Sample records for maximum allowable dose

  1. 49 CFR 230.24 - Maximum allowable stress.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Maximum allowable stress. 230.24 Section 230.24... Allowable Stress § 230.24 Maximum allowable stress. (a) Maximum allowable stress value. The maximum allowable stress value on any component of a steam locomotive boiler shall not exceed 1/4 of the ultimate...

  2. 49 CFR 230.24 - Maximum allowable stress.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Maximum allowable stress. 230.24 Section 230.24... Allowable Stress § 230.24 Maximum allowable stress. (a) Maximum allowable stress value. The maximum allowable stress value on any component of a steam locomotive boiler shall not exceed 1/4 of the ultimate...

  3. 49 CFR 230.24 - Maximum allowable stress.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 4 2012-10-01 2012-10-01 false Maximum allowable stress. 230.24 Section 230.24... Allowable Stress § 230.24 Maximum allowable stress. (a) Maximum allowable stress value. The maximum allowable stress value on any component of a steam locomotive boiler shall not exceed 1/4 of the ultimate...

  4. 49 CFR 230.24 - Maximum allowable stress.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 4 2014-10-01 2014-10-01 false Maximum allowable stress. 230.24 Section 230.24... Allowable Stress § 230.24 Maximum allowable stress. (a) Maximum allowable stress value. The maximum allowable stress value on any component of a steam locomotive boiler shall not exceed 1/4 of the ultimate...

  5. 49 CFR 230.24 - Maximum allowable stress.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 4 2013-10-01 2013-10-01 false Maximum allowable stress. 230.24 Section 230.24... Allowable Stress § 230.24 Maximum allowable stress. (a) Maximum allowable stress value. The maximum allowable stress value on any component of a steam locomotive boiler shall not exceed 1/4 of the ultimate...

  6. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Maximum allowable project cost. 35.2205... ASSISTANCE STATE AND LOCAL ASSISTANCE Grants for Construction of Treatment Works § 35.2205 Maximum allowable... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

  7. 32 CFR 842.35 - Depreciation and maximum allowances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Depreciation and maximum allowances. 842.35... LITIGATION ADMINISTRATIVE CLAIMS Personnel Claims (31 U.S.C. 3701, 3721) § 842.35 Depreciation and maximum allowances. The military services have jointly established the “Allowance List-Depreciation Guide” to...

  8. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

  9. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

  10. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

  11. 40 CFR 35.2205 - Maximum allowable project cost.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false Maximum allowable project cost. 35.2205... project cost. (a) Grants awarded on or after the effective date of this regulation. Except as provided in... regulation, the maximum allowable project cost will be the sum of: (1) The allowable cost of the following...

  12. 46 CFR 151.03-37 - Maximum allowable working pressure.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Maximum allowable working pressure. 151.03-37 Section 151.03-37 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-37 Maximum allowable working pressure. The maximum allowable working...

  13. 46 CFR 151.03-37 - Maximum allowable working pressure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Maximum allowable working pressure. 151.03-37 Section 151.03-37 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-37 Maximum allowable working pressure. The maximum allowable working...

  14. 46 CFR 151.03-37 - Maximum allowable working pressure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Maximum allowable working pressure. 151.03-37 Section 151.03-37 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-37 Maximum allowable working pressure. The maximum allowable working...

  15. 46 CFR 151.03-37 - Maximum allowable working pressure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Maximum allowable working pressure. 151.03-37 Section 151.03-37 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-37 Maximum allowable working pressure. The maximum allowable working...

  16. 46 CFR 151.03-37 - Maximum allowable working pressure.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Maximum allowable working pressure. 151.03-37 Section 151.03-37 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES BARGES CARRYING BULK LIQUID HAZARDOUS MATERIAL CARGOES Definitions § 151.03-37 Maximum allowable working pressure. The maximum allowable working...

  17. 49 CFR 174.86 - Maximum allowable operating speed.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 2 2011-10-01 2011-10-01 false Maximum allowable operating speed. 174.86 Section... operating speed. (a) For molten metals and molten glass shipped in packagings other than those prescribed in § 173.247 of this subchapter, the maximum allowable operating speed may not exceed 24 km/hour (15 mph...

  18. 49 CFR 174.86 - Maximum allowable operating speed.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 2 2010-10-01 2010-10-01 false Maximum allowable operating speed. 174.86 Section... operating speed. (a) For molten metals and molten glass shipped in packagings other than those prescribed in § 173.247 of this subchapter, the maximum allowable operating speed may not exceed 24 km/hour (15 mph...

  19. 49 CFR 230.25 - Maximum allowable stress on stays and braces.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Maximum allowable stress on stays and braces. 230... Boilers and Appurtenances Allowable Stress § 230.25 Maximum allowable stress on stays and braces. The maximum allowable stress per square inch of net cross sectional area on fire box and combustion chamber...

  20. Evaluation of the Maximum Allowable Cost Program

    PubMed Central

    Lee, A. James; Hefner, Dennis; Dobson, Allen; Hardy, Ralph

    1983-01-01

    This article summarizes an evaluation of the Maximum Allowable Cost (MAC)-Estimated Acquisition Cost (EAC) program, the Federal Government's cost-containment program for prescription drugs.1 The MAC-EAC regulations which became effective on August 26, 1976, have four major components: (1) Maximum Allowable Cost reimbursement limits for selected multisource or generically available drugs; (2) Estimated Acquisition Cost reimbursement limits for all drugs; (3) “usual and customary” reimbursement limits for all drugs; and (4) a directive that professional fee studies be performed by each State. The study examines the benefits and costs of the MAC reimbursement limits for 15 dosage forms of five multisource drugs and EAC reimbursement limits for all drugs for five selected States as of 1979. PMID:10309857

  1. 49 CFR Appendix A to Part 213 - Maximum Allowable Curving Speeds

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 4 2011-10-01 2011-10-01 false Maximum Allowable Curving Speeds A Appendix A to...—Maximum Allowable Curving Speeds Table 1—Three Inches Unbalance [Elevation of outer rail (inches)] Degree of curvature 0 1/2 1 11/2 2 21/2 3 31/2 4 41/2 5 51/2 6 (12) Maximum allowable operating speed (mph...

  2. 49 CFR Appendix A to Part 213 - Maximum Allowable Curving Speeds

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 4 2010-10-01 2010-10-01 false Maximum Allowable Curving Speeds A Appendix A to...—Maximum Allowable Curving Speeds Table 1—Three Inches Unbalance [Elevation of outer rail (inches)] Degree of curvature 0 1/2 1 11/2 2 21/2 3 31/2 4 41/2 5 51/2 6 (12) Maximum allowable operating speed (mph...

  3. 49 CFR 192.619 - Maximum allowable operating pressure: Steel or plastic pipelines.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Maximum allowable operating pressure: Steel or... Operations § 192.619 Maximum allowable operating pressure: Steel or plastic pipelines. (a) No person may operate a segment of steel or plastic pipeline at a pressure that exceeds a maximum allowable operating...

  4. 49 CFR 192.619 - Maximum allowable operating pressure: Steel or plastic pipelines.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Maximum allowable operating pressure: Steel or... Operations § 192.619 Maximum allowable operating pressure: Steel or plastic pipelines. (a) No person may operate a segment of steel or plastic pipeline at a pressure that exceeds a maximum allowable operating...

  5. 49 CFR 192.619 - Maximum allowable operating pressure: Steel or plastic pipelines.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Maximum allowable operating pressure: Steel or... Operations § 192.619 Maximum allowable operating pressure: Steel or plastic pipelines. (a) No person may operate a segment of steel or plastic pipeline at a pressure that exceeds a maximum allowable operating...

  6. 49 CFR 192.619 - Maximum allowable operating pressure: Steel or plastic pipelines.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Maximum allowable operating pressure: Steel or... Operations § 192.619 Maximum allowable operating pressure: Steel or plastic pipelines. (a) No person may operate a segment of steel or plastic pipeline at a pressure that exceeds a maximum allowable operating...

  7. 49 CFR 230.25 - Maximum allowable stress on stays and braces.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... maximum allowable stress per square inch of net cross sectional area on fire box and combustion chamber stays shall be 7,500 psi. The maximum allowable stress per square inch of net cross sectional area on...

  8. 49 CFR 230.25 - Maximum allowable stress on stays and braces.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... maximum allowable stress per square inch of net cross sectional area on fire box and combustion chamber stays shall be 7,500 psi. The maximum allowable stress per square inch of net cross sectional area on...

  9. 49 CFR 230.25 - Maximum allowable stress on stays and braces.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... maximum allowable stress per square inch of net cross sectional area on fire box and combustion chamber stays shall be 7,500 psi. The maximum allowable stress per square inch of net cross sectional area on...

  10. 49 CFR 230.25 - Maximum allowable stress on stays and braces.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... maximum allowable stress per square inch of net cross sectional area on fire box and combustion chamber stays shall be 7,500 psi. The maximum allowable stress per square inch of net cross sectional area on...

  11. 46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Maximum allowable working pressure (reproduces UG-98). 54.10-5 Section 54.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-5 Maximum allowable working pressure (reproduces UG-98). (a) The maximum allowable...

  12. 46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Maximum allowable working pressure (reproduces UG-98). 54.10-5 Section 54.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-5 Maximum allowable working pressure (reproduces UG-98). (a) The maximum allowable...

  13. 46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Maximum allowable working pressure (reproduces UG-98). 54.10-5 Section 54.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-5 Maximum allowable working pressure (reproduces UG-98). (a) The maximum allowable...

  14. 46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Maximum allowable working pressure (reproduces UG-98). 54.10-5 Section 54.10-5 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING PRESSURE VESSELS Inspection, Reports, and Stamping § 54.10-5 Maximum allowable working pressure (reproduces UG-98). (a) The maximum allowable...

  15. 49 CFR 174.86 - Maximum allowable operating speed.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Handling of Placarded Rail Cars, Transport Vehicles and Freight Containers § 174.86 Maximum allowable operating speed. (a) For molten metals and molten glass shipped in packagings other than those prescribed in...

  16. 49 CFR 174.86 - Maximum allowable operating speed.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Handling of Placarded Rail Cars, Transport Vehicles and Freight Containers § 174.86 Maximum allowable operating speed. (a) For molten metals and molten glass shipped in packagings other than those prescribed in...

  17. 49 CFR 174.86 - Maximum allowable operating speed.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Handling of Placarded Rail Cars, Transport Vehicles and Freight Containers § 174.86 Maximum allowable operating speed. (a) For molten metals and molten glass shipped in packagings other than those prescribed in...

  18. 30 CFR 36.44 - Maximum allowable fuel : air ratio.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... delivered to MSHA with the fuel-injection system adjusted by the applicant and tests of the exhaust-gas... adjustment of the fuel-injection system shall be accepted. The maximum fuel : air ratio determined from the... 30 Mineral Resources 1 2012-07-01 2012-07-01 false Maximum allowable fuel : air ratio. 36.44...

  19. 30 CFR 36.44 - Maximum allowable fuel : air ratio.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... delivered to MSHA with the fuel-injection system adjusted by the applicant and tests of the exhaust-gas... adjustment of the fuel-injection system shall be accepted. The maximum fuel : air ratio determined from the... 30 Mineral Resources 1 2013-07-01 2013-07-01 false Maximum allowable fuel : air ratio. 36.44...

  20. 30 CFR 36.44 - Maximum allowable fuel : air ratio.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... delivered to MSHA with the fuel-injection system adjusted by the applicant and tests of the exhaust-gas... adjustment of the fuel-injection system shall be accepted. The maximum fuel : air ratio determined from the... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Maximum allowable fuel : air ratio. 36.44...

  1. 30 CFR 36.44 - Maximum allowable fuel : air ratio.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... delivered to MSHA with the fuel-injection system adjusted by the applicant and tests of the exhaust-gas... adjustment of the fuel-injection system shall be accepted. The maximum fuel : air ratio determined from the... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Maximum allowable fuel : air ratio. 36.44...

  2. [Estimation of Maximum Entrance Skin Dose during Cerebral Angiography].

    PubMed

    Kawauchi, Satoru; Moritake, Takashi; Hayakawa, Mikito; Hamada, Yusuke; Sakuma, Hideyuki; Yoda, Shogo; Satoh, Masayuki; Sun, Lue; Koguchi, Yasuhiro; Akahane, Keiichi; Chida, Koichi; Matsumaru, Yuji

    2015-09-01

    Using radio-photoluminescence glass dosimeter, we measured the entrance skin dose (ESD) in 46 cases and analyzed the correlations between maximum ESD and angiographic parameters [total fluoroscopic time (TFT); number of digital subtraction angiography (DSA) frames, air kerma at the interventional reference point (AK), and dose-area product (DAP)] to estimate the maximum ESD in real time. Mean (± standard deviation) maximum ESD, dose of the right lens, and dose of the left lens were 431.2 ± 135.8 mGy, 33.6 ± 15.5 mGy, and 58.5 ± 35.0 mGy, respectively. Correlation coefficients (r) between maximum ESD and TFT, number of DSA frames, AK, and DAP were r=0.379 (P<0.01), r=0.702 (P<0.001), r=0.825 (P<0.001), and r=0.709 (P<0.001), respectively. AK was identified as the most useful parameter for real-time prediction of maximum ESD. This study should contribute to the development of new diagnostic reference levels in our country.

  3. 30 CFR 36.44 - Maximum allowable fuel:air ratio.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... delivered to MSHA with the fuel-injection system adjusted by the applicant and tests of the exhaust-gas... adjustment of the fuel-injection system shall be accepted. The maximum fuel:air ratio determined from the... 30 Mineral Resources 1 2014-07-01 2014-07-01 false Maximum allowable fuel:air ratio. 36.44 Section...

  4. Spacecraft maximum allowable concentrations for selected airborne contaminants, volume 1

    NASA Technical Reports Server (NTRS)

    1994-01-01

    As part of its efforts to promote safe conditions aboard spacecraft, NASA requested the National Research Council (NRC) to develop guidelines for establishing spacecraft maximum allowable concentrations (SMAC's) for contaminants, and to review SMAC's for various spacecraft contaminants to determine whether NASA's recommended exposure limits are consistent with the guidelines recommended by the subcommittee. In response to NASA's request, the NRC organized the Subcommittee on Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants within the Committee on Toxicology (COT). In the first phase of its work, the subcommittee developed the criteria and methods for preparing SMAC's for spacecraft contaminants. The subcommittee's report, entitled Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants, was published in 1992. The executive summary of that report is reprinted as Appendix A of this volume. In the second phase of the study, the Subcommittee on Spacecraft Maximum Allowable Concentrations reviewed reports prepared by NASA scientists and contractors recommending SMAC's for 35 spacecraft contaminants. The subcommittee sought to determine whether the SMAC reports were consistent with the 1992 guidelines. Appendix B of this volume contains the first 11 SMAC reports that have been reviewed for their application of the guidelines developed in the first phase of this activity and approved by the subcommittee.

  5. 46 CFR 52.01-55 - Increase in maximum allowable working pressure.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 2 2011-10-01 2011-10-01 false Increase in maximum allowable working pressure. 52.01-55 Section 52.01-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-55 Increase in maximum allowable working pressure. (a) When...

  6. 46 CFR 52.01-55 - Increase in maximum allowable working pressure.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 2 2012-10-01 2012-10-01 false Increase in maximum allowable working pressure. 52.01-55 Section 52.01-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-55 Increase in maximum allowable working pressure. (a) When...

  7. 46 CFR 52.01-55 - Increase in maximum allowable working pressure.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Increase in maximum allowable working pressure. 52.01-55 Section 52.01-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-55 Increase in maximum allowable working pressure. (a) When...

  8. 46 CFR 52.01-55 - Increase in maximum allowable working pressure.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 2 2014-10-01 2014-10-01 false Increase in maximum allowable working pressure. 52.01-55 Section 52.01-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-55 Increase in maximum allowable working pressure. (a) When...

  9. 46 CFR 52.01-55 - Increase in maximum allowable working pressure.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 2 2013-10-01 2013-10-01 false Increase in maximum allowable working pressure. 52.01-55 Section 52.01-55 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE ENGINEERING POWER BOILERS General Requirements § 52.01-55 Increase in maximum allowable working pressure. (a) When...

  10. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants. Volume 2

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The National Aeronautics and Space Administration (NASA) is aware of the potential toxicological hazards to humans that might be associated with prolonged spacecraft missions. Despite major engineering advances in controlling the atmosphere within spacecraft, some contamination of the air appears inevitable. NASA has measured numerous airborne contaminants during space missions. As the missions increase in duration and complexity, ensuring the health and well-being of astronauts traveling and working in this unique environment becomes increasingly difficult. As part of its efforts to promote safe conditions aboard spacecraft, NASA requested the National Research Council (NRC) to develop guidelines for establishing spacecraft maximum allowable concentrations (SMACs) for contaminants, and to review SMACs for various space-craft contaminants to determine whether NASA's recommended exposure limits are consistent with the guidelines recommended by the subcommittee. In response to NASA's request, the NRC organized the Subcommittee on Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants within the Committee On Toxicology (COT). In the first phase of its work, the subcommittee developed the criteria and methods for preparing SMACs for spacecraft contaminants. The subcommittee's report, entitled Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants, was published in 1992. The executive summary of that report is reprinted as Appendix A of this volume. In the second phase of the study, the Subcommittee on Spacecraft Maximum Allowable Concentrations reviewed reports prepared by NASA scientists and contractors recommending SMACs for approximately 35 spacecraft contaminants. The subcommittee sought to determine whether the SMAC reports were consistent with the 1992 guidelines. Appendix B of this volume contains the SMAC reports for 12 chemical contaminants that have been reviewed for

  11. 49 CFR 192.619 - Maximum allowable operating pressure: Steel or plastic pipelines.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... plastic pipelines. 192.619 Section 192.619 Transportation Other Regulations Relating to Transportation... Operations § 192.619 Maximum allowable operating pressure: Steel or plastic pipelines. (a) No person may operate a segment of steel or plastic pipeline at a pressure that exceeds a maximum allowable operating...

  12. Guidelines for developing spacecraft maximum allowable concentrations for Space Station contaminants

    NASA Technical Reports Server (NTRS)

    1992-01-01

    The National Aeronautics and Space Administration (NASA) is preparing to launch a manned space station by the year 1996. Because of concerns about the health, safety, and functioning abilities of the crews, NASA has requested that the National Research Council (NRC) through the Board on Environmental Studies and Toxicology (BEST) provide advice on toxicological matters for the space-station program. The Subcommittee on Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants was established by the Committee on Toxicology (COT) to address NASA's concerns. Spacecraft maximum allowable concentrations (SMAC's) are defined as the maximum concentrations of airborne substances (such as gas, vapor, or aerosol) that will not cause adverse health effects, significant discomfort, or degradation in crew performance.

  13. 42 CFR 447.54 - Maximum allowable and nominal charges.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... nonemergency services furnished in a hospital emergency room. (c) Institutional services. For institutional... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... that cost sharing amounts be nominal. Upon approval from CMS, the requirement that cost sharing charges...

  14. 42 CFR 447.54 - Maximum allowable and nominal charges.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., any co-payments it imposes under a fee-for-service delivery system do not exceed the amounts shown in... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... paragraph (a)(3)(i) of this section for comparable services under a fee-for-service delivery system. When...

  15. 42 CFR 447.54 - Maximum allowable and nominal charges.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ..., any co-payments it imposes under a fee-for-service delivery system do not exceed the amounts shown in... Deductible, Coinsurance, Co-Payment Or Similar Cost-Sharing Charge § 447.54 Maximum allowable and nominal... paragraph (a)(3)(i) of this section for comparable services under a fee-for-service delivery system. When...

  16. Spacecraft Maximum Allowable Concentrations for Airborne Contaminants

    NASA Technical Reports Server (NTRS)

    James, John T.

    2008-01-01

    The enclosed table lists official spacecraft maximum allowable concentrations (SMACs), which are guideline values set by the NASA/JSC Toxicology Group in cooperation with the National Research Council Committee on Toxicology (NRCCOT). These values should not be used for situations other than human space flight without careful consideration of the criteria used to set each value. The SMACs take into account a number of unique factors such as the effect of space-flight stress on human physiology, the uniform good health of the astronauts, and the absence of pregnant or very young individuals. Documentation of the values is given in a 5 volume series of books entitled "Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants" published by the National Academy Press, Washington, D.C. These books can be viewed electronically at http://books.nap.edu/openbook.php?record_id=9786&page=3. Short-term (1 and 24 hour) SMACs are set to manage accidental releases aboard a spacecraft and permit risk of minor, reversible effects such as mild mucosal irritation. In contrast, the long-term SMACs are set to fully protect healthy crewmembers from adverse effects resulting from continuous exposure to specific air pollutants for up to 1000 days. Crewmembers with allergies or unusual sensitivity to trace pollutants may not be afforded complete protection, even when long-term SMACs are not exceeded. Crewmember exposures involve a mixture of contaminants, each at a specific concentration (C(sub n)). These contaminants could interact to elicit symptoms of toxicity even though individual contaminants do not exceed their respective SMACs. The air quality is considered acceptable when the toxicity index (T(sub grp)) for each toxicological group of compounds is less than 1, where T(sub grp), is calculated as follows: T(sub grp) = C(sub 1)/SMAC(sub 1) + C(sub 2/SMAC(sub 2) + ...+C(sub n)/SMAC(sub n).

  17. Developability assessment of clinical drug products with maximum absorbable doses.

    PubMed

    Ding, Xuan; Rose, John P; Van Gelder, Jan

    2012-05-10

    Maximum absorbable dose refers to the maximum amount of an orally administered drug that can be absorbed in the gastrointestinal tract. Maximum absorbable dose, or D(abs), has proved to be an important parameter for quantifying the absorption potential of drug candidates. The purpose of this work is to validate the use of D(abs) in a developability assessment context, and to establish appropriate protocol and interpretation criteria for this application. Three methods for calculating D(abs) were compared by assessing how well the methods predicted the absorption limit for a set of real clinical candidates. D(abs) was calculated for these clinical candidates by means of a simple equation and two computer simulation programs, GastroPlus and an program developed at Eli Lilly and Company. Results from single dose escalation studies in Phase I clinical trials were analyzed to identify the maximum absorbable doses for these compounds. Compared to the clinical results, the equation and both simulation programs provide conservative estimates of D(abs), but in general D(abs) from the computer simulations are more accurate, which may find obvious advantage for the simulations in developability assessment. Computer simulations also revealed the complex behavior associated with absorption saturation and suggested in most cases that the D(abs) limit is not likely to be achieved in a typical clinical dose range. On the basis of the validation findings, an approach is proposed for assessing absorption potential, and best practices are discussed for the use of D(abs) estimates to inform clinical formulation development strategies. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants. Volume 5

    NASA Technical Reports Server (NTRS)

    2008-01-01

    To protect space crews from air contaminants, NASA requested that the National Research Council (NRC) provide guidance for developing spacecraft maximum allowable concentrations (SMACs) and review NASA's development of exposure guidelines for specific chemicals. The NRC convened the Committee on Spacecraft Exposure Guidelines to address this task. The committee published Guidelines for Developing Spacecraft Maximum Allowable Concentrations for Space Station Contaminants (NRC 1992). The reason for the review of chemicals in Volume 5 is that many of them have not been examined for more than 10 years, and new research necessitates examining the documents to ensure that they reflect current knowledge. New knowledge can be in the form of toxicologic data or in the application of new approaches for analysis of available data. In addition, because NASA anticipates longer space missions beyond low Earth orbit, SMACs for 1,000-d exposures have also been developed.

  19. 5 CFR 591.104 - Higher initial maximum uniform allowance rate.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Higher initial maximum uniform allowance rate. 591.104 Section 591.104 Administrative Personnel OFFICE OF PERSONNEL MANAGEMENT CIVIL SERVICE... initial year a new style or type of minimum basic uniform is required for a category of employees, an...

  20. Maximum dose rate is a determinant of hypothyroidism after 131I therapy of Graves' disease but the total thyroid absorbed dose is not.

    PubMed

    Krohn, Thomas; Hänscheid, Heribert; Müller, Berthold; Behrendt, Florian F; Heinzel, Alexander; Mottaghy, Felix M; Verburg, Frederik A

    2014-11-01

    The determinants of successful (131)I therapy of Graves' disease (GD) are unclear. To relate dosimetry parameters to outcome of therapy to identify significant determinants eu- and/or hypothyroidism after (131)I therapy in patients with GD. A retrospective study in which 206 Patients with GD treated in University Hospital between November 1999 and January 2011. All received (131)I therapy aiming at a total absorbed dose to the thyroid of 250 Gy based on pre-therapeutic dosimetry. Post-therapy dosimetric thyroid measurements were performed twice daily until discharge. From these measurements, thyroid (131)I half-life, the total thyroid absorbed dose, and the maximum dose rate after (131)I administration were calculated. In all, 48.5% of patients were hypothyroid and 28.6% of patients were euthyroid after (131)I therapy. In univariate analysis, nonhyperthyroid and hyperthyroid patients only differed by sex. A lower thyroid mass, a higher activity per gram thyroid tissue, a shorter effective thyroidal (131)I half-life, and a higher maximum dose rate, but not the total thyroid absorbed dose, were significantly associated with hypothyroidism. In multivariate analysis, the maximum dose rate remained the only significant determinant of hypothyroidism (P < .001). Maximum dose rates of 2.2 Gy/h and higher were associated with a 100% hypothyroidism rate. Not the total thyroid absorbed dose, but the maximum dose rate is a determinant of successfully achieving hypothyroidism in Graves' disease. Dosimetric concepts aiming at a specific total thyroid absorbed dose will therefore require reconsideration if our data are confirmed prospectively.

  1. FDA-sunlamp recommended Maximum Timer Interval And Exposure Schedule: consensus ISO/CIE dose equivalence.

    PubMed

    Dowdy, John C; Czako, Eugene A; Stepp, Michael E; Schlitt, Steven C; Bender, Gregory R; Khan, Lateef U; Shinneman, Kenneth D; Karos, Manuel G; Shepherd, James G; Sayre, Robert M

    2011-09-01

    The authors compared calculations of sunlamp maximum exposure times following current USFDA Guidance Policy on the Maximum Timer Interval and Exposure Schedule, with USFDA/CDRH proposals revising these to equivalent erythemal exposures of ISO/CIE Standard Erythema Dose (SED). In 2003, [USFDA/CDRH proposed replacing their unique CDRH/Lytle] erythema action spectrum with the ISO/CIE erythema action spectrum and revising the sunlamp maximum exposure timer to 600 J m(-2) ISO/CIE effective dose, presented as being biologically equivalent. Preliminary analysis failed to confirm said equivalence, indicating instead ∼38% increased exposure when applying these proposed revisions. To confirm and refine this finding, a collaboration of tanning bed and UV lamp manufacturers compiled 89 UV spectra representing a broad sampling of U.S. indoor tanning equipment. USFDA maximum recommended exposure time (Te) per current sunlamp guidance and CIE erythemal effectiveness per ISO/CIE standard were calculated. The CIE effective dose delivered per Te averaged 456 J(CIE) m(-2) (SD = 0.17) or ∼4.5 SED. The authors found that CDRH's proposed 600 J(CIE) m(-2) recommended maximum sunlamp exposure exceeds current Te erythemal dose by ∼33%. The current USFDA 0.75 MED initial exposure was ∼0.9 SED, consistent with 1.0 SED initial dose in existing international sunlamp standards. As no sunlamps analyzed exceeded 5 SED, a revised maximum exposure of 500 J(CIE) m(-2) (∼80% of CDRH's proposal) should be compatible with existing tanning equipment. A tanning acclimatization schedule is proposed beginning at 1 SED thrice-weekly, increasing uniformly stepwise over 4 wk to a 5 SED maximum exposure in conjunction with a tan maintenance schedule of twice-weekly 5 SED sessions, as biologically equivalent to current USFDA sunlamp policy.

  2. The maximum single dose of resistant maltodextrin that does not cause diarrhea in humans.

    PubMed

    Kishimoto, Yuka; Kanahori, Sumiko; Sakano, Katsuhisa; Ebihara, Shukuko

    2013-01-01

    The objective of the present study was to determine the maximum dose of resistant maltodextrin (Fibersol)-2, a non-viscous water-soluble dietary fiber), that does not induce transitory diarrhea. Ten healthy adult subjects (5 men and 5 women) ingested Fibersol-2 at increasing dose levels of 0.7, 0.8, 0.9, 1.0, and 1.1 g/kg body weight (bw). Each administration was separated from the previous dose by an interval of 1 wk. The highest dose level that did not cause diarrhea in any subject was regarded as the maximum non-effective level for a single dose. The results showed that no subject of either sex experienced diarrhea at dose levels of 0.7, 0.8, 0.9, or 1.0 g/kg bw. At the highest dose level of 1.1 g/kg bw, no female subject experienced diarrhea, whereas 1 male subject developed diarrhea with muddy stools 2 h after ingestion of the test substance. Consequently, the maximum non-effective level for a single dose of the resistant maltodextrin Fibersol-2 is 1.0 g/kg bw for men and >1.1 g/kg bw for women. Gastrointestinal symptoms were gurgling sounds in 4 subjects (7 events) and flatus in 5 subjects (9 events), although no association with dose level was observed. These symptoms were mild and transient and resolved without treatment.

  3. 42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... maximum amount of $11.35 for services furnished in a hospital emergency room if those services are not... 42 Public Health 4 2012-10-01 2012-10-01 false Maximum allowable cost-sharing charges on targeted... Requirements: Enrollee Financial Responsibilities § 457.555 Maximum allowable cost-sharing charges on targeted...

  4. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Additional construction requirements for steel pipe using alternative maximum allowable operating pressure. 192.328 Section 192.328 Transportation... Lines and Mains § 192.328 Additional construction requirements for steel pipe using alternative maximum...

  5. 49 CFR 192.328 - Additional construction requirements for steel pipe using alternative maximum allowable operating...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Additional construction requirements for steel pipe using alternative maximum allowable operating pressure. 192.328 Section 192.328 Transportation... Lines and Mains § 192.328 Additional construction requirements for steel pipe using alternative maximum...

  6. 49 CFR 192.621 - Maximum allowable operating pressure: High-pressure distribution systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... STANDARDS Operations § 192.621 Maximum allowable operating pressure: High-pressure distribution systems. (a) No person may operate a segment of a high pressure distribution system at a pressure that exceeds the... segment of a distribution system otherwise designed to operate at over 60 p.s.i. (414 kPa) gage, unless...

  7. 49 CFR 192.621 - Maximum allowable operating pressure: High-pressure distribution systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... STANDARDS Operations § 192.621 Maximum allowable operating pressure: High-pressure distribution systems. (a) No person may operate a segment of a high pressure distribution system at a pressure that exceeds the... segment of a distribution system otherwise designed to operate at over 60 p.s.i. (414 kPa) gage, unless...

  8. 49 CFR 192.621 - Maximum allowable operating pressure: High-pressure distribution systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... STANDARDS Operations § 192.621 Maximum allowable operating pressure: High-pressure distribution systems. (a) No person may operate a segment of a high pressure distribution system at a pressure that exceeds the... segment of a distribution system otherwise designed to operate at over 60 p.s.i. (414 kPa) gage, unless...

  9. 49 CFR 192.621 - Maximum allowable operating pressure: High-pressure distribution systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... STANDARDS Operations § 192.621 Maximum allowable operating pressure: High-pressure distribution systems. (a) No person may operate a segment of a high pressure distribution system at a pressure that exceeds the... segment of a distribution system otherwise designed to operate at over 60 p.s.i. (414 kPa) gage, unless...

  10. 49 CFR 192.621 - Maximum allowable operating pressure: High-pressure distribution systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... STANDARDS Operations § 192.621 Maximum allowable operating pressure: High-pressure distribution systems. (a) No person may operate a segment of a high pressure distribution system at a pressure that exceeds the... segment of a distribution system otherwise designed to operate at over 60 p.s.i. (414 kPa) gage, unless...

  11. Dose Titration Algorithm Tuning (DTAT) should supersede 'the' Maximum Tolerated Dose (MTD) in oncology dose-finding trials.

    PubMed

    Norris, David C

    2017-01-01

    Background . Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent 'confirmatory' Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of 'the' maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as 'dose-finding', but as dose titration algorithm (DTA) -finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug's population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace 'the' MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically in relation to

  12. 42 CFR 84.97 - Test for carbon dioxide in inspired gas; open- and closed-circuit apparatus; maximum allowable...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... closed-circuit apparatus; maximum allowable limits. 84.97 Section 84.97 Public Health PUBLIC HEALTH... ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.97 Test for carbon dioxide in inspired gas; open- and closed-circuit apparatus; maximum allowable limits. (a) Open...

  13. 42 CFR 84.97 - Test for carbon dioxide in inspired gas; open- and closed-circuit apparatus; maximum allowable...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... closed-circuit apparatus; maximum allowable limits. 84.97 Section 84.97 Public Health PUBLIC HEALTH... ACTIVITIES APPROVAL OF RESPIRATORY PROTECTIVE DEVICES Self-Contained Breathing Apparatus § 84.97 Test for carbon dioxide in inspired gas; open- and closed-circuit apparatus; maximum allowable limits. (a) Open...

  14. 49 CFR 192.620 - Alternative maximum allowable operating pressure for certain steel pipelines.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... for certain steel pipelines. 192.620 Section 192.620 Transportation Other Regulations Relating to... STANDARDS Operations § 192.620 Alternative maximum allowable operating pressure for certain steel pipelines..., 2, or 3 location; (2) The pipeline segment is constructed of steel pipe meeting the additional...

  15. 49 CFR 192.620 - Alternative maximum allowable operating pressure for certain steel pipelines.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... of a maximum allowable operating pressure based on higher stress levels in the following areas: Take... pipeline at the increased stress level under this section with conventional operation; and (ii) Describe... targeted audience; and (B) Include information about the integrity management activities performed under...

  16. 49 CFR 192.620 - Alternative maximum allowable operating pressure for certain steel pipelines.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... of a maximum allowable operating pressure based on higher stress levels in the following areas: Take... pipeline at the increased stress level under this section with conventional operation; and (ii) Describe... targeted audience; and (B) Include information about the integrity management activities performed under...

  17. 49 CFR 192.620 - Alternative maximum allowable operating pressure for certain steel pipelines.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... of a maximum allowable operating pressure based on higher stress levels in the following areas: Take... pipeline at the increased stress level under this section with conventional operation; and (ii) Describe... targeted audience; and (B) Include information about the integrity management activities performed under...

  18. Use of iodine for water disinfection: iodine toxicity and maximum recommended dose.

    PubMed Central

    Backer, H; Hollowell, J

    2000-01-01

    Iodine is an effective, simple, and cost-efficient means of water disinfection for people who vacation, travel, or work in areas where municipal water treatment is not reliable. However, there is considerable controversy about the maximum safe iodine dose and duration of use when iodine is ingested in excess of the recommended daily dietary amount. The major health effect of concern with excess iodine ingestion is thyroid disorders, primarily hypothyroidism with or without iodine-induced goiter. A review of the human trials on the safety of iodine ingestion indicates that neither the maximum recommended dietary dose (2 mg/day) nor the maximum recommended duration of use (3 weeks) has a firm basis. Rather than a clear threshold response level or a linear and temporal dose-response relationship between iodine intake and thyroid function, there appears to be marked individual sensitivity, often resulting from unmasking of underlying thyroid disease. The use of iodine for water disinfection requires a risk-benefit decision based on iodine's benefit as a disinfectant and the changes it induces in thyroid physiology. By using appropriate disinfection techniques and monitoring thyroid function, most people can use iodine for water treatment over a prolonged period of time. PMID:10964787

  19. Identifying a maximum tolerated contour in two-dimensional dose-finding

    PubMed Central

    Wages, Nolan A.

    2016-01-01

    The majority of Phase I methods for multi-agent trials have focused on identifying a single maximum tolerated dose combination (MTDC) among those being investigated. Some published methods in the area have been based on the notion that there is no unique MTDC, and that the set of dose combinations with acceptable toxicity forms an equivalence contour in two dimensions. Therefore, it may be of interest to find multiple MTDC's for further testing for efficacy in a Phase II setting. In this paper, we present a new dose-finding method that extends the continual reassessment method to account for the location of multiple MTDC's. Operating characteristics are demonstrated through simulation studies, and are compared to existing methodology. Some brief discussion of implementation and available software is also provided. PMID:26910586

  20. Dose Titration Algorithm Tuning (DTAT) should supersede ‘the’ Maximum Tolerated Dose (MTD) in oncology dose-finding trials

    PubMed Central

    Norris, David C.

    2017-01-01

    Background. Absent adaptive, individualized dose-finding in early-phase oncology trials, subsequent ‘confirmatory’ Phase III trials risk suboptimal dosing, with resulting loss of statistical power and reduced probability of technical success for the investigational therapy. While progress has been made toward explicitly adaptive dose-finding and quantitative modeling of dose-response relationships, most such work continues to be organized around a concept of ‘the’ maximum tolerated dose (MTD). The purpose of this paper is to demonstrate concretely how the aim of early-phase trials might be conceived, not as ‘dose-finding’, but as dose titration algorithm (DTA)-finding. Methods. A Phase I dosing study is simulated, for a notional cytotoxic chemotherapy drug, with neutropenia constituting the critical dose-limiting toxicity. The drug’s population pharmacokinetics and myelosuppression dynamics are simulated using published parameter estimates for docetaxel. The amenability of this model to linearization is explored empirically. The properties of a simple DTA targeting neutrophil nadir of 500 cells/mm 3 using a Newton-Raphson heuristic are explored through simulation in 25 simulated study subjects. Results. Individual-level myelosuppression dynamics in the simulation model approximately linearize under simple transformations of neutrophil concentration and drug dose. The simulated dose titration exhibits largely satisfactory convergence, with great variance in individualized optimal dosing. Some titration courses exhibit overshooting. Conclusions. The large inter-individual variability in simulated optimal dosing underscores the need to replace ‘the’ MTD with an individualized concept of MTD i . To illustrate this principle, the simplest possible DTA capable of realizing such a concept is demonstrated. Qualitative phenomena observed in this demonstration support discussion of the notion of tuning such algorithms. Although here illustrated specifically

  1. Effect of the Maximum Dose on White Matter Fiber Bundles Using Longitudinal Diffusion Tensor Imaging

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

    Zhu, Tong; Chapman, Christopher H.; Tsien, Christina

    2016-11-01

    Purpose: Previous efforts to decrease neurocognitive effects of radiation focused on sparing isolated cortical structures. We hypothesize that understanding temporal, spatial, and dosimetric patterns of radiation damage to whole-brain white matter (WM) after partial-brain irradiation might also be important. Therefore, we carried out a study to develop the methodology to assess radiation therapy (RT)–induced damage to whole-brain WM bundles. Methods and Materials: An atlas-based, automated WM tractography analysis was implemented to quantify longitudinal changes in indices of diffusion tensor imaging (DTI) of 22 major WM fibers in 33 patients with predominantly low-grade or benign brain tumors treated by RT. Sixmore » DTI scans per patient were performed from before RT to 18 months after RT. The DTI indices and planned doses (maximum and mean doses) were mapped onto profiles of each of 22 WM bundles. A multivariate linear regression was performed to determine the main dose effect as well as the influence of other clinical factors on longitudinal percentage changes in axial diffusivity (AD) and radial diffusivity (RD) from before RT. Results: Among 22 fiber bundles, AD or RD changes in 12 bundles were affected significantly by doses (P<.05), as the effect was progressive over time. In 9 elongated tracts, decreased AD or RD was significantly related to maximum doses received, consistent with a serial structure. In individual bundles, AD changes were up to 11.5% at the maximum dose locations 18 months after RT. The dose effect on WM was greater in older female patients than younger male patients. Conclusions: Our study demonstrates for the first time that the maximum dose to the elongated WM bundles causes post-RT damage in WM. Validation and correlative studies are necessary to determine the ability and impact of sparing these bundles on preserving neurocognitive function after RT.« less

  2. Maximum tolerated dose of nalmefene in patients receiving epidural fentanyl and dilute bupivacaine for postoperative analgesia.

    PubMed

    Dougherty, T B; Porche, V H; Thall, P F

    2000-04-01

    This study investigated the ability of the modified continual reassessment method (MCRM) to determine the maximum tolerated dose of the opioid antagonist nalmefene, which does not reverse analgesia in an acceptable number of postoperative patients receiving epidural fentanyl in 0.075% bupivacaine. In the postanesthetic care unit, patients received a single intravenous dose of 0.25, 0.50, 0.75, or 1.00 microg/kg nalmefene. Reversal of analgesia was defined as an increase in pain score of two or more integers above baseline on a visual analog scale from 0 through 10 after nalmefene administration. Patients were treated in cohorts of one, starting with the lowest dose. The maximum tolerated dose of nalmefene was defined as that dose, among the four studied, with a final mean probability of reversal of anesthesia (PROA) closest to 0.20 (ie., a 20% chance of causing reversal). The modified continual reassessment method is an iterative Bayesian statistical procedure that, in this study, selected the dose for each successive cohort as that having a mean PROA closest to the preselected target PROA of 0.20. The modified continual reassessment method repeatedly updated the PROA of each dose level as successive patients were observed for presence or absence of ROA. After 25 patients, the maximum tolerated dose of nalmefene was selected as 0.50 microg/kg (final mean PROA = 0.18). The 1.00-microg/kg dose was never tried because its projected PROA was far above 0.20. The modified continual reassessment method facilitated determination of the maximum tolerated dose ofnalmefene . Operating characteristics of the modified continual reassessment method suggest it may be an effective statistical tool for dose-finding in trials of selected analgesic or anesthetic agents.

  3. Spacecraft Maximum Allowable Concentrations (SMACs) for C3 to C8 Aliphatic Saturated Aldehydes

    NASA Technical Reports Server (NTRS)

    Langford, Shannon D.

    2007-01-01

    Spacecraft maximum allowable concentrations (SMACs) for C3 to C8, straight-chain, aliphatic aldehydes have been previously assessed and have been documented in volume 4 of Spacecraft Maximum Allowable Concentrations for Selected Airborne Contaminants (James, 2000). These aldehydes as well as associated physical properties are shown in Table 1. The C3 to C8 aliphatic aldehydes can enter the habitable compartments and contaminate breathing air of spacecraft by several routes including incomplete oxidation of alcohols in the Environmental Control and Life Support System (ECLSS) air revitalization subsystem, as a byproduct of human metabolism, through materials off-gassing, or during food preparation. These aldehydes have been detected in the atmosphere of manned space vehicles in the past. Analysis performed by NASA of crew cabin air samples from the Russian Mir Space Station revealed the presence of C3 to C8 aldehydes at concentrations peaking at approximately 0.1 mg/cu m.

  4. 49 CFR 192.623 - Maximum and minimum allowable operating pressure; Low-pressure distribution systems.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... distribution systems. (a) No person may operate a low-pressure distribution system at a pressure high enough to...) No person may operate a low pressure distribution system at a pressure lower than the minimum... 49 Transportation 3 2012-10-01 2012-10-01 false Maximum and minimum allowable operating pressure...

  5. 49 CFR 192.623 - Maximum and minimum allowable operating pressure; Low-pressure distribution systems.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... distribution systems. (a) No person may operate a low-pressure distribution system at a pressure high enough to...) No person may operate a low pressure distribution system at a pressure lower than the minimum... 49 Transportation 3 2011-10-01 2011-10-01 false Maximum and minimum allowable operating pressure...

  6. 49 CFR 192.623 - Maximum and minimum allowable operating pressure; Low-pressure distribution systems.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... distribution systems. (a) No person may operate a low-pressure distribution system at a pressure high enough to...) No person may operate a low pressure distribution system at a pressure lower than the minimum... 49 Transportation 3 2013-10-01 2013-10-01 false Maximum and minimum allowable operating pressure...

  7. 49 CFR 192.623 - Maximum and minimum allowable operating pressure; Low-pressure distribution systems.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... distribution systems. (a) No person may operate a low-pressure distribution system at a pressure high enough to...) No person may operate a low pressure distribution system at a pressure lower than the minimum... 49 Transportation 3 2014-10-01 2014-10-01 false Maximum and minimum allowable operating pressure...

  8. 49 CFR 192.623 - Maximum and minimum allowable operating pressure; Low-pressure distribution systems.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... distribution systems. (a) No person may operate a low-pressure distribution system at a pressure high enough to...) No person may operate a low pressure distribution system at a pressure lower than the minimum... 49 Transportation 3 2010-10-01 2010-10-01 false Maximum and minimum allowable operating pressure...

  9. A Practical Bayesian Design to Identify the Maximum Tolerated Dose Contour for Drug Combination Trials

    PubMed Central

    Zhang, Liangcai; Yuan, Ying

    2016-01-01

    Drug combination therapy has become the mainstream approach to cancer treatment. One fundamental feature that makes combination trials different from single-agent trials is the existence of the maximum tolerated dose (MTD) contour, i.e., multiple MTDs. As a result, unlike single-agent phase I trials, which aim to find a single MTD, it is often of interest to find the MTD contour for combination trials. We propose a new dose-finding design, the waterfall design, to find the MTD contour for drug combination trials. Taking the divide-and-conquer strategy, the waterfall design divides the task of finding the MTD contour into a sequence of one-dimensional dose-finding processes, known as subtrials. The subtrials are conducted sequentially in a certain order, such that the results of each subtrial will be used to inform the design of subsequent subtrials. Such information borrowing allows the waterfall design to explore the two-dimensional dose space efficiently using a limited sample size, and decreases the chance of overdosing and underdosing patients. To accommodate the consideration that doses on the MTD contour may have very different efficacy or synergistic effects due to drug-drug interaction, we further extend our approach to a phase I/II design with the goal of finding the MTD with the highest efficacy. Simulation studies show that the waterfall design is safer and has higher probability of identifying the true MTD contour than some existing designs. The R package “BOIN” to implement the waterfall design is freely available from CRAN. PMID:27580928

  10. SU-E-T-578: On Definition of Minimum and Maximum Dose for Target Volume

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

    Gong, Y; Yu, J; Xiao, Y

    Purpose: This study aims to investigate the impact of different minimum and maximum dose definitions in radiotherapy treatment plan quality evaluation criteria by using tumor control probability (TCP) models. Methods: Dosimetric criteria used in RTOG 1308 protocol are used in the investigation. RTOG 1308 is a phase III randomized trial comparing overall survival after photon versus proton chemoradiotherapy for inoperable stage II-IIIB NSCLC. The prescription dose for planning target volume (PTV) is 70Gy. Maximum dose (Dmax) should not exceed 84Gy and minimum dose (Dmin) should not go below 59.5Gy in order for the plan to be “per protocol” (satisfactory).A mathematicalmore » model that simulates the characteristics of PTV dose volume histogram (DVH) curve with normalized volume is built. The Dmax and Dmin are noted as percentage volumes Dη% and D(100-δ)%, with η and d ranging from 0 to 3.5. The model includes three straight line sections and goes through four points: D95%= 70Gy, Dη%= 84Gy, D(100-δ)%= 59.5 Gy, and D100%= 0Gy. For each set of η and δ, the TCP value is calculated using the inhomogeneously irradiated tumor logistic model with D50= 74.5Gy and γ50=3.52. Results: TCP varies within 0.9% with η; and δ values between 0 and 1. With η and η varies between 0 and 2, TCP change was up to 2.4%. With η and δ variations from 0 to 3.5, maximum of 8.3% TCP difference is seen. Conclusion: When defined maximum and minimum volume varied more than 2%, significant TCP variations were seen. It is recommended less than 2% volume used in definition of Dmax or Dmin for target dosimetric evaluation criteria. This project was supported by NIH grants U10CA180868, U10CA180822, U24CA180803, U24CA12014 and PA CURE Grant.« less

  11. Gastrointestinal safety and tolerance of ibuprofen at maximum over-the-counter dose.

    PubMed

    Doyle, G; Furey, S; Berlin, R; Cooper, S; Jayawardena, S; Ashraf, E; Baird, L

    1999-07-01

    Delineation of non-steroidal anti-inflammatory drug (NSAID) gastrointestinal toxicity has largely depended on retrospective epidemiologic studies which demonstrate that lower doses of NSAIDs pose a lower risk of gastrointestinal toxicity. Ibuprofen, a propionic acid NSAID, has, in most such studies, exhibited a favourable profile in terms of gastrointestinal bleeding. Since 1984, ibuprofen has been available as a non-prescription analgesic/antipyretic with a limit of 1200 mg/day for 10 days of continuous use. Trials and spontaneously reported adverse experiences suggest that gastrointestinal symptoms and bleeding are rare. This study prospectively evaluated the gastrointestinal tolerability, as compared to placebo, of the maximum non-prescription dose and duration of ibuprofen use in healthy subjects representative of a non-prescription analgesic user population. Gastrointestinal adverse experiences were similar in the placebo and ibuprofen groups (67 out of 413, 16% with placebo vs. 161 out of 833, 19% with ibuprofen). There was no difference between the two groups in the proportion discontinuing due to a gastrointestinal event. Gastrointestinal adverse experiences reported by >/= 1% of subjects were: dyspepsia, abdominal pain, nausea, diarrhoea, flatulence, and constipation. Seventeen (1.4%) subjects had positive occult blood tests: their frequency was comparable between treatments. When used as directed to treat episodic pain, non-prescription ibuprofen at the maximum dose of 1200 mg/day for 10 days, is well-tolerated.

  12. Implied Maximum Dose Analysis of Standard Values of 25 Pesticides Based on Major Human Exposure Pathways

    PubMed Central

    Li, Zijian; Jennings, Aaron A.

    2017-01-01

    Worldwide jurisdictions are making efforts to regulate pesticide standard values in residential soil, drinking water, air, and agricultural commodity to lower the risk of pesticide impacts on human health. Because human may exposure to pesticides from many ways, such as ingestion, inhalation, and dermal contact, it is important to examine pesticide standards by considering all major exposure pathways. Analysis of implied maximum dose limits for commonly historical and current used pesticides was adopted in this study to examine whether worldwide pesticide standard values are enough to prevent human health impact or not. Studies show that only U.S. has regulated pesticides standard in the air. Only 4% of the total number of implied maximum dose limits is based on three major exposures. For Chlorpyrifos, at least 77.5% of the total implied maximum dose limits are above the acceptable daily intake. It also shows that most jurisdictions haven't provided pesticide standards in all major exposures yet, and some of the standards are not good enough to protect human health. PMID:29546224

  13. 42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...-emergency use of the emergency room. For Federal FY 2009, for targeted low-income children whose household...-institutional services, up to a maximum amount of $11.35 for services furnished in a hospital emergency room if... 42 Public Health 4 2013-10-01 2013-10-01 false Maximum allowable cost-sharing charges on targeted...

  14. 42 CFR 457.555 - Maximum allowable cost-sharing charges on targeted low-income children in families with income...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...-emergency use of the emergency room. For Federal FY 2009, for targeted low-income children whose household...-institutional services, up to a maximum amount of $11.35 for services furnished in a hospital emergency room if... 42 Public Health 4 2014-10-01 2014-10-01 false Maximum allowable cost-sharing charges on targeted...

  15. Cefixime allows greater dose escalation of oral irinotecan: a phase I study in pediatric patients with refractory solid tumors.

    PubMed

    Furman, Wayne L; Crews, Kristine R; Billups, Catherine; Wu, Jianrong; Gajjar, Amar J; Daw, Najat C; Patrick, Christian C; Rodriguez-Galindo, Carlos; Stewart, Clinton F; Dome, Jeffrey S; Panetta, John C; Houghton, Peter J; Santana, Victor M

    2006-02-01

    Irinotecan is active against a variety of malignancies; however, severe diarrhea limits its usefulness. In our phase I study, the intravenous formulation of irinotecan was administered orally daily for 5 days for 2 consecutive weeks (repeated every 21 days) to children with refractory solid tumors. Our objectives were to determine the maximum-tolerated dose (MTD), dose-limiting toxicity, and pharmacokinetics of oral irinotecan and to evaluate whether coadministration of cefixime (8 mg/kg/d beginning 5 days before irinotecan and continuing throughout the course) ameliorates irinotecan-induced diarrhea. In separate cohorts, irinotecan doses were escalated from 15 to 45 mg/m2/d without cefixime and then from 45 to 60 and 75 mg/m2/d with cefixime. Without cefixime, diarrhea was dose limiting at irinotecan 45 mg/m2/d. Myelotoxicity was not significant at any dose. The MTD was 40 mg/m2/d without cefixime but 60 mg/m2/d with cefixime. Systemic exposure to SN-38 at the MTD was significantly higher with cefixime than without cefixime (mean SN-38 area under the curve: 19.5 ng x h/mL; standard deviation [SD], 6.8 ng x h/mL v 10.4 ng x h/mL; SD, 4.3 ng x h/mL, respectively; P = .030). Cefixime administered with oral irinotecan is well tolerated in children and allows greater dose escalation of irinotecan. Because diarrhea is a major adverse effect of both intravenous and oral irinotecan, further evaluation of the use of cefixime to ameliorate this adverse effect is warranted.

  16. 40 CFR Appendix B to Subpart II to... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 10 2010-07-01 2010-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II to Part 63 Protection of...—Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density EC01MY92.046 ...

  17. 40 CFR Appendix B to Subpart II to... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 11 2012-07-01 2012-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II to Part 63 Protection of...—Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density EC01MY92.046 ...

  18. 40 CFR Appendix B to Subpart II of... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 11 2014-07-01 2014-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II of Part 63 Protection of...—Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density EC01MY92.046 ...

  19. Toxicological approach to setting spacecraft maximum allowable concentrations for carbon monoxide

    NASA Technical Reports Server (NTRS)

    Wong, K. L.; Limero, T. F.; James, J. T.

    1992-01-01

    The Spacecraft Maximum Allowable Concentrations (SMACs) are exposure limits for airborne chemicals used by NASA in spacecraft. The aim of these SMACs is to protect the spacecrew against adverse health effects and performance decrements that would interfere with mission objectives. Because of the 1 and 24 hr SMACs are set for contingencies, minor reversible toxic effects that do not affect mission objectives are acceptable. The 7, 30, or 180 day SMACs are aimed at nominal operations, so they are established at levels that would not cause noncarcinogenic toxic effects and more than one case of tumor per 1000 exposed individuals over the background. The process used to set the SMACs for carbon monoxide (CO) is described to illustrate the approach used by NASA. After the toxicological literature on CO was reviewed, the data were summarized and separated into acute, subchronic, and chronic toxicity data. CO's toxicity depends on the formation of carboxyhemoglobin (COHb) in the blood, reducing the blood's oxygen carrying capacity. The initial task was to estimate the COHb levels that would not produce toxic effects in the brain and heart.

  20. Rainfall Threshold Assessment Corresponding to the Maximum Allowable Turbidity for Source Water.

    PubMed

    Fan, Shu-Kai S; Kuan, Wen-Hui; Fan, Chihhao; Chen, Chiu-Yang

    2016-12-01

      This study aims to assess the upstream rainfall thresholds corresponding to the maximum allowable turbidity of source water, using monitoring data and artificial neural network computation. The Taipei Water Source Domain was selected as the study area, and the upstream rainfall records were collected for statistical analysis. Using analysis of variance (ANOVA), the cumulative rainfall records of one-day Ping-lin, two-day Ping-lin, two-day Tong-hou, one-day Guie-shan, and one-day Tai-ping (rainfall in the previous 24 or 48 hours at the named weather stations) were found to be the five most significant parameters for downstream turbidity development. An artificial neural network model was constructed to predict the downstream turbidity in the area investigated. The observed and model-calculated turbidity data were applied to assess the rainfall thresholds in the studied area. By setting preselected turbidity criteria, the upstream rainfall thresholds for these statistically determined rain gauge stations were calculated.

  1. Estimation of maximum tolerated dose for long-term bioassays from acute lethal dose and structure by QSAR

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

    Gombar, V.K.; Enslein, K.; Hart, J.B.

    1991-09-01

    A quantitative structure-activity relationship (QSAR) model has been developed to estimate maximum tolerated doses (MTD) from structural features of chemicals and the corresponding oral acute lethal doses (LD50) as determined in male rats. The model is based on a set of 269 diverse chemicals which have been tested under the National Cancer Institute/National Toxicology Program (NCI/NTP) protocols. The rat oral LD50 value was the strongest predictor. Additionally, 22 structural descriptors comprising nine substructural MOLSTAC(c) keys, three molecular connectivity indices, and sigma charges on 10 molecular fragments were identified as endpoint predictors. The model explains 76% of the variance and ismore » significant (F = 35.7) at p less than 0.0001 with a standard error of the estimate of 0.40 in the log (1/mol) units used in Hansch-type equations. Cross-validation showed that the difference between the average deleted residual square (0.179) and the model residual square (0.160) was not significant (t = 0.98).« less

  2. The Maximum Free Magnetic Energy Allowed in a Solar Active Region

    NASA Technical Reports Server (NTRS)

    Moore, Ronald L.; Falconer, David A.

