileaf collimator. This system consisted of a water container, a scintillator screen, a charge-coupled device camera, and a portable personal computer. The scintillation image was captured by the camera. The pixel value in this image indicated the dose value in the scintillation screen. Images of radiation fields of known spatial distributions were used to calibrate the device. The verification was performed by comparing the image acquired from the measurement with a dose distribution from the IMRT plan. Because of light scattering in the scintillator screen, the image was blurred. A correction for this was developed by recognizing that the blur function could be fitted to a multiple Gaussian. The blur function was computed using the measured image of a 10 cm x 10 cm x-ray beam and the result of the dose distribution calculated using the Monte Carlo method. Based on the blur function derived using this method, an iterative reconstruction algorithm was applied to recover the dose distribution for an IMRT plan from the measured WBIS image. The reconstructed dose distribution was compared with Monte Carlo simulation result. Reasonable agreement was obtained from the comparison. The proposed approach makes it possible to carry out a real-time comparison of the dose distribution in a transverse plane between the measurement and the reference when we do an IMRT dose verification.

  1. Fundamentals of Reference

    ERIC Educational Resources Information Center

    Mulac, Carolyn M.

    2012-01-01

    The all-in-one "Reference reference" you've been waiting for, this invaluable book offers a concise introduction to reference sources and services for a variety of readers, from library staff members who are asked to work in the reference department to managers and others who wish to familiarize themselves with this important area of…

  2. Live, Digital Reference.

    ERIC Educational Resources Information Center

    Kenney, Brian

    2002-01-01

    Discusses digital reference services, also known as virtual reference, chat reference, or online reference, based on a round table discussion at the 2002 American Library Association annual conference in Atlanta. Topics include numbers and marketing; sustainability; competition and models; evaluation methods; outsourcing; staffing and training;…

  3. Statistical Reference Datasets

    National Institute of Standards and Technology Data Gateway

    Statistical Reference Datasets (Web, free access)   The Statistical Reference Datasets is also supported by the Standard Reference Data Program. The purpose of this project is to improve the accuracy of statistical software by providing reference datasets with certified computational results that enable the objective evaluation of statistical software.

  4. Live, Digital Reference.

    ERIC Educational Resources Information Center

    Kenney, Brian

    2002-01-01

    Discusses digital reference services, also known as virtual reference, chat reference, or online reference, based on a round table discussion at the 2002 American Library Association annual conference in Atlanta. Topics include numbers and marketing; sustainability; competition and models; evaluation methods; outsourcing; staffing and training;…

  5. PROPOSED ORAL REFERENCE DOSE (RFD) FOR BARIUM AND COMPOUNDS

    EPA Science Inventory

    The Integrated Risk Information System (IRIS) is a database of EPA's consensus opinion of the human health effects that may result from exposure to various substances found in the environment. A Toxicological Review and IRIS Summary were prepared for barium and compounds in 1998 ...

  6. Predictor-Based Model Reference Adaptive Control

    NASA Technical Reports Server (NTRS)

    Lavretsky, Eugene; Gadient, Ross; Gregory, Irene M.

    2010-01-01

    This paper is devoted to the design and analysis of a predictor-based model reference adaptive control. Stable adaptive laws are derived using Lyapunov framework. The proposed architecture is compared with the now classical model reference adaptive control. A simulation example is presented in which numerical evidence indicates that the proposed controller yields improved transient characteristics.

  7. ["Pro Ana": Psychodynamic References for Anorexia Nervosa].

    PubMed

    Siefert, Linda

    2017-02-01

    "Pro Ana": Psychodynamic References for Anorexia Nervosa The internet-based phenomenon "Pro Ana" refers to the eating disorder anorexia nervosa in a positive way. To understand what the phenomenon "Pro Ana" represents, the websites are used as a starting point of the current analysis. Based on these results, similarities and differences between "Pro Ana" and the eating disorder anorexia nervosa are discussed. Furthermore psychodynamic references for anorexia nervosa are derived and finally their importance for treatment motivation will be considered.

  8. Radiation dose estimates for radiopharmaceuticals

    SciTech Connect

    Stabin, M.G.; Stubbs, J.B.; Toohey, R.E.

    1996-04-01

    Tables of radiation dose estimates based on the Cristy-Eckerman adult male phantom are provided for a number of radiopharmaceuticals commonly used in nuclear medicine. Radiation dose estimates are listed for all major source organs, and several other organs of interest. The dose estimates were calculated using the MIRD Technique as implemented in the MIRDOSE3 computer code, developed by the Oak Ridge Institute for Science and Education, Radiation Internal Dose Information Center. In this code, residence times for source organs are used with decay data from the MIRD Radionuclide Data and Decay Schemes to produce estimates of radiation dose to organs of standardized phantoms representing individuals of different ages. The adult male phantom of the Cristy-Eckerman phantom series is different from the MIRD 5, or Reference Man phantom in several aspects, the most important of which is the difference in the masses and absorbed fractions for the active (red) marrow. The absorbed fractions for flow energy photons striking the marrow are also different. Other minor differences exist, but are not likely to significantly affect dose estimates calculated with the two phantoms. Assumptions which support each of the dose estimates appears at the bottom of the table of estimates for a given radiopharmaceutical. In most cases, the model kinetics or organ residence times are explicitly given. The results presented here can easily be extended to include other radiopharmaceuticals or phantoms.

  9. Repeatability of dose painting by numbers treatment planning in prostate cancer radiotherapy based on multiparametric magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    van Schie, Marcel A.; Steenbergen, Peter; Viet Dinh, Cuong; Ghobadi, Ghazaleh; van Houdt, Petra J.; Pos, Floris J.; Heijmink, Stijn W. T. J. P.; van der Poel, Henk G.; Renisch, Steffen; Vik, Torbjørn; van der Heide, Uulke A.

    2017-07-01

    Dose painting by numbers (DPBN) refers to a voxel-wise prescription of radiation dose modelled from functional image characteristics, in contrast to dose painting by contours which requires delineations to define the target for dose escalation. The direct relation between functional imaging characteristics and DPBN implies that random variations in images may propagate into the dose distribution. The stability of MR-only prostate cancer treatment planning based on DPBN with respect to these variations is as yet unknown. We conducted a test-retest study to investigate the stability of DPBN for prostate cancer in a semi-automated MR-only treatment planning workflow. Twelve patients received a multiparametric MRI on two separate days prior to prostatectomy. The tumor probability (TP) within the prostate was derived from image features with a logistic regression model. Dose mapping functions were applied to acquire a DPBN prescription map that served to generate an intensity modulated radiation therapy (IMRT) treatment plan. Dose calculations were done on a pseudo-CT derived from the MRI. The TP and DPBN map and the IMRT dose distribution were compared between both MRI sessions, using the intraclass correlation coefficient (ICC) to quantify repeatability of the planning pipeline. The quality of each treatment plan was measured with a quality factor (QF). Median ICC values for the TP and DPBN map and the IMRT dose distribution were 0.82, 0.82 and 0.88, respectively, for linear dose mapping and 0.82, 0.84 and 0.94 for square root dose mapping. A median QF of 3.4% was found among all treatment plans. We demonstrated the stability of DPBN radiotherapy treatment planning in prostate cancer, with excellent overall repeatability and acceptable treatment plan quality. Using validated tumor probability modelling and simple dose mapping techniques it was shown that despite day-to-day variations in imaging data still consistent treatment plans were obtained.

  10. Dosimetry of a cone beam CT device for oral and maxillofacial radiology using Monte Carlo techniques and ICRP adult reference computational phantoms

    PubMed Central

    Morant, JJ; Salvadó, M; Hernández-Girón, I; Casanovas, R; Ortega, R; Calzado, A

    2013-01-01

    Objectives: The aim of this study was to calculate organ and effective doses for a range of available protocols in a particular cone beam CT (CBCT) scanner dedicated to dentistry and to derive effective dose conversion factors. Methods: Monte Carlo simulations were used to calculate organ and effective doses using the International Commission on Radiological Protection voxel adult male and female reference phantoms (AM and AF) in an i-CAT CBCT. Nine different fields of view (FOVs) were simulated considering full- and half-rotation modes, and also a high-resolution acquisition for a particular protocol. Dose–area product (DAP) was measured. Results: Dose to organs varied for the different FOVs, usually being higher in the AF phantom. For 360°, effective doses were in the range of 25–66 μSv, and 46 μSv for full head. Higher contributions to the effective dose corresponded to the remainder (31%; 27–36 range), salivary glands (23%; 20–29%), thyroid (13%; 8–17%), red bone marrow (10%; 9–11%) and oesophagus (7%; 4–10%). The high-resolution protocol doubled the standard resolution doses. DAP values were between 181 mGy cm2 and 556 mGy cm2 for 360°. For 180° protocols, dose to organs, effective dose and DAP were approximately 40% lower. A conversion factor (DAP to effective dose) of 0.130 ± 0.006 μSv mGy−1 cm−2 was derived for all the protocols, excluding full head. A wide variation in dose to eye lens and thyroid was found when shifting the FOV in the AF phantom. Conclusions: Organ and effective doses varied according to field size, acquisition angle and positioning of the beam relative to radiosensitive organs. Good positive correlation between calculated effective dose and measured DAP was found. PMID:22933532

  11. Reference change values.

    PubMed

    Fraser, Callum G

    2011-09-30

    Reference change values (RCV) provide objective tools for assessment of the significance of differences in serial results from an individual. The concept is simple and the calculation easy, since all laboratories know their analytical imprecision (CV(A)) and estimates of within-subject biological variation (CV(I)) are available for a large number of quantities. Generally, CV(I) are constant over time, geography, methodology and in health and chronic stable disease. The formula is RCV=2(1/2) · Z · (CV(A)(2) + CV(I)(2))(1/2), where Z is the number of standard deviations appropriate to the probability. Correct interpretation of the semantics describing the clinical use of RCV is vital for selection of the Z-score. Many quantities of clinically importance exist for which good estimates of RCV are unavailable. Derivation of CV(I) may be difficult for such quantities: flair and imagination are required in selecting populations with chronic but stable disease on whom CV(I) can be determined. RCV can be used for delta-checking and auto-verification and laboratory information management systems (LIMS) can be adapted to do this. Recently, log-normal transformation to obtain unidirectional RCV has been used. Gaps in knowledge of RCV still require filling since the need for measures of change is clearly expressed in guidelines.

  12. A conversion method of air kerma from the primary, scatter, and leakage radiations to effective dose for calculating x-ray shielding barriers in mammography.

    PubMed

    Kharrati, Hedi

    2005-05-01

    In this study, a new approach has been introduced for derivation of the effective dose from air kerma to calculate shielding requirements in mammography facilities. This new approach has been used to compute the conversion coefficients relating air kerma to the effective dose for the mammography reference beam series of the Netherlands Metrology Institute Van Swinden Laboratorium, National Institute of Standards and Technology, and International Atomic Energy Agency laboratories. The results show that, in all cases, the effective dose in mammography energy range is less than 25% of the incident air kerma for the primary and the scatter radiations and does not exceed 75% for the leakage radiation.

  13. Proposed reference models for atomic oxygen in the terrestrial atmosphere

    NASA Technical Reports Server (NTRS)

    Llewellyn, E. J.; Mcdade, I. C.; Lockerbie, M. D.

    1989-01-01

    A provisional Atomic Oxygen Reference model was derived from average monthly ozone profiles and the MSIS-86 reference model atmosphere. The concentrations are presented in tabular form for the altitude range 40 to 130 km.

  14. Reference dosimetry for light-ion beams based on graphite calorimetry.

    PubMed

    Rossomme, S; Palmans, H; Thomas, R; Lee, N; Duane, S; Bailey, M; Shipley, D; Bertrand, D; Romano, F; Cirrone, P; Cuttone, G; Vynckier, S

    2014-10-01

    Developments in hadron therapy require efforts to improve the accuracy of the dose delivered to a target volume. Here, the determination of the absorbed dose under reference conditions was analysed. Based on the International Atomic Energy Agency TRS-398 code of practice, for hadron beams, the combined standard uncertainty on absorbed dose to water under reference conditions, derived from ionisation chambers, is too large. This uncertainty is dominated by the beam quality correction factors, [Formula: see text], mainly due to the mean energy to produce one ion pair in air, wair. A method to reduce this uncertainty is to carry out primary dosimetry, using calorimetry. A [Formula: see text]-value can be derived from a direct comparison between calorimetry and ionometry. Here, this comparison is performed using a graphite calorimeter in an 80-MeV A(-1) carbon ion beam. Assuming recommended TRS-398 values of water-to-graphite stopping power ratio and the perturbation factor for an ionisation chamber, preliminary results indicate a wair-value of 35.5 ± 0.9 J C(-1).

  15. Genetics Home Reference

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Genetics Home Reference Past Issues / Spring 2007 Table of ... of this page please turn Javascript on. The Genetics Home Reference (GHR) Web site — ghr.nlm.nih. ...

  16. The Test of Reference.

    ERIC Educational Resources Information Center

    Childers, Thomas

    1980-01-01

    Reports the results of an unobtrusive study, from a user's viewpoint, of reference services available in the Suffolk Cooperative Library System. The study raises questions of policy centering around user expectations of library reference services. (RAA)

  17. The Floating Reference Librarian

    ERIC Educational Resources Information Center

    Hernon, Peter; Pastine, Maureen

    1972-01-01

    The floating librarian'' is one who interprets and adjusts the formal library structure to meet legitimate needs. This is one of the ways the academic reference librarian can gain greater acceptance with students and faculty. (9 references) (Author/NH)

  18. Academic Reference Service

    ERIC Educational Resources Information Center

    Lopez, Manuel D.