    2009-01-01

    Two whole-active-region magnetic quantities that can be measured from a line-of-sight magnetogram are (sup L) WL(sub SG), a gauge of the total free energy in an active region's magnetic field, and sup L(sub theta), a measure of the active region's total magnetic flux. From these two quantities measured from 1865 SOHO/MDI magnetograms that tracked 44 sunspot active regions across the 0.5 R(sub Sun) central disk, together with each active region's observed production of CMEs, X flares, and M flares, Falconer et al (2009, ApJ, submitted) found that (1) active regions have a maximum attainable free magnetic energy that increases with the magnetic size (sup L) (sub theta) of the active region, (2) in (Log (sup L)WL(sub SG), Log(sup L) theta) space, CME/flare-productive active regions are concentrated in a straight-line main sequence along which the free magnetic energy is near its upper limit, and (3) X and M flares are restricted to large active regions. Here, from (a) these results, (b) the observation that even the greatest X flares produce at most only subtle changes in active region magnetograms, and (c) measurements from MSFC vector magnetograms and from MDI line-of-sight magnetograms showing that practically all sunspot active regions have nearly the same area-averaged magnetic field strength: =- theta/A approximately equal to 300 G, where theta is the active region's total photospheric flux of field stronger than 100 G and A is the area of that flux, we infer that (1) the maximum allowed ratio of an active region's free magnetic energy to its potential-field energy is 1, and (2) any one CME/flare eruption releases no more than a small fraction (less than 10%) of the active region's free magnetic energy. This work was funded by NASA's Heliophysics Division and NSF's Division of Atmospheric Sciences.

  3. Evaluating the efficacies of Maximum Tolerated Dose and metronomic chemotherapies: A mathematical approach

    NASA Astrophysics Data System (ADS)

    Guiraldello, Rafael T.; Martins, Marcelo L.; Mancera, Paulo F. A.

    2016-08-01

    We present a mathematical model based on partial differential equations that is applied to understand tumor development and its response to chemotherapy. Our primary aim is to evaluate comparatively the efficacies of two chemotherapeutic protocols, Maximum Tolerated Dose (MTD) and metronomic, as well as two methods of drug delivery. Concerning therapeutic outcomes, the metronomic protocol proves more effective in prolonging the patient's life than MTD. Moreover, a uniform drug delivery method combined with the metronomic protocol is the most efficient strategy to reduce tumor density.

  4. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose (MTD) in Future Studies.

    PubMed

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2015-07-01

    High doses in Tg.rasH2 carcinogenicity studies are usually set at the maximum tolerated dose (MTD), although this dose selection strategy has not been critically evaluated. We analyzed the body weight gains (BWGs), mortality, and tumor response in control and treated groups of 29 Tg.rasH2 studies conducted at BioReliance. Based on our analysis, it is evident that the MTD was exceeded at the high and/or mid-doses in several studies. The incidence of tumors in high doses was lower when compared to the low and mid-doses of both sexes. Thus, we recommend that the high dose in male mice should not exceed one-half of the estimated MTD (EMTD), as it is currently chosen, and the next dose should be one-fourth of the EMTD. Because females were less sensitive to decrements in BWG, the high dose in female mice should not exceed two-third of EMTD and the next dose group should be one-third of EMTD. If needed, a third dose group should be set at one-eighth EMTD in males and one-sixth EMTD in females. In addition, for compounds that do not show toxicity in the range finding studies, a limit dose should be applied for the 26-week carcinogenicity studies. © 2014 by The Author(s).

  5. Dexmedetomidine inhibits activation of the MAPK pathway and protects PC12 and NG108-15 cells from lidocaine-induced cytotoxicity at its maximum safe dose.

    PubMed

    Wang, Qiong; Tan, Yonghong; Zhang, Na; Xu, Yingyi; Wei, Wei; She, Yingjun; Bi, Xiaobao; Zhao, Baisong; Ruan, Xiangcai

    2017-07-01

    The developing brains of pediatric patients are highly vulnerable to anesthetic regimen (e.g., lidocaine), potentially causing neurological impairment. Recently, dexmedetomidine (DEX) has been used as an adjunct for sedation, and was shown to exert dose-dependent neuroprotective effects during brain injury. However, the maximum safe dose of DEX is unclear, and its protective effects against lidocaine-related neurotoxicity need to be confirmed. In this study, PC12 and NG108-15 cells were used to estimate safe, non-cytotoxic doses of DEX. We found that 100 and 60μM are the maximum safe dose of DEX for PC12 and NG108-15 cells, respectively, with no significant cytotoxicity. Lidocaine was found to remarkably inhibit cell vitality, but could be reversed by different doses of DEX, especially its maximum safe dose. Furthermore, the apoptosis induced by lidocaine was also assessed, and 100 and 60μM DEX showed optimal protective effects in PC12 and NG108-15 cells, respectively. Mechanistically, DEX activated the mitogen-activated protein kinase (MAPK) pathway, impaired caspase-3 expression, and enhanced anti-apoptotic factor Bcl-2 to resist lidocaine-induced apoptosis, indicating that the optimal dose of DEX alleviates lidocaine-induced cytotoxicity and should be considered in clinical application. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  6. Effective chemotherapy of heterogeneous and drug-resistant early colon cancers by intermittent dose schedules: a computer simulation study.

    PubMed

    Axelrod, David E; Vedula, Sudeepti; Obaniyi, James

    2017-05-01

    The effectiveness of cancer chemotherapy is limited by intra-tumor heterogeneity, the emergence of spontaneous and induced drug-resistant mutant subclones, and the maximum dose to which normal tissues can be exposed without adverse side effects. The goal of this project was to determine if intermittent schedules of the maximum dose that allows colon crypt maintenance could overcome these limitations, specifically by eliminating mixtures of drug-resistant mutants from heterogeneous early colon adenomas while maintaining colon crypt function. A computer model of cell dynamics in human colon crypts was calibrated with measurements of human biopsy specimens. The model allowed simulation of continuous and intermittent dose schedules of a cytotoxic chemotherapeutic drug, as well as the drug's effect on the elimination of mutant cells and the maintenance of crypt function. Colon crypts can tolerate a tenfold greater intermittent dose than constant dose. This allows elimination of a mixture of relatively drug-sensitive and drug-resistant mutant subclones from heterogeneous colon crypts. Mutants can be eliminated whether they arise spontaneously or are induced by the cytotoxic drug. An intermittent dose, at the maximum that allows colon crypt maintenance, can be effective in eliminating a heterogeneous mixture of mutant subclones before they fill the crypt and form an adenoma.

  7. Feasibility study of stereotactic body radiotherapy for peripheral lung tumors with a maximum dose of 100 Gy in five fractions and a heterogeneous dose distribution in the planning target volume.

    PubMed

    Takeda, Atsuya; Oku, Yohei; Sanuki, Naoko; Eriguchi, Takahisa; Aoki, Yousuke; Enomoto, Tatsuji; Kaneko, Takeshi; Nishimura, Shuichi; Kunieda, Etsuo

    2014-09-01

    We evaluated toxicity and outcomes for patients with peripheral lung tumors treated with stereotactic body radiation therapy (SBRT) in a dose-escalation and dose-convergence study. A total of 15 patients were enrolled. SBRT was performed with 60 Gy in 5 fractions (fr.) prescribed to the 60% isodose line of maximum dose, which was 100 Gy in 5 fr., covering the planning target volume (PTV) surface (60 Gy/5 fr. - (60%-isodose)) using dynamic conformal multiple arc therapy (DCMAT). The primary endpoint was radiation pneumonitis (RP) ≥ Grade 2 within 6 months. Toxicities were graded according to the Common Terminology Criteria for Adverse Events, version 4.0. Using dose-volumetric analysis, the trial regimen of 60 Gy/5 fr. - (60%-isodose) was compared with our institutional conventional regimen of 50 Gy/5 fr. - (80%-isodose). The enrolled consecutive patients had either a solitary peripheral tumor or two ipsilateral tumors. The median follow-up duration was 22.0 (12.0-27.0) months. After 6 months post-SBRT, the respective number of RP Grade 0, 1 and 2 cases was 5, 9 and 1. In the Grade 2 RP patient, the image showed an organizing pneumonia pattern at 6.0 months post-SBRT. No other toxicity was found. At last follow-up, there was no evidence of recurrence of the treated tumors. The target volumes of 60 Gy/ 5 fr. - (60%-isodose) were irradiated with a significantly higher dose than those of 50 Gy/5 fr. - (80%-isodose), while the former dosimetric parameters of normal lung were almost equivalent to the latter. SBRT with 60 Gy/5 fr. - (60%-isodose) using DCMAT allowed the delivery of very high and convergent doses to peripheral lung tumors with feasibility in the acute and subacute phases. Further follow-up is required to assess for late toxicity. © The Author 2014. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

  8. Method of predicting the mean lung dose based on a patient's anatomy and dose-volume histograms

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

    Zawadzka, Anna, E-mail: a.zawadzka@zfm.coi.pl; Nesteruk, Marta; Department of Radiation Oncology, University Hospital Zurich and University of Zurich, Zurich

    The aim of this study was to propose a method to predict the minimum achievable mean lung dose (MLD) and corresponding dosimetric parameters for organs-at-risk (OAR) based on individual patient anatomy. For each patient, the dose for 36 equidistant individual multileaf collimator shaped fields in the treatment planning system (TPS) was calculated. Based on these dose matrices, the MLD for each patient was predicted by the homemade DosePredictor software in which the solution of linear equations was implemented. The software prediction results were validated based on 3D conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) plans previously prepared formore » 16 patients with stage III non–small-cell lung cancer (NSCLC). For each patient, dosimetric parameters derived from plans and the results calculated by DosePredictor were compared. The MLD, the maximum dose to the spinal cord (D{sub max} {sub cord}) and the mean esophageal dose (MED) were analyzed. There was a strong correlation between the MLD calculated by the DosePredictor and those obtained in treatment plans regardless of the technique used. The correlation coefficient was 0.96 for both 3D-CRT and VMAT techniques. In a similar manner, MED correlations of 0.98 and 0.96 were obtained for 3D-CRT and VMAT plans, respectively. The maximum dose to the spinal cord was not predicted very well. The correlation coefficient was 0.30 and 0.61 for 3D-CRT and VMAT, respectively. The presented method allows us to predict the minimum MLD and corresponding dosimetric parameters to OARs without the necessity of plan preparation. The method can serve as a guide during the treatment planning process, for example, as initial constraints in VMAT optimization. It allows the probability of lung pneumonitis to be predicted.« less

  9. Regulatory Forum Opinion Piece*: Retrospective Evaluation of Doses in the 26-week Tg.rasH2 Mice Carcinogenicity Studies: Recommendation to Eliminate High Doses at Maximum Tolerated Dose in Future Studies. A Response to the Counterpoints.

    PubMed

    Paranjpe, Madhav G; Denton, Melissa D; Vidmar, Tom J; Elbekai, Reem H

    2016-01-01

    We recently conducted a retrospective analysis of data collected from 29 Tg.rasH2 carcinogenicity studies conducted at our facility to determine how successful was the strategy of choosing the high dose of the 26-week studies based on an estimated maximum tolerated dose (MTD). As a result of our publication, 2 counterviews were expressed. Both counterviews illustrate very valid points in their interpretation of our data. In this article, we would like to highlight clarifications based on several points and issues they have raised in their papers, namely, the dose-level selection, determining if MTD was exceeded in 26-week studies, and a discussion on the number of dose groups to be used in the studies. © The Author(s) 2015.

  10. Pretreatment with a single, low dose of recombinant human thyrotropin allows dose reduction of radioiodine therapy in patients with nodular goiter.

    PubMed

    Nieuwlaat, Willy-Anne; Huysmans, Dyde A; van den Bosch, Harrie C; Sweep, C G Fred; Ross, H Alec; Corstens, Frans H; Hermus, Ad R

    2003-07-01

    In patients with nodular goiter, radioiodine ((131)I) therapy results in a mean reduction in thyroid volume (TV) of approximately 40% after 1 yr. We have demonstrated that pretreatment with a single, low dose of recombinant human TSH (rhTSH) doubles 24-h radioactive iodine uptake (RAIU) in these patients. We have now studied the safety and efficacy of therapy with a reduced dose of (131)I after pretreatment with rhTSH. Twenty-two patients with nodular goiter received (131)I therapy, 24 h after im administration of 0.01 (n = 12) or 0.03 (n = 10) mg rhTSH. In preceding diagnostic studies using tracer doses of (131)I, 24-h RAIU without and with rhTSH pretreatment (either 0.01 or 0.03 mg) were compared. Therapeutic doses of (131)I were adjusted to the rhTSH-induced increases in 24-h RAIU and were aimed at 100 micro Ci/g thyroid tissue retained at 24 h. Pretreatment with rhTSH allowed dose reduction of (131)I therapy by a factor of 1.9 +/- 0.5 in the 0.01-mg and by a factor of 2.4 +/- 0.4 in the 0.03-mg rhTSH group (P < 0.05, 0.01 vs. 0.03 mg rhTSH). Before and 1 yr after therapy, TV and the smallest cross-sectional area of the tracheal lumen were measured with magnetic resonance imaging. During the year of follow-up, serum TSH, free T(4) (FT(4)), T(3), and TSH receptor antibodies were measured at regular intervals. TV before therapy was 143 +/- 54 ml in the 0.01-mg group and 103 +/- 44 ml in the 0.03-mg rhTSH group. One year after treatment, TV reduction was 35 +/- 14% (0.01 mg rhTSH) and 41 +/- 12% (0.03 mg rhTSH). In both groups, smallest cross-sectional area of the tracheal lumen increased significantly. In the 0.01-mg rhTSH group, serum FT(4) rose, after (131)I treatment, from 15.8 +/- 2.8 to 23.2 +/- 4.4 pM. In the 0.03-mg rhTSH group, serum FT(4) rose from 15.5 +/- 2.5 to 23.5 +/- 5.1 pM. Individual peak FT(4) levels, reached between 1 and 28 d after (131)I treatment, were above the normal range in 12 patients. TSH receptor antibodies were negative in all

  11. A novel ultrafast-low-dose computed tomography protocol allows concomitant coronary artery evaluation and lung cancer screening.

    PubMed

    Gaudio, Carlo; Petriello, Gennaro; Pelliccia, Francesco; Tanzilli, Alessandra; Bandiera, Alberto; Tanzilli, Gaetano; Barillà, Francesco; Paravati, Vincenzo; Pellegrini, Massimo; Mangieri, Enrico; Barillari, Paolo

    2018-05-08

    Cardiac computed tomography (CT) is often performed in patients who are at high risk for lung cancer in whom screening is currently recommended. We tested diagnostic ability and radiation exposure of a novel ultra-low-dose CT protocol that allows concomitant coronary artery evaluation and lung screening. We studied 30 current or former heavy smoker subjects with suspected or known coronary artery disease who underwent CT assessment of both coronary arteries and thoracic area (Revolution CT, General Electric). A new ultrafast-low-dose single protocol was used for ECG-gated helical acquisition of the heart and the whole chest. A single IV iodine bolus (70-90 ml) was used. All patients with CT evidence of coronary stenosis underwent also invasive coronary angiography. All the coronary segments were assessable in 28/30 (93%) patients. Only 8 coronary segments were not assessable in 2 patients due to motion artefacts (assessability: 98%; 477/485 segments). In the assessable segments, 20/21 significant stenoses (> 70% reduction of vessel diameter) were correctly diagnosed. Pulmonary nodules were detected in 5 patients, thus requiring to schedule follow-up surveillance CT thorax. Effective dose was 1.3 ± 0.9 mSv (range: 0.8-3.2 mSv). Noteworthy, no contrast or radiation dose increment was required with the new protocol as compared to conventional coronary CT protocol. The novel ultrafast-low-dose CT protocol allows lung cancer screening at time of coronary artery evaluation. The new approach might enhance the cost-effectiveness of coronary CT in heavy smokers with suspected or known coronary artery disease.

  12. Main clinical, therapeutic and technical factors related to patient's maximum skin dose in interventional cardiology procedures

    PubMed Central

    Journy, N; Sinno-Tellier, S; Maccia, C; Le Tertre, A; Pirard, P; Pagès, P; Eilstein, D; Donadieu, J; Bar, O

    2012-01-01

    Objective The study aimed to characterise the factors related to the X-ray dose delivered to the patient's skin during interventional cardiology procedures. Methods We studied 177 coronary angiographies (CAs) and/or percutaneous transluminal coronary angioplasties (PTCAs) carried out in a French clinic on the same radiography table. The clinical and therapeutic characteristics, and the technical parameters of the procedures, were collected. The dose area product (DAP) and the maximum skin dose (MSD) were measured by an ionisation chamber (Diamentor; Philips, Amsterdam, The Netherlands) and radiosensitive film (Gafchromic; International Specialty Products Advanced Materials Group, Wayne, NJ). Multivariate analyses were used to assess the effects of the factors of interest on dose. Results The mean MSD and DAP were respectively 389 mGy and 65 Gy cm−2 for CAs, and 916 mGy and 69 Gy cm−2 for PTCAs. For 8% of the procedures, the MSD exceeded 2 Gy. Although a linear relationship between the MSD and the DAP was observed for CAs (r=0.93), a simple extrapolation of such a model to PTCAs would lead to an inadequate assessment of the risk, especially for the highest dose values. For PTCAs, the body mass index, the therapeutic complexity, the fluoroscopy time and the number of cine frames were independent explanatory factors of the MSD, whoever the practitioner was. Moreover, the effect of technical factors such as collimation, cinematography settings and X-ray tube orientations on the DAP was shown. Conclusion Optimising the technical options for interventional procedures and training staff on radiation protection might notably reduce the dose and ultimately avoid patient skin lesions. PMID:22457404

  13. Comparison of measured and estimated maximum skin doses during CT fluoroscopy lung biopsies.

    PubMed

    Zanca, F; Jacobs, A; Crijns, W; De Wever, W

    2014-07-01

    To measure patient-specific maximum skin dose (MSD) associated with CT fluoroscopy (CTF) lung biopsies and to compare measured MSD with the MSD estimated from phantom measurements, as well as with the CTDIvol of patient examinations. Data from 50 patients with lung lesions who underwent a CT fluoroscopy-guided biopsy were collected. The CT protocol consisted of a low-kilovoltage (80 kV) protocol used in combination with an algorithm for dose reduction to the radiology staff during the interventional procedure, HandCare (HC). MSD was assessed during each intervention using EBT2 gafchromic films positioned on patient skin. Lesion size, position, total fluoroscopy time, and patient-effective diameter were registered for each patient. Dose rates were also estimated at the surface of a normal-size anthropomorphic thorax phantom using a 10 cm pencil ionization chamber placed at every 30°, for a full rotation, with and without HC. Measured MSD was compared with MSD values estimated from the phantom measurements and with the cumulative CTDIvol of the procedure. The median measured MSD was 141 mGy (range 38-410 mGy) while the median cumulative CTDIvol was 72 mGy (range 24-262 mGy). The ratio between the MSD estimated from phantom measurements and the measured MSD was 0.87 (range 0.12-4.1) on average. In 72% of cases the estimated MSD underestimated the measured MSD, while in 28% of the cases it overestimated it. The same trend was observed for the ratio of cumulative CTDIvol and measured MSD. No trend was observed as a function of patient size. On average, estimated MSD from dose rate measurements on phantom as well as from CTDIvol of patient examinations underestimates the measured value of MSD. This can be attributed to deviations of the patient's body habitus from the standard phantom size and to patient positioning in the gantry during the procedure.

  14. Acute administration of tramadol and tapentadol at effective analgesic and maximum tolerated doses causes hepato- and nephrotoxic effects in Wistar rats.

    PubMed

    Barbosa, Joana; Faria, Juliana; Leal, Sandra; Afonso, Luís Pedro; Lobo, João; Queirós, Odília; Moreira, Roxana; Carvalho, Félix; Dinis-Oliveira, Ricardo Jorge

    2017-08-15

    Tramadol and tapentadol are two atypical synthetic opioid analgesics, with monoamine reuptake inhibition properties. Mainly aimed at the treatment of moderate to severe pain, these drugs are extensively prescribed for multiple clinical applications. Along with the increase in their use, there has been an increment in their abuse, and consequently in the reported number of adverse reactions and intoxications. However, little is known about their mechanisms of toxicity. In this study, we have analyzed the in vivo toxicological effects in liver and kidney resulting from an acute exposure of a rodent animal model to both opioids. Male Wistar rats were intraperitoneally administered with 10, 25 and 50mg/kg tramadol and tapentadol, corresponding to a low, effective analgesic dose, an intermediate dose and the maximum recommended daily dose, respectively, for 24h. Toxicological effects were assessed in terms of oxidative stress, biochemical and metabolic parameters and histopathology, using serum and urine samples, liver and kidney homogenates and tissue specimens. The acute exposure to tapentadol caused a dose-dependent increase in protein oxidation in liver and kidney. Additionally, exposure to both opioids led to hepatic commitment, as shown by increased serum lipid levels, decreased urea concentration, increased alanine aminotransferase and decreased butyrylcholinesterase activities. It also led to renal impairment, as reflected by proteinuria and decreased glomerular filtration rate. Histopathological findings included sinusoidal dilatation, microsteatosis, vacuolization, cell infiltrates and cell degeneration, indicating metabolic changes, inflammation and cell damage. In conclusion, a single effective analgesic dose or the maximum recommended daily dose of both opioids leads to hepatotoxicity and nephrotoxicity, with tapentadol inducing comparatively more toxicity. Whether these effects reflect risks during the therapeutic use or human overdoses requires focused

  15. Maximum dose angle for oblique incidence on primary beam protective barriers in the design of medical radiation therapy facilities.

    PubMed

    Fondevila, Damián; Arbiser, Silvio; Sansogne, Rosana; Brunetto, Mónica; Dosoretz, Bernardo

    2008-05-01

    Primary barrier determinations for the shielding of medical radiation therapy facilities are generally made assuming normal beam incidence on the barrier, since this is geometrically the most unfavorable condition for that shielding barrier whenever the occupation line is allowed to run along the barrier. However, when the occupation line (for example, the wall of an adjacent building) runs perpendicular to the barrier (especially roof barrier), then two opposing factors come in to play: increasing obliquity angle with respect to the barrier increases the attenuation, while the distance to the calculation point decreases, hence, increasing the dose. As a result, there exists an angle (alpha(max)) for which the equivalent dose results in a maximum, constituting the most unfavorable geometric condition for that shielding barrier. Based on the usual NCRP Report No. 151 model, this article presents a simple formula for obtaining alpha(max), which is a function of the thickness of the barrier (t(E)) and the equilibrium tenth-value layer (TVL(e)) of the shielding material for the nominal energy of the beam. It can be seen that alpha(max) increases for increasing TVL(e) (hence, beam energy) and decreases for increasing t(E), with a range of variation that goes from 13 to 40 deg for concrete barriers thicknesses in the range of 50-300 cm and most commercially available teletherapy machines. This parameter has not been calculated in the existing literature for radiotherapy facilities design and has practical applications, as in calculating the required unoccupied roof shielding for the protection of a nearby building located in the plane of the primary beam rotation.

  16. 40 CFR Appendix B to Subpart II of... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 11 2013-07-01 2013-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II of Part 63 Protection of... Shipbuilding and Ship Repair (Surface Coating) Pt. 63, Subpt. II, App. B Appendix B to Subpart II of Part 63...

  17. 40 CFR Appendix B to Subpart II to... - Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 10 2011-07-01 2011-07-01 false Maximum Allowable Thinning Rates as a Function of As Supplied VOC Content and Thinner Density B Appendix B to Subpart II to Part 63 Protection of... Shipbuilding and Ship Repair (Surface Coating) Pt. 63, Subpt. II, App. B Appendix B to Subpart II to Part 63...

  18. Novel formulation of abiraterone acetate might allow significant dose reduction and eliminates substantial positive food effect.

    PubMed

    Solymosi, Tamás; Ötvös, Zsolt; Angi, Réka; Ordasi, Betti; Jordán, Tamás; Molnár, László; McDermott, John; Zann, Vanessa; Church, Ann; Mair, Stuart; Filipcsei, Genovéva; Heltovics, Gábor; Glavinas, Hristos

    2017-10-01

    Zytiga (abiraterone acetate, AA) is known to exhibit very low bioavailability and a significant positive food effect in men. The unfavorable pharmacokinetic properties are attributed to the inadequate and variable dissolution of the compound. Using a continuous flow precipitation technology, a novel AA formulation has been developed with improved solubility and dissolution characteristics. The current study was performed to evaluate the pharmacokinetics and safety of this novel formulation in healthy volunteers. The study was conducted in 11 healthy men aged 47-57 years. All subjects received 3 consecutive single doses of the novel formulation of AA (100 and 200 mg in the fasted state and 200 mg in the fed state). Data were compared with pharmacokinetic and safety data reported for 1000 mg Zytiga, the marketed drug. The novel formulation of AA allows rapid absorption of the compound with t max values within 1 hour. Based on AUC values, a ~250 mg dose of the novel formulation is predicted to give the same exposure as 1000 mg Zytiga in the fasted state. The significant positive food effect was also eliminated; actually, a slight, but statistically significant negative food effect was observed. Variability of exposure was significantly reduced when compared to Zytiga. AA administered in the novel formulation was well tolerated with no IMP-related safety AEs reported. The novel formulation might allow a 75% dose reduction with significant reduction of inter-individual variability. The negative food effect observed requires further investigations; however, elimination of the significant positive food effect could be adequate to negate the restriction of a food label.

  19. 42 CFR 50.504 - Allowable cost of drugs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Allowable cost of drugs. 50.504 Section 50.504... APPLICABILITY Maximum Allowable Cost for Drugs § 50.504 Allowable cost of drugs. (a) The maximum amount which may be expended from program funds for the acquisition of any drug shall be the lowest of (1) The...

  20. 42 CFR 50.504 - Allowable cost of drugs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Allowable cost of drugs. 50.504 Section 50.504... APPLICABILITY Maximum Allowable Cost for Drugs § 50.504 Allowable cost of drugs. (a) The maximum amount which may be expended from program funds for the acquisition of any drug shall be the lowest of (1) The...

  1. 42 CFR 50.504 - Allowable cost of drugs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Allowable cost of drugs. 50.504 Section 50.504... APPLICABILITY Maximum Allowable Cost for Drugs § 50.504 Allowable cost of drugs. (a) The maximum amount which may be expended from program funds for the acquisition of any drug shall be the lowest of (1) The...

  2. 42 CFR 50.504 - Allowable cost of drugs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Allowable cost of drugs. 50.504 Section 50.504... APPLICABILITY Maximum Allowable Cost for Drugs § 50.504 Allowable cost of drugs. (a) The maximum amount which may be expended from program funds for the acquisition of any drug shall be the lowest of (1) The...

  3. [MAXIMUM SINGLE DOSE OF COLLOIDAL SILVER NEGATIVELY AFFECTS ERYTHROPOIESIS IN VITRO].

    PubMed

    Tishevskayal, N V; Zakharovl, Y M; Bolotovl, A A; Arkhipenko, Yu V; Sazontova, T G

    2015-01-01

    Erythroblastic islets (EI) of rat bone marrow were cultured for 24 h in the presence of silver nanoparticles (1.07 · 10(-4) mg/ml; 1.07 · 10(-3) mg/ml; and 1.07 · 10(-2) mg/mL). The colloidal silver at 1.07 · 10(-3) mg/ml concentration inhibited the formation of new Elby disrupting contacts of bone marrow macrophages with CFU-E (erythropoiesis de novo) by 65.3% (p < 0.05). Colloidal silver nanoparticles suppressed the reconstruction of erythropoiesis and inhibited the formation of new EI by disrupting contacts of CFU-E and central macrophages with matured erythroidal "crown" (erythropoiesis de repeto). The colloidal silver concentration of 1.07 · 10(-3) mg/ml in the culture medium also reduced the number of self-reconstructing EI by 67.5% (p <0.05), whereas 1.07 · 10(-2) mg/ml colloidal silver reduced this value by 93.7% (p < 0.05). Silver nanoparticles retarded maturation of erythroid cells at the stage of oxiphylic normoblast denucleation: 1.07 · 10(-3) mg/ml colloidal silver increased the number of mature El by 53% (p < 0.05). The retardation of erythropoiesis by colloidal silver in concentration equivalent to the maximum single dose is related to the effect of silver nanoparticles rather than glycerol present in the colloidal suspension.

  4. SU-E-T-280: Reconstructed Rectal Wall Dose Map-Based Verification of Rectal Dose Sparing Effect According to Rectum Definition Methods and Dose Perturbation by Air Cavity in Endo-Rectal Balloon

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

    Park, J; Research Institute of Biomedical Engineering, The Catholic University of Korea, Seoul; Park, H

    Purpose: Dosimetric effect and discrepancy according to the rectum definition methods and dose perturbation by air cavity in an endo-rectal balloon (ERB) were verified using rectal-wall (Rwall) dose maps considering systematic errors in dose optimization and calculation accuracy in intensity-modulated radiation treatment (IMRT) for prostate cancer patients. Methods: When the inflated ERB having average diameter of 4.5 cm and air volume of 100 cc is used for patient, Rwall doses were predicted by pencil-beam convolution (PBC), anisotropic analytic algorithm (AAA), and AcurosXB (AXB) with material assignment function. The errors of dose optimization and calculation by separating air cavity from themore » whole rectum (Rwhole) were verified with measured rectal doses. The Rwall doses affected by the dose perturbation of air cavity were evaluated using a featured rectal phantom allowing insert of rolled-up gafchromic films and glass rod detectors placed along the rectum perimeter. Inner and outer Rwall doses were verified with reconstructed predicted rectal wall dose maps. Dose errors and extent at dose levels were evaluated with estimated rectal toxicity. Results: While AXB showed insignificant difference of target dose coverage, Rwall doses underestimated by up to 20% in dose optimization for the Rwhole than Rwall at all dose range except for the maximum dose. As dose optimization for Rwall was applied, the Rwall doses presented dose error less than 3% between dose calculation algorithm except for overestimation of maximum rectal dose up to 5% in PBC. Dose optimization for Rwhole caused dose difference of Rwall especially at intermediate doses. Conclusion: Dose optimization for Rwall could be suggested for more accurate prediction of rectal wall dose prediction and dose perturbation effect by air cavity in IMRT for prostate cancer. This research was supported by the Leading Foreign Research Institute Recruitment Program through the National Research Foundation of

  5. Evaluation of methods for calculating maximum allowable standing height in amputees competing in Paralympic athletics.

    PubMed

    Connick, M J; Beckman, E; Ibusuki, T; Malone, L; Tweedy, S M

    2016-11-01

    The International Paralympic Committee has a maximum allowable standing height (MASH) rule that limits stature to a pre-trauma estimation. The MASH rule reduces the probability that bilateral lower limb amputees use disproportionately long prostheses in competition. Although there are several methods for estimating stature, the validity of these methods has not been compared. To identify the most appropriate method for the MASH rule, this study aimed to compare the criterion validity of estimations resulting from the current method, the Contini method, and four Canda methods (Canda-1, Canda-2, Canda-3, and Canda-4). Stature, ulna length, demispan, sitting height, thigh length, upper arm length, and forearm length measurements in 31 males and 30 females were used to calculate the respective estimation for each method. Results showed that Canda-1 (based on four anthropometric variables) produced the smallest error and best fitted the data in males and females. The current method was associated with the largest error of those tests because it increasingly overestimated height in people with smaller stature. The results suggest that the set of Canda equations provide a more valid MASH estimation in people with a range of upper limb and bilateral lower limb amputations compared with the current method. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  6. 14 CFR 23.1527 - Maximum operating altitude.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Maximum operating altitude. 23.1527 Section... Information § 23.1527 Maximum operating altitude. (a) The maximum altitude up to which operation is allowed... established. (b) A maximum operating altitude limitation of not more than 25,000 feet must be established for...

  7. Can image enhancement allow radiation dose to be reduced whilst maintaining the perceived diagnostic image quality required for coronary angiography?

    PubMed Central

    Joshi, Anuja; Gislason-Lee, Amber J; Keeble, Claire; Sivananthan, Uduvil M

    2017-01-01

    Objective: The aim of this research was to quantify the reduction in radiation dose facilitated by image processing alone for percutaneous coronary intervention (PCI) patient angiograms, without reducing the perceived image quality required to confidently make a diagnosis. Methods: Incremental amounts of image noise were added to five PCI angiograms, simulating the angiogram as having been acquired at corresponding lower dose levels (10–89% dose reduction). 16 observers with relevant experience scored the image quality of these angiograms in 3 states—with no image processing and with 2 different modern image processing algorithms applied. These algorithms are used on state-of-the-art and previous generation cardiac interventional X-ray systems. Ordinal regression allowing for random effects and the delta method were used to quantify the dose reduction possible by the processing algorithms, for equivalent image quality scores. Results: Observers rated the quality of the images processed with the state-of-the-art and previous generation image processing with a 24.9% and 15.6% dose reduction, respectively, as equivalent in quality to the unenhanced images. The dose reduction facilitated by the state-of-the-art image processing relative to previous generation processing was 10.3%. Conclusion: Results demonstrate that statistically significant dose reduction can be facilitated with no loss in perceived image quality using modern image enhancement; the most recent processing algorithm was more effective in preserving image quality at lower doses. Advances in knowledge: Image enhancement was shown to maintain perceived image quality in coronary angiography at a reduced level of radiation dose using computer software to produce synthetic images from real angiograms simulating a reduction in dose. PMID:28124572

  8. Individual dose adjustment of riociguat in patients with pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension.

    PubMed

    Hill, Nicholas S; Rahaghi, Franck F; Sood, Namita; Frey, Reiner; Ghofrani, Hossein-Ardeschir

    2017-08-01

    Riociguat is a soluble guanylate cyclase stimulator that has been approved for the treatment of pulmonary arterial hypertension and inoperable chronic thromboembolic pulmonary hypertension or persistent/recurrent pulmonary hypertension following pulmonary endarterectomy. Riociguat is administered using an 8-week individual dose-adjustment scheme whereby a patient initially receives riociguat 1.0 mg three times daily (tid), and the dose is then increased every 2 weeks in the absence of hypotension, indicated by systolic blood pressure measurements and symptoms, up to a maximum dose of 2.5 mg tid. The established riociguat dose-adjustment scheme allows the dose of riociguat to be individually optimized in terms of tolerability and efficacy. The majority of patients in the phase III clinical trials and their long-term extension phases achieved the maximum riociguat dose, whereas some patients remained on lower doses. There is evidence that these patients may experience benefits at riociguat doses lower than 2.5 mg tid, with improvement in exercise capacity being observed after only 2-4 weeks of treatment in the phase III studies and in the exploratory 1.5 mg-maximum patient group of PATENT-1. This review aims to provide an overview of the rationale behind the riociguat dose-adjustment scheme and examine its application to both clinical trials and real-life clinical practice. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. 14 CFR 27.1527 - Maximum operating altitude.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Maximum operating altitude. 27.1527 Section 27.1527 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... § 27.1527 Maximum operating altitude. The maximum altitude up to which operation is allowed, as limited...

  10. 14 CFR 29.1527 - Maximum operating altitude.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 1 2010-01-01 2010-01-01 false Maximum operating altitude. 29.1527 Section 29.1527 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION AIRCRAFT... Limitations § 29.1527 Maximum operating altitude. The maximum altitude up to which operation is allowed, as...

  11. Colorado SIP: Reg 11, Motor Vehicle Emissions Inspection Program—Part F, Maximum Allowable Emissions Limits for Motor Vehicle Exhaust, Evaporative and Visible Emissions for Light-Duty and Heavy-Duty Vehicles

    EPA Pesticide Factsheets

    Colorado SIP: Reg 11, Motor Vehicle Emissions Inspection Program—Part F, Maximum Allowable Emissions Limits for Motor Vehicle Exhaust, Evaporative and Visible Emissions for Light-Duty and Heavy-Duty Vehicles

  12. 7 CFR 3565.210 - Maximum interest rate.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 15 2010-01-01 2010-01-01 false Maximum interest rate. 3565.210 Section 3565.210... AGRICULTURE GUARANTEED RURAL RENTAL HOUSING PROGRAM Loan Requirements § 3565.210 Maximum interest rate. The interest rate for a guaranteed loan must not exceed the maximum allowable rate specified by the Agency in...

  13. 46 CFR 54.10-5 - Maximum allowable working pressure (reproduces UG-98).

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... section VIII of the ASME Boiler and Pressure Vessel Code, together with the effect of any combination of... operating temperature, using for each temperature the applicable allowable stress value. Note: Table 54.10-5...

  14. Maximum tolerated dose evaluation of the AMPA modulator Org 26576 in healthy volunteers and depressed patients: a summary and method analysis of bridging research in support of phase II dose selection.

    PubMed

    Nations, Kari R; Bursi, Roberta; Dogterom, Peter; Ereshefsky, Larry; Gertsik, Lev; Mant, Tim; Schipper, Jacques

    2012-09-01

    A key challenge to dose selection in early central nervous system (CNS) clinical drug development is that patient tolerability profiles often differ from those of healthy volunteers (HVs), yet HVs are the modal population for determining doses to be investigated in phase II trials. Without clear tolerability data from the target patient population, first efficacy trials may include doses that are either too high or too low, creating undue risk for study participants and the development program overall. Bridging trials address this challenge by carefully investigating safety and tolerability in the target population prior to full-scale proof-of-concept trials. Org 26576 is an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor positive allosteric modulator that acts by modulating ionotropic AMPA-type glutamate receptors to enhance glutamatergic neurotransmission. In preparation for phase II efficacy trials in major depressive disorder (MDD), two separate phase I trials were conducted to evaluate safety, tolerability, and pharmacokinetics in HVs and in the target patient population. Both trials were randomized and placebo controlled, and included multiple rising-dose cohorts (HV range 100-400 mg bid; MDD range 100-600 mg bid). HVs (n = 36) and patients with MDD (n = 54) were dosed under similarly controlled conditions in an inpatient facility, HVs for up to 14 days and MDD patients for up to 28 days. Safety, tolerability, and pharmacokinetics were assessed frequently. Despite comparable pharmacokinetic profiles, the maximum tolerated dose (MTD) in depressed patients was 450 mg bid, twice the MTD established in HVs. No clinically relevant safety issues associated with Org 26576 were noted. This article presents safety, tolerability, and pharmacokinetic data from two different populations examined under similar dosing conditions. The important implications of such bridging work in phase II dose selection are discussed, as are study

  15. IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

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

    Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

    2016-08-01

    Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

  16. SU-G-TeP1-01: A Simulation Study to Investigate Maximum Allowable Deformations of Implant Geometry Before Plan Objectives Are Violated in Prostate HDR Brachytherapy

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

    Babier, A; Joshi, C; Cancer Center of Southeastern Ontario, Kingston General Hospital, Kingston, Ontario

    Purpose: In prostate HDR brachytherapy dose distributions are highly sensitive to changes in prostate volume and catheter displacements. We investigate the maximum deformations in implant geometry before planning objectives are violated. Methods: A typical prostate Ir-192 HDR brachytherapy reference plan was calculated on the Oncentra planning system, which used CT images from a tissue equivalent prostate phantom (CIRS Model 053S) embedded inside a pelvis wax phantom. The prostate was deformed and catheters were displaced in simulations using a code written in MATLAB. For each deformation dose distributions were calculated, based on TG43 methods, using the MATLAB code. The calculations weremore » validated through comparison with Oncentra calculations for the reference plan, and agreed within 0.12%SD and 0.3%SD for dose and volume, respectively. Isotropic prostate volume deformations of up to +34% to −27% relative to its original volume, and longitudinal catheter displacements of 7.5 mm in superior and inferior directions were simulated. Planning objectives were based on American Brachytherapy Society guidelines for prostate and urethra volumes. A plan violated the planning objectives when less than 90% of the prostate volume received the prescribed dose or higher (V{sub 100}), or the urethral volume receiving 125% of prescribed dose or higher was more than 1 cc (U{sub 125}). Lastly, the dose homogeneity index (DHI=1-V{sub 150}/V{sub 100}) was evaluated; a plan was considered sub-optimal when the DHI fell below 0.62. Results and Conclusion: Planning objectives were violated when the prostate expanded by 10.7±0.5% or contracted by 11.0±0.2%; objectives were also violated when catheters were displaced by 4.15±0.15 mm and 3.70±0.15 mm in the superior and inferior directions, respectively. The DHI changes did not affect the plan optimality, except in the case of prostate compression. In general, catheter displacements have a significantly larger impact on plan

  17. Radioiodine therapy of hyperfunctioning thyroid nodules: usefulness of an implemented dose calculation algorithm allowing reduction of radioiodine amount.

    PubMed

    Schiavo, M; Bagnara, M C; Pomposelli, E; Altrinetti, V; Calamia, I; Camerieri, L; Giusti, M; Pesce, G; Reitano, C; Bagnasco, M; Caputo, M

    2013-09-01

    Radioiodine is a common option for treatment of hyperfunctioning thyroid nodules. Due to the expected selective radioiodine uptake by adenoma, relatively high "fixed" activities are often used. Alternatively, the activity is individually calculated upon the prescription of a fixed value of target absorbed dose. We evaluated the use of an algorithm for personalized radioiodine activity calculation, which allows as a rule the administration of lower radioiodine activities. Seventy-five patients with single hyperfunctioning thyroid nodule eligible for 131I treatment were studied. The activities of 131I to be administered were estimated by the method described by Traino et al. and developed for Graves'disease, assuming selective and homogeneous 131I uptake by adenoma. The method takes into account 131I uptake and its effective half-life, target (adenoma) volume and its expected volume reduction during treatment. A comparison with the activities calculated by other dosimetric protocols, and the "fixed" activity method was performed. 131I uptake was measured by external counting, thyroid nodule volume by ultrasonography, thyroid hormones and TSH by ELISA. Remission of hyperthyroidism was observed in all but one patient; volume reduction of adenoma was closely similar to that assumed by our model. Effective half-life was highly variable in different patients, and critically affected dose calculation. The administered activities were clearly lower with respect to "fixed" activities and other protocols' prescription. The proposed algorithm proved to be effective also for single hyperfunctioning thyroid nodule treatment and allowed a significant reduction of administered 131I activities, without loss of clinical efficacy.

  18. Dose and Dose Risk Caused by Natural Phenomena - Proposed Powder Metallurgy Core Manufacturing Facility

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

    Holmes, W.G.

    2001-08-16

    The offsite radiological effects from high velocity straight winds, tornadoes, and earthquakes have been estimated for a proposed facility for manufacturing enriched uranium fuel cores by powder metallurgy. Projected doses range up to 30 mrem/event to the maximum offsite individual for high winds and up to 85 mrem/event for very severe earthquakes. Even under conservative assumptions on meteorological conditions, the maximum offsite dose would be about 20 per cent of the DOE limit for accidents involving enriched uranium storage facilities. The total dose risk is low and is dominated by the risk from earthquakes. This report discusses this test.

  19. Maximum entropy production allows a simple representation of heterogeneity in semiarid ecosystems.

    PubMed

    Schymanski, Stanislaus J; Kleidon, Axel; Stieglitz, Marc; Narula, Jatin

    2010-05-12

    Feedbacks between water use, biomass and infiltration capacity in semiarid ecosystems have been shown to lead to the spontaneous formation of vegetation patterns in a simple model. The formation of patterns permits the maintenance of larger overall biomass at low rainfall rates compared with homogeneous vegetation. This results in a bias of models run at larger scales neglecting subgrid-scale variability. In the present study, we investigate the question whether subgrid-scale heterogeneity can be parameterized as the outcome of optimal partitioning between bare soil and vegetated area. We find that a two-box model reproduces the time-averaged biomass of the patterns emerging in a 100 x 100 grid model if the vegetated fraction is optimized for maximum entropy production (MEP). This suggests that the proposed optimality-based representation of subgrid-scale heterogeneity may be generally applicable to different systems and at different scales. The implications for our understanding of self-organized behaviour and its modelling are discussed.

  20. Evaluation of various approaches for assessing dose indicators and patient organ doses resulting from radiotherapy cone-beam CT

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

    Rampado, Osvaldo, E-mail: orampado@cittadellasalute.to.it; Giglioli, Francesca Romana; Rossetti, Veronica

    Purpose: The aim of this study was to evaluate various approaches for assessing patient organ doses resulting from radiotherapy cone-beam CT (CBCT), by the use of thermoluminescent dosimeter (TLD) measurements in anthropomorphic phantoms, a Monte Carlo based dose calculation software, and different dose indicators as presently defined. Methods: Dose evaluations were performed on a CBCT Elekta XVI (Elekta, Crawley, UK) for different protocols and anatomical regions. The first part of the study focuses on using PCXMC software (PCXMC 2.0, STUK, Helsinki, Finland) for calculating organ doses, adapting the input parameters to simulate the exposure geometry, and beam dose distribution inmore » an appropriate way. The calculated doses were compared to readouts of TLDs placed in an anthropomorphic Rando phantom. After this validation, the software was used for analyzing organ dose variability associated with patients’ differences in size and gender. At the same time, various dose indicators were evaluated: kerma area product (KAP), cumulative air-kerma at the isocenter (K{sub air}), cone-beam dose index, and central cumulative dose. The latter was evaluated in a single phantom and in a stack of three adjacent computed tomography dose index phantoms. Based on the different dose indicators, a set of coefficients was calculated to estimate organ doses for a range of patient morphologies, using their equivalent diameters. Results: Maximum organ doses were about 1 mGy for head and neck and 25 mGy for chest and pelvis protocols. The differences between PCXMC and TLDs doses were generally below 10% for organs within the field of view and approximately 15% for organs at the boundaries of the radiation beam. When considering patient size and gender variability, differences in organ doses up to 40% were observed especially in the pelvic region; for the organs in the thorax, the maximum differences ranged between 20% and 30%. Phantom dose indexes provided better correlation with

  1. A population pharmacokinetic model of AT9283 in adults and children to predict the maximum tolerated dose in children with leukaemia.

    PubMed

    Duong, Janna K; Griffin, Melanie J; Hargrave, Darren; Vormoor, Josef; Edwards, David; Boddy, Alan V

    2017-08-01

    AT9283 is used to treat patients with solid tumours and patients with leukaemia. However, the maximum tolerated dose (MTD) for children with leukaemia remains unknown due to early termination of the Phase I trial. The aim of this study was to develop a population model of AT9283 to describe the pharmacokinetics in adults and children and to estimate the MTD in children with leukaemia. Data from Phase I dose-escalation studies in adults and children were used to build a population pharmacokinetic model (NONMEM v7.3). Potential covariates investigated included body weight, body surface area (BSA), glomerular filtration rate (GFR), age and sex. Model-derived area under the concentration-time curve was used to investigate the relationship between dose and exposure in adults and children. The plasma concentrations of AT9283 (n = 1770) from 92 patients (53 adults, 39 children) were used to build a two-compartment model with all pharmacokinetic parameters scaled using body weight. Renal function (GFR), but not BSA, was a significant covariate for the clearance of AT9283. In children with leukaemia (median weight 16 kg), a flat dose of 500 mg 72 h -1 provided similar drug exposures at the MTD as the adult population. The estimated MTD for children with leukaemia, therefore, is 30 mg kg -1  72 h -1 . For adults, GFR was a significant predictor of clearance, whilst body-weight based dosing was more useful than BSA in determining the drug exposure in children. The MTD was estimated to be 30 mg kg -1  72 h -1 children with leukaemia. © 2017 The British Pharmacological Society.

  2. Advanced techniques in neoadjuvant radiotherapy allow dose escalation without increased dose to the organs at risk : Planning study in esophageal carcinoma.

    PubMed

    Fakhrian, K; Oechsner, M; Kampfer, S; Schuster, T; Molls, M; Geinitz, H

    2013-04-01

    The goal of this work was to investigate the potential of advanced radiation techniques in dose escalation in the radiotherapy (RT) for the treatment of esophageal carcinoma. A total of 15 locally advanced esophageal cancer (LAEC) patients were selected for the present study. For all 15 patients, we created a 3D conformal RT plan (3D-45) with 45 Gy in fractions of 1.8 Gy to the planning target volume (PTV1), which we usually use to employ in the neoadjuvant treatment of LAEC. Additionally, a 3D boost (as in the primary RT of LAEC) was calculated with 9 Gy in fractions of 1.8 Gy to the boost volume (PTV2) (Dmean) to a total dose of 54 Gy (3D-54 Gy), which we routinely use for the definitive treatment of LAEC. Three plans with a simultaneous integrated boost (SIB) were then calculated for each patient: sliding window intensity-modulated radiotherapy (IMRT-SIB), volumetric modulated arc therapy (VMAT-SIB), and helical tomotherapy (HT-SIB). For the SIB plans, the requirement was that 95 % of the PTV1 receive ≥ 100 % of the prescription dose (45 Gy in fractions of 1.8 Gy, D95) and the PTV2 was dose escalated to 52.5 Gy in fractions of 2.1 Gy (D95). The median PTV2 dose for 3D-45, 3D-54, HT-SIB, VMAT-SIB, and IMRT-SIB was 45, 55, 54, 56, and 55 Gy, respectively. Therefore, the dose to PTV2 in the SIB plans was comparable to the 3D-54 plan. The lung dose in the SIB plans was in the range of the standard 3D-45, which is applied for neoadjuvant radiotherapy. The mean lung dose for the same plans was 13, 15, 12, 12, and 13 Gy, respectively. The V5 lung volumes were 71, 74, 79, 75, and 73 %, respectively. The V20 lung volumes were 20, 25, 16, 18, and 19 %, respectively. New treatment planning techniques enable higher doses to be delivered for neoadjuvant radiotherapy of LAEC without a significant increase in the delivered dose to the organs at risk. Clinical investigations are warranted to study the clinical safety and feasibility of applying higher

  3. The Maximum Mass of Rotating Strange Stars

    NASA Astrophysics Data System (ADS)

    Szkudlarek, M.; Gondek-Rosiń; ska, D.; Villain, L.; Ansorg, M.

    2012-12-01

    Strange quark stars are considered as a possible alternative to neutron stars as compact objects (e.g. Weber 2003). A hot compact star (a proto-neutron star or a strange star) born in a supernova explosion or a remnant of neutron stars binary merger are expected to rotate differentially and be important sources of gravitational waves. We present results of the first relativistic calculations of differentially rotating strange quark stars for broad ranges of degree of differential rotation and maximum densities. Using a highly accurate, relativistic code we show that rotation may cause a significant increase of maximum allowed mass of strange stars, much larger than in the case of neutron stars with the same degree of differential rotation. Depending on the maximum allowed mass a massive neutron star (strange star) can be temporarily stabilized by differential rotation or collapse to a black hole.

  4. MO-F-CAMPUS-I-02: Occupational Conceptus Doses From Fluoroscopically-Guided Interventional Procedures

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

    Damilakis, J; Perisinakis, K; Solomou, G

    Purpose: The aim of this method was to provide dosimetric data on conceptus dose for the pregnant employee who participates in fluoroscopically-guided interventional procedures. Methods: Scattered air-kerma dose rates were obtained for 17 fluoroscopic projections involved in interventional procedures. These projections were simulated on an anthropomorphic phantom placed on the examination table supine. The operating theater was divided into two grids relative to the long table sides. Each grid consisted of 33 cells spaced 0.50 m apart. During the simulated exposures, at each cell, scatter air-kerma rate was measured at 110 cm from the floor i.e. at the height ofmore » the waist of the pregnant worker. Air-kerma rates were divided by the dose area product (DAP) rate of each exposure to obtain normalized data. For each projection, measurements were performed for 3 kVp and 3 filtration values i.e. for 9 different x-ray spectra. All measurements were performed by using a modern C-arm angiographic system (Siemens Axiom Artis, Siemens, Germany) and a radiation meter equipped with an ionization chamber. Results: The results consist of 153 iso-dose maps, which show the spatial distribution of DAP-normalized scattered air-kerma doses at the waist level of a pregnant worker. Conceptus dose estimation is possible using air-kerma to embryo/fetal dose conversion coefficients published in a previous study (J Cardiovasc Electrophysiol, Vol. 16, pp. 1–8, July 2005). Using these maps, occupationally exposed pregnant personnel may select a working position for a certain projection that keeps abdominal dose as low as reasonably achievable. Taking into consideration the regulatory conceptus dose limit for occupational exposure, determination of the maximum workload allowed for the pregnant personnel is also possible. Conclusion: Data produced in this work allow for the anticipation of conceptus dose and the determination of the maximum workload for a pregnant worker from any

  5. Surface dose measurements for highly oblique electron beams.

    PubMed

    Ostwald, P M; Kron, T

    1996-08-01

    Clinical applications of electrons may involve oblique incidence of beams, and although dose variations for angles up to 60 degrees from normal incidence are well documented, no results are available for highly oblique beams. Surface dose measurements in highly oblique beams were made using parallel-plate ion chambers and both standard LiF:Mg, Ti and carbon-loaded LiF Thermoluminescent Dosimeters (TLD). Obliquity factors (OBF) or surface dose at an oblique angle divided by the surface dose at perpendicular incidence, were obtained for electron energies between 4 and 20 MeV. Measurements were performed on a flat solid water phantom without a collimator at 100 cm SSD. Comparisons were also made to collimated beams. The OBFs of surface doses plotted against the angle of incidence increased to a maximum dose followed by a rapid dropoff in dose. The increase in OBF was more rapid for higher energies. The maximum OBF occurred at larger angles for higher-energy beams and ranged from 73 degrees for 4 MeV to 84 degrees for 20 MeV. At the dose maximum, OBFs were between 130% and 160% of direct beam doses, yielding surface doses of up to 150% of Dmax for the 20 MeV beam. At 2 mm depth the dose ratio was found to increase initially with angle and then decrease as Dmax moved closer to the surface. A higher maximum dose was measured at 2 mm depth than at the surface. A comparison of ion chamber types showed that a chamber with a small electrode spacing and large guard ring is required for oblique dose measurement. A semiempirical equation was used to model the dose increase at the surface with different energy electron beams.

  6. Radiation-induced rib fracture after stereotactic body radiotherapy with a total dose of 54-56 Gy given in 9-7 fractions for patients with peripheral lung tumor: impact of maximum dose and fraction size.

    PubMed

    Aoki, Masahiko; Sato, Mariko; Hirose, Katsumi; Akimoto, Hiroyoshi; Kawaguchi, Hideo; Hatayama, Yoshiomi; Ono, Shuichi; Takai, Yoshihiro

    2015-04-22

    Radiation-induced rib fracture after stereotactic body radiotherapy (SBRT) for lung cancer has been recently reported. However, incidence of radiation-induced rib fracture after SBRT using moderate fraction sizes with a long-term follow-up time are not clarified. We examined incidence and risk factors of radiation-induced rib fracture after SBRT using moderate fraction sizes for the patients with peripherally located lung tumor. During 2003-2008, 41 patients with 42 lung tumors were treated with SBRT to 54-56 Gy in 9-7 fractions. The endpoint in the study was radiation-induced rib fracture detected by CT scan after the treatment. All ribs where the irradiated doses were more than 80% of prescribed dose were selected and contoured to build the dose-volume histograms (DVHs). Comparisons of the several factors obtained from the DVHs and the probabilities of rib fracture calculated by Kaplan-Meier method were performed in the study. Median follow-up time was 68 months. Among 75 contoured ribs, 23 rib fractures were observed in 34% of the patients during 16-48 months after SBRT, however, no patients complained of chest wall pain. The 4-year probabilities of rib fracture for maximum dose of ribs (Dmax) more than and less than 54 Gy were 47.7% and 12.9% (p = 0.0184), and for fraction size of 6, 7 and 8 Gy were 19.5%, 31.2% and 55.7% (p = 0.0458), respectively. Other factors, such as D2cc, mean dose of ribs, V10-55, age, sex, and planning target volume were not significantly different. The doses and fractionations used in this study resulted in no clinically significant rib fractures for this population, but that higher Dmax and dose per fraction treatments resulted in an increase in asymptomatic grade 1 rib fractures.

  7. Cosmic shear measurement with maximum likelihood and maximum a posteriori inference

    NASA Astrophysics Data System (ADS)

    Hall, Alex; Taylor, Andy

    2017-06-01

    We investigate the problem of noise bias in maximum likelihood and maximum a posteriori estimators for cosmic shear. We derive the leading and next-to-leading order biases and compute them in the context of galaxy ellipticity measurements, extending previous work on maximum likelihood inference for weak lensing. We show that a large part of the bias on these point estimators can be removed using information already contained in the likelihood when a galaxy model is specified, without the need for external calibration. We test these bias-corrected estimators on simulated galaxy images similar to those expected from planned space-based weak lensing surveys, with promising results. We find that the introduction of an intrinsic shape prior can help with mitigation of noise bias, such that the maximum a posteriori estimate can be made less biased than the maximum likelihood estimate. Second-order terms offer a check on the convergence of the estimators, but are largely subdominant. We show how biases propagate to shear estimates, demonstrating in our simple set-up that shear biases can be reduced by orders of magnitude and potentially to within the requirements of planned space-based surveys at mild signal-to-noise ratio. We find that second-order terms can exhibit significant cancellations at low signal-to-noise ratio when Gaussian noise is assumed, which has implications for inferring the performance of shear-measurement algorithms from simplified simulations. We discuss the viability of our point estimators as tools for lensing inference, arguing that they allow for the robust measurement of ellipticity and shear.

  8. Georgia fishery study: implications for dose calculations. Revision 1

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

    Turcotte, M.D.S.

    Fish consumption will contribute a major portion of the estimated individual and population doses from L-Reactor liquid releases and Cs-137 remobilization in Steel Creek. It is therefore important that the values for fish consumption used in dose calculations be as realistic as possible. Since publication of the L-Reactor Environmental Information Document (EID), data have become available on sport fishing in the Savannah River. These data provide SRP with a site-specific sport fish harvest and consumption values for use in dose calculations. The Georgia fishery data support the total population fish consumption and calculated dose reported in the EID. The datamore » indicate, however, that both the EID average and maximum individual fish consumption have been underestimated, although each to a different degree. The average fish consumption value used in the EID is approximately 3% below the lower limit of the fish consumption range calculated using the Georgia data. Maximum fish consumption in the EID has been underestimated by approximately 60%, and doses to the maximum individual should also be recalculated. Future dose calculations should utilize an average adult fish consumption value of 11.3 kg/yr, and a maximum adult fish consumption value of 34 kg/yr. Consumption values for the teen and child age groups should be increased proportionally: (1) teen average = 8.5; maximum = 25.9 kg/yr; and (2) child average = 3.6; maximum = 11.2 kg/yr. 8 refs.« less

  9. Dose-Dependent Suppression of Gonadotropins and Ovarian Hormones by Elagolix in Healthy Premenopausal Women.

    PubMed

    Ng, Juki; Chwalisz, Kristof; Carter, David C; Klein, Cheri E

    2017-05-01

    Elagolix is a nonpeptide, oral gonadotropin-releasing hormone (GnRH) antagonist being developed for sex-hormone-dependent diseases in women. We evaluated the pharmacokinetics and pharmacodynamics of elagolix. This study was a randomized, double-blind, placebo-controlled, multiple-ascending dose study in 45 healthy premenopausal women at a research unit. Elagolix [150 mg once daily or 100, 200, 300, or 400 mg twice daily (BID)] or placebo was administered for 21 days. Main outcome measures were elagolix pharmacokinetics, suppression of gonadotropics [follicle-stimulating hormone (FSH), luteinizing hormone (LH)] and ovarian hormones [estradiol (E2), progesterone (P)], and adverse events. Elagolix was rapidly absorbed after oral dosing, reaching maximum concentrations at 1.0 to 1.5 hours, with a half-life of 4 to 6 hours. FSH, LH, and E2 were suppressed within hours of elagolix administration on day 1. Dose-dependent suppression of E2 was observed, with maximum suppression achieved with elagolix 200 mg BID. Dose-dependent suppression of FSH and LH was also observed, with maximal or near-maximal suppression achieved at 300 mg BID and 200 mg BID, respectively. At elagolix doses ≥100 mg BID, P concentrations remained at anovulatory levels throughout 21 days of dosing. The most frequently reported adverse events were headache and hot flush. Elagolix administration allows for modulation of gonadotropin and ovarian hormone concentrations, from partial suppression at lower doses to nearly full suppression at higher doses. The results of this study provide a rationale for elagolix dose selection for treatment of sex hormone-dependent diseases in women. Copyright © 2017 Endocrine Society

  10. Estimation of the total effective dose from low-dose CT scans and radiopharmaceutical administrations delivered to patients undergoing SPECT/CT explorations.

    PubMed

    Montes, Carlos; Tamayo, Pilar; Hernandez, Jorge; Gomez-Caminero, Felipe; García, Sofia; Martín, Carlos; Rosero, Angela

    2013-08-01

    Hybrid imaging, such as SPECT/CT, is used in routine clinical practice, allowing coregistered images of the functional and structural information provided by the two imaging modalities. However, this multimodality imaging may mean that patients are exposed to a higher radiation dose than those receiving SPECT alone. The study aimed to determine the radiation exposure of patients who had undergone SPECT/CT examinations and to relate this to the Background Equivalent Radiation Time (BERT). 145 SPECT/CT studies were used to estimate the total effective dose to patients due to both radiopharmaceutical administrations and low-dose CT scans. The CT contribution was estimated by the Dose-Length Product method. Specific conversion coefficients were calculated for SPECT explorations. The radiation dose from low-dose CTs ranged between 0.6 mSv for head and neck CT and 2.6 mSv for whole body CT scan, representing a maximum of 1 year of background radiation exposure. These values represent a decrease of 80-85% with respect to the radiation dose from diagnostic CT. The radiation exposure from radiopharmaceutical administration varied from 2.1 mSv for stress myocardial perfusion SPECT to 26 mSv for gallium SPECT in patients with lymphoma. The BERT ranged from 1 to 11 years. The contribution of low-dose CT scans to the total radiation dose to patients undergoing SPECT/CT examinations is relatively low compared with the effective dose from radiopharmaceutical administration. When a CT scan is only acquired for anatomical localization and attenuation correction, low-dose CT scan is justified on the basis of its lower dose.

  11. 40 CFR 82.20 - Availability of consumption allowances in addition to baseline consumption allowances for class...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... period some quantity of consumption that the nation is permitted under the Montreal Protocol. (2) Trade... Party to the Protocol as set forth in this paragraph (b). A person may only receive consumption from... maximum consumption that the nation is allowed under the Protocol minus the quantity (in kilograms) traded...

  12. 40 CFR 82.20 - Availability of consumption allowances in addition to baseline consumption allowances for class...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... period some quantity of consumption that the nation is permitted under the Montreal Protocol. (2) Trade... Party to the Protocol as set forth in this paragraph (b). A person may only receive consumption from... maximum consumption that the nation is allowed under the Protocol minus the quantity (in kilograms) traded...

  13. 40 CFR 82.20 - Availability of consumption allowances in addition to baseline consumption allowances for class...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... period some quantity of consumption that the nation is permitted under the Montreal Protocol. (2) Trade... Party to the Protocol as set forth in this paragraph (b). A person may only receive consumption from... maximum consumption that the nation is allowed under the Protocol minus the quantity (in kilograms) traded...

  14. 40 CFR 82.20 - Availability of consumption allowances in addition to baseline consumption allowances for class...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... period some quantity of consumption that the nation is permitted under the Montreal Protocol. (2) Trade... Party to the Protocol as set forth in this paragraph (b). A person may only receive consumption from... maximum consumption that the nation is allowed under the Protocol minus the quantity (in kilograms) traded...

  15. 40 CFR 82.20 - Availability of consumption allowances in addition to baseline consumption allowances for class...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... period some quantity of consumption that the nation is permitted under the Montreal Protocol. (2) Trade... Party to the Protocol as set forth in this paragraph (b). A person may only receive consumption from... maximum consumption that the nation is allowed under the Protocol minus the quantity (in kilograms) traded...

  16. Influence of intravenous opioid dose on postoperative ileus.

    PubMed

    Barletta, Jeffrey F; Asgeirsson, Theodor; Senagore, Anthony J

    2011-07-01

    Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI. Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain

  17. Excel-Based Tool for Pharmacokinetically Guided Dose Adjustment of Paclitaxel.

    PubMed

    Kraff, Stefanie; Lindauer, Andreas; Joerger, Markus; Salamone, Salvatore J; Jaehde, Ulrich

    2015-12-01

    Neutropenia is a frequent and severe adverse event in patients receiving paclitaxel chemotherapy. The time above a paclitaxel threshold concentration of 0.05 μmol/L (Tc > 0.05 μmol/L) is a strong predictor for paclitaxel-associated neutropenia and has been proposed as a target pharmacokinetic (PK) parameter for paclitaxel therapeutic drug monitoring and dose adaptation. Up to now, individual Tc > 0.05 μmol/L values are estimated based on a published PK model of paclitaxel by using the software NONMEM. Because many clinicians are not familiar with the use of NONMEM, an Excel-based dosing tool was developed to allow calculation of paclitaxel Tc > 0.05 μmol/L and give clinicians an easy-to-use tool. Population PK parameters of paclitaxel were taken from a published PK model. An Alglib VBA code was implemented in Excel 2007 to compute differential equations for the paclitaxel PK model. Maximum a posteriori Bayesian estimates of the PK parameters were determined with the Excel Solver using individual drug concentrations. Concentrations from 250 patients were simulated receiving 1 cycle of paclitaxel chemotherapy. Predictions of paclitaxel Tc > 0.05 μmol/L as calculated by the Excel tool were compared with NONMEM, whereby maximum a posteriori Bayesian estimates were obtained using the POSTHOC function. There was a good concordance and comparable predictive performance between Excel and NONMEM regarding predicted paclitaxel plasma concentrations and Tc > 0.05 μmol/L values. Tc > 0.05 μmol/L had a maximum bias of 3% and an error on precision of <12%. The median relative deviation of the estimated Tc > 0.05 μmol/L values between both programs was 1%. The Excel-based tool can estimate the time above a paclitaxel threshold concentration of 0.05 μmol/L with acceptable accuracy and precision. The presented Excel tool allows reliable calculation of paclitaxel Tc > 0.05 μmol/L and thus allows target concentration intervention to improve the benefit-risk ratio of the

  18. Single-event and total-dose effects in geo-stationary transfer orbit during solar-activity maximum period measured by the Tsubasa satellite

    NASA Astrophysics Data System (ADS)

    Koshiishi, H.; Kimoto, Y.; Matsumoto, H.; Goka, T.

    The Tsubasa satellite developed by the Japan Aerospace Exploration Agency was launched in Feb 2002 into Geo-stationary Transfer Orbit GTO Perigee 500km Apogee 36000km and had been operated well until Sep 2003 The objective of this satellite was to verify the function of commercial parts and new technologies of bus-system components in space Thus the on-board experiments were conducted in the more severe radiation environment of GTO rather than in Geo-stationary Earth Orbit GEO or Low Earth Orbit LEO The Space Environment Data Acquisition equipment SEDA on board the Tsubasa satellite had the Single-event Upset Monitor SUM and the DOSimeter DOS to evaluate influences on electronic devices caused by radiation environment that was also measured by the particle detectors of the SEDA the Standard DOse Monitor SDOM for measurements of light particles and the Heavy Ion Telescope HIT for measurements of heavy ions The SUM monitored single-event upsets and single-event latch-ups occurred in the test sample of two 64-Mbit DRAMs The DOS measured accumulated radiation dose at fifty-six locations in the body of the Tsubasa satellite Using the data obtained by these instruments single-event and total-dose effects in GTO during solar-activity maximum period especially their rapid changes due to solar flares and CMEs in the region from L 1 1 through L 11 is discussed in this paper

  19. A new concept of pencil beam dose calculation for 40-200 keV photons using analytical dose kernels.

    PubMed

    Bartzsch, Stefan; Oelfke, Uwe

    2013-11-01

    The advent of widespread kV-cone beam computer tomography in image guided radiation therapy and special therapeutic application of keV photons, e.g., in microbeam radiation therapy (MRT) require accurate and fast dose calculations for photon beams with energies between 40 and 200 keV. Multiple photon scattering originating from Compton scattering and the strong dependence of the photoelectric cross section on the atomic number of the interacting tissue render these dose calculations by far more challenging than the ones established for corresponding MeV beams. That is why so far developed analytical models of kV photon dose calculations fail to provide the required accuracy and one has to rely on time consuming Monte Carlo simulation techniques. In this paper, the authors introduce a novel analytical approach for kV photon dose calculations with an accuracy that is almost comparable to the one of Monte Carlo simulations. First, analytical point dose and pencil beam kernels are derived for homogeneous media and compared to Monte Carlo simulations performed with the Geant4 toolkit. The dose contributions are systematically separated into contributions from the relevant orders of multiple photon scattering. Moreover, approximate scaling laws for the extension of the algorithm to inhomogeneous media are derived. The comparison of the analytically derived dose kernels in water showed an excellent agreement with the Monte Carlo method. Calculated values deviate less than 5% from Monte Carlo derived dose values, for doses above 1% of the maximum dose. The analytical structure of the kernels allows adaption to arbitrary materials and photon spectra in the given energy range of 40-200 keV. The presented analytical methods can be employed in a fast treatment planning system for MRT. In convolution based algorithms dose calculation times can be reduced to a few minutes.

  20. Optimizing drug-dose alerts using commercial software throughout an integrated health care system.

    PubMed

    Saiyed, Salim M; Greco, Peter J; Fernandes, Glenn; Kaelber, David C

    2017-11-01

    All default electronic health record and drug reference database vendor drug-dose alerting recommendations (single dose, daily dose, dose frequency, and dose duration) were silently turned on in inpatient, outpatient, and emergency department areas for pediatric-only and nonpediatric-only populations. Drug-dose alerts were evaluated during a 3-month period. Drug-dose alerts fired on 12% of orders (104 098/834 911). System-level and drug-specific strategies to decrease drug-dose alerts were analyzed. System-level strategies included: (1) turning off all minimum drug-dosing alerts, (2) turning off all incomplete information drug-dosing alerts, (3) increasing the maximum single-dose drug-dose alert threshold to 125%, (4) increasing the daily dose maximum drug-dose alert threshold to 125%, and (5) increasing the dose frequency drug-dose alert threshold to more than 2 doses per day above initial threshold. Drug-specific strategies included changing drug-specific maximum single and maximum daily drug-dose alerting parameters for the top 22 drug categories by alert frequency. System-level approaches decreased alerting to 5% (46 988/834 911) and drug-specific approaches decreased alerts to 3% (25 455/834 911). Drug-dose alerts varied between care settings and patient populations. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. 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.

  2. 44 CFR 11.73 - Allowable claims.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... supervisor, but these claims shall be limited to a maximum of $1,000.00. (4) Mobile homes. Claims may be allowed for damage to or loss of mobile homes and their content under the provisions of paragraph (c)(2) of this section. Claims for structural damage to mobile homes resulting from such structural damage...

  3. 44 CFR 11.73 - Allowable claims.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... supervisor, but these claims shall be limited to a maximum of $1,000.00. (4) Mobile homes. Claims may be allowed for damage to or loss of mobile homes and their content under the provisions of paragraph (c)(2) of this section. Claims for structural damage to mobile homes resulting from such structural damage...

  4. 44 CFR 11.73 - Allowable claims.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... supervisor, but these claims shall be limited to a maximum of $1,000.00. (4) Mobile homes. Claims may be allowed for damage to or loss of mobile homes and their content under the provisions of paragraph (c)(2) of this section. Claims for structural damage to mobile homes resulting from such structural damage...

  5. 44 CFR 11.73 - Allowable claims.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... supervisor, but these claims shall be limited to a maximum of $1,000.00. (4) Mobile homes. Claims may be allowed for damage to or loss of mobile homes and their content under the provisions of paragraph (c)(2) of this section. Claims for structural damage to mobile homes resulting from such structural damage...

  6. 44 CFR 11.73 - Allowable claims.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... supervisor, but these claims shall be limited to a maximum of $1,000.00. (4) Mobile homes. Claims may be allowed for damage to or loss of mobile homes and their content under the provisions of paragraph (c)(2) of this section. Claims for structural damage to mobile homes resulting from such structural damage...

  7. Can contrast media increase organ doses in CT examinations? A clinical study.

    PubMed

    Amato, Ernesto; Salamone, Ignazio; Naso, Serena; Bottari, Antonio; Gaeta, Michele; Blandino, Alfredo

    2013-06-01

    The purpose of this article is to quantify the CT radiation dose increment in five organs resulting from the administration of iodinated contrast medium. Forty consecutive patients who underwent both un-enhanced and contrast-enhanced thoracoabdominal CT were included in our retrospective study. The dose increase between CT before and after contrast agent administration was evaluated in the portal phase for the thyroid, liver, spleen, pancreas, and kidneys by applying a previously validated method. An increase in radiation dose was noted in all organs studied. Average dose increments were 19% for liver, 71% for kidneys, 33% for spleen and pancreas, and 41% for thyroid. Kidneys exhibited the maximum dose increment, whereas the pancreas showed the widest variance because of the differences in fibro-fatty involution. Finally, thyroids with high attenuation values on unenhanced CT showed a lower Hounsfield unit increase and, thus, a smaller increment in the dose. Our study showed an increase in radiation dose in several parenchymatous tissues on contrast-enhanced CT. Our method allowed us to evaluate the dose increase from the change in attenuation measured in Hounsfield units. Because diagnostic protocols require multiple acquisitions after the contrast agent administration, such a dose increase should be considered when optimizing these protocols.

  8. Independent calculation-based verification of IMRT plans using a 3D dose-calculation engine.

    PubMed

    Arumugam, Sankar; Xing, Aitang; Goozee, Gary; Holloway, Lois

    2013-01-01

    Independent monitor unit verification of intensity-modulated radiation therapy (IMRT) plans requires detailed 3-dimensional (3D) dose verification. The aim of this study was to investigate using a 3D dose engine in a second commercial treatment planning system (TPS) for this task, facilitated by in-house software. Our department has XiO and Pinnacle TPSs, both with IMRT planning capability and modeled for an Elekta-Synergy 6MV photon beam. These systems allow the transfer of computed tomography (CT) data and RT structures between them but do not allow IMRT plans to be transferred. To provide this connectivity, an in-house computer programme was developed to convert radiation therapy prescription (RTP) files as generated by many planning systems into either XiO or Pinnacle IMRT file formats. Utilization of the technique and software was assessed by transferring 14 IMRT plans from XiO and Pinnacle onto the other system and performing 3D dose verification. The accuracy of the conversion process was checked by comparing the 3D dose matrices and dose volume histograms (DVHs) of structures for the recalculated plan on the same system. The developed software successfully transferred IMRT plans generated by 1 planning system into the other. Comparison of planning target volume (TV) DVHs for the original and recalculated plans showed good agreement; a maximum difference of 2% in mean dose, - 2.5% in D95, and 2.9% in V95 was observed. Similarly, a DVH comparison of organs at risk showed a maximum difference of +7.7% between the original and recalculated plans for structures in both high- and medium-dose regions. However, for structures in low-dose regions (less than 15% of prescription dose) a difference in mean dose up to +21.1% was observed between XiO and Pinnacle calculations. A dose matrix comparison of original and recalculated plans in XiO and Pinnacle TPSs was performed using gamma analysis with 3%/3mm criteria. The mean and standard deviation of pixels passing gamma

  9. Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies.

    PubMed

    Silva-Rodríguez, Jesús; Aguiar, Pablo; Sánchez, Manuel; Mosquera, Javier; Luna-Vega, Víctor; Cortés, Julia; Garrido, Miguel; Pombar, Miguel; Ruibal, Alvaro

    2014-05-01

    Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manual ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.

  10. Correction for FDG PET dose extravasations: Monte Carlo validation and quantitative evaluation of patient studies

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

    Silva-Rodríguez, Jesús, E-mail: jesus.silva.rodriguez@sergas.es; Aguiar, Pablo, E-mail: pablo.aguiar.fernandez@sergas.es; Servicio de Medicina Nuclear, Complexo Hospitalario Universidade de Santiago de Compostela

    Purpose: Current procedure guidelines for whole body [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET) state that studies with visible dose extravasations should be rejected for quantification protocols. Our work is focused on the development and validation of methods for estimating extravasated doses in order to correct standard uptake value (SUV) values for this effect in clinical routine. Methods: One thousand three hundred sixty-seven consecutive whole body FDG-PET studies were visually inspected looking for extravasation cases. Two methods for estimating the extravasated dose were proposed and validated in different scenarios using Monte Carlo simulations. All visible extravasations were retrospectively evaluated using a manualmore » ROI based method. In addition, the 50 patients with higher extravasated doses were also evaluated using a threshold-based method. Results: Simulation studies showed that the proposed methods for estimating extravasated doses allow us to compensate the impact of extravasations on SUV values with an error below 5%. The quantitative evaluation of patient studies revealed that paravenous injection is a relatively frequent effect (18%) with a small fraction of patients presenting considerable extravasations ranging from 1% to a maximum of 22% of the injected dose. A criterion based on the extravasated volume and maximum concentration was established in order to identify this fraction of patients that might be corrected for paravenous injection effect. Conclusions: The authors propose the use of a manual ROI based method for estimating the effectively administered FDG dose and then correct SUV quantification in those patients fulfilling the proposed criterion.« less

  11. Dose Calculations for [131I] Meta-Iodobenzylguanidine-Induced Bystander Effects

    PubMed Central

    Gow, M. D.; Seymour, C. B.; Boyd, M.; Mairs, R. J.; Prestiwch, W. V.; Mothersill, C. E.

    2014-01-01

    Targeted radiotherapy is a potentially useful treatment for some cancers and may be potentiated by bystander effects. However, without estimation of absorbed dose, it is difficult to compare the effects with conventional external radiation treatment. Methods: Using the Vynckier – Wambersie dose point kernel, a model for dose rate evaluation was created allowing for calculation of absorbed dose values to two cell lines transfected with the noradrenaline transporter (NAT) gene and treated with [131I]MIBG. Results: The mean doses required to decrease surviving fractions of UVW/NAT and EJ138/NAT cells, which received medium from [131I]MIBG-treated cells, to 25 – 30% were 1.6 and 1.7 Gy respectively. The maximum mean dose rates achieved during [131I]MIBG treatment were 0.09 – 0.75 Gy/h for UVW/NAT and 0.07 – 0.78 Gy/h for EJ138/NAT. These were significantly lower than the external beam gamma radiation dose rate of 15 Gy/h. In the case of control lines which were incapable of [131I]MIBG uptake the mean absorbed doses following radiopharmaceutical were 0.03 – 0.23 Gy for UVW and 0.03 – 0.32 Gy for EJ138. Conclusion: [131I]MIBG treatment for ICCM production elicited a bystander dose-response profile similar to that generated by external beam gamma irradiation but with significantly greater cell death. PMID:24659931

  12. Implementation of a dose gradient method into optimization of dose distribution in prostate cancer 3D-CRT plans

    PubMed Central

    Giżyńska, Marta K.; Kukołowicz, Paweł F.; Kordowski, Paweł

    2014-01-01

    Aim The aim of this work is to present a method of beam weight and wedge angle optimization for patients with prostate cancer. Background 3D-CRT is usually realized with forward planning based on a trial and error method. Several authors have published a few methods of beam weight optimization applicable to the 3D-CRT. Still, none on these methods is in common use. Materials and methods Optimization is based on the assumption that the best plan is achieved if dose gradient at ICRU point is equal to zero. Our optimization algorithm requires beam quality index, depth of maximum dose, profiles of wedged fields and maximum dose to femoral heads. The method was tested for 10 patients with prostate cancer, treated with the 3-field technique. Optimized plans were compared with plans prepared by 12 experienced planners. Dose standard deviation in target volume, and minimum and maximum doses were analyzed. Results The quality of plans obtained with the proposed optimization algorithms was comparable to that prepared by experienced planners. Mean difference in target dose standard deviation was 0.1% in favor of the plans prepared by planners for optimization of beam weights and wedge angles. Introducing a correction factor for patient body outline for dose gradient at ICRU point improved dose distribution homogeneity. On average, a 0.1% lower standard deviation was achieved with the optimization algorithm. No significant difference in mean dose–volume histogram for the rectum was observed. Conclusions Optimization shortens very much time planning. The average planning time was 5 min and less than a minute for forward and computer optimization, respectively. PMID:25337411

  13. 20 CFR 10.806 - How are the maximum fees defined?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... AMENDED Information for Medical Providers Medical Fee Schedule § 10.806 How are the maximum fees defined? For professional medical services, the Director shall maintain a schedule of maximum allowable fees... Procedural Terminology (HCPCS/CPT) code which represents the relative skill, effort, risk and time required...

  14. 20 CFR 10.806 - How are the maximum fees defined?

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... AMENDED Information for Medical Providers Medical Fee Schedule § 10.806 How are the maximum fees defined? For professional medical services, the Director shall maintain a schedule of maximum allowable fees.../Current Procedural Terminology (HCPCS/CPT) code which represents the relative skill, effort, risk and time...

  15. 20 CFR 10.806 - How are the maximum fees defined?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... AMENDED Information for Medical Providers Medical Fee Schedule § 10.806 How are the maximum fees defined? For professional medical services, the Director shall maintain a schedule of maximum allowable fees... Procedural Terminology (HCPCS/CPT) code which represents the relative skill, effort, risk and time required...

  16. 20 CFR 10.806 - How are the maximum fees defined?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... AMENDED Information for Medical Providers Medical Fee Schedule § 10.806 How are the maximum fees defined? For professional medical services, the Director shall maintain a schedule of maximum allowable fees... Procedural Terminology (HCPCS/CPT) code which represents the relative skill, effort, risk and time required...

  17. 20 CFR 10.806 - How are the maximum fees defined?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... AMENDED Information for Medical Providers Medical Fee Schedule § 10.806 How are the maximum fees defined? For professional medical services, the Director shall maintain a schedule of maximum allowable fees.../Current Procedural Terminology (HCPCS/CPT) code which represents the relative skill, effort, risk and time...

  18. SU-G-201-14: Is Maximum Skin Dose a Reliable Metric for Accelerated Partial Breast Irradiation with Brachytherapy?

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

    Park, S; Ragab, O; Patel, S

    Purpose: To evaluate the reliability of the maximum point dose (Dmax) to the skin surface as a dosimetric constraint, we investigated the correlation between Dmax at the skin surface and dose metrics at various definitions of skin thickness. Methods: 42 patients treated with APBI using a Strut Adjusted Volume Implant (SAVI) applicator between 2010 and 2014 were retrospectively reviewed. Target (PTV-EVAL) and organs at risk (OARs: skin, lung, and ribs) were delineated on a CT following NSABP B-39 guidelines. Six skin structures were contoured: a rind 3cm external to the body surface and 1, 2, 3, 4, and 5mm thickmore » rinds deep to the body surface. Inverse planning simulated annealing optimization was used to deliver 32–34Gy in 8-10 fractions to the target while minimizing OAR doses. Dmax, D0.1cc, D1.0cc, and D2.0cc to the various skin structures were calculated. Linear regressions between the metrics were evaluated using the coefficient of determination (R{sup 2}). Results: The average±SD PTV-EVAL volume and cavity-to-skin distances were 71.1±28.5cc and 6.9±5.0mm. The target V90 and V95 were 97.3±2.3% and 95.1±3.2%. The Dmax to the skin structures were 78.7±10.2% (skin surface), 82.2±10.7% (skin-1mm), 89.4±12.6% (skin-2mm), 97.9±15.4% (skin-3mm), 114.1±32.5% (skin-4mm), and 157.0±85.3% (skin-5mm). Linear regression analysis showed D1.0cc and D2.0cc to the skin 1mm and Dmax to the skin-4mm and 5mm were poorly correlated with other metrics (R{sup 2}=0.413±0.204). Dmax to the skin surface was well correlated (R{sup 2}=0.910±0.047) and D1.0cc to the skin-3mm was strongly correlated with all subsurface skin layers (R{sup 2}=0.935±0.050). Conclusion: Dmax to the skin surface is a relevant metric for breast skin dose. Contouring discontinuities in the skin with a 1mm subsurface rind and the active dwells in the skin 4 and 5mm introduced significant variations in skin DVH. D0.1cc, D1.0cc, and D2.0cc to a 3mm skin rind are more robust metrics in breast

  19. Dose profile variation with voltage in head CT scans using radiochromic films

    NASA Astrophysics Data System (ADS)

    Mourão, A. P.; Alonso, T. C.; DaSilva, T. A.

    2014-02-01

    The voltage source used in an X-ray tube is an important part of defining the generated beam spectrum energy profile. The X-ray spectrum energy defines the X-ray beam absorption as well as the characteristics of the energy deposition in an irradiated object. Although CT scanners allow one to choose between four different voltage values, most of them employ a voltage of 120 kV in their scanning protocols, regardless of the patient characteristics. Based on this fact, this work investigated the deposited dose in a polymethyl methacrylate (PMMA) cylindrical head phantom. The entire volume was irradiated twice. Two CT scanning protocols were used with two different voltage values: 100 and 120 kV. The phantom volume was irradiated, and radiochromic films were employed to record dose profiles. Measurements were conducted with a calibrated pencil ionization chamber, which was positioned in the center and in four peripheral bores of the head PMMA phantom, to calibrate the radiochromic films. The central slice was then irradiated. This procedure allowed us to find the conversion factors necessary to obtain dose values recorded in the films. The data obtained allowed us to observe the dose variation profile inside the phantom head as well as in the peripheral and central regions. The peripheral region showed higher dose values than those of the central region for scans using both voltage values: approximately 31% higher for scanning with 120 kV and 25% higher with 100 kV. Doses recorded with the highest voltage are significantly higher, approximately 50% higher in the peripheral region and 40% higher in the central region. A longitudinal variation could be observed, and the maximum dose was recorded at the peripheral region, at the midpoint of the longitudinal axis. The obtained results will most likely contribute to the dissemination of proper procedure as well as to optimize dosimetry and tests of quality control in CT because the choice of protocols with different voltage

  20. Shading correction for cone-beam CT in radiotherapy: validation of dose calculation accuracy using clinical images

    NASA Astrophysics Data System (ADS)

    Marchant, T. E.; Joshi, K. D.; Moore, C. J.

    2017-03-01

    Cone-beam CT (CBCT) images are routinely acquired to verify patient position in radiotherapy (RT), but are typically not calibrated in Hounsfield Units (HU) and feature non-uniformity due to X-ray scatter and detector persistence effects. This prevents direct use of CBCT for re-calculation of RT delivered dose. We previously developed a prior-image based correction method to restore HU values and improve uniformity of CBCT images. Here we validate the accuracy with which corrected CBCT can be used for dosimetric assessment of RT delivery, using CBCT images and RT plans for 45 patients including pelvis, lung and head sites. Dose distributions were calculated based on each patient's original RT plan and using CBCT image values for tissue heterogeneity correction. Clinically relevant dose metrics were calculated (e.g. median and minimum target dose, maximum organ at risk dose). Accuracy of CBCT based dose metrics was determined using an "override ratio" method where the ratio of the dose metric to that calculated on a bulk-density assigned version of the image is assumed to be constant for each patient, allowing comparison to "gold standard" CT. For pelvis and head images the proportion of dose errors >2% was reduced from 40% to 1.3% after applying shading correction. For lung images the proportion of dose errors >3% was reduced from 66% to 2.2%. Application of shading correction to CBCT images greatly improves their utility for dosimetric assessment of RT delivery, allowing high confidence that CBCT dose calculations are accurate within 2-3%.

  1. Mars surface radiation exposure for solar maximum conditions and 1989 solar proton events

    NASA Technical Reports Server (NTRS)

    Simonsen, Lisa C.; Nealy, John E.

    1992-01-01

    The Langley heavy-ion/nucleon transport code, HZETRN, and the high-energy nucleon transport code, BRYNTRN, are used to predict the propagation of galactic cosmic rays (GCR's) and solar flare protons through the carbon dioxide atmosphere of Mars. Particle fluences and the resulting doses are estimated on the surface of Mars for GCR's during solar maximum conditions and the Aug., Sep., and Oct. 1989 solar proton events. These results extend previously calculated surface estimates for GCR's at solar minimum conditions and the Feb. 1956, Nov. 1960, and Aug. 1972 solar proton events. Surface doses are estimated with both a low-density and a high-density carbon dioxide model of the atmosphere for altitudes of 0, 4, 8, and 12 km above the surface. A solar modulation function is incorporated to estimate the GCR dose variation between solar minimum and maximum conditions over the 11-year solar cycle. By using current Mars mission scenarios, doses to the skin, eye, and blood-forming organs are predicted for short- and long-duration stay times on the Martian surface throughout the solar cycle.

  2. Gating window dependency on scanned carbon-ion beam dose distribution and imaging dose for thoracoabdominal treatment.

    PubMed

    Mori, Shinichiro; Karube, Masataka; Yasuda, Shigeo; Yamamoto, Naoyoshi; Tsuji, Hiroshi; Kamada, Tadashi

    2017-06-01

    To explore the trade-off between dose assessment and imaging dose in respiratory gating with radiographic fluoroscopic imaging, we evaluated the relationship between dose assessment and fluoroscopic imaging dose in various gating windows, retrospectively. Four-dimensional (4D) CT images acquired for 10 patients with lung and liver tumours were used for 4D treatment planning for scanned carbon ion beam. Imaging dose from two oblique directions was calculated by the number of images multiplied by the air kerma per image. Necessary beam-on time was calculated from the treatment log file. Accumulated dose distribution was calculated. The gating window was defined as tumour position not respiratory phase and changed from 0-100% duty cycle on 4DCT. These metrics were individually evaluated for every case. For lung cases, sufficient dose conformation was achieved in respective gating windows [D 95 -clinical target volume (CTV) > 99%]. V 20 -lung values for 50%- and 30%-duty cycles were 2.5% and 6.0% of that for 100%-duty cycle. Maximum doses (cord/oesophagus) for 30%-duty cycle decreased 6.8%/7.4% to those for 100%-duty cycle. For liver cases, V 10 -liver values for 50%- and 30%-duty cycles were 9.4% and 12.8% of those for 100%-duty cycle, respectively. Maximum doses (cord/oesophagus) for 50%- and 30%-duty cycles also decreased 17.2%/19.3% and 24.6%/29.8% to those for 100%-duty cycle, respectively. Total imaging doses increased 43.5% and 115.8% for 50%- and 30%-duty cycles to that for the 100%-duty cycle. When normal tissue doses are below the tolerance level, the gating window should be expanded to minimize imaging dose and treatment time. Advances in knowledge: The skin dose from imaging might not be counterbalanced to the OAR dose; however, imaging dose is a particularly important factor.

  3. Occupational dose constraints for the lens of the eye for interventional radiologists and interventional cardiologists in the UK.

    PubMed

    Mairs, William DA

    2016-06-01

    The International Commission on Radiological Protection (ICRP) has recommended a 20 mSv year(-1) dose limit for the lens of the eye, which has been adopted in the European Union Basic Safety Standards. Interventional radiologists (IRs) and interventional cardiologists (ICs) are likely to be affected by this. The effects of radiation in the lens are somewhat uncertain, and the ICRP explicitly recommend optimization. Occupational dose constraints are part of the optimization process and define a level of dose which ought to be achievable in a well-managed practice. This commentary calls on the professional bodies to review a need for national constraints to guide local decisions. Consideration is given to developing such constraints using maximum expected doses in high-workload facilities with good radiation protection practices and application of a factor allowing for attenuation by lead glasses (LG). Doses are based on a Public Health England survey of eye dose in the UK. Maximum expected doses for ICs are approximately 21 mSv year(-1), neglecting LG. However, the extent of IR exposure is not yet fully known, and further evidence is required before conclusions are drawn. A Health and Safety Laboratory review of LG established a conservative dose reduction factor of 3 for models available in 2012. Application of this factor provides a dose constraint of 7 mSv year(-1) to the eye for ICs. To achieve this constraint, those employers with the most exposed ICs will have to provide and ensure the correct use of a ceiling-suspended eye shield and LG.

  4. 40 CFR 35.669 - Maximum federal share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATE AND LOCAL ASSISTANCE Environmental Program Grants for Tribes Pollution Prevention Grants (section 6605) § 35.669 Maximum federal share. The federal share for Pollution Prevention Grants will not exceed 50 percent of the allowable Tribe and Intertribal Consortium Pollution Prevention project cost...

  5. Estimation of eye lens doses received by pediatric interventional cardiologists.

    PubMed

    Alejo, L; Koren, C; Ferrer, C; Corredoira, E; Serrada, A

    2015-09-01

    Maximum Hp(0.07) dose to the eye lens received in a year by the pediatric interventional cardiologists has been estimated. Optically stimulated luminescence dosimeters were placed on the eyes of an anthropomorphic phantom, whose position in the room simulates the most common irradiation conditions. Maximum workload was considered with data collected from procedures performed in the Hospital. None of the maximum values obtained exceed the dose limit of 20 mSv recommended by ICRP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. 40 CFR 35.349 - Maximum federal share.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... STATE AND LOCAL ASSISTANCE Environmental Program Grants Pollution Prevention State Grants (section 6605) § 35.349 Maximum federal share. The federal share for Pollution Prevention State Grants will not exceed 50 percent of the allowable pollution prevention State grant project cost. Water Quality Cooperative...

  7. Dose responses for adaption to low doses of (60)Co gamma rays and (3)H beta particles in normal human fibroblasts.

    PubMed

    Broome, E J; Brown, D L; Mitchel, R E J

    2002-08-01

    The dose response for adaption to radiation at low doses was compared in normal human fibroblasts (AG1522) exposed to either (60)Co gamma rays or (3)H beta particles. Cells were grown in culture to confluence and exposed at either 37 degrees C or 0 degrees C to (3)H beta-particle or (60)Co gamma-ray adapting doses ranging from 0.1 mGy to 500 mGy. These cells, and unexposed control cells, were allowed to adapt during a fixed 3-h, 37 degrees C incubation prior to a 4-Gy challenge dose of (60)Co gamma rays. Adaption was assessed by measuring micronucleus frequency in cytokinesis-blocked, binucleate cells. No adaption was detected in cells exposed to (60)Co gamma radiation at 37 degrees C after a dose of 0.1 mGy given at a low dose rate or to 500 mGy given at a high dose rate. However, low-dose-rate exposure (1-3 mGy/min) to any dose between 1 and 500 mGy from either radiation, delivered at either temperature, caused cells to adapt and reduced the micronucleus frequency that resulted from the subsequent 4-Gy exposure. Within this dose range, the magnitude of the reduction was the same, regardless of the dose or radiation type. These results demonstrate that doses as low as (on average) about one track per cell (1 mGy) produce the same maximum adaptive response as do doses that deposit many tracks per cell, and that the two radiations were not different in this regard. Exposure at a temperature where metabolic processes, including DNA repair, were inactive (0 degrees C) did not alter the result, indicating that the adaptive response is not sensitive to changes in the accumulation of DNA damage within this range. The results also show that the RBE for low doses of tritium beta-particle radiation is 1, using adaption as the end point.

  8. Confusion: acetaminophen dosing changes based on NO evidence in adults.

    PubMed

    Krenzelok, Edward P; Royal, Mike A

    2012-06-01

    Acetaminophen (paracetamol) plays a vital role in American health care, with in excess of 25 billion doses being used annually as a nonprescription medication. Over 200 million acetaminophen-containing prescriptions, usually in combination with an opioid, are dispensed annually. While acetaminophen is recognized as a safe and effective analgesic and antipyretic, it is also associated with significant morbidity and mortality (hepatotoxicity) if doses in excess of the therapeutic amount are ingested inappropriately. The maximum daily therapeutic dose of 3900-4000 mg was established in separate actions in 1977 and 1988, respectively, via the Food and Drug Administration (FDA) monograph process for nonprescription medications. The FDA has conducted multiple advisory committee meetings to evaluate acetaminophen and its safety profile, and has suggested (but not mandated) a reduction in the maximum daily dosage from 3900-4000 mg to 3000-3250 mg. In 2011, McNeil, the producer of the Tylenol® brand of acetaminophen, voluntarily reduced the maximum daily dose of its 500 mg tablet product to 3000 mg/day, and it has pledged to change the labeling of its 325 mg/tablet product to reflect a maximum of 3250 mg/day. Generic manufacturers have not changed their dosing regimens and they have remained consistent with the established monograph dose. Therefore, confusion will be inevitable as both consumers and health care professionals try to determine the proper therapeutic dose of acetaminophen. Which is the correct dose of acetaminophen: 3000 mg if 500 mg tablets are used, 3250 mg with 325 mg tablets, or 3900 mg when 650 mg arthritis-strength products are used?

  9. SU-E-T-248: An Extended Generalized Equivalent Uniform Dose Accounting for Dose-Range Dependency of Radio-Biological Parameters.

    PubMed

    Troeller, A; Soehn, M; Yan, D

    2012-06-01

    Introducing an extended, phenomenological, generalized equivalent uniform dose (eEUD) that incorporates multiple volume-effect parameters for different dose-ranges. The generalized EUD (gEUD) was introduced as an estimate of the EUD that incorporates a single, tissue-specific parameter - the volume-effect-parameter (VEP) 'a'. As a purely phenomenological concept, its radio-biological equivalency to a given inhomogeneous dose distribution is not a priori clear and mechanistic models based on radio-biological parameters are assumed to better resemble the underlying biology. However, for normal organs mechanistic models are hard to derive, since the structural organization of the tissue plays a significant role. Consequently, phenomenological approaches might be especially useful in order to describe dose-response for normal tissues. However, the single parameter used to estimate the gEUD may not suffice in accurately representing more complex biological effects that have been discussed in the literature. For instance, radio-biological parameters and hence the effects of fractionation are known to be dose-range dependent. Therefore, we propose an extended phenomenological eEUD formula that incorporates multiple VEPs accounting for dose-range dependency. The eEUD introduced is a piecewise polynomial expansion of the gEUD formula. In general, it allows for an arbitrary number of VEPs, each valid for a certain dose-range. We proved that the formula fulfills required mathematical and physical criteria such as invertibility of the underlying dose-effect and continuity in dose. Furthermore, it contains the gEUD as a special case, if all VEPs are equal to 'a' from the gEUD model. The eEUD is a concept that expands the gEUD such that it can theoretically represent dose-range dependent effects. Its practicality, however, remains to be shown. As a next step, this will be done by estimating the eEUD from patient data using maximum-likelihood based NTCP modelling in the same way

  10. 43 CFR 418.13 - Maximum allowable limits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... OF THE INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA... 308,319 acre-feet for the 1995 Example. The sample MAD corresponds to a system efficiency for full... Expected Project Distribution System Efficiency shows the target efficiencies which will be used over the...

  11. 43 CFR 418.38 - Maximum allowable diversion.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

  12. 43 CFR 418.38 - Maximum allowable diversion.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... water right holder the full water entitlement for irrigable eligible acres and includes distribution... deliveries at farm headgates have been approximately 90 percent of entitlements. This practice is expected to... efficiency target for the examples shown in the Newlands Project Water Budget table would be: 285,243 AF and...

  13. 43 CFR 418.13 - Maximum allowable limits.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... OF THE INTERIOR OPERATING CRITERIA AND PROCEDURES FOR THE NEWLANDS RECLAMATION PROJECT, NEVADA... 308,319 acre-feet for the 1995 Example. The sample MAD corresponds to a system efficiency for full... Expected Project Distribution System Efficiency shows the target efficiencies which will be used over the...

  14. The Application of an Army Prospective Payment Model Structured on the Standards Set Forth by the CHAMPUS Maximum Allowable Charges and the Center for Medicare and Medicaid Services: An Academic Approach

    DTIC Science & Technology

    2005-04-29

    To) 29-04-2005 Final Report July 2004 to July 2005 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER The appli’eation of an army prospective payment model structured...Z39.18 Prospective Payment Model 1 The Application of an Army Prospective Payment Model Structured on the Standards Set Forth by the CHAMPUS Maximum...Health Care Administration 20060315 090 Prospective Payment Model 2 Acknowledgments I would like to acknowledge my wife, Karen, who allowed me the

  15. 20170308 - Higher Throughput Toxicokinetics to Allow ...

    EPA Pesticide Factsheets

    As part of "Ongoing EDSP Directions & Activities" I will present CSS research on high throughput toxicokinetics, including in vitro data and models to allow rapid determination of the real world doses that may cause endocrine disruption. This is a presentation as part of the U.S. Environmental Protection Agency – Japan Ministry of the Environment 12th Bilateral Meeting on Endocrine Disruption Test Methods Development.

  16. Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film.

    PubMed

    Sonier, Marcus; Wronski, Matt; Yeboah, Collins

    2015-03-08

    Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose pro-files under large-area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central-axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤ 10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ~ 25% occur-ring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level.

  17. Evaluation of lens dose from anterior electron beams: comparison of Pinnacle and Gafchromic EBT3 film

    PubMed Central

    Wronski, Matt; Yeboah, Collins

    2015-01-01

    Lens dose is a concern during the treatment of facial lesions with anterior electron beams. Lead shielding is routinely employed to reduce lens dose and minimize late complications. The purpose of this work is twofold: 1) to measure dose profiles under large‐area lead shielding at the lens depth for clinical electron energies via film dosimetry; and 2) to assess the accuracy of the Pinnacle treatment planning system in calculating doses under lead shields. First, to simulate the clinical geometry, EBT3 film and 4 cm wide lead shields were incorporated into a Solid Water phantom. With the lead shield inside the phantom, the film was positioned at a depth of 0.7 cm below the lead, while a variable thickness of solid water, simulating bolus, was placed on top. This geometry was reproduced in Pinnacle to calculate dose profiles using the pencil beam electron algorithm. The measured and calculated dose profiles were normalized to the central‐axis dose maximum in a homogeneous phantom with no lead shielding. The resulting measured profiles, functions of bolus thickness and incident electron energy, can be used to estimate the lens dose under various clinical scenarios. These profiles showed a minimum lead margin of 0.5 cm beyond the lens boundary is required to shield the lens to ≤10% of the dose maximum. Comparisons with Pinnacle showed a consistent overestimation of dose under the lead shield with discrepancies of ∼25% occurring near the shield edge. This discrepancy was found to increase with electron energy and bolus thickness and decrease with distance from the lead edge. Thus, the Pinnacle electron algorithm is not recommended for estimating lens dose in this situation. The film measurements, however, allow for a reasonable estimate of lens dose from electron beams and for clinicians to assess the lead margin required to reduce the lens dose to an acceptable level. PACS number(s): 87.53.Bn, 87.53.Kn, 87.55.‐x, 87.55.D‐ PMID:27074448

  18. Single-Dose and Multiple-Dose Pharmacokinetics of Nicotine 6 mg Gum.

    PubMed

    Hansson, Anna; Rasmussen, Thomas; Kraiczi, Holger

    2017-04-01

    Under-dosing is a recognized problem with current nicotine replacement therapy (NRT). Therefore, a new 6mg nicotine gum has been developed. To compare the nicotine uptake from the 6mg gum versus currently available NRT products, two pharmacokinetic studies were performed. In one randomized crossover study, 44 healthy adult smokers received single doses of 6, 4, and 2mg nicotine gum, and 4mg nicotine lozenge on separate occasions. In a separate randomized crossover multiple-dose study over 11 hours, 50 healthy adult smokers received one 6mg gum every hour and 90 minutes, respectively, one 4mg gum every hour, and one 4mg lozenge every hour. In both studies, blood samples were collected over 12 hours to determine single-dose and multiple-dose pharmacokinetic variables. In the single-dose study, the amount of nicotine released from the 2, 4, and 6mg gums (1.44, 3.36, and 4.94mg) as well as the resulting maximum concentration and area under the curve (5.9, 10.1, and 13.8ng/mL, and 17.1, 30.7, 46.2ng/mL × h, respectively) increased with dose. The maximum concentration and area under the curve of the 6mg gum were 44% and 30% greater, respectively, than those for 4mg lozenge. Upon hourly administration, the steady-state average plasma nicotine concentration with 6mg gum (37.4ng/mL) was significantly higher than those for 4mg lozenge (28.3ng/mL) and 4mg gum (27.1ng/mL). Nicotine delivery via the 6mg gum results in higher plasma nicotine concentrations after a single dose and at steady state than with currently available oral NRT. Under-dosing is a recognized problem with current NRT. Therefore, a new 6mg nicotine gum has been developed. Our studies show that upon single-dose and multiple-dose administration, the 6mg gum releases and delivers more nicotine to the systemic circulation than 2mg gum, 4mg gum, and 4mg lozenge. Thus, each 6mg nicotine gum provides a higher degree of nicotine substitution and/or lasts for a longer period of time than currently available nicotine

  19. Evaluation of the adverse event profile and pharmacodynamics of toceranib phosphate administered to dogs with solid tumors at doses below the maximum tolerated dose

    PubMed Central

    2013-01-01

    Background The receptor kinase inhibitor toceranib phosphate (Palladia) was approved for use in dogs in 2009 using a dose of 3.25 mg/kg administered every other day. Preliminary data suggests that lower doses of toeceranib may be associated with a reduced adverse event profile while maintaining sufficient drug exposure to provide biologic activity. The purpose of this study was to determine the Cmax of toceranib in dogs with solid tumors receiving 2.5-2.75 mg/kg every other day and to document the adverse events associated with this dose rate. Secondary objectives included determination of plasma VEGF concentrations in treated dogs and response to therapy. Results Dogs with solid tumors were administered toceranib at an intended target dose ranging from 2.5-2.75 mg/kg every other day and plasma samples were obtained for analysis of toceranib and VEGF plasma concentrations on days 0, 7, 14 and 30 of the study at 6 and 8 hours post drug administration. Additionally, plasma samples were obtained at 0, 1, 2, 6, 8, and 12 hours from dogs on day 30 for confirmation of Cmax. Response to therapy was assessed using standard RECIST criteria and adverse events were characterized using the VCOG-CTCAE. Toceranib administered at doses between 2.4-2.9 mg/kg every other day resulted in an average 6–8 hr plasma concentration ranging from 100–120 ng/ml, well above the 40 ng/ml concentration associated with target inhibition. Plasma VEGF concentrations increased significantly over the 30 day treatment period indicating that VEGFR2 inhibition was likely achieved in the majority of dogs. The lower doses of toceranib used in this study were associated with a substantially reduced adverse event profile compared to the established label dose of 3.25 mg/kg EOD. Conclusions Doses of toceranib ranging from 2.4-2.9 mg/kg every other day provide drug exposure considered sufficient for target inhibition while resulting in an adverse event profile substantially reduced from that

  20. Direct measurement of a patient's entrance skin dose during pediatric cardiac catheterization

    PubMed Central

    Sun, Lue; Mizuno, Yusuke; Iwamoto, Mari; Goto, Takahisa; Koguchi, Yasuhiro; Miyamoto, Yuka; Tsuboi, Koji; Chida, Koichi; Moritake, Takashi

    2014-01-01

    Children with complex congenital heart diseases often require repeated cardiac catheterization; however, children are more radiosensitive than adults. Therefore, radiation-induced carcinogenesis is an important consideration for children who undergo those procedures. We measured entrance skin doses (ESDs) using radio-photoluminescence dosimeter (RPLD) chips during cardiac catheterization for 15 pediatric patients (median age, 1.92 years; males, n = 9; females, n = 6) with cardiac diseases. Four RPLD chips were placed on the patient's posterior and right side of the chest. Correlations between maximum ESD and dose–area products (DAP), total number of frames, total fluoroscopic time, number of cine runs, cumulative dose at the interventional reference point (IRP), body weight, chest thickness, and height were analyzed. The maximum ESD was 80 ± 59 (mean ± standard deviation) mGy. Maximum ESD closely correlated with both DAP (r = 0.78) and cumulative dose at the IRP (r = 0.82). Maximum ESD for coiling and ballooning tended to be higher than that for ablation, balloon atrial septostomy, and diagnostic procedures. In conclusion, we directly measured ESD using RPLD chips and found that maximum ESD could be estimated in real-time using angiographic parameters, such as DAP and cumulative dose at the IRP. Children requiring repeated catheterizations would be exposed to high radiation levels throughout their lives, although treatment influences radiation dose. Therefore, the radiation dose associated with individual cardiac catheterizations should be analyzed, and the effects of radiation throughout the lives of such patients should be followed. PMID:24968708

  1. Uncertainties in estimating heart doses from 2D-tangential breast cancer radiotherapy.

    PubMed

    Lorenzen, Ebbe L; Brink, Carsten; Taylor, Carolyn W; Darby, Sarah C; Ewertz, Marianne

    2016-04-01

    We evaluated the accuracy of three methods of estimating radiation dose to the heart from two-dimensional tangential radiotherapy for breast cancer, as used in Denmark during 1982-2002. Three tangential radiotherapy regimens were reconstructed using CT-based planning scans for 40 patients with left-sided and 10 with right-sided breast cancer. Setup errors and organ motion were simulated using estimated uncertainties. For left-sided patients, mean heart dose was related to maximum heart distance in the medial field. For left-sided breast cancer, mean heart dose estimated from individual CT-scans varied from <1Gy to >8Gy, and maximum dose from 5 to 50Gy for all three regimens, so that estimates based only on regimen had substantial uncertainty. When maximum heart distance was taken into account, the uncertainty was reduced and was comparable to the uncertainty of estimates based on individual CT-scans. For right-sided breast cancer patients, mean heart dose based on individual CT-scans was always <1Gy and maximum dose always <5Gy for all three regimens. The use of stored individual simulator films provides a method for estimating heart doses in left-tangential radiotherapy for breast cancer that is almost as accurate as estimates based on individual CT-scans. Copyright © 2016. Published by Elsevier Ireland Ltd.

  2. Dose gradient curve: A new tool for evaluating dose gradient.

    PubMed

    Sung, KiHoon; Choi, Young Eun

    2018-01-01

    Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice.

  3. Dose gradient curve: A new tool for evaluating dose gradient

    PubMed Central

    Choi, Young Eun

    2018-01-01

    Purpose Stereotactic radiotherapy, which delivers an ablative high radiation dose to a target volume for maximum local tumor control, requires a rapid dose fall-off outside the target volume to prevent extensive damage to nearby normal tissue. Currently, there is no tool to comprehensively evaluate the dose gradient near the target volume. We propose the dose gradient curve (DGC) as a new tool to evaluate the quality of a treatment plan with respect to the dose fall-off characteristics. Methods The average distance between two isodose surfaces was represented by the dose gradient index (DGI) estimated by a simple equation using the volume and surface area of isodose levels. The surface area was calculated by mesh generation and surface triangulation. The DGC was defined as a plot of the DGI of each dose interval as a function of the dose. Two types of DGCs, differential and cumulative, were generated. The performance of the DGC was evaluated using stereotactic radiosurgery plans for virtual targets. Results Over the range of dose distributions, the dose gradient of each dose interval was well-characterized by the DGC in an easily understandable graph format. Significant changes in the DGC were observed reflecting the differences in planning situations and various prescription doses. Conclusions The DGC is a rational method for visualizing the dose gradient as the average distance between two isodose surfaces; the shorter the distance, the steeper the dose gradient. By combining the DGC with the dose-volume histogram (DVH) in a single plot, the DGC can be utilized to evaluate not only the dose gradient but also the target coverage in routine clinical practice. PMID:29698471

  4. A two-dimensional biased coin design for dual-agent dose-finding trials.

    PubMed

    Sun, Zhichao; Braun, Thomas M

    2015-12-01

    Given the limited efficacy observed with single agents, there is growing interest in Phase I clinical trial designs that allow for identification of the maximum tolerated combination of two agents. Existing parametric designs may suffer from over- or under-parameterization. Thus, we have designed a nonparametric approach that can be easily understood and implemented for combination trials. We propose a two-stage adaptive biased coin design that extends existing methods for single-agent trials to dual-agent dose-finding trials. The basic idea of our design is to divide the entire trial into two stages and apply the biased coin design, with modification, in each stage. We compare the operating characteristics of our design to four competing parametric approaches via simulation in several numerical examples. Under all simulation scenarios we have examined, our method performs well in terms of identification of the maximum tolerated combination and allocation of patients relative to the performance of its competitors. In our design, stopping rule criteria and the distribution of the total sample size among the two stages are context-dependent, and both need careful consideration before adopting our design in practice. Efficacy is not a part of the dose-assignment algorithm, nor used to define the maximum tolerated combination. Our design inherits the favorable statistical properties of the biased coin design, is competitive with existing designs, and promotes patient safety by limiting patient exposure to toxic combinations whenever possible. © The Author(s) 2015.

  5. [Decision process of Notification Value by the Dose Index Registry system in X-ray computed tomography].