    1973-01-01

    Cost benefit accounting is not being used in academic reference libraries today but administrators are beginning to require quantitative evaluation of services provided. Several systems are described and evaluated. (35 references) (DH)

  19. Do changes in biomarkers from space radiation reflect dose or risk?

    NASA Astrophysics Data System (ADS)

    Brooks, A.

    The space environment is made up of many different kinds of radiation so that the proper use of biomarkers is essential to estimate radiation risk. This presentation will evaluate differences between biomarkers of dose and risk and demonstrate why they should not be confused following radiation exposures in deep space. Dose is a physical quantity, while risk is a biological quantity. Many examples exist w ereh dose or changes in biomarkers of dose are inappropriately used as predictors of risk. Without information on the biology of the system, the biomarkers of dose provide little help in predicting risk in tissues or radiation exposure types where no excess risk can be demonstrated. Many of these biomarkers of dose only reflect changes in radiation dose or exposure. However, these markers are often incorrectly used to predict risk. For example, exposure of the trachea or of the deep lung to high-LET alpha particles results in similar changes in the biomarker chromosome damage in these two tissues. Such an observation would predict that the risk for cancer induction would be similar in these two tissues. It has been noted , however, that there has never been a tracheal tumor observed in rats that inhaled radon, but with the same exposure, large numbers of tumors were produced in the deep lung. The biology of the different tissues is the major determinant of the risk rather than the radiation dose. Recognition of this fact has resulted in the generation of tissue weighting factors for use in radiation protection. When tissue weighting factors are used the values derived are still called "dose". It is important to recognize that tissue specific observations have been corrected to reflect risk, and therefore should no longer be viewed as dose. The relative biological effectiveness (RBE) is also used to estimate radiation risk. The use of biomarkers to derive RBE is a difficult since it involves the use of a biological response to a standard low-LET reference radiation

  20. ORGAN DOSES AND EFFECTIVE DOSE FOR FIVE PET RADIOPHARMACEUTICALS.

    PubMed

    Andersson, Martin; Johansson, Lennart; Mattsson, Sören; Minarik, David; Leide-Svegborn, Sigrid

    2016-06-01

    Diagnostic investigations with positron-emitting radiopharmaceuticals are dominated by (18)F-fluorodeoxyglucose ((18)F-FDG), but other radiopharmaceuticals are also commercially available or under development. Five of them, which are all clinically important, are (18)F-fluoride, (18)F-fluoroethyltyrosine ((18)F-FET), (18)F-deoxyfluorothymidine ((18)F-FLT), (18)F-fluorocholine ((18)F-choline) and (11)C-raclopride. To estimate the potential risk of stochastic effects (mainly lethal cancer) to a population, organ doses and effective dose values were updated for all five radiopharmaceuticals. Dose calculations were performed using the computer program IDAC2.0, which bases its calculations on the ICRP/ICRU adult reference voxel phantoms and the tissue weighting factors from ICRP publication 103. The biokinetic models were taken from ICRP publication 128. For organ doses, there are substantial changes. The only significant change in effective dose compared with previous estimations was a 46 % reduction for (18)F-fluoride. The estimated effective dose in mSv MBq(-1) was 1.5E-02 for (18)F-FET, 1.5E-02 for (18)F-FLT, 2.0E-02 for (18)F-choline, 9.0E-03 for (18)F-fluoride and 4.4E-03 for (11)C-raclopride.

  1. Screening Doses for Induction of Cancers Calculated with the Interactive RadioEpidemiological Program (IREP)

    DTIC Science & Technology

    2007-03-01

    ABSTRACT This report presents tabulations of equivalent doses of ionizing radiation, referred to as screening doses , that correspond to an estimated ...cancer by veterans of military services. 15. SUBJECT TERMS Nuclear Test Personnel Review, NTPR, Veteran, Atmospheric Nuclear Testing, Hiroshima Nagasaki ...report presents tabulations of equivalent doses of ionizing radiation, referred to as screening doses , that correspond to an estimated probability of

  2. Virtual Reference Interferometry: Theory & Experiment

    NASA Astrophysics Data System (ADS)

    Galle, Michael Anthony

    This thesis introduces the idea that a simulated interferogram can be used as a reference for an interferometer. This new concept represents a paradigm shift from the conventional thinking, where a reference is the phase of a wavefront that traverses a known path. The simulated interferogram used as a reference is called a virtual reference. This thesis develops the theory of virtual reference interferometry and uses it for the characterization of chromatic dispersion in short length (<1m) fibers and optical components. Characterization of chromatic dispersion on short length fiber and optical components is a very difficult challenge. Accurate measurement of first and second order dispersion is important for applications from optical component design to nonlinear photonics, sensing and communications. Techniques for short-length dispersion characterization are therefore critical to the development of many photonic systems. The current generation of short-length dispersion measurement techniques are either easy to operate but lack sufficient accuracy, or have sufficient accuracy but are difficult to operate. The use of a virtual reference combines the advantages of these techniques so that it is both accurate and easy to operate. Chromatic dispersion measurements based on virtual reference interferometry have similar accuracy as the best conventional measurement techniques due to the ability to measure first and second order dispersion directly from the interference pattern. Unique capabilities of virtual reference interferometry are demonstrated, followed by a derivation of the operational constraints and system parameters. The technique is also applied to the characterization of few-mode fibers, a hot topic in telecommunications research where mode division multiplexing promises to expand network bandwidth. Also introduced is the theory of dispersive virtual reference interferometry, which can be used to overcome the bandwidth limitations associated with the

  3. Herbal reference standards.

    PubMed

    Schwarz, Michael; Klier, Bernhard; Sievers, Hartwig

    2009-06-01

    This review describes the current definitions and regulatory requirements that apply to reference standards that are used to analyse herbal products. It also describes and discusses the current use of reference substances and reference extracts in the European and United States pharmacopoeias.

  4. Academic Library Reference Services.

    ERIC Educational Resources Information Center

    Batt, Fred

    This examination of the philosophy and objectives of academic library reference services provides an overview of the major reference approaches to fulfilling the following primary objectives of reference services: (1) providing accurate answers to patrons' questions and/or helping patrons find sources to pursue their research needs; (2) building…

  5. Academic Library Reference Services.

    ERIC Educational Resources Information Center

    Batt, Fred

    This examination of the philosophy and objectives of academic library reference services provides an overview of the major reference approaches to fulfilling the following primary objectives of reference services: (1) providing accurate answers to patrons' questions and/or helping patrons find sources to pursue their research needs; (2) building…

  6. Assessment of Reference Services.

    ERIC Educational Resources Information Center

    Von Seggern, Marilyn

    1987-01-01

    This annotated bibliography of materials dealing with the evaluation of library reference services is arranged by category including literature success, quality, and accuracy of answers; cost and task analysis; interviews and communication; classification of reference questions; reference collections; staff availability; use and nonuse of…

  7. References for marine science

    NASA Astrophysics Data System (ADS)

    1990-06-01

    Standard and Reference Materials for Marine Science, National Oceanic and Atmospheric Administration Technical Memo OMA-51 (2nd edition, 434 pp.), by A. Y. Cantillo, is now available. This compilation of reference materials was prepared at the request of the Group of Experts on Standards and Reference Materials and was printed by NOAA. GESREM is sponsored by the International Atomic Energy Agency, the Intergovernmental Oceanographic Commission, and the United Nations Program.Reference materials are included on ashes, gases, instrument performance materials, oils, physical properties, rocks, sediments, sludges, tissues and waters. For each reference material, source, description and preparation, analyses and values, cost, references, and comments are given. Indices are included for elements, isotopes and organic compounds. Cross references to Chemical Abstracts Service registry numbers and alternate names and chemical structures of organic compounds are also provided.