    PubMed

    Shinozaki, Masafumi; Muramatsu, Yoshihisa; Sasaki, Toru

    2014-01-01

    A new technical standard for X-ray computed tomography (CT) has been published by the National Electrical Manufacturers Association (NEMA) that allows the Alert Value and Notification Value for cumulative dose to be configurable by CT systems operators in conjunction with the XR-25 (Dose check) standard. In this study, a decision method of the Notification Values for reducing the radiation dose was examined using the dose index registry (DIR) system, during 122 continuous days from August 1, 2012 to November 30, 2012. CT images were obtained using the Discovery CT 750HD (GE Healthcare) and the dose index was calculated using the DoseWatch DIR system. The CT dose index-volume (CTDIvol) and dose-length product (DLP) were output from the DIR system in comma-separated value (CSV) file format for each examination protocol. All data were shown as a schematic boxplot using statistical processing software. The CTDIvol of a routine chest examination showed the following values (maximum: 23.84 mGy; minimum: 2.55 mGy; median: 7.60 mGy; 75% tile: 10.01 mGy; 25% tile: 6.54 mGy). DLP showed the following values (maximum: 944.56 mGy·cm; minimum: 97.25 mGy·cm; median: 307.35 mGy·cm; 75% tile: 406.87 mGy·cm; 25% tile: 255.75 mGy·cm). These results indicate that the 75% tile of CTDIvol and DLP as an initial value proved to be safe and efficient for CT examination and operation. We have thus established one way of determining the Notification Value from the output of the DIR system. Transfer back to the protocol of the CT and automated processing each numeric value in the DIR system is desired.

  6. The effect of dose heterogeneity on radiation risk in medical imaging.

    PubMed

    Samei, Ehsan; Li, Xiang; Chen, Baiyu; Reiman, Robert

    2013-06-01

    The current estimations of risk associated with medical imaging procedures rely on assessing the organ dose via direct measurements or simulation. The dose to each organ is assumed to be homogeneous. To take into account the differences in radiation sensitivities, the mean organ doses are weighted by a corresponding tissue-weighting coefficients provided by ICRP to calculate the effective dose, which has been used as a surrogate of radiation risk. However, those coefficients were derived under the assumption of a homogeneous dose distribution within each organ. That assumption is significantly violated in most medical-imaging procedures. In helical chest CT, for example, superficial organs (e.g. breasts) demonstrate a heterogeneous dose distribution, whereas organs on the peripheries of the irradiation field (e.g. liver) might possess a discontinuous dose profile. Projection radiography and mammography involve an even higher level of organ dose heterogeneity spanning up to two orders of magnitude. As such, mean dose or point measured dose values do not reflect the maximum energy deposited per unit volume of the organ. In this paper, the magnitude of the dose heterogeneity in both CT and projection X-ray imaging was reported, using Monte Carlo methods. The lung dose demonstrated factors of 1.7 and 2.2 difference between the mean and maximum dose for chest CT and radiography, respectively. The corresponding values for the liver were 1.9 and 3.5. For mammography and breast tomosynthesis, the difference between mean glandular dose and maximum glandular dose was 3.1. Risk models based on the mean dose were found to provide a reasonable reflection of cancer risk. However, for leukaemia, they were found to significantly under-represent the risk when the organ dose distribution is heterogeneous. A systematic study is needed to develop a risk model for heterogeneous dose distributions.

  7. Knowledge of appropriate acetaminophen doses and potential toxicities in an adult clinic population.

    PubMed

    Stumpf, Janice L; Skyles, Amy J; Alaniz, Cesar; Erickson, Steven R

    2007-01-01

    To evaluate the knowledge of appropriate doses and potential toxicities of acetaminophen and assess the ability to recognize products containing acetaminophen in an adult outpatient setting. Cross-sectional, prospective study. University adult general internal medicine (AGIM) clinic. 104 adult patients presenting to the clinic over consecutive weekdays in December 2003. Three-page, written questionnaire. Ability of patients to identify maximum daily doses and potential toxicities of acetaminophen and recognize products that contain acetaminophen. A large percentage of participants (68.3%) reported pain on a daily or weekly basis, and 78.9% reported use of acetaminophen in the past 6 months. Only 2 patients correctly identified the maximum daily dose of regular acetaminophen, and just 3 correctly identified the maximum dose of extra-strength acetaminophen. Furthermore, 28 patients were unsure of the maximum dose of either product. Approximately 63% of participants either had not received or were unsure whether information on the possible danger of high doses of acetaminophen had been previously provided to them. When asked to identify potential problems associated with high doses of acetaminophen, 43.3% of patients noted the liver would be affected. The majority of the patients (71.2%) recognized Tylenol as containing acetaminophen, but fewer than 15% correctly identified Vicodin, Darvocet, Tylox, Percocet, and Lorcet as containing acetaminophen. Although nearly 80% of this AGIM population reported recent acetaminophen use, their knowledge of the maximum daily acetaminophen doses and potential toxicities associated with higher doses was poor and appeared to be independent of education level, age, and race. This indicates a need for educational efforts to all patients receiving acetaminophen-containing products, especially since the ability to recognize multi-ingredient products containing acetaminophen was likewise poor.

  8. Perturbative expansion for the maximum of fractional Brownian motion.

    PubMed

    Delorme, Mathieu; Wiese, Kay Jörg

    2016-07-01

    Brownian motion is the only random process which is Gaussian, scale invariant, and Markovian. Dropping the Markovian property, i.e., allowing for memory, one obtains a class of processes called fractional Brownian motion, indexed by the Hurst exponent H. For H=1/2, Brownian motion is recovered. We develop a perturbative approach to treat the nonlocality in time in an expansion in ɛ=H-1/2. This allows us to derive analytic results beyond scaling exponents for various observables related to extreme value statistics: the maximum m of the process and the time t_{max} at which this maximum is reached, as well as their joint distribution. We test our analytical predictions with extensive numerical simulations for different values of H. They show excellent agreement, even for H far from 1/2.

  9. SU-F-T-113: Inherent Functional Dependence of Spinal Cord Doses of Variable Irradiated Volumes in Spine SBRT

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

    Ma, L; Braunstein, S; Chiu, J

    2016-06-15

    Purpose: Spinal cord tolerance for SBRT has been recommended for the maximum point dose level or at irradiated volumes such as 0.35 mL or 10% of contoured volumes. In this study, we investigated an inherent functional relationship that associates these dose surrogates for irradiated spinal cord volumes of up to 3.0 mL. Methods: A hidden variable termed as Effective Dose Radius (EDR) was formulated based on a dose fall-off model to correlate dose at irradiated spinal cord volumes ranging from 0 mL (point maximum) to 3.0 mL. A cohort of 15 spine SBRT cases was randomly selected to derive anmore » EDR-parameterized formula. The mean prescription dose for the studied cases was 21.0±8.0 Gy (range, 10–40Gy) delivered in 3±1 fractions with target volumes of 39.1 ± 70.6 mL. Linear regression and variance analysis were performed for the fitting parameters of variable EDR values. Results: No direct correlation was found between the dose at maximum point and doses at variable spinal cord volumes. For example, Pearson R{sup 2} = 0.643 and R{sup 2}= 0.491 were obtained when correlating the point maximum dose with the spinal cord dose at 1 mL and 3 mL, respectively. However, near perfect correlation (R{sup 2} ≥0.99) was obtained when corresponding parameterized EDRs. Specifically, Pearson R{sup 2}= 0.996 and R{sup 2} = 0.990 were obtained when correlating EDR (maximum point dose) with EDR (dose at 1 mL) and EDR(dose at 3 mL), respectively. As a result, high confidence level look-up tables were established to correlate spinal cord doses at the maximum point to any finite irradiated volumes. Conclusion: An inherent functional relationship was demonstrated for spine SBRT. Such a relationship unifies dose surrogates at variable cord volumes and proves that a single dose surrogate (e.g. point maximum dose) is mathematically sufficient in constraining the overall spinal cord dose tolerance for SBRT.« less

  10. Reducing dose to the lungs through loosing target dose homogeneity requirement for radiotherapy of non small cell lung cancer.

    PubMed

    Miao, Junjie; Yan, Hui; Tian, Yuan; Ma, Pan; Liu, Zhiqiang; Li, Minghui; Ren, Wenting; Chen, Jiayun; Zhang, Ye; Dai, Jianrong

    2017-11-01

    It is important to minimize lung dose during intensity-modulated radiation therapy (IMRT) of nonsmall cell lung cancer (NSCLC). In this study, an approach was proposed to reduce lung dose by relaxing the constraint of target dose homogeneity during treatment planning of IMRT. Ten NSCLC patients with lung tumor on the right side were selected. The total dose for planning target volume (PTV) was 60 Gy (2 Gy/fraction). For each patient, two IMRT plans with six beams were created in Pinnacle treatment planning system. The dose homogeneity of target was controlled by constraints on the maximum and uniform doses of target volume. One IMRT plan was made with homogeneous target dose (the resulting target dose was within 95%-107% of the prescribed dose), while another IMRT plan was made with inhomogeneous target dose (the resulting target dose was more than 95% of the prescribed dose). During plan optimization, the dose of cord and heart in two types of IMRT plans were kept nearly the same. The doses of lungs, PTV and organs at risk (OARs) between two types of IMRT plans were compared and analyzed quantitatively. For all patients, the lung dose was decreased in the IMRT plans with inhomogeneous target dose. On average, the mean dose, V5, V20, and V30 of lung were reduced by 1.4 Gy, 4.8%, 3.7%, and 1.7%, respectively, and the dose to normal tissue was also reduced. These reductions in DVH values were all statistically significant (P < 0.05). There were no significant differences between the two IMRT plans on V25, V30, V40, V50 and mean dose for heart. The maximum doses of cords in two type IMRT plans were nearly the same. IMRT plans with inhomogeneous target dose could protect lungs better and may be considered as a choice for treating NSCLC. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  11. Whole-remnant and maximum-voxel SPECT/CT dosimetry in {sup 131}I-NaI treatments of differentiated thyroid cancer

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

    Mínguez, Pablo, E-mail: pablo.minguezgabina@osakid

    Purpose: To investigate the possible differences between SPECT/CT based whole-remnant and maximum-voxel dosimetry in patients receiving radio-iodine ablation treatment of differentiated thyroid cancer (DTC). Methods: Eighteen DTC patients were administered 1.11 GBq of {sup 131}I-NaI after near-total thyroidectomy and rhTSH stimulation. Two patients had two remnants, so in total dosimetry was performed for 20 sites. Three SPECT/CT scans were performed for each patient at 1, 2, and 3–7 days after administration. The activity, the remnant mass, and the maximum-voxel activity were determined from these images and from a recovery-coefficient curve derived from experimental phantom measurements. The cumulated activity was estimatedmore » using trapezoidal-exponential integration. Finally, the absorbed dose was calculated using S-values for unit-density spheres in whole-remnant dosimetry and S-values for voxels in maximum-voxel dosimetry. Results: The mean absorbed dose obtained from whole-remnant dosimetry was 40 Gy (range 2–176 Gy) and from maximum-voxel dosimetry 34 Gy (range 2–145 Gy). For any given patient, the activity concentrations for each of the three time-points were approximately the same for the two methods. The effective half-lives varied (R = 0.865), mainly due to discrepancies in estimation of the longer effective half-lives. On average, absorbed doses obtained from whole-remnant dosimetry were 1.2 ± 0.2 (1 SD) higher than for maximum-voxel dosimetry, mainly due to differences in the S-values. The method-related differences were however small in comparison to the wide range of absorbed doses obtained in patients. Conclusions: Simple and consistent procedures for SPECT/CT based whole-volume and maximum-voxel dosimetry have been described, both based on experimentally determined recovery coefficients. Generally the results from the two approaches are consistent, although there is a small, systematic difference in the absorbed dose due to differences

  12. Estimate of radiation release from MIT reactor with un-finned LEU core during Maximum Hypothetical Accident

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

    Sun, Kaichao; Hu, Lin-wen; Newton, Thomas

    2017-05-01

    The Massachusetts Institute of Technology Reactor (MITR-II) is a research reactor in Cambridge, Massachusetts designed primarily for experiments using neutron beam and in-core irradiation facilities. At 6 MW, it delivers neutron flux and energy spectrum comparable to light water reactor (LWR) power reactors in a compact core using highly enriched uranium (HEU) fuel. In the framework of nonproliferation policy, the international community aims to minimize the use of HEU in civilian facilities. Within this context, research and test reactors have started a program to convert HEU fuel to low enriched uranium (LEU) fuel. A new type of LEU fuel basedmore » on a high density alloy of uranium and molybdenum (U-10Mo) is expected to allow the conversion of U.S. domestic high performance reactors like MITR. The current study focuses on the impacts of MITR Maximum Hypothetical Accident (MHA), which is also the Design Basis Accident (DBA), with LEU fuel. The MHA for the MITR is postulated to be a coolant flow blockage in the fuel element that contains the hottest fuel plate. It is assumed that the entire active portion of five fuel plates melts. The analysis shows that, within a 2-h period and by considering all the possible radiation sources and dose pathways, the overall off-site dose is 302.1 mrem (1 rem ¼ 0.01 Sv) Total Effective Dose Equivalent (TEDE) at 8 m exclusion area boundary (EAB) and a higher dose of 392.8 mrem TEDE is found at 21 m EAB. In all cases the dose remains below the 500 mrem total TEDE limit goal based on NUREG-1537 guidelines.« less

  13. Prediction of Normal Organ Absorbed Doses for [177Lu]Lu-PSMA-617 Using [44Sc]Sc-PSMA-617 Pharmacokinetics in Patients With Metastatic Castration Resistant Prostate Carcinoma.

    PubMed

    Khawar, Ambreen; Eppard, Elisabeth; Sinnes, Jean Phlippe; Roesch, Frank; Ahmadzadehfar, Hojjat; Kürpig, Stefan; Meisenheimer, Michael; Gaertner, Florian C; Essler, Markus; Bundschuh, Ralph A

    2018-04-23

    In vivo pharmacokinetic analysis of [Sc]Sc-PSMA-617 was used to determine the normal organ-absorbed doses that may result from therapeutic activity of [Lu]Lu-PSMA-617 and to predict the maximum permissible activity of [Lu]Lu-PSMA-617 for patients with metastatic castration-resistant prostate carcinoma. Pharmacokinetics of [Sc]Sc-PSMA-617 was evaluated in 5 patients with metastatic castration-resistant prostate carcinoma using dynamic PET/CT, followed by 3 static PET/CT acquisitions and blood sample collection over 19.5 hours, as well as urine sample collection at 2 time points. Total activity measured in source organs by PET imaging, as well as counts per milliliter measured in blood and urine samples, was decay corrected back to the time of injection using the half-life of Sc. Afterward, forward decay correction using the half-life of Lu was performed, extrapolating the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617. Source organs residence times and organ-absorbed doses for [Lu]Lu-PSMA-617 were calculated using OLINDA/EXM software. Bone marrow self-dose was determined with indirect blood-based method, and urinary bladder contents residence time was estimated by trapezoidal approximation. The maximum permissible activity of [Lu]Lu-PSMA-617 was calculated for each patient considering external beam radiotherapy toxicity limits for radiation absorbed doses to kidneys, bone marrow, salivary glands, and whole body. The predicted mean organ-absorbed doses were highest in the kidneys (0.44 mSv/MBq), followed by the salivary glands (0.23 mSv/MBq). The maximum permissible activity was highly variable among patients; limited by whole body-absorbed dose (1 patient), marrow-absorbed dose (1 patient), and kidney-absorbed dose (3 patients). [Sc]Sc-PSMA-617 PET/CT imaging is feasible and allows theoretical extrapolation of the pharmacokinetics of [Sc]Sc-PSMA-617 to that of [Lu]Lu-PSMA-617, with the intent of predicting normal organ-absorbed doses and maximum

  14. 24 CFR 965.505 - Standards for allowances for utilities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... PHA installs air conditioning, it shall provide, to the maximum extent economically feasible, systems... systems that offer each resident the option to choose air conditioning shall include retail meters or... allowances. For systems that offer residents the option to choose air conditioning but cannot be checkmetered...

  15. HADOC: a computer code for calculation of external and inhalation doses from acute radionuclide releases

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

    Strenge, D.L.; Peloquin, R.A.

    The computer code HADOC (Hanford Acute Dose Calculations) is described and instructions for its use are presented. The code calculates external dose from air submersion and inhalation doses following acute radionuclide releases. Atmospheric dispersion is calculated using the Hanford model with options to determine maximum conditions. Building wake effects and terrain variation may also be considered. Doses are calculated using dose conversion factor supplied in a data library. Doses are reported for one and fifty year dose commitment periods for the maximum individual and the regional population (within 50 miles). The fractional contribution to dose by radionuclide and exposure modemore » are also printed if requested.« less

  16. Maximum life spur gear design

    NASA Technical Reports Server (NTRS)

    Savage, M.; Mackulin, M. J.; Coe, H. H.; Coy, J. J.

    1991-01-01

    Optimization procedures allow one to design a spur gear reduction for maximum life and other end use criteria. A modified feasible directions search algorithm permits a wide variety of inequality constraints and exact design requirements to be met with low sensitivity to initial guess values. The optimization algorithm is described, and the models for gear life and performance are presented. The algorithm is compact and has been programmed for execution on a desk top computer. Two examples are presented to illustrate the method and its application.

  17. Maximum Relative Entropy of Coherence: An Operational Coherence Measure.

    PubMed

    Bu, Kaifeng; Singh, Uttam; Fei, Shao-Ming; Pati, Arun Kumar; Wu, Junde

    2017-10-13

    The operational characterization of quantum coherence is the cornerstone in the development of the resource theory of coherence. We introduce a new coherence quantifier based on maximum relative entropy. We prove that the maximum relative entropy of coherence is directly related to the maximum overlap with maximally coherent states under a particular class of operations, which provides an operational interpretation of the maximum relative entropy of coherence. Moreover, we show that, for any coherent state, there are examples of subchannel discrimination problems such that this coherent state allows for a higher probability of successfully discriminating subchannels than that of all incoherent states. This advantage of coherent states in subchannel discrimination can be exactly characterized by the maximum relative entropy of coherence. By introducing a suitable smooth maximum relative entropy of coherence, we prove that the smooth maximum relative entropy of coherence provides a lower bound of one-shot coherence cost, and the maximum relative entropy of coherence is equivalent to the relative entropy of coherence in the asymptotic limit. Similar to the maximum relative entropy of coherence, the minimum relative entropy of coherence has also been investigated. We show that the minimum relative entropy of coherence provides an upper bound of one-shot coherence distillation, and in the asymptotic limit the minimum relative entropy of coherence is equivalent to the relative entropy of coherence.

  18. The maximal cumulative solar UVB dose allowed to maintain healthy and young skin and prevent premature photoaging.

    PubMed

    Ichihashi, Masamitsu; Ando, Hideya

    2014-10-01

    The young facial skin of children with a smooth healthy appearance changes over time to photoaged skin having mottled pigmentation, solar lentigines, wrinkles, dry and rough skin, leathery texture, and benign and malignant tumors after exposure to chronic, repeated solar radiation. The first sign of photoaging in Japanese subjects is usually solar lentigines appearing around 20 years of age on the face. Fine wrinkles can then appear after 30 years of age, and benign skin tumors, seborrhoeic keratoses, can occur after 35 years of age in sun-exposed skin. We theoretically calculated the maximal daily exposure time to solar radiation, which could prevent the development of photoaged skin until 60 and 80 years of age, based on published data of personal solar UVB doses in sun-exposed skin. One MED (minimal erythema dose) was determined to be 20 mJ/cm(2) , and 200 MED was used as the average yearly dose of Japanese children. Further, we hypothesized that the annual dose of Japanese adults is the same as that of the children. The cumulative UVB dose at 20 years of age was thus calculated to be 4000 MED, and 22 MED was used as the maximal daily UVB dose based on data measured in Kobe, located in the central area of Japan. We used the solar UVB dose from 10:00 a.m. to 14:00 p.m. which occupies 60% of the total daily UV dose, to obtain the maximal UVB per hour in a day, and calculated the maximal daily UV exposure time that would delay the onset of solar lentigines until 60 or 80 years of age. The mean daily sun exposure time to maintain healthy skin until 80 years of age in the summer was calculated to be 2.54 min (0.14 MED) for unprotected skin and 127 min with the use of a sunscreen of SPF (sun protection factor) of 50. In this study, we did not evaluate the photoaging effect of UVA radiation, but findings of the adverse effects of UVA radiation on the skin have accumulated in the last decade. Therefore, it will be important to estimate the maximal dose of solar

  19. SU-F-T-340: Direct Editing of Dose Volume Histograms: Algorithms and a Unified Convex Formulation for Treatment Planning with Dose Constraints

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

    Ungun, B; Stanford University School of Medicine, Stanford, CA; Fu, A

    2016-06-15

    Purpose: To develop a procedure for including dose constraints in convex programming-based approaches to treatment planning, and to support dynamic modification of such constraints during planning. Methods: We present a mathematical approach that allows mean dose, maximum dose, minimum dose and dose volume (i.e., percentile) constraints to be appended to any convex formulation of an inverse planning problem. The first three constraint types are convex and readily incorporated. Dose volume constraints are not convex, however, so we introduce a convex restriction that is related to CVaR-based approaches previously proposed in the literature. To compensate for the conservatism of this restriction,more » we propose a new two-pass algorithm that solves the restricted problem on a first pass and uses this solution to form exact constraints on a second pass. In another variant, we introduce slack variables for each dose constraint to prevent the problem from becoming infeasible when the user specifies an incompatible set of constraints. We implement the proposed methods in Python using the convex programming package cvxpy in conjunction with the open source convex solvers SCS and ECOS. Results: We show, for several cases taken from the clinic, that our proposed method meets specified constraints (often with margin) when they are feasible. Constraints are met exactly when we use the two-pass method, and infeasible constraints are replaced with the nearest feasible constraint when slacks are used. Finally, we introduce ConRad, a Python-embedded free software package for convex radiation therapy planning. ConRad implements the methods described above and offers a simple interface for specifying prescriptions and dose constraints. Conclusion: This work demonstrates the feasibility of using modifiable dose constraints in a convex formulation, making it practical to guide the treatment planning process with interactively specified dose constraints. This work was supported by

  20. Pharmacokinetics of gabapentin in a novel gastric-retentive extended-release formulation: comparison with an immediate-release formulation and effect of dose escalation and food.

    PubMed

    Chen, Cuiping; Cowles, Verne E; Hou, Eddie

    2011-03-01

    The objectives of the 3 phase I studies described herein were (1) to compare the pharmacokinetics of gabapentin delivered from a novel gastric-retentive dosage form vs an immediate-release formulation, (2) to assess the dose proportionality of the gastric-retentive extended-release formulation, and (3) to determine the effect of food on the pharmacokinetics of gabapentin delivered from this formulation. The time to reach maximum plasma concentration (t(max)) was extended for gabapentin delivered from the gastric-retentive extended-release formulation compared with the immediate-release formulation. A dose-related increase in both the maximum plasma concentration (C(max)) and the area under the plasma concentration-time curve (AUC) was observed as the gabapentin dose increased from 600 to 2400 mg. Fed status and increased fat content delayed t(max) and enhanced C(max) and AUC in proportion to the fat content. The pharmacokinetics of gabapentin delivered from this extended-release formulation allows a reduced dosing frequency while maintaining bioavailability and possibly diminishing the occurrence of adverse events attributable to a slower increase to the peak concentration compared with the immediate-release dosage form.

  1. Radiation measurements and doses at SST altitudes

    NASA Technical Reports Server (NTRS)

    Foelsche, T.

    1972-01-01

    Radiation components and dose equivalents due to galactic and solar cosmic rays in the high atmosphere, especially at SST altitudes, are presented. The dose equivalent rate for the flight personnel flying 500 hours per year in cruise altitudes of 60,000-65,000 feet (18-19.5 km) in high magnetic latitudes is about 0.75-1.0 rem per year averaged over the solar cycle, or about 15-20 percent of the maximum permissible dose rate.

  2. RADIATION DOSE ASSESSMENT FOR THE BIOTA OF TERRESTRIAL ECOSYSTEMS IN THE SHORELINE ZONE OF THE CHERNOBYL NUCLEAR POWER PLANT COOLING POND

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

    Farfan, E.; Jannik, T.

    2011-10-01

    Radiation exposure of the biota in the shoreline area of the Chernobyl Nuclear Power Plant Cooling Pond was assessed to evaluate radiological consequences from the decommissioning of the Cooling Pond. The article addresses studies of radioactive contamination of the terrestrial faunal complex and radionuclide concentration ratios in bodies of small birds, small mammals, amphibians, and reptiles living in the area. The data were used to calculate doses to biota using the ERICA Tool software. Doses from {sup 90}Sr and {sup 137}Cs were calculated using the default parameters of the ERICA Tool and were shown to be consistent with biota dosesmore » calculated from the field data. However, the ERICA dose calculations for plutonium isotopes were much higher (2-5 times for small mammals and 10-14 times for birds) than the doses calculated using the experimental data. Currently, the total doses for the terrestrial biota do not exceed maximum recommended levels. However, if the Cooling Pond is allowed to drawdown naturally and the contaminants of the bottom sediments are exposed and enter the biological cycle, the calculated doses to biota may exceed the maximum recommended values. The study is important in establishing the current exposure conditions such that a baseline exists from which changes can be documented following the lowering of the reservoir water. Additionally, the study provided useful radioecological data on biota concentration ratios for some species that are poorly represented in the literature.« less

  3. Experience of micromultileaf collimator linear accelerator based single fraction stereotactic radiosurgery: Tumor dose inhomogeneity, conformity, and dose fall off

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

    Hong, Linda X.; Garg, Madhur; Lasala, Patrick

    2011-03-15

    Purpose: Sharp dose fall off outside a tumor is essential for high dose single fraction stereotactic radiosurgery (SRS) plans. This study explores the relationship among tumor dose inhomogeneity, conformity, and dose fall off in normal tissues for micromultileaf collimator (mMLC) linear accelerator (LINAC) based cranial SRS plans. Methods: Between January 2007 and July 2009, 65 patients with single cranial lesions were treated with LINAC-based SRS. Among them, tumors had maximum diameters {<=}20 mm: 31; between 20 and 30 mm: 21; and >30 mm: 13. All patients were treated with 6 MV photons on a Trilogy linear accelerator (Varian Medical Systems,more » Palo Alto, CA) with a tertiary m3 high-resolution mMLC (Brainlab, Feldkirchen, Germany), using either noncoplanar conformal fixed fields or dynamic conformal arcs. The authors also created retrospective study plans with identical beam arrangement as the treated plan but with different tumor dose inhomogeneity by varying the beam margins around the planning target volume (PTV). All retrospective study plans were normalized so that the minimum PTV dose was the prescription dose (PD). Isocenter dose, mean PTV dose, RTOG conformity index (CI), RTOG homogeneity index (HI), dose gradient index R{sub 50}-R{sub 100} (defined as the difference between equivalent sphere radius of 50% isodose volume and prescription isodose volume), and normal tissue volume (as a ratio to PTV volume) receiving 50% prescription dose (NTV{sub 50}) were calculated. Results: HI was inversely related to the beam margins around the PTV. CI had a ''V'' shaped relationship with HI, reaching a minimum when HI was approximately 1.3. Isocenter dose and mean PTV dose (as percentage of PD) increased linearly with HI. R{sub 50}-R{sub 100} and NTV{sub 50} initially declined with HI and then reached a plateau when HI was approximately 1.3. These trends also held when tumors were grouped according to their maximum diameters. The smallest tumor group (maximum

  4. Optimizing bevacizumab dosing in glioblastoma: less is more.

    PubMed

    Ajlan, Abdulrazag; Thomas, Piia; Albakr, Abdulrahman; Nagpal, Seema; Recht, Lawrence

    2017-10-01

    Compared to traditional chemotherapies, where dose limiting toxicities represent the maximum possible dose, monoclonal antibody therapies are used at doses well below maximum tolerated dose. However, there has been little effort to ascertain whether there is a submaximal dose at which the efficacy/complication ratio is maximized. Thus, despite the general practice of using Bevacizumab (BEV) at dosages of 10 mg/kg every other week for glioma patients, there has not been much prior work examining whether the relatively high complication rates reported with this agent can be decreased by lowering the dose without impairing efficacy. We assessed charts from 80 patients who received BEV for glioblastoma to survey the incidence of complications relative to BEV dose. All patients were treated with standard upfront chemoradiation. The toxicity was graded based on the NCI CTCAE, version 4.03. The rate of BEV serious related adverse events was 12.5% (n = 10/80). There were no serious adverse events (≥grade 3) when the administered dose was (<3 mg/kg/week), compared to a 21% incidence in those who received higher doses (≥3 mg/kg/week) (P < 0.01). Importantly, the three patient deaths attributable to BEV administration occurred in patients receiving higher doses. Patients who received lower doses also had a better survival rate, although this did not reach statistical significance [median OS 39 for low dose group vs. 17.3 for high dose group (P = 0.07)]. Lower rates of serious BEV related toxicities are noted when lower dosages are used without diminishing positive clinical impact. Further work aimed at optimizing BEV dosage is justified.

  5. Comparison of 2D and 3D Imaging and Treatment Planning for Postoperative Vaginal Apex High-Dose Rate Brachytherapy for Endometrial Cancer

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

    Russo, James K.; Armeson, Kent E.; Richardson, Susan, E-mail: srichardson@radonc.wustl.edu

    2012-05-01

    Purpose: To evaluate bladder and rectal doses using two-dimensional (2D) and 3D treatment planning for vaginal cuff high-dose rate (HDR) in endometrial cancer. Methods and Materials: Ninety-one consecutive patients treated between 2000 and 2007 were evaluated. Seventy-one and 20 patients underwent 2D and 3D planning, respectively. Each patient received six fractions prescribed at 0.5 cm to the superior 3 cm of the vagina. International Commission on Radiation Units and Measurements (ICRU) doses were calculated for 2D patients. Maximum and 2-cc doses were calculated for 3D patients. Organ doses were normalized to prescription dose. Results: Bladder maximum doses were 178% ofmore » ICRU doses (p < 0.0001). Two-cubic centimeter doses were no different than ICRU doses (p = 0.22). Two-cubic centimeter doses were 59% of maximum doses (p < 0.0001). Rectal maximum doses were 137% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 87% of ICRU doses (p < 0.0001). Two-cubic centimeter doses were 64% of maximum doses (p < 0.0001). Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final bladder dose to within 10% for 44%, 59%, 83%, 82%, and 89% of patients by using the ICRU dose, and for 45%, 55%, 80%, 85%, and 85% of patients by using the maximum dose, and for 37%, 68%, 79%, 79%, and 84% of patients by using the 2-cc dose. Using the first 1, 2, 3, 4 or 5 fractions, we predicted the final rectal dose to within 10% for 100%, 100%, 100%, 100%, and 100% of patients by using the ICRU dose, and for 60%, 65%, 70%, 75%, and 75% of patients by using the maximum dose, and for 68%, 95%, 84%, 84%, and 84% of patients by using the 2-cc dose. Conclusions: Doses to organs at risk vary depending on the calculation method. In some cases, final dose accuracy appears to plateau after the third fraction, indicating that simulation and planning may not be necessary in all fractions. A clinically relevant level of accuracy should be determined and further research conducted to

  6. Safety and maximum tolerated dose of superselective intraarterial cerebral infusion of bevacizumab after osmotic blood-brain barrier disruption for recurrent malignant glioma. Clinical article.

    PubMed

    Boockvar, John A; Tsiouris, Apostolos J; Hofstetter, Christoph P; Kovanlikaya, Ilhami; Fralin, Sherese; Kesavabhotla, Kartik; Seedial, Stephen M; Pannullo, Susan C; Schwartz, Theodore H; Stieg, Philip; Zimmerman, Robert D; Knopman, Jared; Scheff, Ronald J; Christos, Paul; Vallabhajosula, Shankar; Riina, Howard A

    2011-03-01

    The authors assessed the safety and maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of bevacizumab after osmotic disruption of the blood-brain barrier (BBB) with mannitol in patients with recurrent malignant glioma. A total of 30 patients with recurrent malignant glioma were included in the current study. The authors report no dose-limiting toxicity from a single dose of SIACI of bevacizumab up to 15 mg/kg after osmotic BBB disruption with mannitol. Two groups of patients were studied; those without prior bevacizumab exposure (naïve patients; Group I) and those who had received previous intravenous bevacizumab (exposed patients; Group II). Radiographic changes demonstrated on MR imaging were assessed at 1 month postprocedure. In Group I patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 34.7%, a median reduction in the volume of tumor enhancement of 46.9%, a median MR perfusion (MRP) reduction of 32.14%, and a T2-weighted/FLAIR signal decrease in 9 (47.4%) of 19 patients. In Group II patients, MR imaging at 1 month showed a median reduction in the area of tumor enhancement of 15.2%, a median volume reduction of 8.3%, a median MRP reduction of 25.5%, and a T2-weighted FLAIR decrease in 0 (0%) of 11 patients. The authors conclude that SIACI of mannitol followed by bevacizumab (up to 15 mg/kg) for recurrent malignant glioma is safe and well tolerated. Magnetic resonance imaging shows that SIACI treatment with bevacizumab can lead to reduction in tumor area, volume, perfusion, and T2-weighted/FLAIR signal.

  7. Dose calculation of dynamic trajectory radiotherapy using Monte Carlo.

    PubMed

    Manser, P; Frauchiger, D; Frei, D; Volken, W; Terribilini, D; Fix, M K

    2018-04-06

    Using volumetric modulated arc therapy (VMAT) delivery technique gantry position, multi-leaf collimator (MLC) as well as dose rate change dynamically during the application. However, additional components can be dynamically altered throughout the dose delivery such as the collimator or the couch. Thus, the degrees of freedom increase allowing almost arbitrary dynamic trajectories for the beam. While the dose delivery of such dynamic trajectories for linear accelerators is technically possible, there is currently no dose calculation and validation tool available. Thus, the aim of this work is to develop a dose calculation and verification tool for dynamic trajectories using Monte Carlo (MC) methods. The dose calculation for dynamic trajectories is implemented in the previously developed Swiss Monte Carlo Plan (SMCP). SMCP interfaces the treatment planning system Eclipse with a MC dose calculation algorithm and is already able to handle dynamic MLC and gantry rotations. Hence, the additional dynamic components, namely the collimator and the couch, are described similarly to the dynamic MLC by defining data pairs of positions of the dynamic component and the corresponding MU-fractions. For validation purposes, measurements are performed with the Delta4 phantom and film measurements using the developer mode on a TrueBeam linear accelerator. These measured dose distributions are then compared with the corresponding calculations using SMCP. First, simple academic cases applying one-dimensional movements are investigated and second, more complex dynamic trajectories with several simultaneously moving components are compared considering academic cases as well as a clinically motivated prostate case. The dose calculation for dynamic trajectories is successfully implemented into SMCP. The comparisons between the measured and calculated dose distributions for the simple as well as for the more complex situations show an agreement which is generally within 3% of the maximum

  8. A phase I report of paclitaxel dose escalation combined with a fixed dose of carboplatin in the treatment of head and neck carcinoma.

    PubMed

    Dunphy, F R; Boyd, J H; Kim, H J; Dunphy, C H; Harrison, B R; Dunleavy, T L; Rodriguez, J J; McDonough, E M; Minster, J R; Hilton, J G

    1997-05-15

    Standard therapy for advanced head and neck carcinoma is surgery and radiation, and the subsequent 5-year survival with this treatment has been less than 50%. New combined modality treatment strategies are being tested to improve survival. New chemotherapy combinations are being developed and administered simultaneously with, or sequenced with, radiation and surgery. This article reports the Phase I results of administering paclitaxel and carboplatin preoperatively. The authors' objective was to develop an outpatient chemotherapy that would downstage tumors and allow organ preservation with equal or improved survival as compared with standard therapy. Thirty-six patients with untreated Stage III/IV head and neck carcinoma were treated and were evaluable for toxicity. All patients had lesions that were measurable in perpendicular planes. A nonrandomized, Phase I design was used, according to which cohorts of patients were treated every 21 days with escalating doses of paclitaxel (150-265 mg/m2) given as a 3-hour infusion immediately preceding carboplatin. Premedication was used to avoid acute hypersensitivity reactions. Carboplatin was administered intravenously over 1 hour at a constant dose calculated with the Calvert formula (area under the curve, 7.5). The dose-limiting toxicities were neuropathy and thrombocytopenia at a paclitaxel dose of 265 mg/m2. Neutropenic fever was observed in 30% of patients at a paclitaxel dose of 250-265 mg/m2. Other observed adverse effects included pruritus, myalgia, arthralgia, alopecia, nausea, and vomiting. Toxicity was acceptable. The maximum tolerated dose of paclitaxel was 230 mg/m2 without hematopoietic growth factor, or 250 mg/m2 with hematopoietic growth factor, the carboplatin dose held constant, calculated at area under the curve of 7.5. Phase II studies of this combination are warranted in the treatment of these carcinomas.

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

    PubMed

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

    2014-03-01

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

  10. Maximum allowable exposure to different heat radiation levels in three types of heat protective clothing

    PubMed Central

    HEUS, Ronald; DENHARTOG, Emiel A.

    2017-01-01

    To determine safe working conditions in emergency situations at petro-chemical plants in the Netherlands a study was performed on three protective clothing combinations (operator’s, firefighter’s and aluminized). The clothing was evaluated at four different heat radiation levels (3.0, 4.6, 6.3 and 10.0 k∙W∙m−2) in standing and walking posture with a thermal manikin RadMan™. Time till pain threshold (43°C) is set as a cut-off criterion for regular activities. Operator’s clothing did not fulfil requirements to serve as protective clothing for necessary activities at heat radiation levels above 1.5 k∙W∙m−2 as was stated earlier by Den Hartog and Heus1). With firefighter’s clothing it was possible to work almost three min up to 4.6 k∙W∙m−2. At higher heat radiation levels firefighter’s clothing gave insufficient protection and aluminized clothing should be used. Maximum working times in aluminized clothing at 6.3 k∙W∙m−2 was about five min. At levels of 10.0 k∙W∙m−2 (emergency conditions) emergency responders should move immediately to lower heat radiation levels. PMID:28978903

  11. Dynamically accumulated dose and 4D accumulated dose for moving tumors

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

    Li Heng; Li Yupeng; Zhang Xiaodong

    2012-12-15

    Purpose: The purpose of this work was to investigate the relationship between dynamically accumulated dose (dynamic dose) and 4D accumulated dose (4D dose) for irradiation of moving tumors, and to quantify the dose uncertainty induced by tumor motion. Methods: The authors established that regardless of treatment modality and delivery properties, the dynamic dose will converge to the 4D dose, instead of the 3D static dose, after multiple deliveries. The bounds of dynamic dose, or the maximum estimation error using 4D or static dose, were established for the 4D and static doses, respectively. Numerical simulations were performed (1) to prove themore » principle that for each phase, after multiple deliveries, the average number of deliveries for any given time converges to the total number of fractions (K) over the number of phases (N); (2) to investigate the dose difference between the 4D and dynamic doses as a function of the number of deliveries for deliveries of a 'pulsed beam'; and (3) to investigate the dose difference between 4D dose and dynamic doses as a function of delivery time for deliveries of a 'continuous beam.' A Poisson model was developed to estimate the mean dose error as a function of number of deliveries or delivered time for both pulsed beam and continuous beam. Results: The numerical simulations confirmed that the number of deliveries for each phase converges to K/N, assuming a random starting phase. Simulations for the pulsed beam and continuous beam also suggested that the dose error is a strong function of the number of deliveries and/or total deliver time and could be a function of the breathing cycle, depending on the mode of delivery. The Poisson model agrees well with the simulation. Conclusions: Dynamically accumulated dose will converge to the 4D accumulated dose after multiple deliveries, regardless of treatment modality. Bounds of the dynamic dose could be determined using quantities derived from 4D doses, and the mean dose

  12. “Hallucinations” Following Acute Cannabis Dosing: A Case Report and Comparison to Other Hallucinogenic Drugs

    PubMed Central

    Barrett, Frederick S.; Schlienz, Nicolas J.; Lembeck, Natalie; Waqas, Muhammad; Vandrey, Ryan

    2018-01-01

    Abstract Introduction: Cannabis has been historically classified as a hallucinogen. However, subjective cannabis effects do not typically include hallucinogen-like effects. Empirical reports of hallucinogen-like effects produced by cannabis in controlled settings, particularly among healthy research volunteers, are rare and have mostly occurred after administration of purified Δ-9 tetrahydrocannabinol (THC) rather than whole plant cannabis. Methods: The case of a healthy 30-year-old male who experienced auditory and visual hallucinations in a controlled laboratory study after inhaling vaporized cannabis that contained 25 mg THC (case dose) is presented. Ratings on the Hallucinogen Rating Scale (HRS) following the case dose are compared with HRS ratings obtained from the participant after other doses of cannabis and with archival HRS data from laboratory studies involving acute doses of cannabis, psilocybin, dextromethorphan (DXM), and salvinorin A. Results: Scores on the Volition subscale of the HRS were greater for the case dose than for the maximum dose administered in any other comparison study. Scores on the Intensity and Perception subscales were greater for the case dose than for the maximum dose of cannabis, psilocybin, or salvinorin A. Scores on the Somaesthesia subscale were greater for the case dose than for the maximum dose of DXM, salvinorin A, or cannabis. Scores on the Affect and Cognition subscales for the case dose were significantly lower than for the maximum doses of psilocybin and DXM. Conclusion: Acute cannabis exposure in a healthy adult male resulted in self-reported hallucinations that rated high in magnitude on several subscales of the HRS. However, the hallucinatory experience in this case was qualitatively different than that typically experienced by participants receiving classic and atypical hallucinogens, suggesting that the hallucinatory effects of cannabis may have a unique pharmacological mechanism of action. This type of adverse

  13. Calculation of midplane dose for total body irradiation from entrance and exit dose MOSFET measurements.

    PubMed

    Satory, P R

    2012-03-01

    This work is the development of a MOSFET based surface in vivo dosimetry system for total body irradiation patients treated with bilateral extended SSD beams using PMMA missing tissue compensators adjacent to the patient. An empirical formula to calculate midplane dose from MOSFET measured entrance and exit doses has been derived. The dependency of surface dose on the air-gap between the spoiler and the surface was investigated by suspending a spoiler above a water phantom, and taking percentage depth dose measurements (PDD). Exit and entrances doses were measured with MOSFETs in conjunction with midplane doses measured with an ion chamber. The entrance and exit doses were combined using an exponential attenuation formula to give an estimate of midplane dose and were compared to the midplane ion chamber measurement for a range of phantom thicknesses. Having a maximum PDD at the surface simplifies the prediction of midplane dose, which is achieved by ensuring that the air gap between the compensator and the surface is less than 10 cm. The comparison of estimated midplane dose and measured midplane dose showed no dependence on phantom thickness and an average correction factor of 0.88 was found. If the missing tissue compensators are kept within 10 cm of the patient then MOSFET measurements of entrance and exit dose can predict the midplane dose for the patient.

  14. Isotretinoin kinetics after 80 to 320 mg oral doses.

    PubMed

    Colburn, W A; Gibson, D M

    1985-04-01

    Twelve healthy male subjects received 80, 160, 240, and 320 mg doses of oral isotretinoin as multiples of 40 mg capsules separated by 2-week washout periods in a randomized, crossover design. Blood samples were drawn at specific times over a 72-hour period after dosing. Blood concentrations of isotretinoin as well as its major metabolite, 4-oxo-isotretinoin, were determined by a specific HPLC method. In addition to the normal laboratory battery of tests, serum triglyceride levels were determined before the first dose and again 72 hours after each of the four doses. Mean (+/- SD) maximum concentrations after 80 to 320 mg doses were 366 +/- 159, 820 +/- 474, 1056 +/- 547, and 981 +/- 381 ng/ml, whereas the respective AUC0-infinity values were 3690 +/- 1280, 7030 +/- 4140, 9780 +/- 6080, and 9040 +/- 2900 ng X hr/ml. The observed apparent elimination t1/2 remained approximately the same (14.7 hours) for each dose. The maximum concentration and AUC values for isotretinoin appear to be dose proportional from 80 to 240 mg but plateau at the 320 mg dose level. Therefore, because isotretinoin blood concentrations may not increase with higher doses in the fasting state, single, oral doses in excess of 240 mg should be used with caution. The data also suggest that elevated triglyceride levels are not a simple function of isotretinoin blood concentrations across the entire study population and dose range studied, but that in subjects with triglyceride levels in excess of the normal range triglyceride levels were positively related to isotretinoin blood concentrations.

  15. Low-dose megavoltage cone-beam computed tomography for lung tumors using a high-efficiency image receptor

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

    Sillanpaa, Jussi; Chang Jenghwa; Mageras, Gikas

    2006-09-15

    We report on the capabilities of a low-dose megavoltage cone-beam computed tomography (MV CBCT) system. The high-efficiency image receptor consists of a photodiode array coupled to a scintillator composed of individual CsI crystals. The CBCT system uses the 6 MV beam from a linear accelerator. A synchronization circuit allows us to limit the exposure to one beam pulse [0.028 monitor units (MU)] per projection image. 150-500 images (4.2-13.9 MU total) are collected during a one-minute scan and reconstructed using a filtered backprojection algorithm. Anthropomorphic and contrast phantoms are imaged and the contrast-to-noise ratio of the reconstruction is studied as amore » function of the number of projections and the error in the projection angles. The detector dose response is linear (R{sup 2} value 0.9989). A 2% electron density difference is discernible using 460 projection images and a total exposure of 13 MU (corresponding to a maximum absorbed dose of about 12 cGy in a patient). We present first patient images acquired with this system. Tumors in lung are clearly visible and skeletal anatomy is observed in sufficient detail to allow reproducible registration with the planning kV CT images. The MV CBCT system is shown to be capable of obtaining good quality three-dimensional reconstructions at relatively low dose and to be clinically usable for improving the accuracy of radiotherapy patient positioning.« less

  16. Location Modification Factors for Potential Dose Estimation

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

    Snyder, Sandra F.; Barnett, J. Matthew

    2017-01-01

    A Department of Energy facility must comply with the National Emission Standard for Hazardous Air Pollutants for radioactive air emissions. The standard is an effective dose of less than 0.1 mSv yr-1 to the maximum public receptor. Additionally, a lower dose level may be assigned to a specific emission point in a State issued permit. A method to efficiently estimate the expected dose for future emissions is described. This method is most appropriately applied to a research facility with several emission points with generally low emission levels of numerous isotopes.

  17. Net fractional depth dose: a basis for a unified analytical description of FDD, TAR, TMR, and TPR

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

    van de Geijn, J.; Fraass, B.A.

    The net fractional depth dose (NFD) is defined as the fractional depth dose (FDD) corrected for inverse square law. Analysis of its behavior as a function of depth, field size, and source-surface distance has led to an analytical description with only seven model parameters related to straightforward physical properties. The determination of the characteristic parameter values requires only seven experimentally determined FDDs. The validity of the description has been tested for beam qualities ranging from /sup 60/Co gamma rays to 18-MV x rays, using published data from several different sources as well as locally measured data sets. The small numbermore » of model parameters is attractive for computer or hand-held calculator applications. The small amount of required measured data is important in view of practical data acquisition for implementation of a computer-based dose calculation system. The generating function allows easy and accurate generation of FDD, tissue-air ratio, tissue-maximum ratio, and tissue-phantom ratio tables.« less

  18. 10 CFR 800.200 - Maximum loan; allowable costs.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., but are not limited to: (1) Bid bond premiums. (2) Financial, accounting, legal, engineering and other professional, consulting or similar fees and service charges. (3) Printing and reproduction costs. (4) Travel...

  19. 10 CFR 800.200 - Maximum loan; allowable costs.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., but are not limited to: (1) Bid bond premiums. (2) Financial, accounting, legal, engineering and other professional, consulting or similar fees and service charges. (3) Printing and reproduction costs. (4) Travel...

  20. 10 CFR 800.200 - Maximum loan; allowable costs.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., but are not limited to: (1) Bid bond premiums. (2) Financial, accounting, legal, engineering and other professional, consulting or similar fees and service charges. (3) Printing and reproduction costs. (4) Travel...

  1. 10 CFR 800.200 - Maximum loan; allowable costs.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., but are not limited to: (1) Bid bond premiums. (2) Financial, accounting, legal, engineering and other professional, consulting or similar fees and service charges. (3) Printing and reproduction costs. (4) Travel...

  2. 10 CFR 800.200 - Maximum loan; allowable costs.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., but are not limited to: (1) Bid bond premiums. (2) Financial, accounting, legal, engineering and other professional, consulting or similar fees and service charges. (3) Printing and reproduction costs. (4) Travel...

  3. In vivo urethral dose measurements: a method to verify high dose rate prostate treatments.

    PubMed

    Brezovich, I A; Duan, J; Pareek, P N; Fiveash, J; Ezekiel, M

    2000-10-01

    Radiation doses delivered in high dose rate (HDR) brachytherapy are susceptible to many inaccuracies and errors, including imaging, planning and delivery. Consequently, the dose delivered to the patient may deviate substantially from the treatment plan. We investigated the feasibility of using TLD measurements in the urethra to estimate the discrepancy in treatments for prostate cancer. The dose response of the 1 mm diam, 6 mm long LiF rods that we used for the in vivo measurements was calibrated with the 192Ir HDR source, as well as a 60Co teletherapy unit. A train of 20 rods contained in a sterile plastic tube was inserted into the urethral (Foley) catheter for the duration of a treatment fraction, and the measured doses were compared to the treatment plan. Initial results from a total of seven treatments in four patients show good agreement between theory and experiment. Analysis of any one treatment showed agreement within 11.7% +/- 6.2% for the highest dose encountered in the central prostatic urethra, and within 10.4% +/- 4.4% for the mean dose. Taking the average over all seven treatments shows agreement within 1.7% for the maximum urethral dose, and within 1.5% for the mean urethral dose. Based on these initial findings it seems that planned prostate doses can be accurately reproduced in the clinic.

  4. Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials

    PubMed Central

    Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L.; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

    2016-01-01

    Purpose The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. Patients and Methods We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. Results A total of 13,008 toxicities were captured: 46% of patients’ first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m2, the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. Conclusions When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. PMID:26926682

  5. Case Example of Dose Optimization Using Data From Bortezomib Dose-Finding Clinical Trials.

    PubMed

    Lee, Shing M; Backenroth, Daniel; Cheung, Ying Kuen Ken; Hershman, Dawn L; Vulih, Diana; Anderson, Barry; Ivy, Percy; Minasian, Lori

    2016-04-20

    The current dose-finding methodology for estimating the maximum tolerated dose of investigational anticancer agents is based on the cytotoxic chemotherapy paradigm. Molecularly targeted agents (MTAs) have different toxicity profiles, which may lead to more long-lasting mild or moderate toxicities as well as to late-onset and cumulative toxicities. Several approved MTAs have been poorly tolerated during long-term administration, leading to postmarketing dose optimization studies to re-evaluate the optimal treatment dose. Using data from completed bortezomib dose-finding trials, we explore its toxicity profile, optimize its dose, and examine the appropriateness of current designs for identifying an optimal dose. We classified the toxicities captured from 481 patients in 14 bortezomib dose-finding studies conducted through the National Cancer Institute Cancer Therapy Evaluation Program, computed the incidence of late-onset toxicities, and compared the incidence of dose-limiting toxicities (DLTs) among groups of patients receiving different doses of bortezomib. A total of 13,008 toxicities were captured: 46% of patients' first DLTs and 88% of dose reductions or discontinuations of treatment because of toxicity were observed after the first cycle. Moreover, for the approved dose of 1.3 mg/m(2), the estimated cumulative incidence of DLT was > 50%, and the estimated cumulative incidence of dose reduction or treatment discontinuation because of toxicity was nearly 40%. When considering the entire course of treatment, the approved bortezomib dose exceeds the conventional ceiling DLT rate of 20% to 33%. Retrospective analysis of trial data provides an opportunity for dose optimization of MTAs. Future dose-finding studies of MTAs should take into account late-onset toxicities to ensure that a tolerable dose is identified for future efficacy and comparative trials. © 2016 by American Society of Clinical Oncology.

  6. Proton depth dose distribution: 3-D calculation of dose distributions from solar flare irradiation

    NASA Astrophysics Data System (ADS)

    Leavitt, Dennis D.

    1990-11-01

    Relative depth dose distribution to the head from 3 typical solar flare proton events were calculated for 3 different exposure geometries: (1) single directional radiation incident upon a fixed head; (2) single directional radiation incident upon head rotating axially (2-D rotation); and (3) omnidirectional radiation incident upon head (3-D rotation). Isodose distributions in the transverse plane intersecting isocenter are presented for each of the 3 solar flare events in all 3 exposure geometries. In all 3 calculation configurations the maximum predicted dose occurred on the surface of the head. The dose at the isocenter of the head relative to the surface dose for the 2-D and 3-D rotation geometries ranged from 2 to 19 percent, increasing with increasing energy of the event. The calculations suggest the superficially located organs (lens of the eye and skin) are at greatest risk for the proton events studied here.

  7. Allowable levels of take for the trade in Nearctic songbirds.

    PubMed

    Johnson, Fred A; Walters, Matthew A H; Boomer, G Scott

    2012-06-01

    The take of Nearctic songbirds for the caged-bird trade is an important cultural and economic activity in Mexico, but its sustainability has been questioned. We relied on the theta-logistic population model to explore options for setting allowable levels of take for 11 species of passerines that were subject to legal take in Mexico in 2010. Because estimates of population size necessary for making-periodic adjustments to levels of take are not routinely available, we examined the conditions under which a constant level of take might contribute to population depletion (i.e., a population below its level of maximum net productivity). The chance of depleting a population is highest when levels of take are based on population sizes that happen to be much lower or higher than the level of maximum net productivity, when environmental variation is relatively high and serially correlated, and when the interval between estimation of population size is relatively long (> or = 5 years). To estimate demographic rates of songbirds involved in the Mexican trade we relied on published information and allometric relationships to develop probability distributions for key rates, and then sampled from those distributions to characterize the uncertainty in potential levels of take. Estimates of the intrinsic rate of growth (r) were highly variable, but median estimates were consistent with those expected for relatively short-lived, highly fecund species. Allowing for the possibility of nonlinear density dependence generally resulted in allowable levels of take that were lower than would have been the case under an assumption of linearity. Levels of take authorized by the Mexican government in 2010 for the 11 species we examined were small in comparison to relatively conservative allowable levels of take (i.e., those intended to achieve 50% of maximum sustainable yield). However, the actual levels of take in Mexico are unknown and almost certainly exceed the authorized take. Also, the

  8. Allowable levels of take for the trade in Nearctic songbirds

    USGS Publications Warehouse

    Johnson, Fred A.; Walters, Matthew A.H.; Boomer, G. Scott

    2012-01-01

    The take of Nearctic songbirds for the caged-bird trade is an important cultural and economic activity in Mexico, but its sustainability has been questioned. We relied on the theta-logistic population model to explore options for setting allowable levels of take for 11 species of passerines that were subject to legal take in Mexico in 2010. Because estimates of population size necessary for making periodic adjustments to levels of take are not routinely available, we examined the conditions under which a constant level of take might contribute to population depletion (i.e., a population below its level of maximum net productivity). The chance of depleting a population is highest when levels of take are based on population sizes that happen to be much lower or higher than the level of maximum net productivity, when environmental variation is relatively high and serially correlated, and when the interval between estimation of population size is relatively long (≥5 years). To estimate demographic rates of songbirds involved in the Mexican trade we relied on published information and allometric relationships to develop probability distributions for key rates, and then sampled from those distributions to characterize the uncertainty in potential levels of take. Estimates of the intrinsic rate of growth (r) were highly variable, but median estimates were consistent with those expected for relatively short-lived, highly fecund species. Allowing for the possibility of nonlinear density dependence generally resulted in allowable levels of take that were lower than would have been the case under an assumption of linearity. Levels of take authorized by the Mexican government in 2010 for the 11 species we examined were small in comparison to relatively conservative allowable levels of take (i.e., those intended to achieve 50% of maximum sustainable yield). However, the actual levels of take in Mexico are unknown and almost certainly exceed the authorized take. Also, the take

  9. Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL).

    PubMed

    Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

    2014-03-01

    With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus transverse diameter on the axial surface, percutaneous puncture depth

  10. Determination of the maximum-depth to potential field sources by a maximum structural index method

    NASA Astrophysics Data System (ADS)

    Fedi, M.; Florio, G.