  8. Radiation dose from MDCT using Monte Carlo simulations: estimating fetal dose due to pulmonary embolism scans accounting for overscan

    NASA Astrophysics Data System (ADS)

    Angel, E.; Wellnitz, C.; Goodsitt, M.; DeMarco, J.; Cagnon, C.; Ghatali, M.; Cody, D.; Stevens, D.; McCollough, C.; Primak, A.; McNitt-Gray, M.

    2007-03-01

    Pregnant women with shortness of breath are increasingly referred for CT Angiography to rule out Pulmonary Embolism (PE). While this exam is typically focused on the lungs, extending scan boundaries and overscan can add to the irradiated volume and have implications on fetal dose. The purpose of this work was to estimate radiation dose to the fetus when various levels of overscan were encountered. Two voxelized models of pregnant patients derived from actual patient anatomy were created based on image data. The models represent an early (< 7 weeks) and late term pregnancy (36 weeks). A previously validated Monte Carlo model of an MDCT scanner was used that takes into account physical details of the scanner. Simulated helical scans used 120 kVp, 4x5 mm beam collimation, pitch 1, and varying beam-off locations (edge of the irradiated volume) were used to represent different protocols plus overscan. Normalized dose (mGy/100mAs) was calculated for each fetus. For the early term and the late term pregnancy models, fetal dose estimates for a standard thoracic PE exam were estimated to be 0.05 and 0.3 mGy/100mAs, respectively, increasing to 9 mGy/100mAs when the beam-off location was extended to encompass the fetus. When performing PE exams to rule out PE in pregnant patients, the beam-off location may have a large effect on fetal dose, especially for late term pregnancies. Careful consideration of ending location of the x-ray beam - and not the end of image data - could result in significant reduction in radiation dose to the fetus.

  9. Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

    SciTech Connect

    Li Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.

    2011-01-15

    patients. However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDI{sub vol} underestimated dose to large organs in the scan coverage by 30%-48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by -57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by -63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients' clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols.

  10. Patient-specific radiation dose and cancer risk estimation in CT: Part II. Application to patients

    PubMed Central

    Li, Xiang; Samei, Ehsan; Segars, W. Paul; Sturgeon, Gregory M.; Colsher, James G.; Toncheva, Greta; Yoshizumi, Terry T.; Frush, Donald P.

    2011-01-01

    . However, the overall risk of cancer incidence attributable to the CT examination was much higher for the newborn (2.4 in 1000) than for the teenager (0.7 in 1000). For the two pediatric-aged patients in our study, CTDIvol underestimated dose to large organs in the scan coverage by 30%–48%. The effective dose derived from DLP using published conversion coefficients differed from that calculated using patient-specific organ dose values by −57% to 13%, when the tissue weighting factors of ICRP 60 were used, and by −63% to 28%, when the tissue weighting factors of ICRP 103 were used. Conclusions: It is possible to estimate patient-specific radiation dose and cancer risk from CT examinations by combining a validated Monte Carlo program with patient-specific anatomical models that are derived from the patients’ clinical CT data and supplemented by transformed models of reference adults. With the construction of a large library of patient-specific computer models encompassing patients of all ages and weight percentiles, dose and risk can be estimated for any patient prior to or after a CT examination. Such information may aid in decisions for image utilization and can further guide the design and optimization of CT technologies and scan protocols. PMID:21361209

  11. Revised reference values for selenium intake.

    PubMed

    Kipp, A P; Strohm, D; Brigelius-Flohé, R; Schomburg, L; Bechthold, A; Leschik-Bonnet, E; Heseker, H

    2015-10-01

    The German, Austrian and Swiss nutrition societies are the joint editors of the 'reference values for nutrient intake'. They have revised the reference values for the intake of selenium and published them in February 2015. The saturation of selenoprotein P (SePP) in plasma is used as a criterion for the derivation of reference values for selenium intake in adults. For persons from selenium-deficient regions (China) SePP saturation was achieved with a daily intake of 49μg of selenium. When using the reference body weights the D-A-CH reference values are based upon, the resulting estimated value for selenium intake is 70μg/day for men and 60μg/day for women. The estimated value for selenium intake for children and adolescents is extrapolated using the estimated value for adults in relation to body weight. For infants aged 0 to under 4 months the estimated value of 10μg/day was derived from the basis of selenium intake via breast milk. For infants aged 4 to under 12 months this estimated value was used and taking into account the differences regarding body weight an estimated value of 15μg/day was derived. For lactating women compared to non-lactating women a higher reference value of 75μg/day is indicated due to the release of selenium with breast milk. The additional selenium requirement for pregnant women is negligible, so that no increased reference value is indicated.

  12. Evaluation of Rectal Dose During High-Dose-Rate Intracavitary Brachytherapy for Cervical Carcinoma

    SciTech Connect

    Sha, Rajib Lochan; Reddy, Palreddy Yadagiri; Rao, Ramakrishna; Muralidhar, Kanaparthy R.; Kudchadker, Rajat J.

    2011-01-01

    High-dose-rate intracavitary brachytherapy (HDR-ICBT) for carcinoma of the uterine cervix often results in high doses being delivered to surrounding organs at risk (OARs) such as the rectum and bladder. Therefore, it is important to accurately determine and closely monitor the dose delivered to these OARs. In this study, we measured the dose delivered to the rectum by intracavitary applications and compared this measured dose to the International Commission on Radiation Units and Measurements rectal reference point dose calculated by the treatment planning system (TPS). To measure the dose, we inserted a miniature (0.1 cm{sup 3}) ionization chamber into the rectum of 86 patients undergoing radiation therapy for cervical carcinoma. The response of the miniature chamber modified by 3 thin lead marker rings for identification purposes during imaging was also characterized. The difference between the TPS-calculated maximum dose and the measured dose was <5% in 52 patients, 5-10% in 26 patients, and 10-14% in 8 patients. The TPS-calculated maximum dose was typically higher than the measured dose. Our study indicates that it is possible to measure the rectal dose for cervical carcinoma patients undergoing HDR-ICBT. We also conclude that the dose delivered to the rectum can be reasonably predicted by the TPS-calculated dose.