    2013-01-01

    A simple and fast determination of the limiting depth to the sources may represent a significant help to the data interpretation. To this end we explore the possibility of determining those source parameters shared by all the classes of models fitting the data. One approach is to determine the maximum depth-to-source compatible with the measured data, by using for example the well-known Bott-Smith rules. These rules involve only the knowledge of the field and its horizontal gradient maxima, and are independent from the density contrast. Thanks to the direct relationship between structural index and depth to sources we work out a simple and fast strategy to obtain the maximum depth by using the semi-automated methods, such as Euler deconvolution or depth-from-extreme-points method (DEXP). The proposed method consists in estimating the maximum depth as the one obtained for the highest allowable value of the structural index (Nmax). Nmax may be easily determined, since it depends only on the dimensionality of the problem (2D/3D) and on the nature of the analyzed field (e.g., gravity field or magnetic field). We tested our approach on synthetic models against the results obtained by the classical Bott-Smith formulas and the results are in fact very similar, confirming the validity of this method. However, while Bott-Smith formulas are restricted to the gravity field only, our method is applicable also to the magnetic field and to any derivative of the gravity and magnetic field. Our method yields a useful criterion to assess the source model based on the (∂f/∂x)max/fmax ratio. The usefulness of the method in real cases is demonstrated for a salt wall in the Mississippi basin, where the estimation of the maximum depth agrees with the seismic information.

  11. Higher Throughput Toxicokinetics to Allow Extrapolation (EPA-Japan Bilateral EDSP meeting)

    EPA Science Inventory

    As part of "Ongoing EDSP Directions & Activities" I will present CSS research on high throughput toxicokinetics, including in vitro data and models to allow rapid determination of the real world doses that may cause endocrine disruption.

  12. Spatio-temporal observations of tertiary ozone maximum

    NASA Astrophysics Data System (ADS)

    Sofieva, V. F.; Kyrölä, E.; Verronen, P. T.; Seppälä, A.; Tamminen, J.; Marsh, D. R.; Smith, A. K.; Bertaux, J.-L.; Hauchecorne, A.; Dalaudier, F.; Fussen, D.; Vanhellemont, F.; Fanton D'Andon, O.; Barrot, G.; Guirlet, M.; Fehr, T.; Saavedra, L.

    2009-03-01

    We present spatio-temporal distributions of tertiary ozone maximum (TOM), based on GOMOS (Global Ozone Monitoring by Occultation of Stars) ozone measurements in 2002-2006. The tertiary ozone maximum is typically observed in the high-latitude winter mesosphere at altitude ~72 km. Although the explanation for this phenomenon has been found recently - low concentrations of odd-hydrogen cause the subsequent decrease in odd-oxygen losses - models have had significant deviations from existing observations until recently. Good coverage of polar night regions by GOMOS data has allowed for the first time obtaining spatial and temporal observational distributions of night-time ozone mixing ratio in the mesosphere. The distributions obtained from GOMOS data have specific features, which are variable from year to year. In particular, due to a long lifetime of ozone in polar night conditions, the downward transport of polar air by the meridional circulation is clearly observed in the tertiary ozone maximum time series. Although the maximum tertiary ozone mixing ratio is achieved close to the polar night terminator (as predicted by the theory), TOM can be observed also at very high latitudes, not only in the beginning and at the end, but also in the middle of winter. We have compared the observational spatio-temporal distributions of tertiary ozone maximum with that obtained using WACCM (Whole Atmosphere Community Climate Model) and found that the specific features are reproduced satisfactorily by the model. Since ozone in the mesosphere is very sensitive to HOx concentrations, energetic particle precipitation can significantly modify the shape of the ozone profiles. In particular, GOMOS observations have shown that the tertiary ozone maximum was temporarily destroyed during the January 2005 and December 2006 solar proton events as a result of the HOx enhancement from the increased ionization.

  13. Intra-patient comparison of reduced-dose model-based iterative reconstruction with standard-dose adaptive statistical iterative reconstruction in the CT diagnosis and follow-up of urolithiasis.

    PubMed

    Tenant, Sean; Pang, Chun Lap; Dissanayake, Prageeth; Vardhanabhuti, Varut; Stuckey, Colin; Gutteridge, Catherine; Hyde, Christopher; Roobottom, Carl

    2017-10-01

    To evaluate the accuracy of reduced-dose CT scans reconstructed using a new generation of model-based iterative reconstruction (MBIR) in the imaging of urinary tract stone disease, compared with a standard-dose CT using 30% adaptive statistical iterative reconstruction. This single-institution prospective study recruited 125 patients presenting either with acute renal colic or for follow-up of known urinary tract stones. They underwent two immediately consecutive scans, one at standard dose settings and one at the lowest dose (highest noise index) the scanner would allow. The reduced-dose scans were reconstructed using both ASIR 30% and MBIR algorithms and reviewed independently by two radiologists. Objective and subjective image quality measures as well as diagnostic data were obtained. The reduced-dose MBIR scan was 100% concordant with the reference standard for the assessment of ureteric stones. It was extremely accurate at identifying calculi of 3 mm and above. The algorithm allowed a dose reduction of 58% without any loss of scan quality. A reduced-dose CT scan using MBIR is accurate in acute imaging for renal colic symptoms and for urolithiasis follow-up and allows a significant reduction in dose. • MBIR allows reduced CT dose with similar diagnostic accuracy • MBIR outperforms ASIR when used for the reconstruction of reduced-dose scans • MBIR can be used to accurately assess stones 3 mm and above.

  14. Pareto versus lognormal: A maximum entropy test

    NASA Astrophysics Data System (ADS)

    Bee, Marco; Riccaboni, Massimo; Schiavo, Stefano

    2011-08-01

    It is commonly found that distributions that seem to be lognormal over a broad range change to a power-law (Pareto) distribution for the last few percentiles. The distributions of many physical, natural, and social events (earthquake size, species abundance, income and wealth, as well as file, city, and firm sizes) display this structure. We present a test for the occurrence of power-law tails in statistical distributions based on maximum entropy. This methodology allows one to identify the true data-generating processes even in the case when it is neither lognormal nor Pareto. The maximum entropy approach is then compared with other widely used methods and applied to different levels of aggregation of complex systems. Our results provide support for the theory that distributions with lognormal body and Pareto tail can be generated as mixtures of lognormally distributed units.

  15. Survey of patient knowledge related to acetaminophen recognition, dosing, and toxicity.

    PubMed

    Hornsby, Lori B; Whitley, Heather P; Hester, E Kelly; Thompson, Melissa; Donaldson, Amy

    2010-01-01

    To assess patient knowledge regarding acetaminophen dosing, toxicity, and recognition of acetaminophen-containing products. Descriptive, nonexperimental, cross-sectional study. Alabama, January 2007 to February 2008. 284 patients at four outpatient medical facilities. 12-item investigator-administered questionnaire. Degree of patient knowledge regarding acetaminophen safety, dosing recommendations, toxicity, alternative names and abbreviations, and products. Two-thirds of the 284 patients completing the survey reported current or recent use of pain, cold, or allergy medication. Of these, 25% reported knowing the active ingredient. Of patients, 46% and 13% knew that "acetaminophen" and "APAP," respectively, were synonymous with "Tylenol." Several patients (12%) believed that ingesting a harmful amount of acetaminophen was difficult or impossible. One-third of patients correctly identified the maximum daily dose, 10% reported a dose greater than 4 g, 25% were unsure of the dose, and 7% were unsure whether a maximum dose existed. One-half recognized liver damage as the primary toxicity. Results were similar between acetaminophen users and nonusers. Deficiencies were found in patient knowledge regarding acetaminophen recognition, dosing, and potential for toxicity. The development of effective educational initiatives is warranted to ensure patient awareness and limit the potential for acetaminophen overdose.

  16. Dose-finding design for multi-drug combinations

    PubMed Central

    Wages, Nolan A; Conaway, Mark R; O'Quigley, John

    2012-01-01

    Background Most of the current designs used for Phase I dose finding trials in oncology will either involve only a single cytotoxic agent or will impose some implicit ordering among the doses. The goal of the studies is to estimate the maximum tolerated dose (MTD), the highest dose that can be administered with an acceptable level of toxicity. A key working assumption of these methods is the monotonicity of the dose–toxicity curve. Purpose Here we consider situations in which the monotonicity assumption may fail. These studies are becoming increasingly common in practice, most notably, in phase I trials that involve combinations of agents. Our focus is on studies where there exist pairs of treatment combinations for which the ordering of the probabilities of a dose-limiting toxicity cannot be known a priori. Methods We describe a new dose-finding design which can be used for multiple-drug trials and can be applied to this kind of problem. Our methods proceed by laying out all possible orderings of toxicity probabilities that are consistent with the known orderings among treatment combinations and allowing the continual reassessment method (CRM) to provide efficient estimates of the MTD within these orders. The design can be seen to simplify to the CRM when the full ordering is known. Results We study the properties of the design via simulations that provide comparisons to the Bayesian approach to partial orders (POCRM) of Wages, Conaway, and O'Quigley. The POCRM was shown to perform well when compared to other suggested methods for partial orders. Therefore, we comapre our approach to it in order to assess the performance of the new design. Limitations A limitation concerns the number of possible orders. There are dose-finding studies with combinations of agents that can lead to a large number of possible orders. In this case, it may not be feasible to work with all possible orders. Conclusions The proposed design demonstrates the ability to effectively estimate

  17. The net fractional depth dose: a basis for a unified analytical description of FDD, TAR, TMR, and TPR.

    PubMed

    van de Geijn, J; Fraass, B A

    1984-01-01

    The net fractional depth dose (NFD) is defined as the fractional depth dose (FDD) corrected for inverse square law. Analysis of its behavior as a function of depth, field size, and source-surface distance has led to an analytical description with only seven model parameters related to straightforward physical properties. The determination of the characteristic parameter values requires only seven experimentally determined FDDs. The validity of the description has been tested for beam qualities ranging from 60Co gamma rays to 18-MV x rays, using published data from several different sources as well as locally measured data sets. The small number of model parameters is attractive for computer or hand-held calculator applications. The small amount of required measured data is important in view of practical data acquisition for implementation of a computer-based dose calculation system. The generating function allows easy and accurate generation of FDD, tissue-air ratio, tissue-maximum ratio, and tissue-phantom ratio tables.

  18. 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.

  19. SU-E-T-169: Characterization of Pacemaker/ICD Dose in SAVI HDR Brachytherapy

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

    Kalavagunta, C; Lasio, G; Yi, B

    2015-06-15

    Purpose: It is important to estimate dose to pacemaker (PM)/Implantable Cardioverter Defibrillator (ICD) before undertaking Accelerated Partial Breast Treatment using High Dose Rate (HDR) brachytherapy. Kim et al. have reported HDR PM/ICD dose using a single-source balloon applicator. To the authors knowledge, there have so far not been any published PM/ICD dosimetry literature for the Strut Adjusted Volume Implant (SAVI, Cianna Medical, Aliso Viejo, CA). This study aims to fill this gap by generating a dose look up table (LUT) to predict maximum dose to the PM/ICD in SAVI HDR brachytherapy. Methods: CT scans for 3D dosimetric planning were acquiredmore » for four SAVI applicators (6−1-mini, 6−1, 8−1 and 10−1) expanded to their maximum diameter in air. The CT datasets were imported into the Elekta Oncentra TPS for planning and each applicator was digitized in a multiplanar reconstruction window. A dose of 340 cGy was prescribed to the surface of a 1 cm expansion of the SAVI applicator cavity. Cartesian coordinates of the digitized applicator were determined in the treatment leading to the generation of a dose distribution and corresponding distance-dose prediction look up table (LUT) for distances from 2 to 15 cm (6-mini) and 2 to 20 cm (10–1).The deviation between the LUT doses and the dose to the cardiac device in a clinical case was evaluated. Results: Distance-dose look up table were compared to clinical SAVI plan and the discrepancy between the max dose predicted by the LUT and the clinical plan was found to be in the range (−0.44%, 0.74%) of the prescription dose. Conclusion: The distance-dose look up tables for SAVI applicators can be used to estimate the maximum dose to the ICD/PM, with a potential usefulness for quick assessment of dose to the cardiac device prior to applicator placement.« less

  20. Maximum Likelihood and Restricted Likelihood Solutions in Multiple-Method Studies.

    PubMed

    Rukhin, Andrew L

    2011-01-01

    A formulation of the problem of combining data from several sources is discussed in terms of random effects models. The unknown measurement precision is assumed not to be the same for all methods. We investigate maximum likelihood solutions in this model. By representing the likelihood equations as simultaneous polynomial equations, the exact form of the Groebner basis for their stationary points is derived when there are two methods. A parametrization of these solutions which allows their comparison is suggested. A numerical method for solving likelihood equations is outlined, and an alternative to the maximum likelihood method, the restricted maximum likelihood, is studied. In the situation when methods variances are considered to be known an upper bound on the between-method variance is obtained. The relationship between likelihood equations and moment-type equations is also discussed.

  1. Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology.

    PubMed

    Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody; Song, Daniel Y

    2015-08-01

    Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: (125)I fixed spacing, (125)I variable spacing, (103)Pd fixed spacing, and (103)Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with (103)Pd, and 0.007 and 0.029 with (125)I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with (103)Pd, and 0.012 and 0.037 with (125)I plans. The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy.

  2. 41 CFR 302-7.16 - Is the maximum weight allowance for HHG and temporary storage limited when quarters are furnished...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Federal Travel Regulation System RELOCATION ALLOWANCES TRANSPORTATION AND STORAGE OF PROPERTY 7-TRANSPORTATION AND TEMPORARY STORAGE OF HOUSEHOLD GOODS AND PROFESSIONAL BOOKS, PAPERS, AND EQUIPMENT (PBP&E... allowance for HHG and temporary storage limited when quarters are furnished or partly furnished by the...

  3. MEASUREMENT OF RADIATION DOSES TO THE EYE LENS DURING ORTHOPEDIC SURGERY USING AN C-ARM X-RAY SYSTEM.

    PubMed

    Suzuki, Akira; Matsubara, Kosuke; Sasa, Yuko

    2018-04-01

    The present study aimed to determine doses delivered to the eye lenses of surgeons while using the inverted-C-arm technique and the protective effect of leaded spectacles during orthopedic surgery. The kerma in air was measured at five positions on leaded glasses positioned near the eye lens and on the neck using small optically stimulated luminescence (OSL) dosemeters. The lens equivalent dose was also measured at the neck using an OSL dosemeter. The maximum equivalent dose to the eye lens and the maximum kerma were 0.8 mSv/month and 0.66 mGy/month, respectively. The leaded glasses reduced the exposure by ~60%. Even if the surgeons are exposed to the maximum dose of X-ray radiation for 5 years, the equivalent doses to the eye lens will not exceed the present limit recommended by the ICRP.

  4. Quantifying the impact of immediate reconstruction in postmastectomy radiation: a large, dose-volume histogram-based analysis.

    PubMed

    Ohri, Nisha; Cordeiro, Peter G; Keam, Jennifer; Ballangrud, Ase; Shi, Weiji; Zhang, Zhigang; Nerbun, Claire T; Woch, Katherine M; Stein, Nicholas F; Zhou, Ying; McCormick, Beryl; Powell, Simon N; Ho, Alice Y

    2012-10-01

    To assess the impact of immediate breast reconstruction on postmastectomy radiation (PMRT) using dose-volume histogram (DVH) data. Two hundred forty-seven women underwent PMRT at our center, 196 with implant reconstruction and 51 without reconstruction. Patients with reconstruction were treated with tangential photons, and patients without reconstruction were treated with en-face electron fields and customized bolus. Twenty percent of patients received internal mammary node (IMN) treatment. The DVH data were compared between groups. Ipsilateral lung parameters included V20 (% volume receiving 20 Gy), V40 (% volume receiving 40 Gy), mean dose, and maximum dose. Heart parameters included V25 (% volume receiving 25 Gy), mean dose, and maximum dose. IMN coverage was assessed when applicable. Chest wall coverage was assessed in patients with reconstruction. Propensity-matched analysis adjusted for potential confounders of laterality and IMN treatment. Reconstruction was associated with lower lung V20, mean dose, and maximum dose compared with no reconstruction (all P<.0001). These associations persisted on propensity-matched analysis (all P<.0001). Heart doses were similar between groups (P=NS). Ninety percent of patients with reconstruction had excellent chest wall coverage (D95 >98%). IMN coverage was superior in patients with reconstruction (D95 >92.0 vs 75.7%, P<.001). IMN treatment significantly increased lung and heart parameters in patients with reconstruction (all P<.05) but minimally affected those without reconstruction (all P>.05). Among IMN-treated patients, only lower lung V20 in those without reconstruction persisted (P=.022), and mean and maximum heart doses were higher than in patients without reconstruction (P=.006, P=.015, respectively). Implant reconstruction does not compromise the technical quality of PMRT when the IMNs are untreated. Treatment technique, not reconstruction, is the primary determinant of target coverage and normal tissue doses

  5. Radiation dose to the global flying population.

    PubMed

    Alvarez, Luis E; Eastham, Sebastian D; Barrett, Steven R H

    2016-03-01

    Civil airliner passengers and crew are exposed to elevated levels of radiation relative to being at sea level. Previous studies have assessed the radiation dose received in particular cases or for cohort studies. Here we present the first estimate of the total radiation dose received by the worldwide civilian flying population. We simulated flights globally from 2000 to 2013 using schedule data, applying a radiation propagation code to estimate the dose associated with each flight. Passengers flying in Europe and North America exceed the International Commission on Radiological Protection annual dose limits at an annual average of 510 or 420 flight hours per year, respectively. However, this falls to 160 or 120 h on specific routes under maximum exposure conditions.

  6. Unenhanced low-dose versus standard-dose CT localization in patients with upper urinary calculi for minimally invasive percutaneous nephrolithotomy (MPCNL)

    PubMed Central

    Licheng, Jiang; Yidong, Fan; Ping, Wang; Keqiang, Yan; Xueting, Wang; Yingchen, Zhang; Lei, Gao; Jiyang, Ding; Zhonghua, Xu

    2014-01-01

    Background & objectives: With the ethical concern about the dose of CT scan and wide use of CT in protocol of suspected renal colic, more attention has been paid to low dose CT. The aim of the present study was to make a comparison of unenhanced low-dose spiral CT localization with unenhanced standard-dose spiral CT in patients with upper urinary tract calculi for minimally invasive percutaneous nephrolithotomy (MPCNL) treatment. Methods: Twenty eight patients with ureter and renal calculus, preparing to take MPCNL, underwent both abdominal low-dose CT (25 mAs) and standard-dose CT (100 mAs). Low-dose CT and standard-dose CT were independently evaluated for the characterization of renal/ureteral calculi, perirenal adjacent organs, blood vessels, indirect signs of renal or ureteral calculus (renal enlargement, pyeloureteral dilatation), and the indices of localization (percutaneous puncture angulation and depth) used in the MPCNL procedure. Results: In all 28 patients, low-dose CT was 100 per cent coincidence 100 per cent sensitive and 100 per cent specific for depicting the location of the renal and ureteral calculus, renal enlargement, pyeloureteral dilatation, adjacent organs, and the presumptive puncture point and a 96.3 per cent coincidence 96 per cent sensitivity and 93 per cent specificity for blood vessel signs within the renal sinus, and with an obvious lower radiation exposure for patients when compared to standard-dose CT (P<0.05). The indices of puncture depth, puncture angulation, and maximum calculus transverse diameter on the axial surface showed no significant difference between the two doses of CT scans, with a significant variation in calculus visualization slice numbers (P<0.05). Interpretation & conclusions: Our findings show that unenhanced low-dose CT achieves a sensitivity and accuracy similar to that of standard-dose CT in assessing the localization of renal ureteral calculus and adjacent organs conditions and identifying the maximum calculus

  7. Systemic delivery of atropine sulfate by the MicroDose Dry-Powder Inhaler.

    PubMed

    Corcoran, T E; Venkataramanan, R; Hoffman, R M; George, M P; Petrov, A; Richards, T; Zhang, S; Choi, J; Gao, Y Y; Oakum, C D; Cook, R O; Donahoe, M

    2013-02-01

    Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses × 0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine.

  8. Dose Trends of Aripiprazole from 2004 to 2014 in Psychiatric Inpatients in Korea.

    PubMed

    Woo, Young Sup; Shim, In Hee; Lee, Sang-Yeol; Lee, Dae-Bo; Kim, Moon-Doo; Jung, Young-Eun; Lee, Jonghun; Won, Seunghee; Jon, Duk-In; Bahk, Won-Myong

    2017-05-31

    Although aripiprazole has been widely used to treat various psychiatric disorders, little is known about the adequate dosage for Asian patients in clinical practice. Hence, we evaluated the initial and maximum doses of aripiprazole from 2004 to 2014 to estimate the appropriate dosage for Korean psychiatric inpatients in clinical practice. In this retrospective study, we reviewed the medical records of patients who were hospitalized in five university hospitals in Korea from March 2004 to December 2014. The psychiatric diagnosis according to the text revision of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition during index hospitalization and the initial and maximum doses of aripiprazole were evaluated. There were 74 patients in Wave 1 (2004-2006), 201 patients in Wave 2 (2007-2010), and 353 patients in Wave 3 (2011-2014). The initial doses of aripiprazole in all diagnostic groups were significantly lower in Wave 3 than in Wave 2. The maximum doses of aripiprazole in each diagnostic group were not significantly different among Waves 1, 2, and 3. The relatively low initial doses of aripiprazole documented in our study may reflect a strategy by clinicians to minimize the side effects associated with aripiprazole use, such as akathisia.

  9. Fractionated Radioimmunotherapy With 90Y-Clivatuzumab Tetraxetan and Low-Dose Gemcitabine Is Active in Advanced Pancreatic Cancer

    PubMed Central

    Ocean, Allyson J.; Pennington, Kenneth L.; Guarino, Michael J.; Sheikh, Arif; Bekaii-Saab, Tanios; Serafini, Aldo N.; Lee, Daniel; Sung, Max W.; Gulec, Seza A.; Goldsmith, Stanley J.; Manzone, Timothy; Holt, Michael; O’Neil, Bert H.; Hall, Nathan; Montero, Alberto J.; Kauh, John; Gold, David V.; Horne, Heather; Wegener, William A.; Goldenberg, David M.

    2014-01-01

    BACKGROUND It has been demonstrated that the humanized clivatuzumab tetraxetan (hPAM4) antibody targets pancreatic ductal carcinoma selectively. After a trial of radioimmunotherapy that determined the maximum tolerated dose of single-dose yttrium-90-labeled hPAM4 (90Y-hPAM4) and produced objective responses in patients with advanced pancreatic ductal carcinoma, the authors studied fractionated radioimmunotherapy combined with low-dose gemcitabine in this disease. METHODS Thirty-eight previously untreated patients (33 patients with stage IV disease and 5 patients with stage III disease) received gemcitabine 200 mg/m2 weekly for 4 weeks with 90Y-hPAM4 given weekly in Weeks 2, 3, and 4 (cycle 1), and the same cycle was repeated in 13 patients (cycles 2–4). In the first part of the study, 19 patients received escalating weekly 90Y doses of 6.5 mCi/m2, 9.0 mCi/m2, 12.0 mCi/m2, and 15.0 mCi/m2. In the second portion, 19 additional patients received weekly doses of 9.0 mCi/m2 or 12.0 mCi/m2. RESULTS Grade 3/4 thrombocytopenia or neutropenia (according to version 3.0 of the National Cancer Institute’s Common Terminology Criteria for Adverse Events) developed in 28 of 38 patients after cycle 1 and in all retreated patients; no grade >3 nonhematologic toxicities occurred. Fractionated dosing of cycle 1 allowed almost twice the radiation dose compared with single-dose radioimmunotherapy. The maximum tolerated dose of 90Y-hPAM4 was 12.0 mCi/m2 weekly for 3 weeks for cycle 1, with ≤9.0 mCi/m2 weekly for 3 weeks for subsequent cycles, and that dose will be used in future trials. Six patients (16%) had partial responses according to computed tomography-based Response Evaluation Criteria in Solid Tumors, and 16 patients (42%) had stabilization as their best response (58% disease control). The median overall survival was 7.7 months for all 38 patients, including 11.8 months for those who received repeated cycles (46% [6 of 13 patients] ≥1 year), with improved efficacy at

  10. Ultralow dose computed tomography attenuation correction for pediatric PET CT using adaptive statistical iterative reconstruction

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

    Brady, Samuel L., E-mail: samuel.brady@stjude.org; Shulkin, Barry L.

    2015-02-15

    Purpose: To develop ultralow dose computed tomography (CT) attenuation correction (CTAC) acquisition protocols for pediatric positron emission tomography CT (PET CT). Methods: A GE Discovery 690 PET CT hybrid scanner was used to investigate the change to quantitative PET and CT measurements when operated at ultralow doses (10–35 mA s). CT quantitation: noise, low-contrast resolution, and CT numbers for 11 tissue substitutes were analyzed in-phantom. CT quantitation was analyzed to a reduction of 90% volume computed tomography dose index (0.39/3.64; mGy) from baseline. To minimize noise infiltration, 100% adaptive statistical iterative reconstruction (ASiR) was used for CT reconstruction. PET imagesmore » were reconstructed with the lower-dose CTAC iterations and analyzed for: maximum body weight standardized uptake value (SUV{sub bw}) of various diameter targets (range 8–37 mm), background uniformity, and spatial resolution. Radiation dose and CTAC noise magnitude were compared for 140 patient examinations (76 post-ASiR implementation) to determine relative dose reduction and noise control. Results: CT numbers were constant to within 10% from the nondose reduced CTAC image for 90% dose reduction. No change in SUV{sub bw}, background percent uniformity, or spatial resolution for PET images reconstructed with CTAC protocols was found down to 90% dose reduction. Patient population effective dose analysis demonstrated relative CTAC dose reductions between 62% and 86% (3.2/8.3–0.9/6.2). Noise magnitude in dose-reduced patient images increased but was not statistically different from predose-reduced patient images. Conclusions: Using ASiR allowed for aggressive reduction in CT dose with no change in PET reconstructed images while maintaining sufficient image quality for colocalization of hybrid CT anatomy and PET radioisotope uptake.« less

  11. Effect of a therapeutic maximum allowable cost (MAC) program on the cost and utilization of proton pump inhibitors in an employer-sponsored drug plan in Canada.

    PubMed

    Mabasa, Vincent H; Ma, Johnny

    2006-06-01

    Therapeutic maximum allowable cost (MAC) is a managed care intervention that uses reference pricing in a therapeutic class or category of drugs or an indication (e.g., heartburn). Therapeutic MAC has not been studied in Canada or the United States. The proton pump inhibitor (PPI) rabeprazole was used as the reference drug in this therapeutic MAC program based on prices for PPIs in the province of Ontario. No PPI is available over the counter in Canada. To evaluate the utilization and anticipated drug cost savings for PPIs in an employer-sponsored drug plan in Canada that implemented a therapeutic MAC program for PPIs. An employer group with an average of 6,300 covered members, which adopted the MAC program for PPIs in June 2003, was compared with a comparison group comprising the book of business throughout Canada (approximately 5 million lives) without a PPI MAC program (non-MAC group). Pharmacy claims for PPIs were identified using the first 6 characters of the generic product identifier (GPI 492700) for a 36-month period from June 1, 2002, through May 31, 2005. The primary comparison was the year prior to the intervention (from June 1, 2002, through May 31, 2003) and the first full year following the intervention (June 1, 2004, through May 31, 2005). Drug utilization was evaluated by comparing the market share of each of the PPIs for the 2 time periods and by the days of PPI therapy per patient per year (PPPY) and days of therapy per prescription (Rx). Drug cost was defined as the cost of the drug (ingredient cost), including allowable provincial pharmacy markup but excluding pharmacy dispense fee. Cost savings were calculated from the allowed drug cost per claim, allowed cost per day, and allowed cost PPPY. (All amounts are in Canadian dollars.) The MAC intervention group experienced an 11.7% reduction in the average cost per day of PPI drug therapy, from 2.14 US dollars in the preperiod to 1.89 US dollars in the postperiod, compared with a 3.7% reduction in

  12. Organ dose measurement using Optically Stimulated Luminescence Detector (OSLD) during CT examination

    NASA Astrophysics Data System (ADS)

    Yusuf, Muhammad; Alothmany, Nazeeh; Abdulrahman Kinsara, Abdulraheem

    2017-10-01

    This study provides detailed information regarding the imaging doses to patient radiosensitive organs from a kilovoltage computed tomography (CT) scan procedure using OSLD. The study reports discrepancies between the measured dose and the calculated dose from the ImPACT scan, as well as a comparison with the dose from a chest X-ray radiography procedure. OSLDs were inserted in several organs, including the brain, eyes, thyroid, lung, heart, spinal cord, breast, spleen, stomach, liver and ovaries, of the RANDO phantom. Standard clinical scanning protocols were used for each individual site, including the brain, thyroid, lung, breast, stomach, liver and ovaries. The measured absorbed doses were then compared with the simulated dose obtained from the ImPACT scan. Additionally, the equivalent doses for each organ were calculated and compared with the dose from a chest X-ray radiography procedure. Absorbed organ doses measured by OSLD in the RANDO phantom of up to 17 mGy depend on the organ scanned and the scanning protocols used. A maximum 9.82% difference was observed between the target organ dose measured by OSLD and the results from the ImPACT scan. The maximum equivalent organ dose measured during this experiment was equal to 99.899 times the equivalent dose from a chest X-ray radiography procedure. The discrepancies between the measured dose with the OSLD and the calculated dose from the ImPACT scan were within 10%. This report recommends the use of OSLD for measuring the absorbed organ dose during CT examination.

  13. Neutrons in active proton therapy: Parameterization of dose and dose equivalent.

    PubMed

    Schneider, Uwe; Hälg, Roger A; Lomax, Tony

    2017-06-01

    One of the essential elements of an epidemiological study to decide if proton therapy may be associated with increased or decreased subsequent malignancies compared to photon therapy is an ability to estimate all doses to non-target tissues, including neutron dose. This work therefore aims to predict for patients using proton pencil beam scanning the spatially localized neutron doses and dose equivalents. The proton pencil beam of Gantry 1 at the Paul Scherrer Institute (PSI) was Monte Carlo simulated using GEANT. Based on the simulated neutron dose and neutron spectra an analytical mechanistic dose model was developed. The pencil beam algorithm used for treatment planning at PSI has been extended using the developed model in order to calculate the neutron component of the delivered dose distribution for each treated patient. The neutron dose was estimated for two patient example cases. The analytical neutron dose model represents the three-dimensional Monte Carlo simulated dose distribution up to 85cm from the proton pencil beam with a satisfying precision. The root mean square error between Monte Carlo simulation and model is largest for 138MeV protons and is 19% and 20% for dose and dose equivalent, respectively. The model was successfully integrated into the PSI treatment planning system. In average the neutron dose is increased by 10% or 65% when using 160MeV or 177MeV instead of 138MeV. For the neutron dose equivalent the increase is 8% and 57%. The presented neutron dose calculations allow for estimates of dose that can be used in subsequent epidemiological studies or, should the need arise, to estimate the neutron dose at any point where a subsequent secondary tumour may occur. It was found that the neutron dose to the patient is heavily increased with proton energy. Copyright © 2016. Published by Elsevier GmbH.

  14. Maximum Likelihood and Restricted Likelihood Solutions in Multiple-Method Studies

    PubMed Central

    Rukhin, Andrew L.

    2011-01-01

    A formulation of the problem of combining data from several sources is discussed in terms of random effects models. The unknown measurement precision is assumed not to be the same for all methods. We investigate maximum likelihood solutions in this model. By representing the likelihood equations as simultaneous polynomial equations, the exact form of the Groebner basis for their stationary points is derived when there are two methods. A parametrization of these solutions which allows their comparison is suggested. A numerical method for solving likelihood equations is outlined, and an alternative to the maximum likelihood method, the restricted maximum likelihood, is studied. In the situation when methods variances are considered to be known an upper bound on the between-method variance is obtained. The relationship between likelihood equations and moment-type equations is also discussed. PMID:26989583

  15. The maximum rate of mammal evolution

    NASA Astrophysics Data System (ADS)

    Evans, Alistair R.; Jones, David; Boyer, Alison G.; Brown, James H.; Costa, Daniel P.; Ernest, S. K. Morgan; Fitzgerald, Erich M. G.; Fortelius, Mikael; Gittleman, John L.; Hamilton, Marcus J.; Harding, Larisa E.; Lintulaakso, Kari; Lyons, S. Kathleen; Okie, Jordan G.; Saarinen, Juha J.; Sibly, Richard M.; Smith, Felisa A.; Stephens, Patrick R.; Theodor, Jessica M.; Uhen, Mark D.

    2012-03-01

    How fast can a mammal evolve from the size of a mouse to the size of an elephant? Achieving such a large transformation calls for major biological reorganization. Thus, the speed at which this occurs has important implications for extensive faunal changes, including adaptive radiations and recovery from mass extinctions. To quantify the pace of large-scale evolution we developed a metric, clade maximum rate, which represents the maximum evolutionary rate of a trait within a clade. We applied this metric to body mass evolution in mammals over the last 70 million years, during which multiple large evolutionary transitions occurred in oceans and on continents and islands. Our computations suggest that it took a minimum of 1.6, 5.1, and 10 million generations for terrestrial mammal mass to increase 100-, and 1,000-, and 5,000-fold, respectively. Values for whales were down to half the length (i.e., 1.1, 3, and 5 million generations), perhaps due to the reduced mechanical constraints of living in an aquatic environment. When differences in generation time are considered, we find an exponential increase in maximum mammal body mass during the 35 million years following the Cretaceous-Paleogene (K-Pg) extinction event. Our results also indicate a basic asymmetry in macroevolution: very large decreases (such as extreme insular dwarfism) can happen at more than 10 times the rate of increases. Our findings allow more rigorous comparisons of microevolutionary and macroevolutionary patterns and processes.

  16. Equivalent dose and effective dose from stray radiation during passively scattered proton radiotherapy for prostate cancer

    NASA Astrophysics Data System (ADS)

    Fontenot, Jonas; Taddei, Phillip; Zheng, Yuanshui; Mirkovic, Dragan; Jordan, Thomas; Newhauser, Wayne

    2008-03-01

    Proton therapy reduces the integral therapeutic dose required for local control in prostate patients compared to intensity-modulated radiotherapy. One proposed benefit of this reduction is an associated decrease in the incidence of radiogenic secondary cancers. However, patients are also exposed to stray radiation during the course of treatment. The purpose of this study was to quantify the stray radiation dose received by patients during proton therapy for prostate cancer. Using a Monte Carlo model of a proton therapy nozzle and a computerized anthropomorphic phantom, we determined that the effective dose from stray radiation per therapeutic dose (E/D) for a typical prostate patient was approximately 5.5 mSv Gy-1. Sensitivity analysis revealed that E/D varied by ±30% over the interval of treatment parameter values used for proton therapy of the prostate. Equivalent doses per therapeutic dose (HT/D) in specific organs at risk were found to decrease with distance from the isocenter, with a maximum of 12 mSv Gy-1 in the organ closest to the treatment volume (bladder) and 1.9 mSv Gy-1 in the furthest (esophagus). Neutrons created in the nozzle predominated effective dose, though neutrons created in the patient contributed substantially to the equivalent dose in organs near the proton field. Photons contributed less than 15% to equivalent doses.

  17. A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system.

    PubMed

    Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

    2012-01-01

    The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72-18.55 Gy) and 5.17 Gy (range 0.72-15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system.

  18. Spatio-temporal observations of the tertiary ozone maximum

    NASA Astrophysics Data System (ADS)

    Sofieva, V. F.; Kyrölä, E.; Verronen, P. T.; Seppälä, A.; Tamminen, J.; Marsh, D. R.; Smith, A. K.; Bertaux, J.-L.; Hauchecorne, A.; Dalaudier, F.; Fussen, D.; Vanhellemont, F.; Fanton D'Andon, O.; Barrot, G.; Guirlet, M.; Fehr, T.; Saavedra, L.

    2009-07-01

    We present spatio-temporal distributions of the tertiary ozone maximum (TOM), based on GOMOS (Global Ozone Monitoring by Occultation of Stars) ozone measurements in 2002-2006. The tertiary ozone maximum is typically observed in the high-latitude winter mesosphere at an altitude of ~72 km. Although the explanation for this phenomenon has been found recently - low concentrations of odd-hydrogen cause the subsequent decrease in odd-oxygen losses - models have had significant deviations from existing observations until recently. Good coverage of polar night regions by GOMOS data has allowed for the first time to obtain spatial and temporal observational distributions of night-time ozone mixing ratio in the mesosphere. The distributions obtained from GOMOS data have specific features, which are variable from year to year. In particular, due to a long lifetime of ozone in polar night conditions, the downward transport of polar air by the meridional circulation is clearly observed in the tertiary ozone maximum time series. Although the maximum tertiary ozone mixing ratio is achieved close to the polar night terminator (as predicted by the theory), TOM can be observed also at very high latitudes, not only in the beginning and at the end, but also in the middle of winter. We have compared the observational spatio-temporal distributions of the tertiary ozone maximum with that obtained using WACCM (Whole Atmosphere Community Climate Model) and found that the specific features are reproduced satisfactorily by the model. Since ozone in the mesosphere is very sensitive to HOx concentrations, energetic particle precipitation can significantly modify the shape of the ozone profiles. In particular, GOMOS observations have shown that the tertiary ozone maximum was temporarily destroyed during the January 2005 and December 2006 solar proton events as a result of the HOx enhancement from the increased ionization.

  19. 76 FR 1504 - Pipeline Safety: Establishing Maximum Allowable Operating Pressure or Maximum Operating Pressure...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-10

    ... profile that is dependent upon the pipelines attributes, its geographical location, design, operating... type of threats posed by the pipeline segment, including consideration of the age, design, pipe... calculation. There are several methods available for establishing MAOP or MOP. A hydrostatic pressure test...

  20. [Value of early application of different doses of amino acids in parenteral nutrition among preterm infants].

    PubMed

    Liu, Zhi-Juan; Liu, Guo-Sheng; Chen, Yong-Ge; Zhang, Hui-Li; Wu, Xue-Fen

    2015-01-01

    To study the short-term response and tolerance of different doses of amino acids in parenteral nutrition among preterm infants. This study included 86 preterm infants who had a birth weight between 1 000 to 2 000 g and were admitted to the hospital within 24 hours of birth between March 2013 and June 2014. According to the early application of different doses of amino acids, they were randomized into low-dose group (n=29, 1.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.5 g/kg per day), medium-dose group (n=28, 2.0 g/kg per day with an increase of 1.0 g/kg daily and a maximum of 3.7 g/kg per day), and high-dose group (n=29, 3.0 g/kg per day with an increase of 0.5-1.0 g/kg daily and a maximum of 4.0 g/kg per day). Other routine parenteral nutrition and enteral nutrition support were also applied. The maximum weight loss was lower and the growth rate of head circumference was greater in the high-dose group than in the low-dose group (P<0.05). The infants in the medium- and high-dose groups had faster recovery of birth weight, earlier attainment of 100 kcal/(kg·d) of enteral nutrition, shorter duration of hospital stay, and less hospital cost than those in the low-dose group (P<0.05). Blood urea nitrogen (BUN) levels in the high-dose group increased compared with the other two groups 7 days after birth (P<0.05). The levels of creatinine, pH, bicarbonate, bilirubin, and transaminase and the incidence of complications showed no significant differences between groups (P>0.05). Parenteral administration of high-dose amino acids in preterm infants within 24 hours after birth can improve the short-term nutritional status of preterm infants, but there is a transient increase in BUN level.

  1. 24 CFR 880.503 - Maximum annual commitment and project account.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... may be contracted for in the ACC is the total of the contract rents and utility allowances for all... commitment exceeds the amount actually paid out under the Contract or ACC each year. Payments will be made... the Contract or ACC for a fiscal year exceeds the maximum annual commitment and would cause the amount...

  2. 24 CFR 880.503 - Maximum annual commitment and project account.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... may be contracted for in the ACC is the total of the contract rents and utility allowances for all... commitment exceeds the amount actually paid out under the Contract or ACC each year. Payments will be made... the Contract or ACC for a fiscal year exceeds the maximum annual commitment and would cause the amount...

  3. Maximum entropy, fluctuations and priors

    NASA Astrophysics Data System (ADS)

    Caticha, A.

    2001-05-01

    The method of maximum entropy (ME) is extended to address the following problem: Once one accepts that the ME distribution is to be preferred over all others, the question is to what extent are distributions with lower entropy supposed to be ruled out. Two applications are given. The first is to the theory of thermodynamic fluctuations. The formulation is exact, covariant under changes of coordinates, and allows fluctuations of both the extensive and the conjugate intensive variables. The second application is to the construction of an objective prior for Bayesian inference. The prior obtained by following the ME method to its inevitable conclusion turns out to be a special case (α=1) of what are currently known under the name of entropic priors. .

  4. Failure-probability driven dose painting

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

    Vogelius, Ivan R.; Håkansson, Katrin; Due, Anne K.

    Purpose: To demonstrate a data-driven dose-painting strategy based on the spatial distribution of recurrences in previously treated patients. The result is a quantitative way to define a dose prescription function, optimizing the predicted local control at constant treatment intensity. A dose planning study using the optimized dose prescription in 20 patients is performed.Methods: Patients treated at our center have five tumor subvolumes from the center of the tumor (PET positive volume) and out delineated. The spatial distribution of 48 failures in patients with complete clinical response after (chemo)radiation is used to derive a model for tumor control probability (TCP). Themore » total TCP is fixed to the clinically observed 70% actuarial TCP at five years. Additionally, the authors match the distribution of failures between the five subvolumes to the observed distribution. The steepness of the dose–response is extracted from the literature and the authors assume 30% and 20% risk of subclinical involvement in the elective volumes. The result is a five-compartment dose response model matching the observed distribution of failures. The model is used to optimize the distribution of dose in individual patients, while keeping the treatment intensity constant and the maximum prescribed dose below 85 Gy.Results: The vast majority of failures occur centrally despite the small volumes of the central regions. Thus, optimizing the dose prescription yields higher doses to the central target volumes and lower doses to the elective volumes. The dose planning study shows that the modified prescription is clinically feasible. The optimized TCP is 89% (range: 82%–91%) as compared to the observed TCP of 70%.Conclusions: The observed distribution of locoregional failures was used to derive an objective, data-driven dose prescription function. The optimized dose is predicted to result in a substantial increase in local control without increasing the predicted risk of

  5. Allowable Trajectory Variations for Space Shuttle Orbiter Entry-Aeroheating CFD

    NASA Technical Reports Server (NTRS)

    Wood, William A.; Alter, Stephen J.

    2008-01-01

    Reynolds-number criteria are developed for acceptable variations in Space Shuttle Orbiter entry trajectories for use in computational aeroheating analyses. The criteria determine if an existing computational fluid dynamics solution for a particular trajectory can be extrapolated to a different trajectory. The criteria development begins by estimating uncertainties for seventeen types of computational aeroheating data, such as boundary layer thickness, at exact trajectory conditions. For each type of datum, the allowable uncertainty contribution due to trajectory variation is set to be half of the value of the estimated exact-trajectory uncertainty. Then, for the twelve highest-priority datum types, Reynolds-number relations between trajectory variation and output uncertainty are determined. From these relations the criteria are established for the maximum allowable trajectory variations. The most restrictive criterion allows a 25% variation in Reynolds number at constant Mach number between trajectories.

  6. Maximum of a Fractional Brownian Motion: Analytic Results from Perturbation Theory.

    PubMed

    Delorme, Mathieu; Wiese, Kay Jörg

    2015-11-20

    Fractional Brownian motion is a non-Markovian Gaussian process X_{t}, indexed by the Hurst exponent H. It generalizes standard Brownian motion (corresponding to H=1/2). We study the probability distribution of the maximum m of the process and the time t_{max} at which the maximum is reached. They are encoded in a path integral, which we evaluate perturbatively around a Brownian, setting H=1/2+ϵ. This allows us to derive analytic results beyond the scaling exponents. Extensive numerical simulations for different values of H test these analytical predictions and show excellent agreement, even for large ϵ.

  7. Sodium phenylbutyrate in Huntington's disease: a dose-finding study.

    PubMed

    Hogarth, Penelope; Lovrecic, Luca; Krainc, Dimitri

    2007-10-15

    Transcriptional dysregulation in Huntington's disease (HD) is mediated in part by aberrant patterns of histone acetylation. We performed a dose-finding study in human HD of sodium phenylbutyrate (SPB), a histone deacetylase inhibitor that ameliorates the HD phenotype in animal models. We used a dose-escalation/de-escalation design, using prespecified toxicity criteria and standard clinical and laboratory safety measures. The maximum tolerated dose was 15 g/day. At higher doses, toxicity included vomiting, lightheadedness, confusion, and gait instability. We saw no significant laboratory or electrocardiographic abnormalities. Gene expression changes in blood suggested an inverse dose-response. In conclusion, SPB at 12 to 15 g/day appears to be safe and well-tolerated in human HD. 2007 Movement Disorder Society

  8. A retrospective analysis of rectal and bladder dose for gynecological brachytherapy treatments with GZP6 HDR afterloading system

    PubMed Central

    Bahreyni Toossi, Mohammad Taghi; Ghorbani, Mahdi; Makhdoumi, Yasha; Taheri, Mojtaba; Homaee Shandiz, Fatemeh; Zahed Anaraki, Siavash; Soleimani Meigooni, Ali

    2012-01-01

    Aim The aim of this work is to evaluate rectal and bladder dose for the patients treated for gynecological cancers. Background The GZP6 high dose rate brachytherapy system has been recently introduced to a number of radiation therapy departments in Iran, for treatment of various tumor sites such as cervix and vagina. Materials and methods Our analysis was based on dose measurements for 40 insertions in 28 patients, treated by a GZP6 unit between June 2009 and November 2010. Treatments consisted of combined teletherapy and intracavitary brachytherapy. In vivo dosimetry was performed with TLD-400 chips and TLD-100 microcubes in the rectum and bladder. Results The average of maximum rectal and bladder dose values were found to be 7.62 Gy (range 1.72–18.55 Gy) and 5.17 Gy (range 0.72–15.85 Gy), respectively. It has been recommended by the ICRU that the maximum dose to the rectum and bladder in intracavitary treatment of vaginal or cervical cancer should be lower than 80% of the prescribed dose to point A in the Manchester system. In this study, of the total number of 40 insertions, maximum rectal dose in 29 insertions (72.5% of treatment sessions) and maximum bladder dose in 18 insertions (45% of treatments sessions) were higher than 80% of the prescribed dose to the point of dose prescription. Conclusion In vivo dosimetry for patients undergoing treatment by GZP6 brachytherapy system can be used for evaluation of the quality of brachytherapy treatments by this system. This information could be used as a base for developing the strategy for treatment of patients treated with GZP6 system. PMID:24377037

  9. Maximum Entropy Approach in Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

    PubMed

    Farsani, Zahra Amini; Schmid, Volker J

    2017-01-01

    In the estimation of physiological kinetic parameters from Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) data, the determination of the arterial input function (AIF) plays a key role. This paper proposes a Bayesian method to estimate the physiological parameters of DCE-MRI along with the AIF in situations, where no measurement of the AIF is available. In the proposed algorithm, the maximum entropy method (MEM) is combined with the maximum a posterior approach (MAP). To this end, MEM is used to specify a prior probability distribution of the unknown AIF. The ability of this method to estimate the AIF is validated using the Kullback-Leibler divergence. Subsequently, the kinetic parameters can be estimated with MAP. The proposed algorithm is evaluated with a data set from a breast cancer MRI study. The application shows that the AIF can reliably be determined from the DCE-MRI data using MEM. Kinetic parameters can be estimated subsequently. The maximum entropy method is a powerful tool to reconstructing images from many types of data. This method is useful for generating the probability distribution based on given information. The proposed method gives an alternative way to assess the input function from the existing data. The proposed method allows a good fit of the data and therefore a better estimation of the kinetic parameters. In the end, this allows for a more reliable use of DCE-MRI. Schattauer GmbH.

  10. Kodak EDR2 film for patient skin dose assessment in cardiac catheterization procedures.

    PubMed

    Morrell, R E; Rogers, A T

    2006-07-01

    Patient skin doses were measured using Kodak EDR2 film for 20 coronary angiography (CA) and 32 percutaneous transluminal coronary angioplasty (PTCA) procedures. For CA, all skin doses were well below 1 Gy. However, 23% of PTCA patients received skin doses of 1 Gy or more. Dose-area product (DAP) was also recorded and was found to be an inadequate indicator of maximum skin dose. Practical compliance with ICRP recommendations requires a robust method for skin dosimetry that is more accurate than DAP and is applicable over a wider dose range than EDR2 film.

  11. Clinical implementation and evaluation of the Acuros dose calculation algorithm.

    PubMed

    Yan, Chenyu; Combine, Anthony G; Bednarz, Greg; Lalonde, Ronald J; Hu, Bin; Dickens, Kathy; Wynn, Raymond; Pavord, Daniel C; Saiful Huq, M

    2017-09-01

    computation time for other plans will be discussed at the end. Maximum difference between dose calculated by AAA and dose-to-medium by Acuros XB (Acuros_D m,m ) was 4.3% on patient plans at the isocenter, and maximum difference between D 100 calculated by AAA and by Acuros_D m,m was 11.3%. When calculating the maximum dose to spinal cord on patient plans, differences between dose calculated by AAA and Acuros_D m,m were more than 3%. Compared with AAA, Acuros XB improves accuracy in the presence of inhomogeneity, and also significantly reduces computation time for VMAT plans. Dose differences between AAA and Acuros_D w,m were generally less than the dose differences between AAA and Acuros_D m,m . Clinical practitioners should consider making Acuros XB available in clinics, however, further investigation and clarification is needed about which dose reporting mode (dose-to-water or dose-to-medium) should be used in clinics. © 2017 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

  12. Systemic Delivery of Atropine Sulfate by the MicroDose Dry-Powder Inhaler

    PubMed Central

    Venkataramanan, R.; Hoffman, R.M.; George, M.P.; Petrov, A.; Richards, T.; Zhang, S.; Choi, J.; Gao, Y.Y.; Oakum, C.D.; Cook, R.O.; Donahoe, M.

    2013-01-01

    Abstract Background Inhaled atropine is being developed as a systemic and pulmonary treatment for the extended recovery period after chemical weapons exposure. We performed a pharmacokinetics study comparing inhaled atropine delivery using the MicroDose Therapeutx Dry Powder Inhaler (DPIA) with intramuscular (IM) atropine delivery via auto-injector (AUTO). Methods The MicroDose DPIA utilizes a novel piezoelectric system to aerosolize drug and excipient from a foil dosing blister. Subjects inhaled a 1.95-mg atropine sulfate dose from the dry powder inhaler on one study day [5 doses×0.4 mg per dose (nominal) delivered over 12 min] and received a 2-mg IM injection via the AtroPen® auto-injector on another. Pharmacokinetics, pharmacodynamic response, and safety were studied for 12 hr. Results A total of 17 subjects were enrolled. All subjects completed IM dosing. One subject did not perform inhaled delivery due to a skin reaction from the IM dose. Pharmacokinetic results were as follows: area under the curve concentration, DPIA=20.1±5.8, AUTO=23.7±4.9 ng hr/mL (means±SD); maximum concentration reached, DPIA=7.7±3.5, AUTO=11.0±3.8 ng/mL; time to reach maximum concentration, DPIA=0.25±0.47, AUTO=0.19±0.23 hr. Pharmacodynamic results were as follows: maximum increase in heart rate, DPIA=18±12, AUTO=23±13 beats/min; average change in 1-sec forced expiratory volume at 30 min, DPIA=0.16±0.22 L, AUTO=0.11±0.29 L. The relative bioavailability for DPIA was 87% (based on output dose). Two subjects demonstrated allergic responses: one to the first dose (AUTO), which was mild and transient, and one to the second dose (DPIA), which was moderate in severity, required treatment with oral and intravenous (IV) diphenhydramine and IV steroids, and lasted more than 7 days. Conclusions Dry powder inhalation is a highly bioavailable route for attaining rapid and consistent systemic concentrations of atropine. PMID:22691110

  13. Generation of uniformly distributed dose points for anatomy-based three-dimensional dose optimization methods in brachytherapy.

    PubMed

    Lahanas, M; Baltas, D; Giannouli, S; Milickovic, N; Zamboglou, N

    2000-05-01

    We have studied the accuracy of statistical parameters of dose distributions in brachytherapy using actual clinical implants. These include the mean, minimum and maximum dose values and the variance of the dose distribution inside the PTV (planning target volume), and on the surface of the PTV. These properties have been studied as a function of the number of uniformly distributed sampling points. These parameters, or the variants of these parameters, are used directly or indirectly in optimization procedures or for a description of the dose distribution. The accurate determination of these parameters depends on the sampling point distribution from which they have been obtained. Some optimization methods ignore catheters and critical structures surrounded by the PTV or alternatively consider as surface dose points only those on the contour lines of the PTV. D(min) and D(max) are extreme dose values which are either on the PTV surface or within the PTV. They must be avoided for specification and optimization purposes in brachytherapy. Using D(mean) and the variance of D which we have shown to be stable parameters, achieves a more reliable description of the dose distribution on the PTV surface and within the PTV volume than does D(min) and D(max). Generation of dose points on the real surface of the PTV is obligatory and the consideration of catheter volumes results in a realistic description of anatomical dose distributions.

  14. Identifying the most successful dose (MSD) in dose-finding studies in cancer.

    PubMed

    Zohar, Sarah; O'Quigley, John

    2006-01-01

    For a dose finding study in cancer, the most successful dose (MSD), among a group of available doses, is that dose at which the overall success rate is the highest. This rate is the product of the rate of seeing non-toxicities together with the rate of tumor response. A successful dose finding trial in this context is one where we manage to identify the MSD in an efficient manner. In practice we may also need to consider algorithms for identifying the MSD which can incorporate certain restrictions, the most common restriction maintaining the estimated toxicity rate alone below some maximum rate. In this case the MSD may correspond to a different level than that for the unconstrained MSD and, in providing a final recommendation, it is important to underline that it is subject to the given constraint. We work with the approach described in O'Quigley et al. [Biometrics 2001; 57(4):1018-1029]. The focus of that work was dose finding in HIV where both information on toxicity and efficacy were almost immediately available. Recent cancer studies are beginning to fall under this same heading where, as before, toxicity can be quickly evaluated and, in addition, we can rely on biological markers or other measures of tumor response. Mindful of the particular context of cancer, our purpose here is to consider the methodology developed by O'Quigley et al. and its practical implementation. We also carry out a study on the doubly under-parameterized model, developed by O'Quigley et al. but not

  15. Intracoronary Adenosine: Dose-Response Relationship With Hyperemia.

    PubMed

    Adjedj, Julien; Toth, Gabor G; Johnson, Nils P; Pellicano, Mariano; Ferrara, Angela; Floré, Vincent; Di Gioia, Giuseppe; Barbato, Emanuele; Muller, Olivier; De Bruyne, Bernard

    2015-09-01

    The present study sought to establish the dosage of intracoronary (IC) adenosine associated with minimal side effects and above which no further increase in flow can be expected. Despite the widespread adoption of IC adenosine in clinical practice, no wide-ranging, dose-response study has been conducted. A recurring debate still exists regarding its optimal dose. In 30 patients, Doppler-derived flow velocity measurements were obtained in 10 right coronary arteries (RCAs) and 20 left coronary arteries (LCAs) free of stenoses >20% in diameter. Flow velocity was measured at baseline and after 8 ml bolus administrations of arterial blood, saline, contrast medium, and 9 escalating doses of adenosine (4 to 500 μg). The hyperemic value was expressed in percent of the maximum flow velocity reached in a given artery (Q/Qmax, %). Q/Qmax did not increase significantly beyond dosages of 60 μg for the RCA and 160 μg for LCA. Heart rate did not change, whereas mean arterial blood pressure decreased by a maximum of 7% (p < 0.05) after bolus injections of IC adenosine. The incidence of transient A-V blocks was 40% after injection of 100 μg in the RCA and was 15% after injection of 200 μg in the LCA. The duration of the plateau reached 12 ± 13 s after injection of 100 μg in the RCA and 21 ± 6 s after the injection of 200 μg in the LCA. A progressive prolongation of the time needed to return to baseline was observed. Hyperemic response after injection of 8 ml of contrast medium reached 65 ± 36% of that achieved after injection of 200 μg of adenosine. This wide-ranging, dose-response study indicates that an IC adenosine bolus injection of 100 μg in the RCA and 200 μg in the LCA induces maximum hyperemia while being associated with minimal side effects. Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

  16. A double-gaussian, percentile-based method for estimating maximum blood flow velocity.

    PubMed

    Marzban, Caren; Illian, Paul R; Morison, David; Mourad, Pierre D

    2013-11-01

    Transcranial Doppler sonography allows for the estimation of blood flow velocity, whose maximum value, especially at systole, is often of clinical interest. Given that observed values of flow velocity are subject to noise, a useful notion of "maximum" requires a criterion for separating the signal from the noise. All commonly used criteria produce a point estimate (ie, a single value) of maximum flow velocity at any time and therefore convey no information on the distribution or uncertainty of flow velocity. This limitation has clinical consequences especially for patients in vasospasm, whose largest flow velocities can be difficult to measure. Therefore, a method for estimating flow velocity and its uncertainty is desirable. A gaussian mixture model is used to separate the noise from the signal distribution. The time series of a given percentile of the latter, then, provides a flow velocity envelope. This means of estimating the flow velocity envelope naturally allows for displaying several percentiles (e.g., 95th and 99th), thereby conveying uncertainty in the highest flow velocity. Such envelopes were computed for 59 patients and were shown to provide reasonable and useful estimates of the largest flow velocities compared to a standard algorithm. Moreover, we found that the commonly used envelope was generally consistent with the 90th percentile of the signal distribution derived via the gaussian mixture model. Separating the observed distribution of flow velocity into a noise component and a signal component, using a double-gaussian mixture model, allows for the percentiles of the latter to provide meaningful measures of the largest flow velocities and their uncertainty.