  13. On expedient properties of common biological score functions for multi-modality, adaptive and 4D dose optimization.

    PubMed

    Sobotta, B; Söhn, M; Shaw, W; Alber, M

    2011-05-21

    Frequently, radiotherapy treatments are comprised of several dose distributions computed or optimized in different patient geometries. Therefore, the need arises to compute the comprehensive biological effect or physical figure of merit of the combined dose of a number of distinct geometry instances. For that purpose the dose is typically accumulated in a reference geometry through deformation fields obtained from deformable image registration. However, it is difficult to establish precise voxel-by-voxel relationships between different anatomical images in many cases. In this work, the mathematical properties of commonly used score functions are exploited to derive an upper boundary for the maximum effect for normal tissue and a lower boundary for the minimum effect for the target of accumulated doses on multiple geometry instances.

  14. Synthetic growth reference charts.

    PubMed

    Hermanussen, Michael; Stec, Karol; Aßmann, Christian; Meigen, Christof; Van Buuren, Stef

    2016-01-01

    To reanalyze the between-population variance in height, weight, and body mass index (BMI), and to provide a globally applicable technique for generating synthetic growth reference charts. Using a baseline set of 196 female and 197 male growth studies published since 1831, common factors of height, weight, and BMI are extracted via Principal Components separately for height, weight, and BMI. Combining information from single growth studies and the common factors using in principle a Bayesian rationale allows for provision of completed reference charts. The suggested approach can be used for generating synthetic growth reference charts with LMS values for height, weight, and BMI, from birth to maturity, from any limited set of height and weight measurements of a given population. Generating synthetic growth reference charts by incorporating information from a large set of reference growth studies seems suitable for populations with no autochthonous references at hand yet. © 2015 Wiley Periodicals, Inc.

  15. High frequency reference electrode

    DOEpatents

    Kronberg, James W.

    1994-01-01

    A high frequency reference electrode for electrochemical experiments comprises a mercury-calomel or silver-silver chloride reference electrode with a layer of platinum around it and a layer of a chemically and electrically resistant material such as TEFLON around the platinum covering all but a small ring or "halo" at the tip of the reference electrode, adjacent to the active portion of the reference electrode. The voltage output of the platinum layer, which serves as a redox electrode, and that of the reference electrode are coupled by a capacitor or a set of capacitors and the coupled output transmitted to a standard laboratory potentiostat. The platinum may be applied by thermal decomposition to the surface of the reference electrode. The electrode provides superior high-frequency response over conventional electrodes.

  16. High frequency reference electrode

    DOEpatents

    Kronberg, J.W.

    1994-05-31

    A high frequency reference electrode for electrochemical experiments comprises a mercury-calomel or silver-silver chloride reference electrode with a layer of platinum around it and a layer of a chemically and electrically resistant material such as TEFLON around the platinum covering all but a small ring or halo' at the tip of the reference electrode, adjacent to the active portion of the reference electrode. The voltage output of the platinum layer, which serves as a redox electrode, and that of the reference electrode are coupled by a capacitor or a set of capacitors and the coupled output transmitted to a standard laboratory potentiostat. The platinum may be applied by thermal decomposition to the surface of the reference electrode. The electrode provides superior high-frequency response over conventional electrodes. 4 figs.

  17. Inverse Planning Approach for 3-D MRI-Based Pulse-Dose Rate Intracavitary Brachytherapy in Cervix Cancer

    SciTech Connect

    Chajon, Enrique; Dumas, Isabelle; Touleimat, Mahmoud B.Sc.; Magne, Nicolas; Coulot, Jeremy; Verstraet, Rodolfe; Lefkopoulos, Dimitri; Haie-Meder, Christine

    2007-11-01

    Purpose: The purpose of this study was to evaluate the inverse planning simulated annealing (IPSA) software for the optimization of dose distribution in patients with cervix carcinoma treated with MRI-based pulsed-dose rate intracavitary brachytherapy. Methods and Materials: Thirty patients treated with a technique using a customized vaginal mold were selected. Dose-volume parameters obtained using the IPSA method were compared with the classic manual optimization method (MOM). Target volumes and organs at risk were delineated according to the Gynecological Brachytherapy Group/European Society for Therapeutic Radiology and Oncology recommendations. Because the pulsed dose rate program was based on clinical experience with low dose rate, dwell time values were required to be as homogeneous as possible. To achieve this goal, different modifications of the IPSA program were applied. Results: The first dose distribution calculated by the IPSA algorithm proposed a heterogeneous distribution of dwell time positions. The mean D90, D100, and V100 calculated with both methods did not differ significantly when the constraints were applied. For the bladder, doses calculated at the ICRU reference point derived from the MOM differed significantly from the doses calculated by the IPSA method (mean, 58.4 vs. 55 Gy respectively; p = 0.0001). For the rectum, the doses calculated at the ICRU reference point were also significantly lower with the IPSA method. Conclusions: The inverse planning method provided fast and automatic solutions for the optimization of dose distribution. However, the straightforward use of IPSA generated significant heterogeneity in dwell time values. Caution is therefore recommended in the use of inverse optimization tools with clinical relevance study of new dosimetric rules.

  18. Development of 1-year-old computational phantom and calculation of organ doses during CT scans using Monte Carlo simulation.

    PubMed

    Pan, Yuxi; Qiu, Rui; Gao, Linfeng; Ge, Chaoyong; Zheng, Junzheng; Xie, Wenzhang; Li, Junli

    2014-09-21

    With the rapidly growing number of CT examinations, the consequential radiation risk has aroused more and more attention. The average dose in each organ during CT scans can only be obtained by using Monte Carlo simulation with computational phantoms. Since children tend to have higher radiation sensitivity than adults, the radiation dose of pediatric CT examinations requires special attention and needs to be assessed accurately. So far, studies on organ doses from CT exposures for pediatric patients are still limited. In this work, a 1-year-old computational phantom was constructed. The body contour was obtained from the CT images of a 1-year-old physical phantom and the internal organs were deformed from an existing Chinese reference adult phantom. To ensure the organ locations in the 1-year-old computational phantom were consistent with those of the physical phantom, the organ locations in 1-year-old computational phantom were manually adjusted one by one, and the organ masses were adjusted to the corresponding Chinese reference values. Moreover, a CT scanner model was developed using the Monte Carlo technique and the 1-year-old computational phantom was applied to estimate organ doses derived from simulated CT exposures. As a result, a database including doses to 36 organs and tissues from 47 single axial scans was built. It has been verified by calculation that doses of axial scans are close to those of helical scans; therefore, this database could be applied to helical scans as well. Organ doses were calculated using the database and compared with those obtained from the measurements made in the physical phantom for helical scans. The differences between simulation and measurement were less than 25% for all organs. The result shows that the 1-year-old phantom developed in this work can be used to calculate organ doses in CT exposures, and the dose database provides a method for the estimation of 1-year-old patient doses in a variety of CT examinations.

  19. Task-based image quality evaluation of iterative reconstruction methods for low dose CT using computer simulations

    NASA Astrophysics Data System (ADS)

    Xu, Jingyan; Fuld, Matthew K.; Fung, George S. K.; Tsui, Benjamin M. W.

    2015-04-01

    Iterative reconstruction (IR) methods for x-ray CT is a promising approach to improve image quality or reduce radiation dose to patients. The goal of this work was to use task based image quality measures and the channelized Hotelling observer (CHO) to evaluate both analytic and IR methods for clinical x-ray CT applications. We performed realistic computer simulations at five radiation dose levels, from a clinical reference low dose D0 to 25% D0. A fixed size and contrast lesion was inserted at different locations into the liver of the XCAT phantom to simulate a weak signal. The simulated data were reconstructed on a commercial CT scanner (SOMATOM Definition Flash; Siemens, Forchheim, Germany) using the vendor-provided analytic (WFBP) and IR (SAFIRE) methods. The reconstructed images were analyzed by CHOs with both rotationally symmetric (RS) and rotationally oriented (RO) channels, and with different numbers of lesion locations (5, 10, and 20) in a signal known exactly (SKE), background known exactly but variable (BKEV) detection task. The area under the receiver operating characteristic curve (AUC) was used as a summary measure to compare the IR and analytic methods; the AUC was also used as the equal performance criterion to derive the potential dose reduction factor of IR. In general, there was a good agreement in the relative AUC values of different reconstruction methods using CHOs with RS and RO channels, although the CHO with RO channels achieved higher AUCs than RS channels. The improvement of IR over analytic methods depends on the dose level. The reference dose level D0 was based on a clinical low dose protocol, lower than the standard dose due to the use of IR methods. At 75% D0, the performance improvement was statistically significant (p < 0.05). The potential dose reduction factor also depended on the detection task. For the SKE/BKEV task involving 10 lesion locations, a dose reduction of at least 25% from D0 was achieved.

  20. Development of 1-year-old computational phantom and calculation of organ doses during CT scans using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Pan, Yuxi; Qiu, Rui; Gao, Linfeng; Ge, Chaoyong; Zheng, Junzheng; Xie, Wenzhang; Li, Junli

    2014-09-01

    With the rapidly growing number of CT examinations, the consequential radiation risk has aroused more and more attention. The average dose in each organ during CT scans can only be obtained by using Monte Carlo simulation with computational phantoms. Since children tend to have higher radiation sensitivity than adults, the radiation dose of pediatric CT examinations requires special attention and needs to be assessed accurately. So far, studies on organ doses from CT exposures for pediatric patients are still limited. In this work, a 1-year-old computational phantom was constructed. The body contour was obtained from the CT images of a 1-year-old physical phantom and the internal organs were deformed from an existing Chinese reference adult phantom. To ensure the organ locations in the 1-year-old computational phantom were consistent with those of the physical phantom, the organ locations in 1-year-old computational phantom were manually adjusted one by one, and the organ masses were adjusted to the corresponding Chinese reference values. Moreover, a CT scanner model was developed using the Monte Carlo technique and the 1-year-old computational phantom was applied to estimate organ doses derived from simulated CT exposures. As a result, a database including doses to 36 organs and tissues from 47 single axial scans was built. It has been verified by calculation that doses of axial scans are close to those of helical scans; therefore, this database could be applied to helical scans as well. Organ doses were calculated using the database and compared with those obtained from the measurements made in the physical phantom for helical scans. The differences between simulation and measurement were less than 25% for all organs. The result shows that the 1-year-old phantom developed in this work can be used to calculate organ doses in CT exposures, and the dose database provides a method for the estimation of 1-year-old patient doses in a variety of CT examinations.

  1. Acoustic dose and acoustic dose-rate.

    PubMed

    Duck, Francis

    2009-10-01

    Acoustic dose is defined as the energy deposited by absorption of an acoustic wave per unit mass of the medium supporting the wave. Expressions for acoustic dose and acoustic dose-rate are given for plane-wave conditions, including temporal and frequency dependencies of energy deposition. The relationship between the acoustic dose-rate and the resulting temperature increase is explored, as is the relationship between acoustic dose-rate and radiation force. Energy transfer from the wave to the medium by means of acoustic cavitation is considered, and an approach is proposed in principle that could allow cavitation to be included within the proposed definitions of acoustic dose and acoustic dose-rate.

  2. Preparing the references.

    PubMed

    Peh, W C G; Ng, K H

    2009-07-01

    In a scientific paper, the references serve to provide background information and allow the researcher to compare and contrast the work of others in relation to his own study. Authors are responsible for the accuracy of all references cited. The references quoted should be easily accessible and retrievable by anyone wishing to obtain further information. There is a strong preference for citing journal articles listed in PubMed. The two major reference format systems are the Vancouver and Harvard systems, with increasing preference for the Vancouver system. Authors should adhere exactly to the instructions to authors of the target journal.

  3. Absorbed Dose and Dose Equivalent Calculations for Modeling Effective Dose

    NASA Technical Reports Server (NTRS)

    Welton, Andrew; Lee, Kerry

    2010-01-01

    While in orbit, Astronauts are exposed to a much higher dose of ionizing radiation than when on the ground. It is important to model how shielding designs on spacecraft reduce radiation effective dose pre-flight, and determine whether or not a danger to humans is presented. However, in order to calculate effective dose, dose equivalent calculations are needed. Dose equivalent takes into account an absorbed dose of radiation and the biological effectiveness of ionizing radiation. This is important in preventing long-term, stochastic radiation effects in humans spending time in space. Monte carlo simulations run with the particle transport code FLUKA, give absorbed and equivalent dose data for relevant shielding. The shielding geometry used in the dose calculations is a layered slab design, consisting of aluminum, polyethylene, and water. Water is used to simulate the soft tissues that compose the human body. The results obtained will provide information on how the shielding performs with many thicknesses of each material in the slab. This allows them to be directly applicable to modern spacecraft shielding geometries.

  4. The time course of erythrocyte membrane fatty acid concentrations during and after treatment of non-human primates with increasing doses of an omega-3 rich phospholipid preparation derived from krill-oil.