  17. Allowing for Correlations between Correlations in Random-Effects Meta-Analysis of Correlation Matrices

    ERIC Educational Resources Information Center

    Prevost, A. Toby; Mason, Dan; Griffin, Simon; Kinmonth, Ann-Louise; Sutton, Stephen; Spiegelhalter, David

    2007-01-01

    Practical meta-analysis of correlation matrices generally ignores covariances (and hence correlations) between correlation estimates. The authors consider various methods for allowing for covariances, including generalized least squares, maximum marginal likelihood, and Bayesian approaches, illustrated using a 6-dimensional response in a series of…

  18. 78 FR 67465 - Loan Guaranty: Maximum Allowable Attorney Fees

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... foreclosure attorney fee. This fee recognizes the additional work required to resume the foreclosure action, while also accounting for the expectation that some work from the previous action may be utilized in... for legal fees in connection with the termination of single-family housing loans, including...

  19. 42 CFR 447.54 - Maximum allowable and nominal charges.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... nonemergency services furnished in a hospital emergency room. (c) Institutional services. For institutional... hospital emergency department. (a) The agency may impose cost sharing for non-emergency services provided... exempt from cost sharing under § 447.56(a), the agency may impose cost sharing for non-emergency use of...

  20. 40 CFR 35.2025 - Allowance and advance of allowance.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... advance of allowance. (a) Allowance. Step 2+3 and Step 3 grant agreements will include an allowance for facilities planning and design of the project and Step 7 agreements will include an allowance for facility... 40 Protection of Environment 1 2010-07-01 2010-07-01 false Allowance and advance of allowance. 35...

  1. Reduced dose to urethra and rectum with the use of variable needle spacing in prostate brachytherapy: a potential role for robotic technology

    PubMed Central

    Vyas, Shilpa; Le, Yi; Zhang, Zhe; Armour, Woody

    2015-01-01

    Purpose Several robotic delivery systems for prostate brachytherapy are under development or in pre-clinical testing. One of the features of robotic brachytherapy is the ability to vary spacing of needles at non-fixed intervals. This feature may play an important role in prostate brachytherapy, which is traditionally template-based with fixed needle spacing of 0.5 cm. We sought to quantify potential reductions in the dose to urethra and rectum by utilizing variable needle spacing, as compared to fixed needle spacing. Material and methods Transrectal ultrasound images from 10 patients were used by 3 experienced planners to create 120 treatment plans. Each planner created 4 plan variations per patient with respect to needle positions: 125I fixed spacing, 125I variable spacing, 103Pd fixed spacing, and 103Pd variable spacing. The primary planning objective was to achieve a prostate V100 of 100% while minimizing dose to urethra and rectum. Results All plans met the objective of achieving prostate V100 of 100%. Combined results for all plans show statistically significant improvements in all assessed dosimetric variables for urethra (Umax, Umean, D30, D5) and rectum (Rmax, Rmean, RV100) when using variable spacing. The dose reductions for mean and maximum urethra dose using variable spacing had p values of 0.011 and 0.024 with 103Pd, and 0.007 and 0.029 with 125I plans. Similarly dose reductions for mean and maximum rectal dose using variable spacing had p values of 0.007 and 0.052 with 103Pd, and 0.012 and 0.037 with 125I plans. Conclusions The variable needle spacing achievable by the use of robotics in prostate brachytherapy allows for reductions in both urethral and rectal planned doses while maintaining prostate dose coverage. Such dosimetric advantages have the potential in translating to significant clinical benefits with the use of robotic brachytherapy. PMID:26622227

  2. Fetal radiation dose estimates for I-131 sodium iodide in cases where conception occurs after administration

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

    Sparks, R.B.; Stabin, M.G.

    1999-01-01

    After administration of I-131 to the female patient, the possibility of radiation exposure of the embryo/fetus exists if the patient becomes pregnant while radioiodine remains in the body. Fetal radiation dose estimates for such cases were calculated. Doses were calculated for various maternal thyroid uptakes and time intervals between administration and conception, including euthyroid and hyperthyroid cases. The maximum fetal dose calculating was about 9.8E-03 mGy/MBq, which occurred with 100% maternal thyroid uptake and a 1 week interval between administration and conception. Placental crossover of the small amount of radioiodine remaining 90 days after conception was also considered. Such crossovermore » could result in an additional fetal dose of 9.8E-05 mGy/MBq and a maximum fetal thyroid self dose of 3.5E-04 mGy/MBq.« less

  3. Assessment of the actual light dose in photodynamic therapy.

    PubMed

    Schaberle, Fabio A

    2018-06-09

    Photodynamic therapy (PDT) initiates with the absorption of light, which depends on the spectral overlap between the light source emission and the photosensitizer absorption, resulting in the number of photons absorbed, the key parameter starting PDT processes. Most papers report light doses regardless if the light is only partially absorbed or shifted relatively to the absorption peak, misleading the actual light dose value and not allowing quantitative comparisons between photosensitizers and light sources. In this manuscript a method is presented to calculate the actual light dose delivered by any light source for a given photosensitizer. This method allows comparing light doses delivered for any combination of light source (broad or narrow band or daylight) and photosensitizer. Copyright © 2018. Published by Elsevier B.V.

  4. Uncertainties in Assesment of the Vaginal Dose for Intracavitary Brachytherapy of Cervical Cancer using a Tandem-ring Applicator

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

    Berger, Daniel; Dimopoulos, Johannes; Georg, Petra

    2007-04-01

    Purpose: The vagina has not been widely recognized as organ at risk in brachytherapy for cervical cancer. No widely accepted dose parameters are available. This study analyzes the uncertainties in dose reporting for the vaginal wall using tandem-ring applicators. Methods and Materials: Organ wall contours were delineated on axial magnetic resonance (MR) slices to perform dose-volume histogram (DVH) analysis. Different DVH parameters were used in a feasibility study based on 40 magnetic resonance imaging (MRI)-based treatment plans of different cervical cancer patients. Dose to the most irradiated, 0.1 cm{sup 3}, 1 cm{sup 3}, 2 cm{sup 3}, and at defined pointsmore » on the ring surface and at 5-mm tissue depth were reported. Treatment-planning systems allow different methods of dose point definition. Film dosimetry was used to verify the maximum dose at the surface of the ring applicator in an experimental setup. Results: Dose reporting for the vagina is extremely sensitive to geometrical uncertainties with variations of 25% for 1 mm shifts. Accurate delineation of the vaginal wall is limited by the finite pixel size of MRI and available treatment-planning systems. No significant correlation was found between dose-point and dose-volume parameters. The DVH parameters were often related to noncontiguous volumes and were not able to detect very different situations of spatial dose distributions inside the vaginal wall. Deviations between measured and calculated doses were up to 21%. Conclusions: Reporting either point dose values or DVH parameters for the vaginal wall is based on high inaccuracies because of contouring and geometric positioning. Therefore, the use of prospective dose constraints for individual treatment plans is not to be recommended at present. However, for large patient groups treated within one protocol correlation with vaginal morbidity can be evaluated.« less

  5. Extracting volatility signal using maximum a posteriori estimation

    NASA Astrophysics Data System (ADS)

    Neto, David

    2016-11-01

    This paper outlines a methodology to estimate a denoised volatility signal for foreign exchange rates using a hidden Markov model (HMM). For this purpose a maximum a posteriori (MAP) estimation is performed. A double exponential prior is used for the state variable (the log-volatility) in order to allow sharp jumps in realizations and then log-returns marginal distributions with heavy tails. We consider two routes to choose the regularization and we compare our MAP estimate to realized volatility measure for three exchange rates.

  6. Reconstruction of Absorbed Doses to Fibroglandular Tissue of the Breast of Women undergoing Mammography (1960 to the Present)

    PubMed Central

    Thierry-Chef, Isabelle; Simon, Steven L.; Weinstock, Robert M.; Kwon, Deukwoo; Linet, Martha S.

    2013-01-01

    The assessment of potential benefits versus harms from mammographic examinations as described in the controversial breast cancer screening recommendations of the U.S. Preventive Task Force included limited consideration of absorbed dose to the fibroglandular tissue of the breast (glandular tissue dose), the tissue at risk for breast cancer. Epidemiological studies on cancer risks associated with diagnostic radiological examinations often lack accurate information on glandular tissue dose, and there is a clear need for better estimates of these doses. Our objective was to develop a quantitative summary of glandular tissue doses from mammography by considering sources of variation over time in key parameters including imaging protocols, x-ray target materials, voltage, filtration, incident air kerma, compressed breast thickness, and breast composition. We estimated the minimum, maximum, and mean values for glandular tissue dose for populations of exposed women within 5-year periods from 1960 to the present, with the minimum to maximum range likely including 90% to 95% of the entirety of the dose range from mammography in North America and Europe. Glandular tissue dose from a single view in mammography is presently about 2 mGy, about one-sixth the dose in the 1960s. The ratio of our estimates of maximum to minimum glandular tissue doses for average-size breasts was about 100 in the 1960s compared to a ratio of about 5 in recent years. Findings from our analysis provide quantitative information on glandular tissue doses from mammographic examinations which can be used in epidemiologic studies of breast cancer. PMID:21988547

  7. Dose-response effects of corneal anesthetics.

    PubMed

    Polse, K A; Keener, R J; Jauregui, M J

    1978-01-01

    With double-masking procedures, the dose-response curves for 0.1, 0.2, and 0.4% benoxinate and 0.125, 0.25, and 0.50% proparacaine hydrochloride were determined by monitoring changes in corneal touch threshold after applying each anesthetic. The level of corneal anesthesia necessary for applanation tonometry was also determined. The maximum increase in threshold that could be measured following instillation of 50 microliter of the drug was 200 mg/mm2 All 6 anesthetic solutions produced this amount of decreased corneal sensitivity. Recovery from the anesthetic was exponential for all concentrations; however, the lower doses had the shortest duration. For applanation tonometry, the corneal threshold for touch must be 75 mg/mm2 or higher. We conclude that a quarter to a half of the commonly used anesthetic dose is sufficient for routine tonometric evaluation.

  8. Stratified and Maximum Information Item Selection Procedures in Computer Adaptive Testing

    ERIC Educational Resources Information Center

    Deng, Hui; Ansley, Timothy; Chang, Hua-Hua

    2010-01-01

    In this study we evaluated and compared three item selection procedures: the maximum Fisher information procedure (F), the a-stratified multistage computer adaptive testing (CAT) (STR), and a refined stratification procedure that allows more items to be selected from the high a strata and fewer items from the low a strata (USTR), along with…

  9. A comparison of skin and chest wall dose delivered with multicatheter, Contura multilumen balloon, and MammoSite breast brachytherapy.

    PubMed

    Cuttino, Laurie W; Todor, Dorin; Rosu, Mihaela; Arthur, Douglas W

    2011-01-01

    Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS. Copyright © 2011 Elsevier Inc. All rights reserved.

  10. A Comparison of Skin and Chest Wall Dose Delivered With Multicatheter, Contura Multilumen Balloon, and MammoSite Breast Brachytherapy

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

    Cuttino, Laurie W., E-mail: lcuttino@mcvh-vcu.ed; Todor, Dorin; Rosu, Mihaela

    2011-01-01

    Purpose: Skin and chest wall doses have been correlated with toxicity in patients treated with breast brachytherapy . This investigation compared the ability to control skin and chest wall doses between patients treated with multicatheter (MC), Contura multilumen balloon (CMLB), and MammoSite (MS) brachytherapy. Methods and Materials: 43 patients treated with the MC technique, 45 patients treated with the CMLB, and 83 patients treated with the MS were reviewed. The maximum doses delivered to the skin and chest wall were calculated for all patients. Results: The mean maximum skin doses for the MC, CMLB, and MS were 2.3 Gy (67%more » of prescription dose), 2.8 Gy (82% of prescription dose), and 3.2 Gy per fraction (94% of prescription dose), respectively. Although the skin distances were similar (p = 0.23) for the two balloon techniques, the mean skin dose with the CMLB was significantly lower than with the MS (p = 0.05). The mean maximum rib doses for the MC, CMLB, and MS were 2.3 Gy (67% of prescription dose), 2.8 Gy (82% of prescription dose), and 3.6 Gy per fraction (105% of prescription dose), respectively. Again, the mean rib dose with the CMLB was significantly lower than with the MS (p = 0.002). Conclusion: The MC and CMLB techniques are associated with significantly lower mean skin and rib doses than is the MS. Treatment with the MS was associated with significantly more patients receiving doses to the skin or rib in excess of 125% of the prescription. Treatment with the CMLB may prove to yield less normal tissue toxicity than treatment with the MS.« less

  11. Effect of ultra-low doses, ASIR and MBIR on density and noise levels of MDCT images of dental implant sites.

    PubMed

    Widmann, Gerlig; Al-Shawaf, Reema; Schullian, Peter; Al-Sadhan, Ra'ed; Hörmann, Romed; Al-Ekrish, Asma'a A

    2017-05-01

    Differences in noise and density values in MDCT images obtained using ultra-low doses with FBP, ASIR, and MBIR may possibly affect implant site density analysis. The aim of this study was to compare density and noise measurements recorded from dental implant sites using ultra-low doses combined with FBP, ASIR, and MBIR. Cadavers were scanned using a standard protocol and four low-dose protocols. Scans were reconstructed using FBP, ASIR-50, ASIR-100, and MBIR, and either a bone or standard reconstruction kernel. Density (mean Hounsfield units [HUs]) of alveolar bone and noise levels (mean standard deviation of HUs) was recorded from all datasets and measurements were compared by paired t tests and two-way ANOVA with repeated measures. Significant differences in density and noise were found between the reference dose/FBP protocol and almost all test combinations. Maximum mean differences in HU were 178.35 (bone kernel) and 273.74 (standard kernel), and in noise, were 243.73 (bone kernel) and 153.88 (standard kernel). Decreasing radiation dose increased density and noise regardless of reconstruction technique and kernel. The effect of reconstruction technique on density and noise depends on the reconstruction kernel used. • Ultra-low-dose MDCT protocols allowed more than 90 % reductions in dose. • Decreasing the dose generally increased density and noise. • Effect of IRT on density and noise varies with reconstruction kernel. • Accuracy of low-dose protocols for interpretation of bony anatomy not known. • Effect of low doses on accuracy of computer-aided design models unknown.

  12. Radiation leakage dose from Elekta electron collimation system

    PubMed Central

    Hogstrom, Kenneth R.; Carver, Robert L.

    2016-01-01

    This study provided baseline data required for a greater project, whose objective was to design a new Elekta electron collimation system having significantly lighter electron applicators with equally low out‐of field leakage dose. Specifically, off‐axis dose profiles for the electron collimation system of our uniquely configured Elekta Infinity accelerator with the MLCi2 treatment head were measured and calculated for two primary purposes: 1) to evaluate and document the out‐of‐field leakage dose in the patient plane and 2) to validate the dose distributions calculated using a BEAMnrc Monte Carlo (MC) model for out‐of‐field dose profiles. Off‐axis dose profiles were measured in a water phantom at 100 cm SSD for 1 and 2 cm depths along the in‐plane, cross‐plane, and both diagonal axes using a cylindrical ionization chamber with the 10×10 and 20×20 cm2 applicators and 7, 13, and 20 MeV beams. Dose distributions were calculated using a previously developed BEAMnrc MC model of the Elekta Infinity accelerator for the same beam energies and applicator sizes and compared with measurements. Measured results showed that the in‐field beam flatness met our acceptance criteria (±3% on major and ±4% on diagonal axes) and that out‐of‐field mean and maximum percent leakage doses in the patient plane met acceptance criteria as specified by the International Electrotechnical Commission (IEC). Cross‐plane out‐of‐field dose profiles showed greater leakage dose than in‐plane profiles, attributed to the curved edges of the upper X‐ray jaws and multileaf collimator. Mean leakage doses increased with beam energy, being 0.93% and 0.85% of maximum central axis dose for the 10×10 and 20×20 cm2 applicators, respectively, at 20 MeV. MC calculations predicted the measured dose to within 0.1% in most profiles outside the radiation field; however, excluding modeling of nontrimmer applicator components led to calculations exceeding measured data by as

  13. The influence of the dose calculation resolution of VMAT plans on the calculated dose for eye lens and optic pathway.

    PubMed

    Park, Jong Min; Park, So-Yeon; Kim, Jung-In; Carlson, Joel; Kim, Jin Ho

    2017-03-01

    To investigate the effect of dose calculation grid on calculated dose-volumetric parameters for eye lenses and optic pathways. A total of 30 patients treated using the volumetric modulated arc therapy (VMAT) technique, were retrospectively selected. For each patient, dose distributions were calculated with calculation grids ranging from 1 to 5 mm at 1 mm intervals. Identical structures were used for VMAT planning. The changes in dose-volumetric parameters according to the size of the calculation grid were investigated. Compared to dose calculation with 1 mm grid, the maximum doses to the eye lens with calculation grids of 2, 3, 4 and 5 mm increased by 0.2 ± 0.2 Gy, 0.5 ± 0.5 Gy, 0.9 ± 0.8 Gy and 1.7 ± 1.5 Gy on average, respectively. The Spearman's correlation coefficient between dose gradients near structures vs. the differences between the calculated doses with 1 mm grid and those with 5 mm grid, were 0.380 (p < 0.001). For the accurate calculation of dose distributions, as well as efficiency, using a grid size of 2 mm appears to be the most appropriate choice.

  14. Doses of external exposure in Jordan house due to gamma-emitting natural radionuclides in building materials.

    PubMed

    Al-Jundi, J; Ulanovsky, A; Pröhl, G

    2009-10-01

    The use of building materials containing naturally occurring radionuclides as (40)K, (232)Th, and (238)U and their progeny results in external exposures of the residents of such buildings. In the present study, indoor dose rates for a typical Jordan concrete room are calculated using Monte Carlo method. Uniform chemical composition of the walls, floor and ceiling as well as uniform mass concentrations of the radionuclides in walls, floor and ceiling are assumed. Using activity concentrations of natural radionuclides typical for the Jordan houses and assuming them to be in secular equilibrium with their progeny, the maximum annual effective doses are estimated to be 0.16, 0.12 and 0.22 mSv a(-1) for (40)K, (232)Th- and (238)U-series, respectively. In a total, the maximum annual effective indoor dose due to external gamma-radiation is 0.50 mSv a(-1). Additionally, organ dose coefficients are calculated for all organs considered in ICRP Publication 74. Breast, skin and eye lenses have the maximum equivalent dose rate values due to indoor exposures caused by the natural radionuclides, while equivalent dose rates for uterus, colon (LLI) and small intestine are found to be the smallest. More specifically, organ dose rates (nSv a(-1)per Bq kg(-1)) vary from 0.044 to 0.060 for (40)K, from 0.44 to 0.60 for radionuclides from (238)U-series and from 0.60 to 0.81 for radionuclides from (232)Th-series. The obtained organ and effective dose conversion coefficients can be conveniently used in practical dose assessment tasks for the rooms of similar geometry and varying activity concentrations and local-specific occupancy factors.

  15. Dose verification to cochlea during gamma knife radiosurgery of acoustic schwannoma using MOSFET dosimeter.

    PubMed

    Sharma, Sunil D; Kumar, Rajesh; Akhilesh, Philomina; Pendse, Anil M; Deshpande, Sudesh; Misra, Basant K

    2012-01-01

    Dose verification to cochlea using metal oxide semiconductor field effect transistor (MOSFET) dosimeter using a specially designed multi slice head and neck phantom during the treatment of acoustic schwannoma by Gamma Knife radiosurgery unit. A multi slice polystyrene head phantom was designed and fabricated for measurement of dose to cochlea during the treatment of the acoustic schwannoma. The phantom has provision to position the MOSFET dosimeters at the desired location precisely. MOSFET dosimeters of 0.2 mm x 0.2 mm x 0.5 μm were used to measure the dose to the cochlea. CT scans of the phantom with MOSFETs in situ were taken along with Leksell frame. The treatment plans of five patients treated earlier for acoustic schwannoma were transferred to the phantom. Dose and coordinates of maximum dose point inside the cochlea were derived. The phantom along with the MOSFET dosimeters was irradiated to deliver the planned treatment and dose received by cochlea were measured. The treatment planning system (TPS) estimated and measured dose to the cochlea were in the range of 7.4 - 8.4 Gy and 7.1 - 8 Gy, respectively. The maximum variation between TPS calculated and measured dose to cochlea was 5%. The measured dose values were found in good agreement with the dose values calculated using the TPS. The MOSFET dosimeter can be a suitable choice for routine dose verification in the Gamma Knife radiosurgery.

  16. Maximum thrust mode evaluation

    NASA Technical Reports Server (NTRS)

    Orme, John S.; Nobbs, Steven G.

    1995-01-01

    Measured reductions in acceleration times which resulted from the application of the F-15 performance seeking control (PSC) maximum thrust mode during the dual-engine test phase is presented as a function of power setting and flight condition. Data were collected at altitudes of 30,000 and 45,000 feet at military and maximum afterburning power settings. The time savings for the supersonic acceleration is less than at subsonic Mach numbers because of the increased modeling and control complexity. In addition, the propulsion system was designed to be optimized at the mid supersonic Mach number range. Recall that even though the engine is at maximum afterburner, PSC does not trim the afterburner for the maximum thrust mode. Subsonically at military power, time to accelerate from Mach 0.6 to 0.95 was cut by between 6 and 8 percent with a single engine application of PSC, and over 14 percent when both engines were optimized. At maximum afterburner, the level of thrust increases were similar in magnitude to the military power results, but because of higher thrust levels at maximum afterburner and higher aircraft drag at supersonic Mach numbers the percentage thrust increase and time to accelerate was less than for the supersonic accelerations. Savings in time to accelerate supersonically at maximum afterburner ranged from 4 to 7 percent. In general, the maximum thrust mode has performed well, demonstrating significant thrust increases at military and maximum afterburner power. Increases of up to 15 percent at typical combat-type flight conditions were identified. Thrust increases of this magnitude could be useful in a combat situation.

  17. Dose-dependent EEG effects of zolpidem provide evidence for GABA(A) receptor subtype selectivity in vivo.

    PubMed

    Visser, S A G; Wolters, F L C; van der Graaf, P H; Peletier, L A; Danhof, M

    2003-03-01

    Zolpidem is a nonbenzodiazepine GABA(A) receptor modulator that binds in vitro with high affinity to GABA(A) receptors expressing alpha(1) subunits but with relatively low affinity to receptors expressing alpha(2), alpha(3), and alpha(5) subunits. In the present study, it was investigated whether this subtype selectivity could be detected and quantified in vivo. Three doses (1.25, 5, and 25 mg) of zolpidem were administered to rats in an intravenous infusion over 5 min. The time course of the plasma concentrations was determined in conjunction with the change in the beta-frequency range of the EEG as pharmacodynamic endpoint. The concentration-effect relationship of the three doses showed a dose-dependent maximum effect and a dose-dependent potency. The data were analyzed for one- or two-site binding using two pharmacodynamic models based on 1) the descriptive model and 2) a novel mechanism-based pharmacokinetic/pharmacodynamic (PK/PD) model for GABA(A) receptor modulators that aims to separates drug- and system-specific properties, thereby allowing the estimation of in vivo affinity and efficacy. The application of two-site models significantly improved the fits compared with one-site models. Furthermore, in contrast to the descriptive model, the mechanism-based PK/PD model yielded dose-independent estimates for affinity (97 +/- 40 and 33,100 +/- 14,800 ng x ml(-1)). In conclusion, the mechanism-based PK/PD model is able to describe and explain the observed dose-dependent EEG effects of zolpidem and suggests the subtype selectivity of zolpidem in vivo.

  18. Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method

    NASA Astrophysics Data System (ADS)

    McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A.; Purdie, Thomas G.

    2017-08-01

    Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

  19. Fully automated treatment planning for head and neck radiotherapy using a voxel-based dose prediction and dose mimicking method.

    PubMed

    McIntosh, Chris; Welch, Mattea; McNiven, Andrea; Jaffray, David A; Purdie, Thomas G

    2017-07-06

    Recent works in automated radiotherapy treatment planning have used machine learning based on historical treatment plans to infer the spatial dose distribution for a novel patient directly from the planning image. We present a probabilistic, atlas-based approach which predicts the dose for novel patients using a set of automatically selected most similar patients (atlases). The output is a spatial dose objective, which specifies the desired dose-per-voxel, and therefore replaces the need to specify and tune dose-volume objectives. Voxel-based dose mimicking optimization then converts the predicted dose distribution to a complete treatment plan with dose calculation using a collapsed cone convolution dose engine. In this study, we investigated automated planning for right-sided oropharaynx head and neck patients treated with IMRT and VMAT. We compare four versions of our dose prediction pipeline using a database of 54 training and 12 independent testing patients by evaluating 14 clinical dose evaluation criteria. Our preliminary results are promising and demonstrate that automated methods can generate comparable dose distributions to clinical. Overall, automated plans achieved an average of 0.6% higher dose for target coverage evaluation criteria, and 2.4% lower dose at the organs at risk criteria levels evaluated compared with clinical. There was no statistically significant difference detected in high-dose conformity between automated and clinical plans as measured by the conformation number. Automated plans achieved nine more unique criteria than clinical across the 12 patients tested and automated plans scored a significantly higher dose at the evaluation limit for two high-risk target coverage criteria and a significantly lower dose in one critical organ maximum dose. The novel dose prediction method with dose mimicking can generate complete treatment plans in 12-13 min without user interaction. It is a promising approach for fully automated treatment

  20. Dose in bone and tissue near bone-tissue interface from electron beam.

    PubMed

    Shiu, A S; Hogstrom, K R

    1991-08-01

    This work has quantitatively studied the variation of dose both within bone and in unit density tissue near bone-tissue interfaces. Dose upstream of a bone-tissue interface is increased because of an increase in the backscattered electrons from the bone. The magnitude of this effect was measured using a thin parallel-plate ionization chamber upstream of a polymethyl methacrylate (PMMA)-hard bone interface. The electron backscatter factor (EBF) increased rapidly with bone thickness until a full EBF was achieved. This occurred at approximately 3.5 mm at 2 MeV and 6 mm at 13.1 MeV. The full EBF at the interface ranged from approximately 1.018 at 13.1 MeV to 1.05 at 2 MeV. It was also observed that the EBF had a dependence on the energy spectrum at the interface. The penetration of the backscattered electrons in the upstream direction of PMMA was also measured. The dose penetration fell off rapidly in the upstream direction of the interface. Dose enhancement to unit density tissue in bone was measured for an electron beam by placing thermoluminescent dosimeters (TLDs) in a PMMA-bone-PMMA phantom. The maximum dose enhancement in bone was approximately 7% of the maximum dose in water. However, the pencil-beam algorithm of Hogstrom et al. predicted an increase of only 1%, primarily owing to the inverse-square correction. Film was also used to measure the dose enhancement in bone. The film plane was aligned either perpendicular or parallel to the central axis of the beam. The film data indicated that the maximum dose enhancement in bone was approximately 8% for the former film alignment (which was similarly predicted by the TLD measurements) and 13% for the latter film alignment. These results confirm that the X ray film is not suitable to be irritated "edge on" in an inhomogeneous phantom without making perturbation corrections resulting from the film acting as a long narrow inhomogeneous cavity within the bone. In addition, the results give the radiotherapist a basis for

  1. Replacing the Measles Ten-Dose Vaccine Presentation with the Single-Dose Presentation in Thailand

    PubMed Central

    Lee, Bruce Y.; Assi, Tina-Marie; Rookkapan, Korngamon; Connor, Diana L.; Rajgopal, Jayant; Sornsrivichai, Vorasith; Brown, Shawn T.; Welling, Joel S.; Norman, Bryan A.; Chen, Sheng-I; Bailey, Rachel R.; Wiringa, Ann E.; Wateska, Angela R.; Jana, Anirban; Van Panhuis, Willem G.; Burke, Donald S.

    2011-01-01

    Introduced to minimize open vial wastage, single-dose vaccine vials require more storage space and therefore may affect vaccine supply chains (i.e., the series of steps and processes entailed to deliver vaccines from manufacturers to patients). We developed a computational model of Thailand’s Trang province vaccine supply chain to analyze the effects of switching from a ten-dose measles vaccine presentation to each of the following: a single-dose Measles-Mumps-Rubella vaccine (which Thailand is currently considering) and a single-dose measles vaccine. While the Trang province vaccine supply chain would generally have enough storage and transport capacity to accommodate the switches, the added volume could push some locations’ storage and transport space utilization close to their limits. Single-dose vaccines would allow for more precise ordering and decrease open vial waste, but decrease reserves for unanticipated demand. Moreover, the added disposal and administration costs could far outweigh the costs saved from preventing open vial wastage. PMID:21439313

  2. Estimation of external dose by car-borne survey in Kerala, India.

    PubMed

    Hosoda, Masahiro; Tokonami, Shinji; Omori, Yasutaka; Sahoo, Sarata Kumar; Akiba, Suminori; Sorimachi, Atsuyuki; Ishikawa, Tetsuo; Nair, Raghu Ram; Jayalekshmi, Padmavathy Amma; Sebastian, Paul; Iwaoka, Kazuki; Akata, Naofumi; Kudo, Hiromi

    2015-01-01

    A car-borne survey was carried out in Kerala, India to estimate external dose. Measurements were made with a 3-in × 3-in NaI(Tl) scintillation spectrometer from September 23 to 27, 2013. The routes were selected from 12 Panchayats in Karunagappally Taluk which were classified into high level, mid-level and low level high background radiation (HBR) areas. A heterogeneous distribution of air kerma rates was seen in the dose rate distribution map. The maximum air kerma rate, 2.1 μGy/h, was observed on a beach sand surface. 232Th activity concentration for the beach sand was higher than that for soil and grass surfaces, and the range of activity concentration was estimated to be 0.7-2.3 kBq/kg. The contribution of 232Th to air kerma rate was over 70% at the measurement points with values larger than 0.34 μGy/h. The maximum value of the annual effective dose in Karunagappally Taluk was observed around coastal areas, and it was estimated to be 13 mSv/y. More than 30% of all the annual effective doses obtained in this survey exceeded 1 mSv/y.

  3. Equivalent uniform dose concept evaluated by theoretical dose volume histograms for thoracic irradiation.

    PubMed

    Dumas, J L; Lorchel, F; Perrot, Y; Aletti, P; Noel, A; Wolf, D; Courvoisier, P; Bosset, J F

    2007-03-01

    The goal of our study was to quantify the limits of the EUD models for use in score functions in inverse planning software, and for clinical application. We focused on oesophagus cancer irradiation. Our evaluation was based on theoretical dose volume histograms (DVH), and we analyzed them using volumetric and linear quadratic EUD models, average and maximum dose concepts, the linear quadratic model and the differential area between each DVH. We evaluated our models using theoretical and more complex DVHs for the above regions of interest. We studied three types of DVH for the target volume: the first followed the ICRU dose homogeneity recommendations; the second was built out of the first requirements and the same average dose was built in for all cases; the third was truncated by a small dose hole. We also built theoretical DVHs for the organs at risk, in order to evaluate the limits of, and the ways to use both EUD(1) and EUD/LQ models, comparing them to the traditional ways of scoring a treatment plan. For each volume of interest we built theoretical treatment plans with differences in the fractionation. We concluded that both volumetric and linear quadratic EUDs should be used. Volumetric EUD(1) takes into account neither hot-cold spot compensation nor the differences in fractionation, but it is more sensitive to the increase of the irradiated volume. With linear quadratic EUD/LQ, a volumetric analysis of fractionation variation effort can be performed.

  4. Comparison of dose volume parameters evaluated using three forward planning – optimization techniques in cervical cancer brachytherapy involving two applicators

    PubMed Central

    Basu-Roy, Somapriya; Kar, Sanjay Kumar; Das, Sounik; Lahiri, Annesha

    2017-01-01

    Purpose This study is intended to compare dose-volume parameters evaluated using different forward planning- optimization techniques, involving two applicator systems in intracavitary brachytherapy for cervical cancer. It looks for the best applicator-optimization combination to fulfill recommended dose-volume objectives in different high-dose-rate (HDR) fractionation schedules. Material and methods We used tandem-ring and Fletcher-style tandem-ovoid applicator in same patients in two fractions of brachytherapy. Six plans were generated for each patient utilizing 3 forward optimization techniques for each applicator used: equal dwell weight/times (‘no optimization’), ‘manual dwell weight/times’, and ‘graphical’. Plans were normalized to left point A and dose of 8 Gy was prescribed. Dose volume and dose point parameters were compared. Results Without graphical optimization, maximum width and thickness of volume enclosed by 100% isodose line, dose to 90%, and 100% of clinical target volume (CTV); minimum, maximum, median, and average dose to both rectum and bladder are significantly higher with Fletcher applicator. Even if it is done, dose to both points B, minimum dose to CTV, and treatment time; dose to 2 cc (D2cc) rectum and rectal point etc.; D2cc, minimum, maximum, median, and average dose to sigmoid colon; D2cc of bladder remain significantly higher with this applicator. Dose to bladder point is similar (p > 0.05) between two applicators, after all optimization techniques. Conclusions Fletcher applicator generates higher dose to both CTV and organs at risk (2 cc volumes) after all optimization techniques. Dose restriction to rectum is possible using graphical optimization only during selected HDR fractionation schedules. Bladder always receives dose higher than recommended, and 2 cc sigmoid colon always gets permissible dose. Contrarily, graphical optimization with ring applicators fulfills all dose volume objectives in all HDR fractionations

  5. Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows.

    PubMed

    Kleinhenz, M D; Gorden, P J; Smith, J S; Schleining, J A; Kleinhenz, K E; Wulf, L L; Sidhu, P K; Rea, D; Coetzee, J F

    2018-06-01

    A transdermal formulation of the nonsteroidal anti-inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single-dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high-pressure liquid chromatography with mass spectroscopy (HPLC-MS). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (Tmax) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half-life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg -1 , and volume of distribution of fraction (Vz/F) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses. © 2018 John Wiley & Sons Ltd.

  6. SU-E-T-639: Proton Dose Calculation for Irregular Motion Using a Sliding Interface

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

    Phillips, J; Gueorguiev, G; Grassberger, C

    2015-06-15

    Purpose: While many techniques exist to evaluate dose to regularly moving lung targets, there are few available to calculate dose at tumor positions not present in the 4DCT. We have previously developed a method that extrapolates an existing dose to a new tumor location. In this abstract, we present a novel technique that accounts for relative anatomical shifts at the chest wall interface. We also utilize this procedure to simulate breathing motion functions on a cohort of eleven patients. Amplitudes exceeding the original range of motion were used to evaluate coverage using several aperture and smearing beam settings. Methods: Themore » water-equivalent depth (WED) technique requires an initial dose and CT image at the corresponding tumor position. Each dose volume was converted from its Cartesian geometry into a beam-specific radiological depth space. The sliding chest wall interface was determined by converting the lung contour into this same space. Any dose proximal to the initial boundary of the warped lung contour was held fixed, while the remaining distal dose was moved in the direction of motion along the interface. Results: V95 coverage was computed for each patient using the updated algorithm. Incorporation of the sliding motion yielded large dose differences, with gamma pass rates as low as 69.7% (3mm, 3%) and V95 coverage differences up to 2.0%. Clinical coverage was maintained for most patients with 5 mm excess simulated breathing motion, and up to 10 mm of excess motion was tolerated for a subset of patients and beam settings. Conclusion: We have established a method to determine the maximum allowable excess breathing motion for a given plan on a patient-by-patient basis. By integrating a sliding chest wall interface into our dose calculation technique, we have analyzed the robustness of breathing patterns that differ during treatment from at the time of 4DCT acquisition.« less

  7. Third-party reimbursement for generic prescription drugs: The prevalence of below-cost reimbursement in an environment of maximum allowable cost-based reimbursement.

    PubMed

    Murry, Logan; Gerleman, Brandon; Urick, Benjamin; Urmie, Julie

    2018-05-31

    To examine average prescription gross margin (GM) for prescriptions and to evaluate the prevalence of below-cost reimbursement for generic prescriptions across different third-party payers and therapeutic categories. A retrospective descriptive study using 2015 dispensing data from a single independently owned pharmacy in Iowa. To calculate GM, the pharmacy's actual acquisition cost was subtracted from the third-party reimbursement rate for each generic prescription. The frequency of negative GMs was calculated for the top 6 plans and the top 10 therapeutic categories by prescription volume. A single, independently owned community pharmacy in Iowa. Prescription dispensing records for the pharmacy's largest private and public payers by prescription volume. Gross margins were calculated on a payer and United States Pharmacopeia (USP) medication category level. GM for generic prescriptions reimbursed under cost for specific payers and USP medication categories. The 2015 prescription volume for the study pharmacy was 70,866 prescriptions, of which 88% were generic. For all prescriptions, the mean GM was $6.63 per prescription, and the median GM was $3.49 per prescription. Generic medications had a mean GM of $4.66 (median, $2.86), and brand name medications had a mean GM of $21.83 (median, $16.15). The percentage of generic prescriptions paid below acquisition cost was 15.1% overall and ranged from 4.1% for Iowa Medicaid to 25.9% for one of the private payers. The most common USP medication category by prescription volume was cardiovascular agents, representing 25.2% of generic prescriptions. For the 10.9% of these prescriptions reimbursed below cost, the mean GM was -$6.80. The 2 USP medication categories with the largest negative mean GM for generic prescriptions were analgesics and anticonvulsants, with mean GMs of -$10.10 and -$11.30, respectively. The current maximum allowable cost-based reimbursement system often results in inadequate payment for generic

  8. Maximum work extraction and implementation costs for nonequilibrium Maxwell's demons.

    PubMed

    Sandberg, Henrik; Delvenne, Jean-Charles; Newton, Nigel J; Mitter, Sanjoy K

    2014-10-01

    We determine the maximum amount of work extractable in finite time by a demon performing continuous measurements on a quadratic Hamiltonian system subjected to thermal fluctuations, in terms of the information extracted from the system. The maximum work demon is found to apply a high-gain continuous feedback involving a Kalman-Bucy estimate of the system state and operates in nonequilibrium. A simple and concrete electrical implementation of the feedback protocol is proposed, which allows for analytic expressions of the flows of energy, entropy, and information inside the demon. This let us show that any implementation of the demon must necessarily include an external power source, which we prove both from classical thermodynamics arguments and from a version of Landauer's memory erasure argument extended to nonequilibrium linear systems.

  9. Using spatial information about recurrence risk for robust optimization of dose-painting prescription functions

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

    Bender, Edward T.

    Purpose: To develop a robust method for deriving dose-painting prescription functions using spatial information about the risk for disease recurrence. Methods: Spatial distributions of radiobiological model parameters are derived from distributions of recurrence risk after uniform irradiation. These model parameters are then used to derive optimal dose-painting prescription functions given a constant mean biologically effective dose. Results: An estimate for the optimal dose distribution can be derived based on spatial information about recurrence risk. Dose painting based on imaging markers that are moderately or poorly correlated with recurrence risk are predicted to potentially result in inferior disease control when comparedmore » the same mean biologically effective dose delivered uniformly. A robust optimization approach may partially mitigate this issue. Conclusions: The methods described here can be used to derive an estimate for a robust, patient-specific prescription function for use in dose painting. Two approximate scaling relationships were observed: First, the optimal choice for the maximum dose differential when using either a linear or two-compartment prescription function is proportional to R, where R is the Pearson correlation coefficient between a given imaging marker and recurrence risk after uniform irradiation. Second, the predicted maximum possible gain in tumor control probability for any robust optimization technique is nearly proportional to the square of R.« less

  10. A new radiotherapy surface dose detector:the MOSFET.

    PubMed

    Butson, M J; Rozenfeld, A; Mathur, J N; Carolan, M; Wong, T P; Metcalfe, P E

    1996-05-01

    Radiotherapy x-ray and electron beam surface doses are accurately measurable by use of a MOS-FET detector system. The MOSFET (Metal Oxide Semiconductor Field Effect Transistor) is approximately 200-microns in diameter and consists of a 0.5-microns Al electrode on top of a 1-microns SiO2 and 300-microns Si substrate. Results for % surface dose were within +/- 2% compared to the Attix chamber and within +/- 3% of TLD extrapolation results for normally incident beams. Detectors were compared using different energies, field size, and beam modifying devices such as block trays and wedges. Percentage surface dose for 10 x 10-cm and 40 x 40-cm field size for 6-MV x rays at 100-cm SSD using the MOSFET were 16% and 42% of maximum, respectively. Factors such as its small size, immediate retrieval of results, high accuracy attainable from low applied doses, and as the MOSFET records its dose history make it a suitable in vivo dosimeter where surface and skin doses need to be determined. This can be achieved within part of the first fraction of dose (i.e., only 10 cGy is required.)

  11. Factors Associated With Chest Wall Toxicity After Accelerated Partial Breast Irradiation Using High-Dose-Rate Brachytherapy

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

    Brown, Sheree, E-mail: shereedst32@hotmail.com; Vicini, Frank; Vanapalli, Jyotsna R.

    2012-07-01

    Purpose: The purpose of this analysis was to evaluate dose-volume relationships associated with a higher probability for developing chest wall toxicity (pain) after accelerated partial breast irradiation (APBI) by using both single-lumen and multilumen brachytherapy. Methods and Materials: Rib dose data were available for 89 patients treated with APBI and were correlated with the development of chest wall/rib pain at any point after treatment. Ribs were contoured on computed tomography planning scans, and rib dose-volume histograms (DVH) along with histograms for other structures were constructed. Rib DVH data for all patients were sampled at all volumes {>=}0.008 cubic centimeter (cc)more » (for maximum dose related to pain) and at volumes of 0.5, 1, 2, and 3 cc for analysis. Rib pain was evaluated at each follow-up visit. Patient responses were marked as yes or no. No attempt was made to grade responses. Eighty-nine responses were available for this analysis. Results: Nineteen patients (21.3%) complained of transient chest wall/rib pain at any point in follow-up. Analysis showed a direct correlation between total dose received and volume of rib irradiated with the probability of developing rib/chest wall pain at any point after follow-up. The median maximum dose at volumes {>=}0.008 cc of rib in patients who experienced chest wall pain was 132% of the prescribed dose versus 95% of the prescribed dose in those patients who did not experience pain (p = 0.0035). Conclusions: Although the incidence of chest wall/rib pain is quite low with APBI brachytherapy, attempts should be made to keep the volume of rib irradiated at a minimum and the maximum dose received by the chest wall as low as reasonably achievable.« less

  12. Monte Carlo and Phantom Study of the Radiation Dose to the Body from Dedicated Computed Tomography of the Breast

    PubMed Central

    Sechopoulos, Ioannis; Vedantham, Srinivasan; Suryanarayanan, Sankararaman; D’Orsi, Carl J.; Karellas, Andrew

    2008-01-01

    Purpose To prospectively determine the radiation dose absorbed by the organs and tissues of the body during a dedicated computed tomography of the breast (DBCT) study using Monte Carlo methods and a phantom. Materials and Methods Using the Geant4 Monte Carlo toolkit, the Cristy anthropomorphic phantom and the geometry of a prototype DBCT was simulated. The simulation was used to track x-rays emitted from the source until their complete absorption or exit from the simulation limits. The interactions of the x-rays with the 65 different volumes representing organs, bones and other tissues of the anthropomorphic phantom that resulted in energy deposition were recorded. These data were used to compute the radiation dose to the organs and tissues during a complete DBCT acquisition relative to the average glandular dose to the imaged breast (ROD, relative organ dose), using the x-ray spectra proposed for DBCT imaging. The effectiveness of a lead shield for reducing the dose to the organs was investigated. Results The maximum ROD among the organs was for the ipsilateral lung with a maximum of 3.25%, followed by the heart and the thymus. Of the skeletal tissues, the sternum received the highest dose with a maximum ROD to the bone marrow of 2.24%, and to the bone surface of 7.74%. The maximum ROD to the uterus, representative of that of an early-stage fetus, was 0.026%. These maxima occurred for the highest energy x-ray spectrum (80 kVp) analyzed. A lead shield does not protect substantially the organs that receive the highest dose from DBCT. Discussion Although the dose to the organs from DBCT is substantially higher than that from planar mammography, they are comparable or considerably lower than those reached by other radiographic procedures and much lower than other CT examinations. PMID:18292479

  13. Impact of cardiosynchronous brain pulsations on Monte Carlo calculated doses for synchrotron micro- and minibeam radiation therapy.

    PubMed

    Manchado de Sola, Francisco; Vilches, Manuel; Prezado, Yolanda; Lallena, Antonio M

    2018-05-15

    The purpose of this study was to assess the effects of brain movements induced by heartbeat on dose distributions in synchrotron micro- and minibeam radiation therapy and to develop a model to help guide decisions and planning for future clinical trials. The Monte Carlo code PENELOPE was used to simulate the irradiation of a human head phantom with a variety of micro- and minibeam arrays, with beams narrower than 100 μm and above 500 μm, respectively, and with radiation fields of 1 × 2 cm and 2 × 2 cm. The dose in the phantom due to these beams was calculated by superposing the dose profiles obtained for a single beam of 1 μm × 2 cm. A parameter δ, accounting for the total displacement of the brain during the irradiation and due to the cardiosynchronous pulsation, was used to quantify the impact on peak-to-valley dose ratios and the full width at half maximum. The difference between the maximum (at the phantom entrance) and the minimum (at the phantom exit) values of the peak-to-valley dose ratio reduces when the parameter δ increases. The full width at half maximum remains almost constant with depth for any δ value. Sudden changes in the two quantities are observed at the interfaces between the various tissues (brain, skull, and skin) present in the head phantom. The peak-to-valley dose ratio at the center of the head phantom reduces when δ increases, remaining above 70% of the static value only for minibeams and δ smaller than ∼200 μm. Optimal setups for brain treatments with synchrotron radiation micro- and minibeam combs depend on the brain displacement due to cardiosynchronous pulsation. Peak-to-valley dose ratios larger than 90% of the maximum values obtained in the static case occur only for minibeams and relatively large dose rates. © 2018 American Association of Physicists in Medicine.

  14. X-ray surface dose measurements using TLD extrapolation.

    PubMed

    Kron, T; Elliot, A; Wong, T; Showell, G; Clubb, B; Metcalfe, P

    1993-01-01

    Surface dose measurements in therapeutic x-ray beams are of importance in determining the dose to the skin of patients undergoing radiotherapy. Measurements were performed in the 6-MV beam of a medical linear accelerator with LiF thermoluminescence dosimeters (TLD) using a solid water phantom. TLD chips (surface area 3.17 x 3.17 cm2) of three different thicknesses (0.230, 0.099, and 0.038 g/cm2) were used to extrapolate dose readings to an infinitesimally thin layer of LiF. This surface dose was measured for field sizes ranging from 1 x 1 cm2 to 40 x 40 cm2. The surface dose relative to maximum dose was found to be 10.0% for a field size of 5 x 5 cm2, 16.3% for 10 x 10 cm2, and 26.9% for 20 x 20 cm2. Using a 6-mm Perspex block tray in the beam increased the surface dose in these fields to 10.7%, 17.7%, and 34.2% respectively. Due to the small size of the TLD chips, TLD extrapolation is applicable also for intracavity and exit dose determinations. The technique used for in vivo dosimetry could provide clinicians information about the build up of dose up to 1-mm depth in addition to an extrapolated surface dose measurement.

  15. Pharmacokinetics of isotretinoin during repetitive dosing to patients.

    PubMed

    Brazzell, R K; Vane, F M; Ehmann, C W; Colburn, W A

    1983-01-01

    The multiple dose pharmacokinetics of isotretinoin and its major blood metabolite, 4-oxo-isotretinoin, were studied in 10 patients with cystic acne and 11 patients with various keratinization disorders. Blood samples were obtained at predetermined times following the first dose, interim doses and the final dose. Blood concentrations of isotretinoin and 4-oxo-isotretinoin were measured by a specific and sensitive HPLC method. A lag time was usually observed prior to the onset of absorption following oral administration of the drug in a soft elastic gelatin capsule. Absorption then proceeded rapidly and maximum blood concentrations usually occurred within 4 h of drug administration. The harmonic mean half-life for the elimination of isotretinoin by the cystic acne patients was approximately 10 h after the initial dose and did not change significantly following 25 days of 40 mg b.i.d. dosing. Steady-state blood concentrations remained relatively constant after the fifth day of dosing. The harmonic mean elimination half-life in the patients with various disorders of keratinization was about 16 h. The results of the 2 studies suggest that no significant changes in the pharmacokinetics of isotretinoin occur during multiple dosing and that the multiple dose pharmacokinetic profile is predictable and can be described using a linear pharmacokinetic model. This suggests that the steady-state concentrations of isotretinoin can be predicted from single dose data.

  16. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  17. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  18. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  19. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  20. 42 CFR 61.9 - Payments: Stipends; dependency allowances; travel allowances.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Payments: Stipends; dependency allowances; travel... FELLOWSHIPS, INTERNSHIPS, TRAINING FELLOWSHIPS Regular Fellowships § 61.9 Payments: Stipends; dependency allowances; travel allowances. Payments for stipends, dependency allowances, and the travel allowances...

  1. TLD extrapolation for skin dose determination in vivo.

    PubMed

    Kron, T; Butson, M; Hunt, F; Denham, J

    1996-11-01

    Prediction of skin reactions requires knowledge of the dose at various depths in the human skin. Using thermoluminescence dosimeters of three different thicknesses, the dose can be extrapolated to the surface and interpolated between the different depths. A TLD holder was designed for these TLD extrapolation measurements on patients during treatment which allowed measurements of entrance and exit skin dose with a day to day variability of +/-7% (S.D. of mean reading). In a pilot study on 18 patients undergoing breast irradiation, it was found that the angle of incidence of the radiation beam is the most significant factor influencing skin entrance dose. In most of these measurements the beam exit dose contributed 50% more to the surface dose than the entrance dose.

  2. A Study of Item Bias for Attitudinal Measurement Using Maximum Likelihood Factor Analysis.

    ERIC Educational Resources Information Center

    Mayberry, Paul W.

    A technique for detecting item bias that is responsive to attitudinal measurement considerations is a maximum likelihood factor analysis procedure comparing multivariate factor structures across various subpopulations, often referred to as SIFASP. The SIFASP technique allows for factorial model comparisons in the testing of various hypotheses…

  3. Comparison of the Light Charged Particles on Scatter Radiation Dose in Thyroid Hadron Therapy

    PubMed Central

    Azizi, M; Mowlavi, AA

    2014-01-01

    Background: Hadron therapy is a novel technique of cancer radiation therapy which employs charged particles beams, 1H and light ions in particular. Due to their physical and radiobiological properties, they allow one to obtain a more conformal treatment, sparing better the healthy tissues located in proximity of the tumor and allowing a higher control of the disease. Objective: As it is well known, these light particles can interact with nuclei in the tissue, and produce the different secondary particles such as neutron and photon. These particles can damage specially the critical organs behind of thyroid gland. Methods: In this research, we simulated neck geometry by MCNPX code and calculated the light particles dose at distance of 2.14 cm in thyroid gland, for different particles beam: 1H, 2H, 3He, and 4He. Thyroid treatment is important because the spine and vertebrae is situated right behind to the thyroid gland on the posterior side. Results: The results show that 2H has the most total flux for photon and neutron, 1.944E-3 and 1.7666E-2, respectively. Whereas 1H and 3He have best conditions, 8.88609E-4 and 1.35431E-3 for photon, 4.90506E-4 and 4.34057E-3 for neutron, respectively. The same calculation has obtained for energy depositions for these particles. Conclusion: In this research, we investigated that which of these light particles can deliver the maximum dose to the normal tissues and the minimum dose to the tumor. By comparing these results for the mentioned light particles, we find out 1H and 3He is the best therapy choices for thyroid glands whereas 2H is the worst. PMID:25505774

  4. Modelling information flow along the human connectome using maximum flow.

    PubMed

    Lyoo, Youngwook; Kim, Jieun E; Yoon, Sujung

    2018-01-01

    The human connectome is a complex network that transmits information between interlinked brain regions. Using graph theory, previously well-known network measures of integration between brain regions have been constructed under the key assumption that information flows strictly along the shortest paths possible between two nodes. However, it is now apparent that information does flow through non-shortest paths in many real-world networks such as cellular networks, social networks, and the internet. In the current hypothesis, we present a novel framework using the maximum flow to quantify information flow along all possible paths within the brain, so as to implement an analogy to network traffic. We hypothesize that the connection strengths of brain networks represent a limit on the amount of information that can flow through the connections per unit of time. This allows us to compute the maximum amount of information flow between two brain regions along all possible paths. Using this novel framework of maximum flow, previous network topological measures are expanded to account for information flow through non-shortest paths. The most important advantage of the current approach using maximum flow is that it can integrate the weighted connectivity data in a way that better reflects the real information flow of the brain network. The current framework and its concept regarding maximum flow provides insight on how network structure shapes information flow in contrast to graph theory, and suggests future applications such as investigating structural and functional connectomes at a neuronal level. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Pharmacokinetics of isotretinoin and its major blood metabolite following a single oral dose to man.

    PubMed

    Colburn, W A; Vane, F M; Shorter, H J

    1983-01-01

    A pharmacokinetic profile of isotretinoin and its major dermatologically active blood metabolite, 4-oxo-isotretinoin, was developed following a single 80 mg oral suspension dose of isotretinoin to 15 normal male subjects. Blood samples were assayed for isotretinoin and 4-oxo-isotretinoin using a newly developed reverse-phase HPLC method. Following rapid absorption from the suspension formulation, isotretinoin is distributed and eliminated with harmonic mean half-lives of 1.3 and 17.4 h, respectively. Maximum concentrations of isotretinoin in blood were observed at 1 to 4 h after dosing. Maximum concentrations of the major blood metabolite of isotretinoin, 4-oxo-isotretinoin, are approximately one-half those of isotretinoin and occur at 6 to 16 h after isotretinoin dosing. The ratio of areas under the curve for metabolite and parent drug following the single dose suggests that average steady-state ratios of metabolite to parent drug during a dosing interval will be approximately 2.5. Both isotretinoin and its metabolite can be adequately described using a single linear pharmacokinetic model.

  6. Proton Therapy Dose Characterization and Verification

    DTIC Science & Technology

    2016-10-01

    than recommended as these patients are on a separate UPENN research study where dose maximum accepted was 6700 cGy. 15... Research Protection Office. 8.0 Data Handling and Record Keeping All patients must have a signed Informed Consent Form and an On - study (confirmation...this award. Phase 1 concentrated on designing and building a Multi-leaf collimator for use in proton therapy. Phase 2 focused on studying the

  7. Dosimetric comparison between VMAT with different dose calculation algorithms and protons for soft-tissue sarcoma radiotherapy.

    PubMed

    Fogliata, Antonella; Scorsetti, Marta; Navarria, Piera; Catalano, Maddalena; Clivio, Alessandro; Cozzi, Luca; Lobefalo, Francesca; Nicolini, Giorgia; Palumbo, Valentina; Pellegrini, Chiara; Reggiori, Giacomo; Roggio, Antonella; Vanetti, Eugenio; Alongi, Filippo; Pentimalli, Sara; Mancosu, Pietro

    2013-04-01

    To appraise the potential of volumetric modulated arc therapy (VMAT, RapidArc) and proton beams to simultaneously achieve target coverage and enhanced sparing of bone tissue in the treatment of soft-tissue sarcoma with adequate target coverage. Ten patients presenting with soft-tissue sarcoma of the leg were collected for the study. Dose was prescribed to 66.5 Gy in 25 fractions to the planning target volume (PTV) while significant maximum dose to the bone was constrained to 50 Gy. Plans were optimised according to the RapidArc technique with 6 MV photon beams or for intensity modulated protons. RapidArc photon plans were computed with: 1) AAA; 2) Acuros XB as dose to medium; and 3) Acuros XB as dose to water. All plans acceptably met the criteria of target coverage (V95% >90-95%) and bone sparing (D(1 cm3) <50 Gy). Significantly higher PTV dose homogeneity was found for proton plans. Near-to-maximum dose to bone was similar for RapidArc and protons, while volume receiving medium/low dose levels was minimised with protons. Similar results were obtained for the remaining normal tissue. Dose distributions calculated with the dose to water option resulted ~5% higher than corresponding ones computed as dose to medium. High plan quality was demonstrated for both VMAT and proton techniques when applied to soft-tissue sarcoma.