    PubMed

    Hals, Petter-Arnt; Wang, Xiaoli; Piscitelli, Fabiana; Di Marzo, Vincenzo; Xiao, Yong-Fu

    2017-01-21

    A commonly used measure to reflect the intake of the long-chain omega-3 fatty acids EPA and DHA is the omega-3 index, defined as the sum of EPA + DHA as % of total fatty acids in erythrocyte membrane. When the omega-3 index changes it follows that the relative fractions of other fatty acids in the membrane are also changed. In the present study, increasing doses of a preparation of omega-3 rich phospholipids extracted from krill oil were administered orally to non-human primates for 12 weeks and the time course of EPA, DHA and 22 other fatty acids in erythrocytes was determined bi-weekly during treatment and for 8 weeks after cessation of treatment. Plasma concentrations of six endocannabinoid-type mediators being downstream metabolites of some fatty acids analyzed in erythrocytes were also determined. Six diabetic, dyslipidemic non-human primates were included, three in a vehicle control group and three being treated with the omega-3 rich phospholipid preparation. The vehicle control and test items were given daily by gavage and the test item doses were 50, 150 and 450 mg phospholipids/kg/day. Each dose level was given for four weeks. Blood was sampled at baseline and thereafter bi-weekly. Fatty acids were determined in erythrocytes by methylation followed by gas-chromatography. Endocannabinoids and endocannabinoid-like mediators were analyzed in plasma by liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry. The treatment resulted in a dose-related increase in the fraction of EPA and DHA in erythrocyte membranes and a dose-related decrease of other poly-unsaturated fatty acids, in particular omega-6 polyunsaturated fatty acids. Erythrocyte concentrations of saturated fatty acids remained unchanged throughout the experiment. Plasma concentrations of endocannabinoids and endocannabinoid-like mediators changed accordingly as those being downstream arachidonic acid decreased, downstream of the saturated palmitic and oleic acids

  5. Marketing Reference Services.

    ERIC Educational Resources Information Center

    Norman, O. Gene

    1995-01-01

    Relates the marketing concept to library reference services. Highlights include a review of the literature and an overview of marketing, including research, the marketing mix, strategic plan, marketing plan, and marketing audit. Marketing principles are applied to reference services through the marketing mix elements of product, price, place, and…

  6. An Online Reference System.

    ERIC Educational Resources Information Center

    Chisman, Janet; Treat, William

    1984-01-01

    Describes a computer aid developed to assist in academic library reference service using the DataPhase Circulation System, an automated system that features full cataloging records in database and permits local programing. Access points (subject, type of reference work, course) and database structure and user screens are highlighted. (EJS)

  7. Marketing Reference Services.

    ERIC Educational Resources Information Center

    Norman, O. Gene

    1995-01-01

    Relates the marketing concept to library reference services. Highlights include a review of the literature and an overview of marketing, including research, the marketing mix, strategic plan, marketing plan, and marketing audit. Marketing principles are applied to reference services through the marketing mix elements of product, price, place, and…

  8. Reference Point Heterogeneity

    PubMed Central

    Terzi, Ayse; Koedijk, Kees; Noussair, Charles N.; Pownall, Rachel

    2016-01-01

    It is well-established that, when confronted with a decision to be taken under risk, individuals use reference payoff levels as important inputs. The purpose of this paper is to study which reference points characterize decisions in a setting in which there are several plausible reference levels of payoff. We report an experiment, in which we investigate which of four potential reference points: (1) a population average payoff level, (2) the announced expected payoff of peers in a similar decision situation, (3) a historical average level of earnings that others have received in the same task, and (4) an announced anticipated individual payoff level, best describes decisions in a decontextualized risky decision making task. We find heterogeneity among individuals in the reference points they employ. The population average payoff level is the modal reference point, followed by experimenter's stated expectation of a participant's individual earnings, followed in turn by the average earnings of other participants in previous sessions of the same experiment. A sizeable share of individuals show multiple reference points simultaneously. The reference point that best fits the choices of the individual is not affected by a shock to her income. PMID:27672374

  9. Creating a Reference Toolbox.

    ERIC Educational Resources Information Center

    Scott, Jane

    1997-01-01

    To help students understand that references are tools used to locate specific information, one librarian has her third-grade students create their own reference toolboxes as she introduces dictionaries, atlases, encyclopedias, and thesauri. Presents a lesson plan to introduce print and nonprint thesauri to third and fourth graders and includes a…

  10. Art Reference, SCLS 1972.

    ERIC Educational Resources Information Center

    Lukac, Milan

    To help librarians answer patrons' questions about art works, especially paintings, the procedures followed by the reference division of the Suffolk Cooperative Library System are outlined, and a list of reference materials is suggested. Topics covered include biographical information about artists, identification of paintings, location of…

  11. Rethinking Virtual Reference

    ERIC Educational Resources Information Center

    Tenopir, Carol

    2004-01-01

    Virtual reference services seem a natural extension of libraries digital collections and the emphasis on access to the library anytime, anywhere. If patrons use the library from home, it makes sense to provide them with person-to-person online reference. The Library of Congress (LC), OCLC, and several large library systems have developed and…

  12. China Connections Reference Book.

    ERIC Educational Resources Information Center

    Kalat, Marie B.; Hoermann, Elizabeth F.

    This reference book focuses on six aspects of the geography of the People's Republic of China. They are: territory, governing units, population and land use, waterways, land forms, and climates. Designed as a primary reference, the book explains how the Chinese people and their lifestyles are affected by China's geography. Special components…

  13. Reference Point Heterogeneity.

    PubMed

    Terzi, Ayse; Koedijk, Kees; Noussair, Charles N; Pownall, Rachel

    2016-01-01

    It is well-established that, when confronted with a decision to be taken under risk, individuals use reference payoff levels as important inputs. The purpose of this paper is to study which reference points characterize decisions in a setting in which there are several plausible reference levels of payoff. We report an experiment, in which we investigate which of four potential reference points: (1) a population average payoff level, (2) the announced expected payoff of peers in a similar decision situation, (3) a historical average level of earnings that others have received in the same task, and (4) an announced anticipated individual payoff level, best describes decisions in a decontextualized risky decision making task. We find heterogeneity among individuals in the reference points they employ. The population average payoff level is the modal reference point, followed by experimenter's stated expectation of a participant's individual earnings, followed in turn by the average earnings of other participants in previous sessions of the same experiment. A sizeable share of individuals show multiple reference points simultaneously. The reference point that best fits the choices of the individual is not affected by a shock to her income.

  14. Library Reference Service.

    ERIC Educational Resources Information Center

    Schippleck, Suzanne

    The Inglewood, California, public library provides a manual on reference service. The theory, purpose, and objectives of reference are noted, and goals and activities are described in terms of budget, personnel, resources, and services. A chapter on organization covers service structure, information services, relationships with other library…

  15. Selecting radiotherapy dose distributions by means of constrained optimization problems.

    PubMed

    Alfonso, J C L; Buttazzo, G; García-Archilla, B; Herrero, M A; Núñez, L

    2014-05-01

    The main steps in planning radiotherapy consist in selecting for any patient diagnosed with a solid tumor (i) a prescribed radiation dose on the tumor, (ii) bounds on the radiation side effects on nearby organs at risk and (iii) a fractionation scheme specifying the number and frequency of therapeutic sessions during treatment. The goal of any radiotherapy treatment is to deliver on the tumor a radiation dose as close as possible to that selected in (i), while at the same time conforming to the constraints prescribed in (ii). To this day, considerable uncertainties remain concerning the best manner in which such issues should be addressed. In particular, the choice of a prescription radiation dose is mostly based on clinical experience accumulated on the particular type of tumor considered, without any direct reference to quantitative radiobiological assessment. Interestingly, mathematical models for the effect of radiation on biological matter have existed for quite some time, and are widely acknowledged by clinicians. However, the difficulty to obtain accurate in vivo measurements of the radiobiological parameters involved has severely restricted their direct application in current clinical practice.In this work, we first propose a mathematical model to select radiation dose distributions as solutions (minimizers) of suitable variational problems, under the assumption that key radiobiological parameters for tumors and organs at risk involved are known. Second, by analyzing the dependence of such solutions on the parameters involved, we then discuss the manner in which the use of those minimizers can improve current decision-making processes to select clinical dosimetries when (as is generally the case) only partial information on model radiosensitivity parameters is available. A comparison of the proposed radiation dose distributions with those actually delivered in a number of clinical cases strongly suggests that solutions of our mathematical model can be

  16. Hanford Environmental Dose Reconstruction Project

    SciTech Connect

    Finch, S. M.; McMakin, A. H.

    1991-09-01

    The objective of the Hanford Environmental Dose Reconstruction Project is to estimate the radiation dose that individuals and populations could have received from nuclear operations at Hanford since 1944. The project is divided into five technical tasks. These tasks correspond to the path radionuclides followed, from release to impact on humans (i.e., dose estimates). The Source Terms Task develops estimates of radioactive emissions from Hanford facilities since 1944. The Environmental Transport Task reconstructs the movements of radioactive particles from the areas of release to populations. The Environmental Monitoring Data Task assemblies, evaluates and reports historical environmental monitoring data. The Demographics, Agriculture and Food Habits Task develops the data needed to identify the populations that could have been affected by the releases. The Environmental Pathways and Dose Estimates Task used the information derived from the other Tasks to estimate the radiation doses individuals could have received from Hanford radiation. This document lists the progress on this project as of September 1991. 3 figs., 2 tabs.

  17. The subduction reference framework

    NASA Astrophysics Data System (ADS)

    Seton, M.; Müller, D.; Gurnis, M.; Flament, N.; Whittaker, J.

    2010-12-01

    Plate tectonic reconstructions are essential for determining the spatial and temporal context for geological and geophysical data and help distinguish competing models for regional plate kinematic histories and the relationships between tectonic features and events. Plate reconstructions, a series of relative plate motions anchored to an absolute reference frame via a plate circuit, can act as surface boundary constraints for mantle convection models, allowing us to link surface processes to the deep earth. One of the limitations in global plate motion models has been to accurately determine the positions of plates through time. Traditionally, this has been based on either palaeomagnetic or hotspot reference frames, however both these methodologies have some shortcomings. Palaeomagnetic reference frames can determine latitudes but not longitudes, with additional inaccuracies due to true polar wander. Hotspot reference frames can only be confidently tied back to about 130 Ma and there is evidence that mantle plumes have moved relative to each other. New “hybrid” reference frames are emerging, which consist of fixed or moving hotspot reference frames merged with true polar wander (TPW) corrected palaeomagnetic reference frames. We have devised a methodology to link plate reconstructions to mantle convection back to Pangaea breakup time to converge on a solution that correctly aligns slab material in the mantle to the locations of subduction zones in the past. We aim to construct a “Subduction Reference Frame” for plate motions since 200 Ma by iteratively matching forward geodynamic models with tomographically imaged slabs in the mantle. Our forward models involve coupling global plate kinematics, the thermal structure of the oceanic lithosphere and slab assimilation to a spherical mantle convection code, CitcomS. Preliminary results have been obtained for a plate motion model using a moving hotspot reference frame to 100 Ma and a TPW corrected reference frame

  18. Comparison of two high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone derived regimens in patients aged under 60 years with low-intermediate risk aggressive lymphoma: a final analysis of the multicenter LNH93-2 protocol.

    PubMed

    Morel, Pierre; Munck, Jean-Nicolas; Coiffier, Bertrand; Gisselbrecht, Christian; Ranta, Dana; Bosly, Andre; Tilly, Hervé; Quesnel, Bruno; Thyss, Antoine; Mounier, Nicolas; Brière, Josette; Molina, Thierry; Reyes, Felix

    2010-09-01

    One-third of patients aged dose intensity of cyclophosphamide, followed by conventional consolidation with an increased amount and dose intensity of cytosine-arabinoside, methotrexate, etoposide, and ifosfamide, in 652 patients with LIR aggressive lymphoma. The overall response rate, 5-year event-free survival (EFS), and survival were estimated to be 86%, 60%, and 74%, respectively, with no differences between the two arms. In patients with diffuse large B-cell lymphoma (DLBCL) who received ACVBP, the 5-year EFS and survival were estimated at 69% and 82%. These findings do not support the use of a chemotherapy regimen more intensive than ACVBP in patients aged

  19. Radiation dose in temporomandibular joint zonography

    SciTech Connect

    Coucke, M.E.; Bourgoignie, R.R.; Dermaut, L.R.; Bourgoignie, K.A.; Jacobs, R.J. )

    1991-06-01

    Temporomandibular joint morphology and function can be evaluated by panoramic zonography. Thermoluminescent dosimetry was applied to evaluate the radiation dose to predetermined sites on a phantom eye, thyroid, pituitary, and parotid, and the dose distribution on the skin of the head and neck when the TMJ program of the Zonarc panoramic x-ray unit was used. Findings are discussed with reference to similar radiographic techniques.

  20. Perchlorate exposure and dose estimates in infants

    PubMed Central

    Valentín-Blasini, Liza; Blount, Benjamin C.; Otero-Santos, Samaret; Cao, Yang; Bernbaum, Judy C.; Rogan, Walter J.

    2011-01-01

    Perchlorate is a naturally occurring inorganic anion used as a component of solid rocket fuel, explosives, and pyrotechnics. Sufficiently high perchlorate intakes can modify thyroid function by competitively inhibiting iodide uptake in adults; however little is known about perchlorate exposure and health effects in infants. Food intake models predict that infants have higher perchlorate exposure doses than adults. For this reason, we measured perchlorate and related anions (nitrate, thiocyanate, and iodide) in 206 urine samples from 92 infants ages 1–377 days and calculated perchlorate intake dose for this population of infants. The median estimated exposure dose for this population of infants was 0.160 μg/kg/day. Of the 205 individual dose estimates, 9% exceeded the reference dose of 0.7 μg/kg/day; 6% of infants providing multiple samples had multiple perchlorate dose estimates above the reference dose. Estimated exposure dose differed by feeding method: breast-fed infants had a higher perchlorate exposure dose (geometric mean 0.220 μg/kg/day) than infants consuming cow milk-based formula (geometric mean 0.103 μg/kg/day, p<0.0001) or soy-based formula (geometric mean 0.027 μg/kg/day, p<0.0001), consistent with dose estimates based on dietary intake data. The ability of perchlorate to block adequate iodide uptake by the thyroid may have been reduced by