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

    PubMed

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

    2012-02-01

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

  9. 41 CFR 302-7.17 - Is the maximum weight allowance for HHG and temporary storage limited when quarters are furnished...

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... and temporary storage that can be transported to that location. Only the authorized weight allowance that was shipped to the OCONUS location may be returned to CONUS upon completion of the tour of duty...

  10. 41 CFR 302-7.16 - Is the maximum weight allowance for HHG and temporary storage limited when quarters are furnished...

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... and temporary storage that can be transported to that location. Only the authorized weight allowance that was shipped to the OCONUS location may be returned to CONUS upon completion of the tour of duty...

  11. 41 CFR 302-7.17 - Is the maximum weight allowance for HHG and temporary storage limited when quarters are furnished...

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... and temporary storage that can be transported to that location. Only the authorized weight allowance that was shipped to the OCONUS location may be returned to CONUS upon completion of the tour of duty...

  12. Bayesian dose-response analysis for epidemiological studies with complex uncertainty in dose estimation.

    PubMed

    Kwon, Deukwoo; Hoffman, F Owen; Moroz, Brian E; Simon, Steven L

    2016-02-10

    Most conventional risk analysis methods rely on a single best estimate of exposure per person, which does not allow for adjustment for exposure-related uncertainty. Here, we propose a Bayesian model averaging method to properly quantify the relationship between radiation dose and disease outcomes by accounting for shared and unshared uncertainty in estimated dose. Our Bayesian risk analysis method utilizes multiple realizations of sets (vectors) of doses generated by a two-dimensional Monte Carlo simulation method that properly separates shared and unshared errors in dose estimation. The exposure model used in this work is taken from a study of the risk of thyroid nodules among a cohort of 2376 subjects who were exposed to fallout from nuclear testing in Kazakhstan. We assessed the performance of our method through an extensive series of simulations and comparisons against conventional regression risk analysis methods. When the estimated doses contain relatively small amounts of uncertainty, the Bayesian method using multiple a priori plausible draws of dose vectors gave similar results to the conventional regression-based methods of dose-response analysis. However, when large and complex mixtures of shared and unshared uncertainties are present, the Bayesian method using multiple dose vectors had significantly lower relative bias than conventional regression-based risk analysis methods and better coverage, that is, a markedly increased capability to include the true risk coefficient within the 95% credible interval of the Bayesian-based risk estimate. An evaluation of the dose-response using our method is presented for an epidemiological study of thyroid disease following radiation exposure. Copyright © 2015 John Wiley & Sons, Ltd.

  13. SU-F-T-672: A Novel Kernel-Based Dose Engine for KeV Photon Beams

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

    Reinhart, M; Fast, M F; Nill, S

    2016-06-15

    Purpose: Mimicking state-of-the-art patient radiotherapy with high precision irradiators for small animals allows advanced dose-effect studies and radiobiological investigations. One example is the implementation of pre-clinical IMRT-like irradiations, which requires the development of inverse planning for keV photon beams. As a first step, we present a novel kernel-based dose calculation engine for keV x-rays with explicit consideration of energy and material dependencies. Methods: We follow a superposition-convolution approach adapted to keV x-rays, based on previously published work on micro-beam therapy. In small animal radiotherapy, we assume local energy deposition at the photon interaction point, since the electron ranges in tissuemore » are of the same order of magnitude as the voxel size. This allows us to use photon-only kernel sets generated by MC simulations, which are pre-calculated for six energy windows and ten base materials. We validate our stand-alone dose engine against Geant4 MC simulations for various beam configurations in water, slab phantoms with bone and lung inserts, and on a mouse CT with (0.275mm)3 voxels. Results: We observe good agreement for all cases. For field sizes of 1mm{sup 2} to 1cm{sup 2} in water, the depth dose curves agree within 1% (mean), with the largest deviations in the first voxel (4%) and at depths>5cm (<2.5%). The out-of-field doses at 1cm depth agree within 8% (mean) for all but the smallest field size. In slab geometries, the mean agreement was within 3%, with maximum deviations of 8% at water-bone interfaces. The γ-index (1mm/1%) passing rate for a single-field mouse irradiation is 71%. Conclusion: The presented dose engine yields an accurate representation of keV-photon doses suitable for inverse treatment planning for IMRT. It has the potential to become a significantly faster yet sufficiently accurate alternative to full MC simulations. Further investigations will focus on energy sampling as well as

  14. Measurement of doses to the extremities of nuclear medicine staff

    NASA Astrophysics Data System (ADS)

    Shousha, Hany A.; Farag, Hamed; Hassan, Ramadan A.

    2010-01-01

    Medical uses of ionizing radiation now represent>95% of all man-made radiation exposure, and is the largest single radiation source after natural background radiation. Therefore, it is important to quantify the amount of radiation received by occupational individuals to optimize the working conditions for staff, and further, to compare doses in different departments to ensure compatibility with the recommended standards. For some groups working with unsealed sources in nuclear medicine units, the hands are more heavily exposed to ionizing radiation than the rest of the body. A personal dosimetry service runs extensively in Egypt. But doses to extremities have not been measured to a wide extent. The purpose of this study was to investigate the equivalent radiation doses to the fingers for five different nuclear medicine staff occupational groups for which heavy irradiation of the hands was suspected. Finger doses were measured for (1) nuclear medicine physicians, (2) technologists, (3) nurses and (4) physicists. The fifth group contains three technicians handling 131I, while the others handled 99mTc. Each staff member working with the radioactive material wore two thermoluminescent dosimeters (TLDs) during the whole testing period, which lasted from 1 to 4 weeks. Staff performed their work on a regular basis throughout the month, and mean annual doses were calculated for these groups. Results showed that the mean equivalent doses to the fingers of technologist, nurse and physicist groups were 30.24±14.5, 30.37±17.5 and 16.3±7.7 μSv/GBq, respectively. Equivalent doses for the physicians could not be calculated per unit of activity because they did not handle the radiopharmaceuticals directly. Their doses were reported in millisieverts (mSv) that accumulated in one week. Similarly, the dose to the fingers of individuals in Group 5 was estimated to be 126.13±38.2 μSv/GBq. The maximum average finger dose, in this study, was noted in the technologists who handled

  15. SU-E-T-374: Evaluation and Verification of Dose Calculation Accuracy with Different Dose Grid Sizes for Intracranial Stereotactic Radiosurgery

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

    Han, C; Schultheiss, T

    Purpose: In this study, we aim to evaluate the effect of dose grid size on the accuracy of calculated dose for small lesions in intracranial stereotactic radiosurgery (SRS), and to verify dose calculation accuracy with radiochromic film dosimetry. Methods: 15 intracranial lesions from previous SRS patients were retrospectively selected for this study. The planning target volume (PTV) ranged from 0.17 to 2.3 cm{sup 3}. A commercial treatment planning system was used to generate SRS plans using the volumetric modulated arc therapy (VMAT) technique using two arc fields. Two convolution-superposition-based dose calculation algorithms (Anisotropic Analytical Algorithm and Acuros XB algorithm) weremore » used to calculate volume dose distribution with dose grid size ranging from 1 mm to 3 mm with 0.5 mm step size. First, while the plan monitor units (MU) were kept constant, PTV dose variations were analyzed. Second, with 95% of the PTV covered by the prescription dose, variations of the plan MUs as a function of dose grid size were analyzed. Radiochomic films were used to compare the delivered dose and profile with the calculated dose distribution with different dose grid sizes. Results: The dose to the PTV, in terms of the mean dose, maximum, and minimum dose, showed steady decrease with increasing dose grid size using both algorithms. With 95% of the PTV covered by the prescription dose, the total MU increased with increasing dose grid size in most of the plans. Radiochromic film measurements showed better agreement with dose distributions calculated with 1-mm dose grid size. Conclusion: Dose grid size has significant impact on calculated dose distribution in intracranial SRS treatment planning with small target volumes. Using the default dose grid size could lead to under-estimation of delivered dose. A small dose grid size should be used to ensure calculation accuracy and agreement with QA measurements.« less

  16. Shuttle radiation dose measurements in the International Space Station orbits

    NASA Technical Reports Server (NTRS)

    Badhwar, Gautam D.

    2002-01-01

    The International Space Station (ISS) is now a reality with the start of a permanent human presence on board. Radiation presents a serious risk to the health and safety of the astronauts, and there is a clear requirement for estimating their exposures prior to and after flights. Predictions of the dose rate at times other than solar minimum or solar maximum have not been possible, because there has been no method to calculate the trapped-particle spectrum at intermediate times. Over the last few years, a tissue-equivalent proportional counter (TEPC) has been flown at a fixed mid-deck location on board the Space Shuttle in 51.65 degrees inclination flights. These flights have provided data that cover the expected changes in the dose rates due to changes in altitude and changes in solar activity from the solar minimum to the solar maximum of the current 23rd solar cycle. Based on these data, a simple function of the solar deceleration potential has been derived that can be used to predict the galactic cosmic radiation (GCR) dose rates to within +/-10%. For altitudes to be covered by the ISS, the dose rate due to the trapped particles is found to be a power-law function, rho(-2/3), of the atmospheric density, rho. This relationship can be used to predict trapped dose rates inside these spacecraft to +/-10% throughout the solar cycle. Thus, given the shielding distribution for a location inside the Space Shuttle or inside an ISS module, this approach can be used to predict the combined GCR + trapped dose rate to better than +/-15% for quiet solar conditions.

  17. Evaluation of the dependence of the exposure dose on the attenuation correction in brain PET/CT scans using 18F-FDG

    NASA Astrophysics Data System (ADS)

    Choi, Eun-Jin; Jeong, Moon-Taeg; Jang, Seong-Joo; Choi, Nam-Gil; Han, Jae-Bok; Yang, Nam-Hee; Dong, Kyung-Rae; Chung, Woon-Kwan; Lee, Yun-Jong; Ryu, Young-Hwan; Choi, Sung-Hyun; Seong, Kyeong-Jeong

    2014-01-01

    This study examined whether scanning could be performed with minimum dose and minimum exposure to the patient after an attenuation correction. A Hoffman 3D Brain Phantom was used in BIO_40 and D_690 PET/CT scanners, and the CT dose for the equipment was classified as a low dose (minimum dose), medium dose (general dose for scanning) and high dose (dose with use of contrast medium) before obtaining the image at a fixed kilo-voltage-peak (kVp) and milliampere (mA) that were adjusted gradually in 17-20 stages. A PET image was then obtained to perform an attenuation correction based on an attenuation map before analyzing the dose difference. Depending on tube current in the range of 33-190 milliampere-second (mAs) when BIO_40 was used, a significant difference in the effective dose was observed between the minimum and the maximum mAs (p < 0.05). According to a Scheffe post-hoc test, the ratio of the minimum to the maximum of the effective dose was increased by approximately 5.26-fold. Depending on the change in the tube current in the range of 10-200 mA when D_690 was used, a significant difference in the effective dose was observed between the minimum and the maximum of mA (p < 0.05). The Scheffe posthoc test revealed a 20.5-fold difference. In conclusion, because effective exposure dose increases with increasing operating current, it is possible to reduce the exposure limit in a brain scan can be reduced if the CT dose can be minimized for a transmission scan.

  18. From total empiricism to a rational design of metronomic chemotherapy phase I dosing trials.

    PubMed

    Lam, Thomas; Hetherington, John W; Greenman, John; Maraveyas, Anthony

    2006-02-01

    'Metronomic chemotherapy' represents a novel anti-angiogenic strategy whereby low-dose chemotherapy is utilized in a continuous fashion in order to target tumor endothelium. There are many potential advantages of this strategy and clinical trials are already underway. However, although the scheduling of metronomic chemotherapy is relatively unequivocal, metronomic dosing principles are at present poorly defined. Arbitrarily, 10-33% of the maximum tolerated dose comprises 'the dose range'. We argue that this is too empirical and propose a set of phase I metronomic chemotherapy dosing strategies based on a principled approach which may help to reduce the problem of empiricism in dosing for metronomic chemotherapy trials.

  19. A comparison of quantum limited dose and noise equivalent dose

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

  20. Spline-based procedures for dose-finding studies with active control

    PubMed Central

    Helms, Hans-Joachim; Benda, Norbert; Zinserling, Jörg; Kneib, Thomas; Friede, Tim

    2015-01-01

    In a dose-finding study with an active control, several doses of a new drug are compared with an established drug (the so-called active control). One goal of such studies is to characterize the dose–response relationship and to find the smallest target dose concentration d*, which leads to the same efficacy as the active control. For this purpose, the intersection point of the mean dose–response function with the expected efficacy of the active control has to be estimated. The focus of this paper is a cubic spline-based method for deriving an estimator of the target dose without assuming a specific dose–response function. Furthermore, the construction of a spline-based bootstrap CI is described. Estimator and CI are compared with other flexible and parametric methods such as linear spline interpolation as well as maximum likelihood regression in simulation studies motivated by a real clinical trial. Also, design considerations for the cubic spline approach with focus on bias minimization are presented. Although the spline-based point estimator can be biased, designs can be chosen to minimize and reasonably limit the maximum absolute bias. Furthermore, the coverage probability of the cubic spline approach is satisfactory, especially for bias minimal designs. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. PMID:25319931

  1. An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations

    NASA Astrophysics Data System (ADS)

    Capelli, Riccardo; Tiana, Guido; Camilloni, Carlo

    2018-05-01

    Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data, and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such a principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow us to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed.

  2. An implementation of the maximum-caliber principle by replica-averaged time-resolved restrained simulations.

    PubMed

    Capelli, Riccardo; Tiana, Guido; Camilloni, Carlo

    2018-05-14

    Inferential methods can be used to integrate experimental informations and molecular simulations. The maximum entropy principle provides a framework for using equilibrium experimental data, and it has been shown that replica-averaged simulations, restrained using a static potential, are a practical and powerful implementation of such a principle. Here we show that replica-averaged simulations restrained using a time-dependent potential are equivalent to the principle of maximum caliber, the dynamic version of the principle of maximum entropy, and thus may allow us to integrate time-resolved data in molecular dynamics simulations. We provide an analytical proof of the equivalence as well as a computational validation making use of simple models and synthetic data. Some limitations and possible solutions are also discussed.

  3. Absolute dose determination in high-energy electron beams: Comparison of IAEA dosimetry protocols

    PubMed Central

    Sathiyan, S.; Ravikumar, M.

    2008-01-01

    In this study, absorbed doses were measured and compared for high-energy electrons (6, 9, 12, 16, and 20 MeV) using International Atomic Energy Agency (IAEA), Technical Reports Series No. 277 (TRS), TRS 381, and TRS 398 dosimetry protocols. Absolute dose measurements were carried out using FC65-G Farmer chamber and Nordic Association of Clinical Physicists (NACP) parallel plate chamber with DOSE1 electrometer in WP1-D water phantom for reference field size of 15 × 15 cm2 at 100 cm source-to-surface distance. The results show that the difference between TRS 398 and TRS 381 was about 0.24% to 1.3% depending upon the energy, and the maximum difference between TRS 398 and TRS 277 was 1.5%. The use of cylindrical chamber in electron beam gives the maximum dose difference between the TRS 398 and TRS 277 in the order of 1.4% for energies above 10 MeV (R50 > 4 g/cm2). It was observed that the accuracy of dose estimation was better with the protocols based on the water calibration procedures, as no conversion quantities are involved for conversion of dose from air to water. The cross-calibration procedure of parallel plate chamber with high-energy electron beams is recommended as it avoids pwall correction factor entering into the determination of kQ,Qo. PMID:19893700

  4. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

    PubMed

    Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-01

    The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

  5. Significance of including field non-uniformities such as the heel effect and beam scatter in the determination of the skin dose distribution during interventional fluoroscopic procedures

    NASA Astrophysics Data System (ADS)

    Rana, Vijay; Gill, Kamaljit; Rudin, Stephen; Bednarek, Daniel R.

    2012-03-01

    The current version of the real-time skin-dose-tracking system (DTS) we have developed assumes the exposure is contained within the collimated beam and is uniform except for inverse-square variation. This study investigates the significance of factors that contribute to beam non-uniformity such as the heel effect and backscatter from the patient to areas of the skin inside and outside the collimated beam. Dose-calibrated Gafchromic film (XR-RV3, ISP) was placed in the beam in the plane of the patient table at a position 15 cm tube-side of isocenter on a Toshiba Infinix C-Arm system. Separate exposures were made with the film in contact with a block of 20-cm solid water providing backscatter and with the film suspended in air without backscatter, both with and without the table in the beam. The film was scanned to obtain dose profiles and comparison of the profiles for the various conditions allowed a determination of field non-uniformity and backscatter contribution. With the solid-water phantom and with the collimator opened completely for the 20-cm mode, the dose profile decreased by about 40% on the anode side of the field. Backscatter falloff at the beam edge was about 10% from the center and extra-beam backscatter decreased slowly with distance from the field, being about 3% of the beam maximum at 6 cm from the edge. Determination of the magnitude of these factors will allow them to be included in the skin-dose-distribution calculation and should provide a more accurate determination of peak-skin dose for the DTS.

  6. The maximum intelligible range of the human voice

    NASA Astrophysics Data System (ADS)

    Boren, Braxton

    This dissertation examines the acoustics of the spoken voice at high levels and the maximum number of people that could hear such a voice unamplified in the open air. In particular, it examines an early auditory experiment by Benjamin Franklin which sought to determine the maximum intelligible crowd for the Anglican preacher George Whitefield in the eighteenth century. Using Franklin's description of the experiment and a noise source on Front Street, the geometry and diffraction effects of such a noise source are examined to more precisely pinpoint Franklin's position when Whitefield's voice ceased to be intelligible. Based on historical maps, drawings, and prints, the geometry and material of Market Street is constructed as a computer model which is then used to construct an acoustic cone tracing model. Based on minimal values of the Speech Transmission Index (STI) at Franklin's position, Whitefield's on-axis Sound Pressure Level (SPL) at 1 m is determined, leading to estimates centering around 90 dBA. Recordings are carried out on trained actors and singers to determine their maximum time-averaged SPL at 1 m. This suggests that the greatest average SPL achievable by the human voice is 90-91 dBA, similar to the median estimates for Whitefield's voice. The sites of Whitefield's largest crowds are acoustically modeled based on historical evidence and maps. Based on Whitefield's SPL, the minimal STI value, and the crowd's background noise, this allows a prediction of the minimally intelligible area for each site. These yield maximum crowd estimates of 50,000 under ideal conditions, while crowds of 20,000 to 30,000 seem more reasonable when the crowd was reasonably quiet and Whitefield's voice was near 90 dBA.

  7. 40 CFR 82.18 - Availability of production in addition to baseline production allowances for class II controlled...

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... permitted under the Montreal Protocol or to receive from the person for the current control period some... production quantities: (A) The maximum production that the nation is allowed under the Protocol minus the...

  8. 20 CFR 228.14 - Family maximum.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 1 2011-04-01 2011-04-01 false Family maximum. 228.14 Section 228.14... SURVIVOR ANNUITIES The Tier I Annuity Component § 228.14 Family maximum. (a) Family maximum defined. Under... person's earnings record is limited. This limited amount is called the family maximum. The family maximum...

  9. 20 CFR 228.14 - Family maximum.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Family maximum. 228.14 Section 228.14... SURVIVOR ANNUITIES The Tier I Annuity Component § 228.14 Family maximum. (a) Family maximum defined. Under... person's earnings record is limited. This limited amount is called the family maximum. The family maximum...

  10. A comprehensive dose reconstruction methodology for former rocketdyne/atomics international radiation workers.

    PubMed

    Boice, John D; Leggett, Richard W; Ellis, Elizabeth Dupree; Wallace, Phillip W; Mumma, Michael; Cohen, Sarah S; Brill, A Bertrand; Chadda, Bandana; Boecker, Bruce B; Yoder, R Craig; Eckerman, Keith F

    2006-05-01

    on a case-by-case basis for workers with committed equivalent doses indicated by screening criteria to be greater than 10 mSv to the organ with the highest internal dose. Overall, 5,801 workers were monitored for radiation at Rocketdyne/AI: 5,743 for external exposure and 2,232 for internal intakes of radionuclides; 41,169 workers were not monitored for radiation. The mean cumulative external dose based on Rocketdyne/AI records alone was 10.0 mSv, and the dose distribution was highly skewed with most workers experiencing low cumulative doses and only a few with high doses (maximum 500 mSv). Only 45 workers received greater than 200 mSv while employed at Rocketdyne/AI. However, nearly 32% (or 1,833) of the Rocketdyne/AI workers had been monitored for radiation at other nuclear facilities and incorporation of these doses increased the mean dose to 13.5 mSv (maximum 1,005 mSv) and the number of workers with >200 mSv to 69. For a small number of workers (n=292), lung doses from internal radionuclide intakes were relatively high (mean 106 mSv; maximum 3,560 mSv) and increased the overall population mean dose to 19.0 mSv and the number of workers with lung dose>200 mSv to 109. Nearly 10% of the radiation workers (584) were monitored for neutron exposures (mean 1.2 mSv) at Rocketdyne/AI, and another 2% were monitored for neutron exposures elsewhere. Interestingly, 1,477 workers not monitored for radiation at Rocketdyne/AI (3.6%) were found to have worn dosimeters at other nuclear facilities (mean external dose of 2.6 mSv, maximum 188 mSv). Without considering all sources of occupational exposure, an incorrect characterization of worker exposure would have occurred with the potential to bias epidemiologic results. For these pioneering workers in the nuclear industry, 26.5% of their total occupational dose (collective dose) was received at other facilities both prior to and after employment at Rocketdyne/AI. In addition, a small number of workers monitored for internal

  11. SU-E-T-113: Dose Distribution Using Respiratory Signals and Machine Parameters During Treatment

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

    Imae, T; Haga, A; Saotome, N

    Purpose: Volumetric modulated arc therapy (VMAT) is a rotational intensity-modulated radiotherapy (IMRT) technique capable of acquiring projection images during treatment. Treatment plans for lung tumors using stereotactic body radiotherapy (SBRT) are calculated with planning computed tomography (CT) images only exhale phase. Purpose of this study is to evaluate dose distribution by reconstructing from only the data such as respiratory signals and machine parameters acquired during treatment. Methods: Phantom and three patients with lung tumor underwent CT scans for treatment planning. They were treated by VMAT while acquiring projection images to derive their respiratory signals and machine parameters including positions ofmore » multi leaf collimators, dose rates and integrated monitor units. The respiratory signals were divided into 4 and 10 phases and machine parameters were correlated with the divided respiratory signals based on the gantry angle. Dose distributions of each respiratory phase were calculated from plans which were reconstructed from the respiratory signals and the machine parameters during treatment. The doses at isocenter, maximum point and the centroid of target were evaluated. Results and Discussion: Dose distributions during treatment were calculated using the machine parameters and the respiratory signals detected from projection images. Maximum dose difference between plan and in treatment distribution was −1.8±0.4% at centroid of target and dose differences of evaluated points between 4 and 10 phases were no significant. Conclusion: The present method successfully evaluated dose distribution using respiratory signals and machine parameters during treatment. This method is feasible to verify the actual dose for moving target.« less

  12. The maximum contraceptive prevalence ‘demand curve’: guiding discussions on programmatic investments

    PubMed Central

    Weinberger, Michelle; Sonneveldt, Emily; Stover, John

    2017-01-01

    Most frameworks for family planning include both access and demand interventions. Understanding how these two are linked and when each should be prioritized is difficult. The maximum contraceptive prevalence ‘demand curve’ was created based on a relationship between the modern contraceptive prevalence rate (mCPR) and mean ideal number of children to allow for a quantitative assessment of the balance between access and demand interventions. The curve represents the maximum mCPR that is likely to be seen given fertility intentions and related norms and constructs that influence contraceptive use. The gap between a country’s mCPR and this maximum is referred to as the ‘potential use gap.’ This concept can be used by countries to prioritize access investments where the gap is large, and discuss implications for future contraceptive use where the gap is small. It is also used within the FP Goals model to ensure mCPR growth from access interventions does not exceed available demand. PMID:29355228

  13. Bone fractures following external beam radiotherapy and limb-preservation surgery for lower extremity soft tissue sarcoma: relationship to irradiated bone length, volume, tumor location and dose.

    PubMed

    Dickie, Colleen I; Parent, Amy L; Griffin, Anthony M; Fung, Sharon; Chung, Peter W M; Catton, Charles N; Ferguson, Peter C; Wunder, Jay S; Bell, Robert S; Sharpe, Michael B; O'Sullivan, Brian

    2009-11-15

    To examine the relationship between tumor location, bone dose, and irradiated bone length on the development of radiation-induced fractures for lower extremity soft tissue sarcoma (LE-STS) patients treated with limb-sparing surgery and radiotherapy (RT). Of 691 LE-STS patients treated from 1989 to 2005, 31 patients developed radiation-induced fractures. Analysis was limited to 21 fracture patients (24 fractures) who were matched based on tumor size and location, age, beam arrangement, and mean total cumulative RT dose to a random sample of 53 nonfracture patients and compared for fracture risk factors. Mean dose to bone, RT field size (FS), maximum dose to a 2-cc volume of bone, and volume of bone irradiated to >or=40 Gy (V40) were compared. Fracture site dose was determined by comparing radiographic images and surgical reports to fracture location on the dose distribution. For fracture patients, mean dose to bone was 45 +/- 8 Gy (mean dose at fracture site 59 +/- 7 Gy), mean FS was 37 +/- 8 cm, maximum dose was 64 +/- 7 Gy, and V40 was 76 +/- 17%, compared with 37 +/- 11 Gy, 32 +/- 9 cm, 59 +/- 8 Gy, and 64 +/- 22% for nonfracture patients. Differences in mean, maximum dose, and V40 were statistically significant (p = 0.01, p = 0.02, p = 0.01). Leg fractures were more common above the knee joint. The risk of radiation-induced fracture appears to be reduced if V40 <64%. Fracture incidence was lower when the mean dose to bone was <37 Gy or maximum dose anywhere along the length of bone was <59 Gy. There was a trend toward lower mean FS for nonfracture patients.

  14. 40 CFR 1042.140 - Maximum engine power, displacement, power density, and maximum in-use engine speed.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 34 2012-07-01 2012-07-01 false Maximum engine power, displacement... Maximum engine power, displacement, power density, and maximum in-use engine speed. This section describes how to determine the maximum engine power, displacement, and power density of an engine for the...

  15. 40 CFR 1042.140 - Maximum engine power, displacement, power density, and maximum in-use engine speed.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 34 2013-07-01 2013-07-01 false Maximum engine power, displacement... Maximum engine power, displacement, power density, and maximum in-use engine speed. This section describes how to determine the maximum engine power, displacement, and power density of an engine for the...

  16. Superfast maximum-likelihood reconstruction for quantum tomography

    NASA Astrophysics Data System (ADS)

    Shang, Jiangwei; Zhang, Zhengyun; Ng, Hui Khoon

    2017-06-01

    Conventional methods for computing maximum-likelihood estimators (MLE) often converge slowly in practical situations, leading to a search for simplifying methods that rely on additional assumptions for their validity. In this work, we provide a fast and reliable algorithm for maximum-likelihood reconstruction that avoids this slow convergence. Our method utilizes the state-of-the-art convex optimization scheme, an accelerated projected-gradient method, that allows one to accommodate the quantum nature of the problem in a different way than in the standard methods. We demonstrate the power of our approach by comparing its performance with other algorithms for n -qubit state tomography. In particular, an eight-qubit situation that purportedly took weeks of computation time in 2005 can now be completed in under a minute for a single set of data, with far higher accuracy than previously possible. This refutes the common claim that MLE reconstruction is slow and reduces the need for alternative methods that often come with difficult-to-verify assumptions. In fact, recent methods assuming Gaussian statistics or relying on compressed sensing ideas are demonstrably inapplicable for the situation under consideration here. Our algorithm can be applied to general optimization problems over the quantum state space; the philosophy of projected gradients can further be utilized for optimization contexts with general constraints.

  17. VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients.

    PubMed

    Ding, Aiping; Gao, Yiming; Liu, Haikuan; Caracappa, Peter F; Long, Daniel J; Bolch, Wesley E; Liu, Bob; Xu, X George

    2015-07-21

    This paper describes the development and testing of VirtualDose--a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the 'software as a service (SaaS)' delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose's functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT-two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

  18. SU-E-J-198: Out-Of-Field Dose and Surface Dose Measurements of MRI-Guided Cobalt-60 Radiotherapy

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

    Lamb, J; Agazaryan, N; Cao, M

    2015-06-15

    Purpose: To measure quantities of dosimetric interest in an MRI-guided cobalt radiotherapy machine that was recently introduced to clinical use. Methods: Out-of-field dose due to photon scatter and leakage was measured using an ion chamber and solid water slabs mimicking a human body. Surface dose was measured by irradiating stacks of radiochromic film and extrapolating to zero thickness. Electron out-of-field dose was characterized using solid water slabs and radiochromic film. Results: For some phantom geometries, up to 50% of Dmax was observed up to 10 cm laterally from the edge of the beam. The maximum penetration was between 1 andmore » 2 mm in solid water, indicating an electron energy not greater than approximately 0.4 MeV. Out-of-field dose from photon scatter measured at 1 cm depth in solid water was found to fall to less than 10% of Dmax at a distance of 1.2 cm from the edge of a 10.5 × 10.5 cm field, and less that 1% of Dmax at a distance of 10 cm from field edge. Surface dose was measured to be 8% of Dmax. Conclusion: Surface dose and out-of-field dose from the MRIguided cobalt radiotherapy machine was measured and found to be within acceptable limits. Electron out-of-field dose, an effect unique to MRI-guided radiotherapy and presumed to arise from low-energy electrons trapped by the Lorentz force, was quantified. Dr. Low is a member of the scientific advisory board of ViewRay, Inc.« less

  19. Minimum detectable dose as a measure of bioassay programme capability.

    PubMed

    Carbaugh, E H

    2003-01-01

    This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programmes for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well established analytical statistic minimum detectable amount (MDA) as the starting point, and assumes MDA detection at a prescribed time post-intake. The resulting dose can then be used as an indication of the adequacy or capability of the programme for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate the effectiveness of different types of monitoring programmes. The inclusion of cost factors for bioassay measurements can allow optimisation.

  20. Real-time eye lens dose monitoring during cerebral angiography procedures.

    PubMed

    Safari, M J; Wong, J H D; Kadir, K A A; Thorpe, N K; Cutajar, D L; Petasecca, M; Lerch, M L F; Rosenfeld, A B; Ng, K H

    2016-01-01

    To develop a real-time dose-monitoring system to measure the patient's eye lens dose during neuro-interventional procedures. Radiation dose received at left outer canthus (LOC) and left eyelid (LE) were measured using Metal-Oxide-Semiconductor Field-Effect Transistor dosimeters on 35 patients who underwent diagnostic or cerebral embolization procedures. The radiation dose received at the LOC region was significantly higher than the dose received by the LE. The maximum eye lens dose of 1492 mGy was measured at LOC region for an AVM case, followed by 907 mGy for an aneurysm case and 665 mGy for a diagnostic angiography procedure. Strong correlations (shown as R(2)) were observed between kerma-area-product and measured eye doses (LOC: 0.78, LE: 0.68). Lateral and frontal air-kerma showed strong correlations with measured dose at LOC (AKL: 0.93, AKF: 0.78) and a weak correlation with measured dose at LE. A moderate correlation was observed between fluoroscopic time and dose measured at LE and LOC regions. The MOSkin dose-monitoring system represents a new tool enabling real-time monitoring of eye lens dose during neuro-interventional procedures. This system can provide interventionalists with information needed to adjust the clinical procedure to control the patient's dose. Real-time patient dose monitoring helps interventionalists to monitor doses. Strong correlation was observed between kerma-area-product and measured eye doses. Radiation dose at left outer canthus was higher than at left eyelid.

  1. A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer

    PubMed Central

    Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang

    2016-01-01

    Lessons Learned This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity. These findings provide clinicians with evidence for application of higher-dose icotinib. Background. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100–200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Methods. Twenty-six patients with advanced NSCLC were treated at doses of 250–625 mg three times daily The EGFR mutation test was not mandatory in this study. Results. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (Tmax) ranged from 1 to 3 hours (1.5–4 hours) after multiple doses. The t1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease

  2. A Phase I Study of the Safety and Pharmacokinetics of Higher-Dose Icotinib in Patients With Advanced Non-Small Cell Lung Cancer.

    PubMed

    Liu, Jian; Wu, Lihua; Wu, Guolan; Hu, Xingjiang; Zhou, Huili; Chen, Junchun; Zhu, Meixiang; Xu, Wei; Tan, Fenlai; Ding, Lieming; Wang, Yinxiang; Shentu, Jianzhong

    2016-11-01

    This phase I study evaluated the maximum tolerated dose, dose-limiting toxicities, safety, pharmacokinetics, and efficacy of icotinib with a starting dose of 250 mg in pretreated, advanced non-small cell lung cancer patients. We observed a maximum tolerated dose of 500 mg with a favorable pharmacokinetics profile and antitumor activity.These findings provide clinicians with evidence for application of higher-dose icotinib. Icotinib, an oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has shown favorable tolerability and antitumor activity at 100-200 mg in previous studies without reaching the maximum tolerated dose (MTD). In July 2011, icotinib was approved by the China Food and Drug Administration at a dose of 125 mg three times daily for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one platinum-based chemotherapy regimen. This study investigated the MTD, tolerability, and pharmacokinetics of higher-dose icotinib in patients with advanced NSCLC. Twenty-six patients with advanced NSCLC were treated at doses of 250-625 mg three times daily The EGFR mutation test was not mandatory in this study. Twenty-four (92.3%) of 26 patients experienced at least one adverse event (AE); rash (61.5%), diarrhea (23.1%), and oral ulceration (11.5%) were most frequent AEs. Dose-limiting toxicities were seen in 2 of 6 patients in the 625-mg group, and the MTD was established at 500 mg. Icotinib was rapidly absorbed and eliminated. The amount of time that the drug was present at the maximum concentration in serum (T max ) ranged from 1 to 3 hours (1.5-4 hours) after multiple doses. The t 1/2 was similar after single- and multiple-dose administration (7.11 and 6.39 hours, respectively). A nonlinear relationship was observed between dose and drug exposure. Responses were seen in 6 (23.1%) patients, and 8 (30.8%) patients had stable disease. This study demonstrated that higher-dose

  3. Probabilistic dose assessment of normal operations and accident conditions for an assured isolation facility in Texas

    NASA Astrophysics Data System (ADS)

    Arno, Matthew Gordon

    Texas is investigating building a long-term waste storage facility, also known as an Assured Isolation Facility. This is an above-ground low-level radioactive waste storage facility that is actively maintained and from which waste may be retrieved. A preliminary, scoping-level analysis has been extended to consider more complex scenarios of radiation streaming and skyshine by using the computer code Monte Carlo N-Particle (MCNP) to model the facility in greater detail. Accidental release scenarios have been studied in more depth to better assess the potential dose to off-site individuals. Using bounding source term assumptions, the projected radiation doses and dose rates are estimated to exceed applicable limits by an order of magnitude. By altering the facility design to fill in the hollow cores of the prefabricated concrete slabs used in the roof over the "high-gamma rooms," where the waste with the highest concentration of gamma emitting radioactive material is stored, dose rates outside the facility decrease by an order of magnitude. With the modified design, the annual dose at the site fenceline is estimated at 86 mrem, below the 100 mrem annual limit for exposure of the public. Within the site perimeter, the dose rates are lowered sufficiently such that it is not necessary to categorize many workers and contractor personnel as radiation workers, saving on costs as well as being advisable under ALARA principles. A detailed analysis of bounding accidents incorporating information on the local meteorological conditions indicate that the maximum committed effective dose equivalent from the passage of a plume of material released in an accident at any of the cities near the facility is 59 :rem in the city of Eunice, NM based on the combined day and night meteorological conditions. Using the daytime meteorological conditions, the maximum dose at any city is 7 :rem, also in the city of Eunice. The maximum dose at the site boundary was determined to be 230 mrem

  4. 42 CFR 61.8 - Benefits: Stipends; dependency allowances; travel allowances; vacation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Benefits: Stipends; dependency allowances; travel...; dependency allowances; travel allowances; vacation. Individuals awarded regular fellowships shall be entitled...) Stipend. (b) Dependency allowances. (c) When authorized in advance, separate allowances for travel. Such...

  5. 42 CFR 61.8 - Benefits: Stipends; dependency allowances; travel allowances; vacation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Benefits: Stipends; dependency allowances; travel...; dependency allowances; travel allowances; vacation. Individuals awarded regular fellowships shall be entitled...) Stipend. (b) Dependency allowances. (c) When authorized in advance, separate allowances for travel. Such...

  6. 42 CFR 61.8 - Benefits: Stipends; dependency allowances; travel allowances; vacation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Benefits: Stipends; dependency allowances; travel...; dependency allowances; travel allowances; vacation. Individuals awarded regular fellowships shall be entitled...) Stipend. (b) Dependency allowances. (c) When authorized in advance, separate allowances for travel. Such...

  7. 42 CFR 61.8 - Benefits: Stipends; dependency allowances; travel allowances; vacation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Benefits: Stipends; dependency allowances; travel...; dependency allowances; travel allowances; vacation. Individuals awarded regular fellowships shall be entitled...) Stipend. (b) Dependency allowances. (c) When authorized in advance, separate allowances for travel. Such...

  8. 42 CFR 61.8 - Benefits: Stipends; dependency allowances; travel allowances; vacation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Benefits: Stipends; dependency allowances; travel...; dependency allowances; travel allowances; vacation. Individuals awarded regular fellowships shall be entitled...) Stipend. (b) Dependency allowances. (c) When authorized in advance, separate allowances for travel. Such...

  9. On the stability and maximum mass of differentially rotating relativistic stars

    NASA Astrophysics Data System (ADS)

    Weih, Lukas R.; Most, Elias R.; Rezzolla, Luciano

    2018-01-01

    The stability properties of rotating relativistic stars against prompt gravitational collapse to a black hole are rather well understood for uniformly rotating models. This is not the case for differentially rotating neutron stars, which are expected to be produced in catastrophic events such as the merger of binary system of neutron stars or the collapse of a massive stellar core. We consider sequences of differentially rotating equilibrium models using the j-constant law and by combining them with their dynamical evolution, we show that a sufficient stability criterion for differentially rotating neutron stars exists similar to the one of their uniformly rotating counterparts. Namely: along a sequence of constant angular momentum, a dynamical instability sets in for central rest-mass densities slightly below the one of the equilibrium solution at the turning point. In addition, following Breu & Rezzolla, we show that `quasi-universal' relations can be found when calculating the turning-point mass. In turn, this allows us to compute the maximum mass allowed by differential rotation, Mmax,dr, in terms of the maximum mass of the non-rotating configuration, M_{_TOV}, finding that M_{max, dr} ˜eq (1.54 ± 0.05) M_{_TOV} for all the equations of state we have considered.

  10. GONADAL AND BONE MARROW DOSE IN MEDICAL DIAGNOSTIC RADIOLOGY

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

    Mahmoud, K.A.; Mahfouz, M.M.; Mahmoud, M.E.

    1961-08-01

    Measurements were made of the active mean bone marrow, integral bone marrow, gonadal, and maximum skin doses from diagnostic x-ray procedures used in Cairo University Hospitals. The active mean marrow dose in cervical, dorsal, and lumbar spine diagnostic exposures were: found to be somewhat smaller than those reported by some western couatries. One of the most striking results of the survey was the relatively high values of the urinary tract cases investigated diagnostically; owing to the high incidence of urinary tract Schistosomiasis. The gonadal dose delivered to males and females was found to be almosi negligible for all diagnostic investigationsmore » of the spine, except for the lumbo-dorsal region which was within the range 50 to 500 mrads. It was also found that the gonadal dose was significant in investigations of the lower gastrointestinal tract, gall bladder, and urinary tract. (P.C.H.)« less

  11. Validation and uncertainty analysis of a pre-treatment 2D dose prediction model

    NASA Astrophysics Data System (ADS)

    Baeza, Jose A.; Wolfs, Cecile J. A.; Nijsten, Sebastiaan M. J. J. G.; Verhaegen, Frank

    2018-02-01

    Independent verification of complex treatment delivery with megavolt photon beam radiotherapy (RT) has been effectively used to detect and prevent errors. This work presents the validation and uncertainty analysis of a model that predicts 2D portal dose images (PDIs) without a patient or phantom in the beam. The prediction model is based on an exponential point dose model with separable primary and secondary photon fluence components. The model includes a scatter kernel, off-axis ratio map, transmission values and penumbra kernels for beam-delimiting components. These parameters were derived through a model fitting procedure supplied with point dose and dose profile measurements of radiation fields. The model was validated against a treatment planning system (TPS; Eclipse) and radiochromic film measurements for complex clinical scenarios, including volumetric modulated arc therapy (VMAT). Confidence limits on fitted model parameters were calculated based on simulated measurements. A sensitivity analysis was performed to evaluate the effect of the parameter uncertainties on the model output. For the maximum uncertainty, the maximum deviating measurement sets were propagated through the fitting procedure and the model. The overall uncertainty was assessed using all simulated measurements. The validation of the prediction model against the TPS and the film showed a good agreement, with on average 90.8% and 90.5% of pixels passing a (2%,2 mm) global gamma analysis respectively, with a low dose threshold of 10%. The maximum and overall uncertainty of the model is dependent on the type of clinical plan used as input. The results can be used to study the robustness of the model. A model for predicting accurate 2D pre-treatment PDIs in complex RT scenarios can be used clinically and its uncertainties can be taken into account.

  12. Collective dose estimates by the marine food pathway from liquid radioactive wastes dumped in the Sea of Japan.

    PubMed

    Togawa, O; Povinec, P P; Pettersson, H B

    1999-09-30

    IAEA-MEL has been engaged in an assessment programme related to radioactive waste dumping by the former USSR and other countries in the western North Pacific Ocean and its marginal seas. This paper focuses on the Sea of Japan and on estimation of collective doses from liquid radioactive wastes. The results from the Japanese-Korean-Russian joint expeditions are summarized, and collective doses for the Japanese population by the marine food pathway are estimated from liquid radioactive wastes dumped in the Sea of Japan and compared with those from global fallout and natural radionuclides. The collective effective dose equivalents by the annual intake of marine products caught in each year show a maximum a few years after the disposals. The total dose from all radionuclides reaches a maximum of 0.8 man Sv in 1990. Approximately 90% of the dose derives from 137Cs, most of which is due to consumption of fish. The total dose from liquid radioactive wastes is approximately 5% of that from global fallout, the contribution of which is below 0.1% of that of natural 210Po.

  13. Determining organ doses from computed tomography scanners using cadaveric subjects

    NASA Astrophysics Data System (ADS)

    Griglock, Thomas M.

    The use of computed tomographic (CT) imaging has increased greatly since its inception in 1972. Technological advances have increased both the applicability of CT exams for common health problems as well as the radiation doses used to perform these exams. The increased radiation exposures have garnered much attention in the media and government agencies, and have brought about numerous attempts to quantify the amount of radiation received by patients. While the overwhelming majority of these attempts have focused on creating models of the human body (physical or computational), this research project sought to directly measure the radiation inside an actual human being. Three female cadaveric subjects of varying sizes were used to represent live patients. Optically-stimulated luminescent (OSL) dosimeters were used to measure the radiation doses. A dosimeter placement system was developed, tested, and optimized to allow accurate and reproducible placement of the dosimeters within the cadaveric subjects. A broad-beam, 320-slice, volumetric CT scanner was utilized to perform all CT exams, including five torso exams, four cardiac exams, and three organ perfusion exams. Organ doses ranged in magnitude from less than 1 to over 120 mGy, with the largest doses measured for perfusion imaging. A methodology has been developed that allows fast and accurate measurement of actual organ doses resulting from CT exams. The measurements made with this methodology represent the first time CT organ doses have been directly measured within a human body. These measurements are of great importance because they allow comparison to the doses measured using previous methods, and can be used to more accurately assess the risks from CT imaging.

  14. Dependence of normal brain integral dose and normal tissue complication probability on the prescription isodose values for γ-knife radiosurgery

    NASA Astrophysics Data System (ADS)

    Ma, Lijun

    2001-11-01

    A recent multi-institutional clinical study suggested possible benefits of lowering the prescription isodose lines for stereotactic radiosurgery procedures. In this study, we investigate the dependence of the normal brain integral dose and the normal tissue complication probability (NTCP) on the prescription isodose values for γ-knife radiosurgery. An analytical dose model was developed for γ-knife treatment planning. The dose model was commissioned by fitting the measured dose profiles for each helmet size. The dose model was validated by comparing its results with the Leksell gamma plan (LGP, version 5.30) calculations. The normal brain integral dose and the NTCP were computed and analysed for an ensemble of treatment cases. The functional dependence of the normal brain integral dose and the NCTP versus the prescribing isodose values was studied for these cases. We found that the normal brain integral dose and the NTCP increase significantly when lowering the prescription isodose lines from 50% to 35% of the maximum tumour dose. Alternatively, the normal brain integral dose and the NTCP decrease significantly when raising the prescribing isodose lines from 50% to 65% of the maximum tumour dose. The results may be used as a guideline for designing future dose escalation studies for γ-knife applications.

  15. SU-E-T-118: Dose Verification for Accuboost Applicators Using TLD, Ion Chamber and Gafchromic Film Measurements

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

    Chisela, W; Yao, R; Dorbu, G

    Purpose: To verify dose delivered with HDR Accuboost applicators using TLD, ion chamber and Gafchromic film measurements and to examine applicator leakage. Methods: A microSelectron HDR unit was used to deliver a dose of 50cGy to the mid-plane of a 62mm thick solid water phantom using dwell times from Monte Carlo pre-calculated nomograms for a 60mm, 70mm Round and 60mm Skin-Dose Optimized (SDO) applicators respectively. GafChromic EBT3+ film was embedded in the phantom midplane horizontally to measure dose distribution. Absolute dose was also measured with TLDs and an ADCL calibrated parallel-plate ion chamber placed in the film plane at fieldmore » center for each applicator. The film was calibrated using 6MV x-ray beam. TLDs were calibrated in a Cs-137 source at UW-Madison calibration laboratory. Radiation leakage through the tungsten alloy shell was measured with a film wrapped around outside surface of a 60mm Round applicator. Results: Measured maximum doses at field center are consistently lower than predicated by 5.8% for TLD, 8.8% for ion chamber, and 2.6% for EBT3+ film on average, with measurement uncertainties of 2.2%, 0.3%, and 2.9% for TLD, chamber, film respectively. The total standard uncertainties for ion chamber and Gafchromic film measurement are 4.9% and 4.6% respectively[1]. The area defined by the applicator aperture was covered by 80% of maximum dose for 62mm compression thickness. When 100cGy is delivered to mid-plane with a 60mm Round applicator, surface dose ranges from 60cGy to a maximum of 145cGy, which occurs at source entrance to the applicator. Conclusion: Measured doses by all three techniques are consistently lower than predicted in our measurements. For a compression thickness of 62 mm, the field size defined by the applicator is only covered by 80% of prescribed dose. Radiation leakage of up to 145cGy was found at the source entrance of applicators.« less

  16. Cyclophosphamide priming reduces intestinal damage in man following high dose melphalan chemotherapy.

    PubMed Central

    Selby, P. J.; Lopes, N.; Mundy, J.; Crofts, M.; Millar, J. L.; McElwain, T. J.

    1987-01-01

    A small pre-treatment 'priming' dose of cyclophosphamide will reduce gut damage due to high dose i.v. melphalan in mice and sheep but efforts to demonstrate this effect in man have been hampered by difficulty in the measurement of gut damage. We have evaluated the 51CR EDTA absorption test, a new method for measuring intestinal permeability, as a means of assessing damage due to high dose melphalan. The test was reliable, with a narrow normal range, easy to use and well tolerated. It detected an increase in intestinal permeability after high dose melphalan with a maximum occurring between 9 and 15 days after treatment and subsequently returning to normal. It was shown in 19 patients that a pre-treatment dose of cyclophosphamide was capable of significantly reducing the abnormalities in intestinal permeability which resulted from high dose melphalan. PMID:3111515

  17. Pharmacokinetics of sarizotan after oral administration of single and repeat doses in healthy subjects.

    PubMed

    Krösser, S; Tillner, J; Fluck, M; Ungethüm, W; Wolna, P; Kovar, A

    2007-05-01

    Sarizotan is a 5-HTIA receptor agonist with high affinity for D3 and D4 receptors. Here we report the pharmacokinetic and tolerability results from four Phase 1 studies. Two single-dose (5 -25 mg, n = 25, 0.5 - 5 mg, n = 16) and two multiple-dose (10 and 20 mg b.i.d., n = 30, 5 mg b.i.d., n = 12) studies with orally administered sarizotan HCl were carried out in healthy subjects. Plasma sarizotan HCl concentrations were measured using a validated HPLC method and fluorescence or MS/MS detection. Pharmacokinetic parameters were obtained using standard non-compartmental methods. Sarizotan was rapidly absorbed, group-median times to reach maximum concentration (tmax) ranged from 0.5 -2.25 h after single doses and during steady state. Maximum plasma concentration (Cmax) and tmax were slightly dependent on formulation and food intake, whereas area under the curve (AUC) was unaffected by these factors. AUC and Cmax increased dose-proportionally over the tested dose range. Independently of dose and time, sarizotan HCl plasma concentrations declined polyexponentially with a terminal elimination half-life (t1/2) of 5 - 7 h. Accumulation factors corresponded to t1/2 values, and steady state was reached within 24 h. Plasma metabolite concentrations were considerably lower than those of the parent drug. The ratio metabolite AUC : parent drug AUC was time- and dose-independent for all three metabolites suggesting that the metabolism of sarizotan is non-saturable in the tested dose range. The pharmacokinetics of sarizotan were dose-proportional and time-independent for the dose range 0.5 -25 mg). The drug was well-tolerated by healthy subjects up to a single dose of 20 mg.

  18. SU-C-BRB-06: Utilizing 3D Scanner and Printer for Dummy Eye-Shield: Artifact-Free CT Images of Tungsten Eye-Shield for Accurate Dose Calculation

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

    Park, J; Lee, J; Institute of Radiation Medicine, Seoul National University Medical Research Center, Seoul

    Purpose: To evaluate the effect of a tungsten eye-shield on the dose distribution of a patient. Methods: A 3D scanner was used to extract the dimension and shape of a tungsten eye-shield in the STL format. Scanned data was transferred into a 3D printer. A dummy eye shield was then produced using bio-resin (3D systems, VisiJet M3 Proplast). For a patient with mucinous carcinoma, the planning CT was obtained with the dummy eye-shield placed on the patient’s right eye. Field shaping of 6 MeV was performed using a patient-specific cerrobend block on the 15 x 15 cm{sup 2} applicator. Themore » gantry angle was 330° to cover the planning target volume near by the lens. EGS4/BEAMnrc was commissioned from our measurement data from a Varian 21EX. For the CT-based dose calculation using EGS4/DOSXYZnrc, the CT images were converted to a phantom file through the ctcreate program. The phantom file had the same resolution as the planning CT images. By assigning the CT numbers of the dummy eye-shield region to 17000, the real dose distributions below the tungsten eye-shield were calculated in EGS4/DOSXYZnrc. In the TPS, the CT number of the dummy eye-shield region was assigned to the maximum allowable CT number (3000). Results: As compared to the maximum dose, the MC dose on the right lens or below the eye shield area was less than 2%, while the corresponding RTP calculated dose was an unrealistic value of approximately 50%. Conclusion: Utilizing a 3D scanner and a 3D printer, a dummy eye-shield for electron treatment can be easily produced. The artifact-free CT images were successfully incorporated into the CT-based Monte Carlo simulations. The developed method was useful in predicting the realistic dose distributions around the lens blocked with the tungsten shield.« less

  19. Repeated dose studies with pure Epigallocatechin-3-gallate demonstrated dose and route dependant hepatotoxicity with associated dyslipidemia.

    PubMed

    Ramachandran, Balaji; Jayavelu, Subramani; Murhekar, Kanchan; Rajkumar, Thangarajan

    2016-01-01

    EGCG (Epigallocatechin-3-gallate) is the major active principle catechin found in green tea. Skepticism regarding the safety of consuming EGCG is gaining attention, despite the fact that it is widely being touted for its potential health benefits, including anti-cancer properties. The lack of scientific data on safe dose levels of pure EGCG is of concern, while EGCG has been commonly studied as a component of GTE (Green tea extract) and not as a single active constituent. This study has been carried out to estimate the maximum tolerated non-toxic dose of pure EGCG and to identify the treatment related risk factors. In a fourteen day consecutive treatment, two different administration modalities were compared, offering an improved [i.p (intraperitoneal)] and limited [p.o (oral)] bioavailability. A trend of dose and route dependant hepatotoxicity was observed particularly with i.p treatment and EGCG increased serum lipid profile in parallel to hepatotoxicity. Fourteen day tolerable dose of EGCG was established as 21.1 mg/kg for i.p and 67.8 mg/kg for p.o. We also observed that, EGCG induced effects by both treatment routes are reversible, subsequent to an observation period for further fourteen days after cessation of treatment. It was demonstrated that the severity of EGCG induced toxicity appears to be a function of dose, route of administration and period of treatment.

  20. Maximum Acceleration Recording Circuit

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr.

    1995-01-01

    Coarsely digitized maximum levels recorded in blown fuses. Circuit feeds power to accelerometer and makes nonvolatile record of maximum level to which output of accelerometer rises during measurement interval. In comparison with inertia-type single-preset-trip-point mechanical maximum-acceleration-recording devices, circuit weighs less, occupies less space, and records accelerations within narrower bands of uncertainty. In comparison with prior electronic data-acquisition systems designed for same purpose, circuit simpler, less bulky, consumes less power, costs and analysis of data recorded in magnetic or electronic memory devices. Circuit used, for example, to record accelerations to which commodities subjected during transportation on trucks.

  1. Bombesin and G-17 dose responses in duodenal ulcer and controls.

    PubMed

    Hirschowitz, B I; Tim, L O; Helman, C A; Molina, E

    1985-11-01

    Gastric acid and pepsin secretion and serum gastrin concentrations were measured in nine patients with uncomplicated duodenal ulcer (DU) and 10 normal controls in the fasting state and in response to graded doses of bombesin, a tetradecapeptide gastrin releaser, and, for reference, synthetic gastrin G-17. Serum gastrin with bombesin stimulation was significantly greater in duodenal ulcer (maximum 467 pg/ml) than in controls (153 pg/ml), while in seven of the DU group tested gastrin levels after a meal were not different from that seen in five of the normal controls. Gastric acid concentrations and outputs were greater in duodenal ulcer with both stimuli. Secretory responses were then related to serum gastrin levels; despite increasing gastrin levels with bombesin stimulation, peak outputs achieved with bombesin were only 50% of G-17 maximum in normals and up to 90% of maximum in duodenal ulcer. Up to the point of peak response to bombesin, acid and pepsin outputs were the same with exogenous and endogenous gastrin, ie, bombesin acted only via G-17. Furthermore, in direct comparison of duodenal ulcer and normals with G-17 infusion, acid and pepsin outputs related to serum gastrin were congruent up to 75% of duodenal ulcer maximum, at which point normals reached their maximum level. These data have shown that duodenal ulcer patients are not more sensitive to either exogenous or endogenous gastrin; we have also shown regulatory defects in duodenal ulcer patients not previously described: an exaggerated release of gastrin with bombesin stimulation, and a defective inhibition of acid and pepsin secretion with higher doses of bombesin.

  2. Hydraulic Limits on Maximum Plant Transpiration

    NASA Astrophysics Data System (ADS)

    Manzoni, S.; Vico, G.; Katul, G. G.; Palmroth, S.; Jackson, R. B.; Porporato, A. M.

    2011-12-01

    Photosynthesis occurs at the expense of water losses through transpiration. As a consequence of this basic carbon-water interaction at the leaf level, plant growth and ecosystem carbon exchanges are tightly coupled to transpiration. In this contribution, the hydraulic constraints that limit transpiration rates under well-watered conditions are examined across plant functional types and climates. The potential water flow through plants is proportional to both xylem hydraulic conductivity (which depends on plant carbon economy) and the difference in water potential between the soil and the atmosphere (the driving force that pulls water from the soil). Differently from previous works, we study how this potential flux changes with the amplitude of the driving force (i.e., we focus on xylem properties and not on stomatal regulation). Xylem hydraulic conductivity decreases as the driving force increases due to cavitation of the tissues. As a result of this negative feedback, more negative leaf (and xylem) water potentials would provide a stronger driving force for water transport, while at the same time limiting xylem hydraulic conductivity due to cavitation. Here, the leaf water potential value that allows an optimum balance between driving force and xylem conductivity is quantified, thus defining the maximum transpiration rate that can be sustained by the soil-to-leaf hydraulic system. To apply the proposed framework at the global scale, a novel database of xylem conductivity and cavitation vulnerability across plant types and biomes is developed. Conductivity and water potential at 50% cavitation are shown to be complementary (in particular between angiosperms and conifers), suggesting a tradeoff between transport efficiency and hydraulic safety. Plants from warmer and drier biomes tend to achieve larger maximum transpiration than plants growing in environments with lower atmospheric water demand. The predicted maximum transpiration and the corresponding leaf water

  3. Spatial frequency performance limitations of radiation dose optimization and beam positioning

    NASA Astrophysics Data System (ADS)

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

    2018-06-01

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

  4. p-MOSFET total dose dosimeter

    NASA Technical Reports Server (NTRS)

    Buehler, Martin G. (Inventor); Blaes, Brent R. (Inventor)

    1994-01-01

    A p-MOSFET total dose dosimeter where the gate voltage is proportional to the incident radiation dose. It is configured in an n-WELL of a p-BODY substrate. It is operated in the saturation region which is ensured by connecting the gate to the drain. The n-well is connected to zero bias. Current flow from source to drain, rather than from peripheral leakage, is ensured by configuring the device as an edgeless MOSFET where the source completely surrounds the drain. The drain junction is the only junction not connected to zero bias. The MOSFET is connected as part of the feedback loop of an operational amplifier. The operational amplifier holds the drain current fixed at a level which minimizes temperature dependence and also fixes the drain voltage. The sensitivity to radiation is made maximum by operating the MOSFET in the OFF state during radiation soak.

  5. Maximum entropy production, carbon assimilation, and the spatial organization of vegetation in river basins

    PubMed Central

    del Jesus, Manuel; Foti, Romano; Rinaldo, Andrea; Rodriguez-Iturbe, Ignacio

    2012-01-01

    The spatial organization of functional vegetation types in river basins is a major determinant of their runoff production, biodiversity, and ecosystem services. The optimization of different objective functions has been suggested to control the adaptive behavior of plants and ecosystems, often without a compelling justification. Maximum entropy production (MEP), rooted in thermodynamics principles, provides a tool to justify the choice of the objective function controlling vegetation organization. The application of MEP at the ecosystem scale results in maximum productivity (i.e., maximum canopy photosynthesis) as the thermodynamic limit toward which the organization of vegetation appears to evolve. Maximum productivity, which incorporates complex hydrologic feedbacks, allows us to reproduce the spatial macroscopic organization of functional types of vegetation in a thoroughly monitored river basin, without the need for a reductionist description of the underlying microscopic dynamics. The methodology incorporates the stochastic characteristics of precipitation and the associated soil moisture on a spatially disaggregated framework. Our results suggest that the spatial organization of functional vegetation types in river basins naturally evolves toward configurations corresponding to dynamically accessible local maxima of the maximum productivity of the ecosystem. PMID:23213227

  6. Fast skin dose estimation system for interventional radiology

    PubMed Central

    Takata, Takeshi; Kotoku, Jun’ichi; Maejima, Hideyuki; Kumagai, Shinobu; Arai, Norikazu; Kobayashi, Takenori; Shiraishi, Kenshiro; Yamamoto, Masayoshi; Kondo, Hiroshi; Furui, Shigeru

    2018-01-01

    Abstract To minimise the radiation dermatitis related to interventional radiology (IR), rapid and accurate dose estimation has been sought for all procedures. We propose a technique for estimating the patient skin dose rapidly and accurately using Monte Carlo (MC) simulation with a graphical processing unit (GPU, GTX 1080; Nvidia Corp.). The skin dose distribution is simulated based on an individual patient’s computed tomography (CT) dataset for fluoroscopic conditions after the CT dataset has been segmented into air, water and bone based on pixel values. The skin is assumed to be one layer at the outer surface of the body. Fluoroscopic conditions are obtained from a log file of a fluoroscopic examination. Estimating the absorbed skin dose distribution requires calibration of the dose simulated by our system. For this purpose, a linear function was used to approximate the relation between the simulated dose and the measured dose using radiophotoluminescence (RPL) glass dosimeters in a water-equivalent phantom. Differences of maximum skin dose between our system and the Particle and Heavy Ion Transport code System (PHITS) were as high as 6.1%. The relative statistical error (2 σ) for the simulated dose obtained using our system was ≤3.5%. Using a GPU, the simulation on the chest CT dataset aiming at the heart was within 3.49 s on average: the GPU is 122 times faster than a CPU (Core i7–7700K; Intel Corp.). Our system (using the GPU, the log file, and the CT dataset) estimated the skin dose more rapidly and more accurately than conventional methods. PMID:29136194

  7. Fast skin dose estimation system for interventional radiology.

    PubMed

    Takata, Takeshi; Kotoku, Jun'ichi; Maejima, Hideyuki; Kumagai, Shinobu; Arai, Norikazu; Kobayashi, Takenori; Shiraishi, Kenshiro; Yamamoto, Masayoshi; Kondo, Hiroshi; Furui, Shigeru

    2018-03-01

    To minimise the radiation dermatitis related to interventional radiology (IR), rapid and accurate dose estimation has been sought for all procedures. We propose a technique for estimating the patient skin dose rapidly and accurately using Monte Carlo (MC) simulation with a graphical processing unit (GPU, GTX 1080; Nvidia Corp.). The skin dose distribution is simulated based on an individual patient's computed tomography (CT) dataset for fluoroscopic conditions after the CT dataset has been segmented into air, water and bone based on pixel values. The skin is assumed to be one layer at the outer surface of the body. Fluoroscopic conditions are obtained from a log file of a fluoroscopic examination. Estimating the absorbed skin dose distribution requires calibration of the dose simulated by our system. For this purpose, a linear function was used to approximate the relation between the simulated dose and the measured dose using radiophotoluminescence (RPL) glass dosimeters in a water-equivalent phantom. Differences of maximum skin dose between our system and the Particle and Heavy Ion Transport code System (PHITS) were as high as 6.1%. The relative statistical error (2 σ) for the simulated dose obtained using our system was ≤3.5%. Using a GPU, the simulation on the chest CT dataset aiming at the heart was within 3.49 s on average: the GPU is 122 times faster than a CPU (Core i7-7700K; Intel Corp.). Our system (using the GPU, the log file, and the CT dataset) estimated the skin dose more rapidly and more accurately than conventional methods.

  8. Rapid Acute Dose Assessment Using MCNP6

    NASA Astrophysics Data System (ADS)

    Owens, Andrew Steven

    Acute radiation doses due to physical contact with a high-activity radioactive source have proven to be an occupational hazard. Multiple radiation injuries have been reported due to manipulating a radioactive source with bare hands or by placing a radioactive source inside a shirt or pants pocket. An effort to reconstruct the radiation dose must be performed to properly assess and medically manage the potential biological effects from such doses. Using the reference computational phantoms defined by the International Commission on Radiological Protection (ICRP) and the Monte Carlo N-Particle transport code (MCNP6), dose rate coefficients are calculated to assess doses for common acute doses due to beta and photon radiation sources. The research investigates doses due to having a radioactive source in either a breast pocket or pants back pocket. The dose rate coefficients are calculated for discrete energies and can be used to interpolate for any given energy of photon or beta emission. The dose rate coefficients allow for quick calculation of whole-body dose, organ dose, and/or skin dose if the source, activity, and time of exposure are known. Doses are calculated with the dose rate coefficients and compared to results from the International Atomic Energy Agency (IAEA) reports from accidents that occurred in Gilan, Iran and Yanango, Peru. Skin and organ doses calculated with the dose rate coefficients appear to agree, but there is a large discrepancy when comparing whole-body doses assessed using biodosimetry and whole-body doses assessed using the dose rate coefficients.

  9. Variability of maximum systolic amplitude of ΔZ/Δt curve in pregnancy. Perennial observations

    NASA Astrophysics Data System (ADS)

    Ilyin, I.; Karpov, A.; Korotkova, M.

    2010-04-01

    Maximum systolic amplitude is quite an important component of the impedance cardiogram ΔZ/Δt curve. Its values make it possible to calculate many hemodynamic indices. Therefore it is necessary to keep informed about monthly, annual and perennial maximum systolic amplitude trend. We can produce the measuring data of the maximum systolic amplitude for a fifteen-year period (from 1994 to 2009). The impedance cardiograms were obtained with the help of an electric impedance analyzer "RA-5" (1 mA, 70 kHz) with disk ECG electrodes. The data analyzed were taken from the pregnant women with non-complicated pregnancy (n=5709). We have analyzed the average monthly and annual changes of the maximum systolic amplitude ΔZ/Δt curve. It allowed us to reveal the six-year periodicity of the maximum systolic amplitude changes. There were discovered statistically significant peak values difference of the amplitude (p>0.001). The data obtained should be taken into consideration when using impedance cardiography in clinical practice. The article is supplied with tables and diagrams.

  10. Radiation dose delivery verification in the treatment of carcinoma-cervix

    NASA Astrophysics Data System (ADS)

    Shrotriya, D.; Kumar, S.; Srivastava, R. N. L.

    2015-06-01

    The accurate dose delivery to the clinical target volume in radiotherapy can be affected by various pelvic tissues heterogeneities. An in-house heterogeneous woman pelvic phantom was designed and used to verify the consistency and computational capability of treatment planning system of radiation dose delivery in the treatment of cancer cervix. Oncentra 3D-TPS with collapsed cone convolution (CCC) dose calculation algorithm was used to generate AP/PA and box field technique plan. the radiation dose was delivered by Primus Linac (Siemens make) employing high energy 15 MV photon beam by isocenter technique. A PTW make, 0.125cc ionization chamber was used for direct measurements at various reference points in cervix, bladder and rectum. The study revealed that maximum variation between computed and measured dose at cervix reference point was 1% in both the techniques and 3% and 4% variation in AP/PA field and 5% and 4.5% in box technique at bladder and rectum points respectively.

  11. Population pharmacokinetics and maximum a posteriori probability Bayesian estimator of abacavir: application of individualized therapy in HIV-infected infants and toddlers.

    PubMed

    Zhao, Wei; Cella, Massimo; Della Pasqua, Oscar; Burger, David; Jacqz-Aigrain, Evelyne

    2012-04-01

    identified weight as the individual factor influencing the apparent oral clearance: CL = 13.4 × (weight/12)1.14. The maximum a posteriori probability Bayesian estimator, based on three concentrations measured at 0, 1 or 2, and 3 h after drug intake allowed predicting individual AUC0–t. The population pharmacokinetic model developed for abacavir in HIV-infected infants and toddlers accurately described both once and twice daily pharmacokinetic profiles. The maximum a posteriori probability Bayesian estimator of AUC(0-) (t) was developed from the final model and can be used routinely to optimize individual dosing. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

  12. Dose-mortality assessment upon reuse and recycling of industrial sludge.

    PubMed

    Lin, Kae-Long; Chen, Bor-Yann

    2007-09-05

    This study provides a novel attempt to put forward, in general toxicological terms, quantitative ranking of toxicity of various sources of sludge for possible reusability in further applications. The high leaching concentrations of copper in printed circuit board (PCB) sludge and chromium in leather sludge apparently exceeded current Taiwan's EPA regulatory thresholds and should be classified as hazardous wastes. Dose-mortality analysis indicated that the toxicity ranking of different sources of sludge was PCB sludge>CaF(2) sludge>leather sludge. PCB sludge was also confirmed as a hazardous waste since the toxicity potency of PCB sludge was nearly identical to CdCl(2). However, leather sludge seemed to be much less toxic than as anticipated, perhaps due to a significant decrease of toxic species bioavailable in the aqueous phase to the reporter bacterium Escherichia coli DH5alpha. For possible reusability of sludge, maximum concentrations allowable to be considered "safe" (ca. EC(100)/100) were 9.68, 42.1 and 176 mgL(-1) for CaF(2) sludge, PCB sludge and leather sludge, respectively.

  13. Minimum Detectable Dose as a Measure of Bioassay Programme Capability

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

    Carbaugh, Eugene H.

    2003-01-01

    This paper suggests that minimum detectable dose (MDD) be used to describe the capability of bioassay programs for which intakes are expected to be rare. This allows expression of the capability in units that correspond directly to primary dose limits. The concept uses the well-established analytical statistic minimum detectable amount (MDA) as the starting point and assumes MDA detection at a prescribed time post intake. The resulting dose can then be used as an indication of the adequacy or capability of the program for demonstrating compliance with the performance criteria. MDDs can be readily tabulated or plotted to demonstrate themore » effectiveness of different types of monitoring programs. The inclusion of cost factors for bioassay measurements can allow optimisation.« less

  14. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source.

    PubMed

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-21

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V(100) reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  15. Applications of tissue heterogeneity corrections and biologically effective dose volume histograms in assessing the doses for accelerated partial breast irradiation using an electronic brachytherapy source

    NASA Astrophysics Data System (ADS)

    Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Eng, Tony; Papanikolaou, Nikos

    2010-09-01

    A low-energy electronic brachytherapy source (EBS), the model S700 Axxent™ x-ray device developed by Xoft Inc., has been used in high dose rate (HDR) intracavitary accelerated partial breast irradiation (APBI) as an alternative to an Ir-192 source. The prescription dose and delivery schema of the electronic brachytherapy APBI plan are the same as the Ir-192 plan. However, due to its lower mean energy than the Ir-192 source, an EBS plan has dosimetric and biological features different from an Ir-192 source plan. Current brachytherapy treatment planning methods may have large errors in treatment outcome prediction for an EBS plan. Two main factors contribute to the errors: the dosimetric influence of tissue heterogeneities and the enhancement of relative biological effectiveness (RBE) of electronic brachytherapy. This study quantified the effects of these two factors and revisited the plan quality of electronic brachytherapy APBI. The influence of tissue heterogeneities is studied by a Monte Carlo method and heterogeneous 'virtual patient' phantoms created from CT images and structure contours; the effect of RBE enhancement in the treatment outcome was estimated by biologically effective dose (BED) distribution. Ten electronic brachytherapy APBI cases were studied. The results showed that, for electronic brachytherapy cases, tissue heterogeneities and patient boundary effect decreased dose to the target and skin but increased dose to the bones. On average, the target dose coverage PTV V100 reduced from 95.0% in water phantoms (planned) to only 66.7% in virtual patient phantoms (actual). The actual maximum dose to the ribs is 3.3 times higher than the planned dose; the actual mean dose to the ipsilateral breast and maximum dose to the skin were reduced by 22% and 17%, respectively. Combining the effect of tissue heterogeneities and RBE enhancement, BED coverage of the target was 89.9% in virtual patient phantoms with RBE enhancement (actual BED) as compared to 95

  16. Patient-specific IMRT verification using independent fluence-based dose calculation software: experimental benchmarking and initial clinical experience.

    PubMed

    Georg, Dietmar; Stock, Markus; Kroupa, Bernhard; Olofsson, Jörgen; Nyholm, Tufve; Ahnesjö, Anders; Karlsson, Mikael

    2007-08-21

    Experimental methods are commonly used for patient-specific intensity-modulated radiotherapy (IMRT) verification. The purpose of this study was to investigate the accuracy and performance of independent dose calculation software (denoted as 'MUV' (monitor unit verification)) for patient-specific quality assurance (QA). 52 patients receiving step-and-shoot IMRT were considered. IMRT plans were recalculated by the treatment planning systems (TPS) in a dedicated QA phantom, in which an experimental 1D and 2D verification (0.3 cm(3) ionization chamber; films) was performed. Additionally, an independent dose calculation was performed. The fluence-based algorithm of MUV accounts for collimator transmission, rounded leaf ends, tongue-and-groove effect, backscatter to the monitor chamber and scatter from the flattening filter. The dose calculation utilizes a pencil beam model based on a beam quality index. DICOM RT files from patient plans, exported from the TPS, were directly used as patient-specific input data in MUV. For composite IMRT plans, average deviations in the high dose region between ionization chamber measurements and point dose calculations performed with the TPS and MUV were 1.6 +/- 1.2% and 0.5 +/- 1.1% (1 S.D.). The dose deviations between MUV and TPS slightly depended on the distance from the isocentre position. For individual intensity-modulated beams (total 367), an average deviation of 1.1 +/- 2.9% was determined between calculations performed with the TPS and with MUV, with maximum deviations up to 14%. However, absolute dose deviations were mostly less than 3 cGy. Based on the current results, we aim to apply a confidence limit of 3% (with respect to the prescribed dose) or 6 cGy for routine IMRT verification. For off-axis points at distances larger than 5 cm and for low dose regions, we consider 5% dose deviation or 10 cGy acceptable. The time needed for an independent calculation compares very favourably with the net time for an experimental

  17. SU-F-J-194: Development of Dose-Based Image Guided Proton Therapy Workflow

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

    Pham, R; Sun, B; Zhao, T

    Purpose: To implement image-guided proton therapy (IGPT) based on daily proton dose distribution. Methods: Unlike x-ray therapy, simple alignment based on anatomy cannot ensure proper dose coverage in proton therapy. Anatomy changes along the beam path may lead to underdosing the target, or overdosing the organ-at-risk (OAR). With an in-room mobile computed tomography (CT) system, we are developing a dose-based IGPT software tool that allows patient positioning and treatment adaption based on daily dose distributions. During an IGPT treatment, daily CT images are acquired in treatment position. After initial positioning based on rigid image registration, proton dose distribution is calculatedmore » on daily CT images. The target and OARs are automatically delineated via deformable image registration. Dose distributions are evaluated to decide if repositioning or plan adaptation is necessary in order to achieve proper coverage of the target and sparing of OARs. Besides online dose-based image guidance, the software tool can also map daily treatment doses to the treatment planning CT images for offline adaptive treatment. Results: An in-room helical CT system is commissioned for IGPT purposes. It produces accurate CT numbers that allow proton dose calculation. GPU-based deformable image registration algorithms are developed and evaluated for automatic ROI-delineation and dose mapping. The online and offline IGPT functionalities are evaluated with daily CT images of the proton patients. Conclusion: The online and offline IGPT software tool may improve the safety and quality of proton treatment by allowing dose-based IGPT and adaptive proton treatments. Research is partially supported by Mevion Medical Systems.« less

  18. SU-F-T-117: A Pilot Study of Organ Dose Reconstruction for Wilms Tumor Patients Treated with Radiation Therapy

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

    Makkia, R; Pelletier, C; Jung, J

    Purpose: To reconstruct major organ doses for the Wilms tumor pediatric patients treated with radiation therapy using pediatric computational phantoms, treatment planning system (TPS), and Monte Carlo (MC) dose calculation methods. Methods: A total of ten female and male pediatric patients (15–88 months old) were selected from the National Wilms Tumor Study cohort and ten pediatric computational phantoms corresponding to the patient’s height and weight were selected for the organ dose reconstruction. Treatment plans were reconstructed on the computational phantoms in a Pinnacle TPS (v9.10) referring to treatment records and exported into DICOM-RT files, which were then used to generatemore » the input files for XVMC MC code. The mean doses to major organs and the dose received by 50% of the heart were calculated and compared between TPS and MC calculations. The same calculations were conducted by replacing the computational human phantoms with a series of diagnostic patient CT images selected by matching the height and weight of the patients to validate the anatomical accuracy of the computational phantoms. Results: Dose to organs located within the treatment fields from the computational phantoms and the diagnostic patient CT images agreed within 2% for all cases for both TPS and MC calculations. The maximum difference of organ doses was 55.9 % (thyroid), but the absolute dose difference in this case was 0.33 Gy which was 0.96% of the prescription dose. The doses to ovaries and testes from MC in out-of-field provided more discrepancy (the maximum difference of 13.2% and 50.8%, respectively). The maximum difference of the 50% heart volume dose between the phantoms and the patient CT images was 40.0%. Conclusion: This study showed the pediatric computational phantoms are applicable to organ doses reconstruction for the radiotherapy patients whose three-dimensional radiological images are not available.« less

  19. SU-E-J-93: Parametrisation of Dose to the Mucosa of the Anterior Rectal Wall in Transrectal Ultrasound Guided High-Dose-Rate Brachytherapy of the Prostate

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

    Aitkenhead, A; Hamlett, L; Wood, D

    2014-06-01

    Purpose: In high-dose-rate (HDR) brachytherapy of the prostate, radiation is delivered from a number of radioactive sources which are inserted via catheter into the target volume. The rectal mucosa also receives dose during the treatment, which may lead to late toxicity effects. To allow possible links between rectal dose and toxicity to be investigated, suitable methods of parametrising the rectal dose are needed. Methods: During treatment of a series of 95 patients, anatomy and catheter locations were monitored by transrectal ultrasound, and target volume positions were contoured on the ultrasound scan by the therapist. The anterior rectal mucosal wall wasmore » identified by contouring the transrectal ultrasound balloon within the ultrasound scan. Source positions and dwell times, along with the dose delivered to the patient were computed using the Oncentra Prostate treatment planning system (TPS). Data for the series of patients were exported from the TPS in Dicom format, and a series of parametrisation methods were developed in a Matlab environment to assess the rectal dose. Results: Contours of the anterior rectal mucosa were voxelised within Matlab to allow the dose to the rectal mucosa to be analysed directly from the 3D dose grid. Dose parametrisations based on dose-surface (DSH) and dose-line (DLH) histograms were obtained. Both lateral and longitudinal extents of the mucosal dose were parametrised using dose-line histograms in the relevant directions. Conclusion: We have developed a series of dose parametrisations for quantifying the dose to the rectal mucosa during HDR prostate brachytherapy which are suitable for future studies investigating potential associations between mucosal dose and late toxicity effects. The geometry of the transrectal probe standardises the rectal anatomy, making this treatment technique particularly suited to studies of this nature.« less

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

    PubMed

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

    2016-08-20

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

  1. A Method of Maximum Power Control in Single-phase Utility Interactive Photovoltaic Generation System by using PWM Current Source Inverter

    NASA Astrophysics Data System (ADS)

    Neba, Yasuhiko

    This paper deals with a maximum power point tracking (MPPT) control of the photovoltaic generation with the single-phase utility interactive inverter. The photovoltaic arrays are connected by employing the PWM current source inverter to the utility. The use of the pulsating dc current and voltage allows the maximum power point to be searched. The inverter can regulate the array voltage and keep the arrays to the maximum power. This paper gives the control method and the experimental results.

  2. Positron Emission Tomography-Guided, Focal-Dose Escalation Using Intensity-Modulated Radiotherapy for Head and Neck Cancer

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

    Madani, Indira; Duthoy, Wim; Derie, Cristina R.N.

    2007-05-01

    Purpose: To assess the feasibility of intensity-modulated radiotherapy (IMRT) using positron emission tomography (PET)-guided dose escalation, and to determine the maximum tolerated dose in head and neck cancer. Methods and Materials: A Phase I clinical trial was designed to escalate the dose limited to the [{sup 18}-F]fluoro-2-deoxy-D-glucose positron emission tomography ({sup 18}F-FDG-PET)-delineated subvolume within the gross tumor volume. Positron emission tomography scanning was performed in the treatment position. Intensity-modulated radiotherapy with an upfront simultaneously integrated boost was employed. Two dose levels were planned: 25 Gy (level I) and 30 Gy (level II), delivered in 10 fractions. Standard IMRT was appliedmore » for the remaining 22 fractions of 2.16 Gy. Results: Between 2003 and 2005, 41 patients were enrolled, with 23 at dose level I, and 18 at dose level II; 39 patients completed the planned therapy. The median follow-up for surviving patients was 14 months. Two cases of dose-limiting toxicity occurred at dose level I (Grade 4 dermitis and Grade 4 dysphagia). One treatment-related death at dose level II halted the study. Complete response was observed in 18 of 21 (86%) and 13 of 16 (81%) evaluated patients at dose levels I and II (p < 0.7), respectively, with actuarial 1-year local control at 85% and 87% (p n.s.), and 1-year overall survival at 82% and 54% (p = 0.06), at dose levels I and II, respectively. In 4 of 9 patients, the site of relapse was in the boosted {sup 18}F-FDG-PET-delineated region. Conclusions: For head and neck cancer, PET-guided dose escalation appears to be well-tolerated. The maximum tolerated dose was not reached at the investigated dose levels.« less

  3. An analytic linear accelerator source model for GPU-based Monte Carlo dose calculations.

    PubMed

    Tian, Zhen; Li, Yongbao; Folkerts, Michael; Shi, Feng; Jiang, Steve B; Jia, Xun

    2015-10-21

    Recently, there has been a lot of research interest in developing fast Monte Carlo (MC) dose calculation methods on graphics processing unit (GPU) platforms. A good linear accelerator (linac) source model is critical for both accuracy and efficiency considerations. In principle, an analytical source model should be more preferred for GPU-based MC dose engines than a phase-space file-based model, in that data loading and CPU-GPU data transfer can be avoided. In this paper, we presented an analytical field-independent source model specifically developed for GPU-based MC dose calculations, associated with a GPU-friendly sampling scheme. A key concept called phase-space-ring (PSR) was proposed. Each PSR contained a group of particles that were of the same type, close in energy and reside in a narrow ring on the phase-space plane located just above the upper jaws. The model parameterized the probability densities of particle location, direction and energy for each primary photon PSR, scattered photon PSR and electron PSR. Models of one 2D Gaussian distribution or multiple Gaussian components were employed to represent the particle direction distributions of these PSRs. A method was developed to analyze a reference phase-space file and derive corresponding model parameters. To efficiently use our model in MC dose calculations on GPU, we proposed a GPU-friendly sampling strategy, which ensured that the particles sampled and transported simultaneously are of the same type and close in energy to alleviate GPU thread divergences. To test the accuracy of our model, dose distributions of a set of open fields in a water phantom were calculated using our source model and compared to those calculated using the reference phase-space files. For the high dose gradient regions, the average distance-to-agreement (DTA) was within 1 mm and the maximum DTA within 2 mm. For relatively low dose gradient regions, the root-mean-square (RMS) dose difference was within 1.1% and the maximum

  4. Comprehensive evaluations of cone-beam CT dose in image-guided radiation therapy via GPU-based Monte Carlo simulations

    NASA Astrophysics Data System (ADS)

    Montanari, Davide; Scolari, Enrica; Silvestri, Chiara; Jiang Graves, Yan; Yan, Hao; Cervino, Laura; Rice, Roger; Jiang, Steve B.; Jia, Xun

    2014-03-01

    Cone beam CT (CBCT) has been widely used for patient setup in image-guided radiation therapy (IGRT). Radiation dose from CBCT scans has become a clinical concern. The purposes of this study are (1) to commission a graphics processing unit (GPU)-based Monte Carlo (MC) dose calculation package gCTD for Varian On-Board Imaging (OBI) system and test the calculation accuracy, and (2) to quantitatively evaluate CBCT dose from the OBI system in typical IGRT scan protocols. We first conducted dose measurements in a water phantom. X-ray source model parameters used in gCTD are obtained through a commissioning process. gCTD accuracy is demonstrated by comparing calculations with measurements in water and in CTDI phantoms. Twenty-five brain cancer patients are used to study dose in a standard-dose head protocol, and 25 prostate cancer patients are used to study dose in pelvis protocol and pelvis spotlight protocol. Mean dose to each organ is calculated. Mean dose to 2% voxels that have the highest dose is also computed to quantify the maximum dose. It is found that the mean dose value to an organ varies largely among patients. Moreover, dose distribution is highly non-homogeneous inside an organ. The maximum dose is found to be 1-3 times higher than the mean dose depending on the organ, and is up to eight times higher for the entire body due to the very high dose region in bony structures. High computational efficiency has also been observed in our studies, such that MC dose calculation time is less than 5 min for a typical case.

  5. Simulation of Dose to Surrounding Normal Structures in Tangential Breast Radiotherapy Due to Setup Error

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

    Prabhakar, Ramachandran; Department of Nuclear Medicine, All India Institute of Medical Sciences, New Delhi; Department of Radiology, All India Institute of Medical Sciences, New Delhi

    Setup error plays a significant role in the final treatment outcome in radiotherapy. The effect of setup error on the planning target volume (PTV) and surrounding critical structures has been studied and the maximum allowed tolerance in setup error with minimal complications to the surrounding critical structure and acceptable tumor control probability is determined. Twelve patients were selected for this study after breast conservation surgery, wherein 8 patients were right-sided and 4 were left-sided breast. Tangential fields were placed on the 3-dimensional-computed tomography (3D-CT) dataset by isocentric technique and the dose to the PTV, ipsilateral lung (IL), contralateral lung (CLL),more » contralateral breast (CLB), heart, and liver were then computed from dose-volume histograms (DVHs). The planning isocenter was shifted for 3 and 10 mm in all 3 directions (X, Y, Z) to simulate the setup error encountered during treatment. Dosimetric studies were performed for each patient for PTV according to ICRU 50 guidelines: mean doses to PTV, IL, CLL, heart, CLB, liver, and percentage of lung volume that received a dose of 20 Gy or more (V20); percentage of heart volume that received a dose of 30 Gy or more (V30); and volume of liver that received a dose of 50 Gy or more (V50) were calculated for all of the above-mentioned isocenter shifts and compared to the results with zero isocenter shift. Simulation of different isocenter shifts in all 3 directions showed that the isocentric shifts along the posterior direction had a very significant effect on the dose to the heart, IL, CLL, and CLB, which was followed by the lateral direction. The setup error in isocenter should be strictly kept below 3 mm. The study shows that isocenter verification in the case of tangential fields should be performed to reduce future complications to adjacent normal tissues.« less

  6. Multileaf collimator tongue-and-groove effect on depth and off-axis doses: A comparison of treatment planning data with measurements and Monte Carlo calculations

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

    Kim, Hee Jung; Department of Biomedical Engineering, Seoul National University, Seoul; Department of Radiation Oncology, Soonchunhyang University Hospital, Seoul

    2015-01-01

    To investigate how accurately treatment planning systems (TPSs) account for the tongue-and-groove (TG) effect, Monte Carlo (MC) simulations and radiochromic film (RCF) measurements were performed for comparison with TPS results. Two commercial TPSs computed the TG effect for Varian Millennium 120 multileaf collimator (MLC). The TG effect on off-axis dose profile at 3 depths of solid water was estimated as the maximum depth and the full width at half maximum (FWHM) of the dose dip at an interleaf position. When compared with the off-axis dose of open field, the maximum depth of the dose dip for MC and RCF rangedmore » from 10.1% to 20.6%; the maximum depth of the dose dip gradually decreased by up to 8.7% with increasing depths of 1.5 to 10 cm and also by up to 4.1% with increasing off-axis distances of 0 to 13 cm. However, TPS results showed at most a 2.7% decrease for the same depth range and a negligible variation for the same off-axis distances. The FWHM of the dose dip was approximately 0.19 cm for MC and 0.17 cm for RCF, but 0.30 cm for Eclipse TPS and 0.45 cm for Pinnacle TPS. Accordingly, the integrated value of TG dose dip for TPS was larger than that for MC and RCF and almost invariant along the depths and off-axis distances. We concluded that the TG dependence on depth and off-axis doses shown in the MC and RCF results could not be appropriately modeled by the TPS versions in this study.« less

  7. Implementation of radiochromic film dosimetry protocol for volumetric dose assessments to various organs during diagnostic CT procedures

    PubMed Central

    Brady, Samuel; Yoshizumi, Terry; Toncheva, Greta; Frush, Donald

    2010-01-01

    the main axis of the CT beam. The consistency in dose response difference allowed for a tissue specific correction to be applied. Once corrected, the average film response agreed to better than 3% (SD±2%) for the CTDI scans, and for the anthropomorphic phantom scans: 3% (SD±3%) for the lungs, 5% (SD±3%) for the liver, and 4% (SD±3%) for the kidneys. Additionally, XRQA film measured a heterogeneous dose distribution within the organ volumes. The extent of the dose distribution heterogeneity was not measurable with the TLDs due to the limitation on the number of TLDs loadable in the regions of the phantom organs. In this regard, XRQA film demonstrated an advantage over the TLD method by discovering a 15% greater maximum dose to lung in a region unmeasured by TLDs. Conclusions: The films demonstrated a lower sensitivity to absorbed dose measurements due to the geometric inefficiency of measuring dose from a beam situated end-on to the film. Once corrected, the film demonstrated equivalent dose measurement accuracy as TLD detectors with the added advantage of relatively simple measurement of high-resolution dose distributions throughout organ volumes. PMID:20964198

  8. Critical Dose of Internal Organs Internal Exposure - 13471

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

    Grigoryan, G.; Amirjanyan, A.; Grigoryan, N.

    2013-07-01

    The health threat posed by radionuclides has stimulated increased efforts to developed characterization on the biological behavior of radionuclides in humans in all ages. In an effort motivated largely by the Chernobyl nuclear accident, the International Commission on Radiological Protection (ICRP) is assembling a set of age specific biokinetic models for environmentally important radioelements. Radioactive substances in the air, mainly through the respiratory system and digestive tract, is inside the body. Radioactive substances are unevenly distributed in various organs and tissues. Therefore, the degree of damage will depend not only on the dose of radiation have but also on themore » critical organ, which is the most accumulation of radioactive substances, which leads to the defeat of the entire human body. The main objective of radiation protection, to avoid exceeding the maximum permissible doses of external and internal exposure of a person to prevent the physical and genetic damage people. The maximum tolerated dose (MTD) of radiation is called a dose of radiation a person in uniform getting her for 50 years does not cause changes in the health of the exposed individual and his progeny. The following classification of critical organs, depending on the category of exposure on their degree of sensitivity to radiation: First group: the whole body, gonads and red bone marrow; Second group: muscle, fat, liver, kidney, spleen, gastrointestinal tract, lungs and lens of the eye; The third group: bone, thyroid and skin; Fourth group: the hands, forearms, feet. MTD exposure whole body, gonads and bone marrow represent the maximum exposures (5 rem per year) experienced by people in their normal activities. The purpose of this article is intended dose received from various internal organs of the radionuclides that may enter the body by inhalation, and gastrointestinal tract. The biokinetic model describes the time dependent distribution and excretion of different

  9. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate.

    PubMed

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J; Ravelli, Raimond B G

    2011-05-01

    Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50-250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e(-)Å(-2) s(-1) or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection combined with

  10. Radiation damage in single-particle cryo-electron microscopy: effects of dose and dose rate

    PubMed Central

    Karuppasamy, Manikandan; Karimi Nejadasl, Fatemeh; Vulovic, Milos; Koster, Abraham J.; Ravelli, Raimond B. G.

    2011-01-01

    Radiation damage is an important resolution limiting factor both in macromolecular X-ray crystallography and cryo-electron microscopy. Systematic studies in macromolecular X-ray crystallography greatly benefited from the use of dose, expressed as energy deposited per mass unit, which is derived from parameters including incident flux, beam energy, beam size, sample composition and sample size. In here, the use of dose is reintroduced for electron microscopy, accounting for the electron energy, incident flux and measured sample thickness and composition. Knowledge of the amount of energy deposited allowed us to compare doses with experimental limits in macromolecular X-ray crystallography, to obtain an upper estimate of radical concentrations that build up in the vitreous sample, and to translate heat-transfer simulations carried out for macromolecular X-ray crystallography to cryo-electron microscopy. Stroboscopic exposure series of 50–250 images were collected for different incident flux densities and integration times from Lumbricus terrestris extracellular hemoglobin. The images within each series were computationally aligned and analyzed with similarity metrics such as Fourier ring correlation, Fourier ring phase residual and figure of merit. Prior to gas bubble formation, the images become linearly brighter with dose, at a rate of approximately 0.1% per 10 MGy. The gradual decomposition of a vitrified hemoglobin sample could be visualized at a series of doses up to 5500 MGy, by which dose the sample was sublimed. Comparison of equal-dose series collected with different incident flux densities showed a dose-rate effect favoring lower flux densities. Heat simulations predict that sample heating will only become an issue for very large dose rates (50 e−Å−2 s−1 or higher) combined with poor thermal contact between the grid and cryo-holder. Secondary radiolytic effects are likely to play a role in dose-rate effects. Stroboscopic data collection

  11. A maximum entropy model for chromatin structure

    NASA Astrophysics Data System (ADS)

    Farre, Pau; Emberly, Eldon; Emberly Group Team

    The DNA inside the nucleus of eukaryotic cells shows a variety of conserved structures at different length scales These structures are formed by interactions between protein complexes that bind to the DNA and regulate gene activity. Recent high throughput sequencing techniques allow for the measurement both of the genome wide contact map of the folded DNA within a cell (HiC) and where various proteins are bound to the DNA (ChIP-seq). In this talk I will present a maximum-entropy method capable of both predicting HiC contact maps from binding data, and binding data from HiC contact maps. This method results in an intuitive Ising-type model that is able to predict how altering the presence of binding factors can modify chromosome conformation, without the need of polymer simulations.

  12. Dosimetric evaluation of the OneDoseTM MOSFET for measuring kilovoltage imaging dose from image-guided radiotherapy procedures.

    PubMed

    Ding, George X; Coffey, Charles W

    2010-09-01

    The purpose of this study is to investigate the feasibility of using a single-use dosimeter, OneDose MOSFET designed for in vivo patient dosimetry, for measuring the radiation dose from kilovoltage (kV) x rays resulting from image-guided procedures. The OneDose MOSFET dosimeters were precalibrated by the manufacturer using Co-60 beams. Their energy response and characteristics for kV x rays were investigated by using an ionization chamber, in which the air-kerma calibration factors were obtained from an Accredited Dosimetry Calibration Laboratory (ADCL). The dosimetric properties have been tested for typical kV beams used in image-guided radiation therapy (IGRT). The direct dose reading from the OneDose system needs to be multiplied by a correction factor ranging from 0.30 to 0.35 for kilovoltage x rays ranging from 50 to 125 kVp, respectively. In addition to energy response, the OneDose dosimeter has up to a 20% reduced sensitivity for beams (70-125 kVp) incident from the back of the OneDose detector. The uncertainty in measuring dose resulting from a kilovoltage beam used in IGRT is approximately 20%; this uncertainty is mainly due to the sensitivity dependence of the incident beam direction relative to the OneDose detector. The ease of use may allow the dosimeter to be suitable for estimating the dose resulting from image-guided procedures.

  13. Dose ratio proton radiography using the proximal side of the Bragg peak

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

    Doolan, P. J., E-mail: paul.doolan.09@ucl.ac.uk; Royle, G.; Gibson, A.

    with a square field equivalent size of 7.6 cm{sup 2}, for a required accuracy in the WET of 3 mm and a 1% noise level in the dose ratio image. The technique showed limited applicability for other patient sites. The CMOS APS demonstrated a good accuracy, with a root-mean-square-error of 1.6 mm WET. The noise in the measured images was found to be σ = 1.2% (standard deviation) and theoretical predictions with a 1.96σ noise level showed good agreement with the measured errors. Conclusions: After validating the theoretical approach with measurements, the authors have shown that the use of the proximal side of the Bragg peak when performing dose ratio imaging is feasible, and allows for a wider dynamic range than when using the distal side. The dynamic range available increases as the demand on the accuracy of the WET decreases. The technique can only be applied to clinical sites with small maximum WETs such as for pediatric brains.« less

  14. An Adaptive Staggered Dose Design for a Normal Endpoint.

    PubMed

    Wu, Joseph; Menon, Sandeep; Chang, Mark

    2015-01-01

    In a clinical trial where several doses are compared to a control, a multi-stage design that combines both the selection of the best dose and the confirmation of this selected dose is desirable. An example is the two-stage drop-the-losers or pick-the-winner design, where inferior doses are dropped after interim analysis. Selection of target dose(s) can be based on ranking of observed effects, hypothesis testing with adjustment for multiplicity, or other criteria at interim stages. A number of methods have been proposed and have made significant gains in trial efficiency. However, many of these designs started off with all doses with equal allocation and did not consider prioritizing the doses using existing dose-response information. We propose an adaptive staggered dose procedure that allows explicit prioritization of doses and applies error spending scheme that favors doses with assumed better responses. This design starts off with only a subset of the doses and adaptively adds new doses depending on interim results. Using simulation, we have shown that this design performs better in terms of increased statistical power than the drop-the-losers design given strong prior information of dose response.

  15. Radiobiological equivalent of low/high dose rate brachytherapy and evaluation of tumor and normal responses to the dose.

    PubMed

    Manimaran, S

    2007-06-01

    The aim of this study was to compare the biological equivalent of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy in terms of the more recent linear quadratic (LQ) model, which leads to theoretical estimation of biological equivalence. One of the key features of the LQ model is that it allows a more systematic radiobiological comparison between different types of treatment because the main parameters alpha/beta and micro are tissue-specific. Such comparisons also allow assessment of the likely change in the therapeutic ratio when switching between LDR and HDR treatments. The main application of LQ methodology, which focuses on by increasing the availability of remote afterloading units, has been to design fractionated HDR treatments that can replace existing LDR techniques. In this study, with LDR treatments (39 Gy in 48 h) equivalent to 11 fractions of HDR irradiation at the experimental level, there are increasing reports of reproducible animal models that may be used to investigate the biological basis of brachytherapy and to help confirm theoretical predictions. This is a timely development owing to the nonavailability of sufficient retrospective patient data analysis. It appears that HDR brachytherapy is likely to be a viable alternative to LDR only if it is delivered without a prohibitively large number of fractions (e.g., fewer than 11). With increased scientific understanding and technological capability, the prospect of a dose equivalent to HDR brachytherapy will allow greater utilization of the concepts discussed in this article.

  16. SU-E-T-609: Perturbation Effects of Pedicle Screws On Radiotherapy Dose Distributions

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

    Bar-Deroma, R; Borzov, E; Nevelsky, A

    2015-06-15

    Purpose: Radiation therapy in conjunction with surgical implant fixation is a common combined treatment in case of bone metastases. However, metal implants generally used in orthopedic implants perturb radiation dose distributions. Carbon-Fiber Reinforced (CFR) PEEK material has been recently introduced for production of intramedullary screws and plates. Gold powder can be added to the CFR-PEEK material in order to enhance visibility of the screws during intraoperative imaging procedures. In this work, we investigated the perturbation effects of the pedicle screws made of CFR-PEEK, CFR-PEEK with added gold powder (CFR-PEEK-AU) and Titanium (Ti) on radiotherapy dose distributions. Methods: Monte Carlo (MC)more » simulations were performed using the EGSnrc code package for 6MV beams with 10×10 fields at SSD=100cm. By means of MC simulations, dose distributions around titanium, CFR- PEEK and CFR-PEEK-AU screws (manufactured by Carbo-Fix Orthopedics LTD, Israel) placed in a water phantom were calculated. The screw axis was either parallel or perpendicular to the beam axis. Dose perturbation (relative to dose in homogeneous water phantom) was assessed. Results: Maximum overdose due to backscatter was 10% for the Ti screws, 5% for the CFR-PEEK-AU screws and effectively zero for the CFR-PEEK screws. Maximum underdose due to attenuation was 25% for the Ti screws, 15% for the CFR-PEEK-AU screws and 5% for the CFR-PEEK screws. Conclusion: Titanium screws introduce the largest distortion on the radiation dose distribution. The gold powder added to the CFR-PEEK material improves visibility at the cost of increased dose perturbation. CFR-PEEK screws caused minimal alteration on the dose distribution. This can decrease possible over and underdose of adjacent tissue and thus favorably influence treatment efficiency. The use of such implants has potential clinical advantage in the treatment of neoplastic bone disease.« less

  17. Model-based dose calculations for COMS eye plaque brachytherapy using an anatomically realistic eye phantom

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

    Lesperance, Marielle; Inglis-Whalen, M.; Thomson, R. M., E-mail: rthomson@physics.carleton.ca

    Purpose : To investigate the effects of the composition and geometry of ocular media and tissues surrounding the eye on dose distributions for COMS eye plaque brachytherapy with{sup 125}I, {sup 103}Pd, or {sup 131}Cs seeds, and to investigate doses to ocular structures. Methods : An anatomically and compositionally realistic voxelized eye model with a medial tumor is developed based on a literature review. Mass energy absorption and attenuation coefficients for ocular media are calculated. Radiation transport and dose deposition are simulated using the EGSnrc Monte Carlo user-code BrachyDose for a fully loaded COMS eye plaque within a water phantom andmore » our full eye model for the three radionuclides. A TG-43 simulation with the same seed configuration in a water phantom neglecting the plaque and interseed effects is also performed. The impact on dose distributions of varying tumor position, as well as tumor and surrounding tissue media is investigated. Each simulation and radionuclide is compared using isodose contours, dose volume histograms for the lens and tumor, maximum, minimum, and average doses to structures of interest, and doses to voxels of interest within the eye. Results : Mass energy absorption and attenuation coefficients of the ocular media differ from those of water by as much as 12% within the 20–30 keV photon energy range. For all radionuclides studied, average doses to the tumor and lens regions in the full eye model differ from those for the plaque in water by 8%–10% and 13%–14%, respectively; the average doses to the tumor and lens regions differ between the full eye model and the TG-43 simulation by 2%–17% and 29%–34%, respectively. Replacing the surrounding tissues in the eye model with water increases the maximum and average doses to the lens by 2% and 3%, respectively. Substituting the tumor medium in the eye model for water, soft tissue, or an alternate melanoma composition affects tumor dose compared to the default eye

  18. A method for converting dose-to-medium to dose-to-tissue in Monte Carlo studies of gold nanoparticle-enhanced radiotherapy

    NASA Astrophysics Data System (ADS)

    Koger, B.; Kirkby, C.

    2016-03-01

    Gold nanoparticles (GNPs) have shown potential in recent years as a means of therapeutic dose enhancement in radiation therapy. However, a major challenge in moving towards clinical implementation is the exact characterisation of the dose enhancement they provide. Monte Carlo studies attempt to explore this property, but they often face computational limitations when examining macroscopic scenarios. In this study, a method of converting dose from macroscopic simulations, where the medium is defined as a mixture containing both gold and tissue components, to a mean dose-to-tissue on a microscopic scale was established. Monte Carlo simulations were run for both explicitly-modeled GNPs in tissue and a homogeneous mixture of tissue and gold. A dose ratio was obtained for the conversion of dose scored in a mixture medium to dose-to-tissue in each case. Dose ratios varied from 0.69 to 1.04 for photon sources and 0.97 to 1.03 for electron sources. The dose ratio is highly dependent on the source energy as well as GNP diameter and concentration, though this effect is less pronounced for electron sources. By appropriately weighting the monoenergetic dose ratios obtained, the dose ratio for any arbitrary spectrum can be determined. This allows complex scenarios to be modeled accurately without explicitly simulating each individual GNP.

  19. Development of sustained and dual drug release co-extrusion formulations for individual dosing.

    PubMed

    Laukamp, Eva Julia; Vynckier, An-Katrien; Voorspoels, Jody; Thommes, Markus; Breitkreutz, Joerg

    2015-01-01

    In personalized medicine and patient-centered medical treatment individual dosing of medicines is crucial. The Solid Dosage Pen (SDP) allows for an individual dosing of solid drug carriers by cutting them into tablet-like slices. The aim of the present study was the development of sustained release and dual release formulations with carbamazepine (CBZ) via hot-melt co-extrusion for the use in the SDP. The selection of appropriate coat- and core-formulations was performed by adapting the mechanical properties (like tensile strength and E-modulus) for example. By using different excipients (polyethyleneglycols, poloxamers, white wax, stearic acid, and carnauba wax) and drug loadings (30-50%) tailored dissolution kinetics was achieved showing cube root or zero order release mechanisms. Besides a biphasic drug release, the dose-dependent dissolution characteristics of sustained release formulations were minimized by a co-extruded wax-coated formulation. The dissolution profiles of the co-extrudates were confirmed during short term stability study (six months at 21.0 ± 0.2 °C, 45%r.h.). Due to a good layer adhesion of core and coat and adequate mechanical properties (maximum cutting force of 35.8 ± 2.0 N and 26.4 ± 2.8 N and E-modulus of 118.1 ± 8.4 and 33.9 ± 4.5 MPa for the dual drug release and the wax-coated co-extrudates, respectively) cutting off doses via the SDP was precise. While differences of the process parameters (like the barrel temperature) between the core- and the coat-layer resulted in unsatisfying content uniformities for the wax-coated co-extrudates, the content uniformity of the dual drug release co-extrudates was found to be in compliance with pharmacopoeial specification. Copyright © 2015 Elsevier B.V. All rights reserved.

  20. Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations.

    PubMed

    Davidson, Scott E; Cui, Jing; Kry, Stephen; Deasy, Joseph O; Ibbott, Geoffrey S; Vicic, Milos; White, R Allen; Followill, David S

    2016-08-01

    A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who uses these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today's modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the data points tested. The model was

  1. Modification and validation of an analytical source model for external beam radiotherapy Monte Carlo dose calculations

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

    Davidson, Scott E., E-mail: sedavids@utmb.edu

    Purpose: A dose calculation tool, which combines the accuracy of the dose planning method (DPM) Monte Carlo code and the versatility of a practical analytical multisource model, which was previously reported has been improved and validated for the Varian 6 and 10 MV linear accelerators (linacs). The calculation tool can be used to calculate doses in advanced clinical application studies. One shortcoming of current clinical trials that report dose from patient plans is the lack of a standardized dose calculation methodology. Because commercial treatment planning systems (TPSs) have their own dose calculation algorithms and the clinical trial participant who usesmore » these systems is responsible for commissioning the beam model, variation exists in the reported calculated dose distributions. Today’s modern linac is manufactured to tight specifications so that variability within a linac model is quite low. The expectation is that a single dose calculation tool for a specific linac model can be used to accurately recalculate dose from patient plans that have been submitted to the clinical trial community from any institution. The calculation tool would provide for a more meaningful outcome analysis. Methods: The analytical source model was described by a primary point source, a secondary extra-focal source, and a contaminant electron source. Off-axis energy softening and fluence effects were also included. The additions of hyperbolic functions have been incorporated into the model to correct for the changes in output and in electron contamination with field size. A multileaf collimator (MLC) model is included to facilitate phantom and patient dose calculations. An offset to the MLC leaf positions was used to correct for the rudimentary assumed primary point source. Results: Dose calculations of the depth dose and profiles for field sizes 4 × 4 to 40 × 40 cm agree with measurement within 2% of the maximum dose or 2 mm distance to agreement (DTA) for 95% of the

  2. Using maximum topology matching to explore differences in species distribution models

    USGS Publications Warehouse

    Poco, Jorge; Doraiswamy, Harish; Talbert, Marian; Morisette, Jeffrey; Silva, Claudio

    2015-01-01

    Species distribution models (SDM) are used to help understand what drives the distribution of various plant and animal species. These models are typically high dimensional scalar functions, where the dimensions of the domain correspond to predictor variables of the model algorithm. Understanding and exploring the differences between models help ecologists understand areas where their data or understanding of the system is incomplete and will help guide further investigation in these regions. These differences can also indicate an important source of model to model uncertainty. However, it is cumbersome and often impractical to perform this analysis using existing tools, which allows for manual exploration of the models usually as 1-dimensional curves. In this paper, we propose a topology-based framework to help ecologists explore the differences in various SDMs directly in the high dimensional domain. In order to accomplish this, we introduce the concept of maximum topology matching that computes a locality-aware correspondence between similar extrema of two scalar functions. The matching is then used to compute the similarity between two functions. We also design a visualization interface that allows ecologists to explore SDMs using their topological features and to study the differences between pairs of models found using maximum topological matching. We demonstrate the utility of the proposed framework through several use cases using different data sets and report the feedback obtained from ecologists.

  3. Evaluation of pliers' grip spans in the maximum gripping task and sub-maximum cutting task.

    PubMed

    Kim, Dae-Min; Kong, Yong-Ku

    2016-12-01

    A total of 25 males participated to investigate the effects of the grip spans of pliers on the total grip force, individual finger forces and muscle activities in the maximum gripping task and wire-cutting tasks. In the maximum gripping task, results showed that the 50-mm grip span had significantly higher total grip strength than the other grip spans. In the cutting task, the 50-mm grip span also showed significantly higher grip strength than the 65-mm and 80-mm grip spans, whereas the muscle activities showed a higher value at 80-mm grip span. The ratios of cutting force to maximum grip strength were also investigated. Ratios of 30.3%, 31.3% and 41.3% were obtained by grip spans of 50-mm, 65-mm, and 80-mm, respectively. Thus, the 50-mm grip span for pliers might be recommended to provide maximum exertion in gripping tasks, as well as lower maximum-cutting force ratios in the cutting tasks.

  4. Control system for maximum use of adhesive forces of a railway vehicle in a tractive mode

    NASA Astrophysics Data System (ADS)

    Spiryagin, Maksym; Lee, Kwan Soo; Yoo, Hong Hee

    2008-04-01

    The realization of maximum adhesive forces for a railway vehicle is a very difficult process, because it involves using tractive efforts and depends on friction characteristics in the contact zone between wheels and rails. Tractive efforts are realized by means of tractive torques of motors, and their maximum values can provide negative effects such as slip and skid. These situations usually happen when information about friction conditions is lacking. The negative processes have a major influence on wearing of contact bodies and tractive units. Therefore, many existing control systems for vehicles use an effect of a prediction of a friction coefficient between wheels and rails because measuring a friction coefficient at the moment of running vehicle movement is very difficult. One of the ways to solve this task is to use noise spectrum analysis for friction coefficient detection. This noise phenomenon has not been clearly studied and analyzed. In this paper, we propose an adhesion control system of railway vehicles based on an observer, which allows one to determine the maximum tractive torque based on the optimal adhesive force between the wheels (wheel pair) of a railway vehicle and rails (rail track) depending on weight load from a wheel to a rail, friction conditions in the contact zone, a lateral displacement of wheel set and wheel sleep. As a result, it allows a railway vehicle to be driven in a tractive mode by the maximum adhesion force for real friction conditions.

  5. SU-F-T-428: An Optimization-Based Commissioning Tool for Finite Size Pencil Beam Dose Calculations

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

    Li, Y; Tian, Z; Song, T

    Purpose: Finite size pencil beam (FSPB) algorithms are commonly used to pre-calculate the beamlet dose distribution for IMRT treatment planning. FSPB commissioning, which usually requires fine tuning of the FSPB kernel parameters, is crucial to the dose calculation accuracy and hence the plan quality. Yet due to the large number of beamlets, FSPB commissioning could be very tedious. This abstract reports an optimization-based FSPB commissioning tool we have developed in MatLab to facilitate the commissioning. Methods: A FSPB dose kernel generally contains two types of parameters: the profile parameters determining the dose kernel shape, and a 2D scaling factors accountingmore » for the longitudinal and off-axis corrections. The former were fitted using the penumbra of a reference broad beam’s dose profile with Levenberg-Marquardt algorithm. Since the dose distribution of a broad beam is simply a linear superposition of the dose kernel of each beamlet calculated with the fitted profile parameters and scaled using the scaling factors, these factors could be determined by solving an optimization problem which minimizes the discrepancies between the calculated dose of broad beams and the reference dose. Results: We have commissioned a FSPB algorithm for three linac photon beams (6MV, 15MV and 6MVFFF). Dose of four field sizes (6*6cm2, 10*10cm2, 15*15cm2 and 20*20cm2) were calculated and compared with the reference dose exported from Eclipse TPS system. For depth dose curves, the differences are less than 1% of maximum dose after maximum dose depth for most cases. For lateral dose profiles, the differences are less than 2% of central dose at inner-beam regions. The differences of the output factors are within 1% for all the three beams. Conclusion: We have developed an optimization-based commissioning tool for FSPB algorithms to facilitate the commissioning, providing sufficient accuracy of beamlet dose calculation for IMRT optimization.« less

  6. Calculation of Absorbed Dose in Target Tissue and Equivalent Dose in Sensitive Tissues of Patients Treated by BNCT Using MCNP4C

    NASA Astrophysics Data System (ADS)

    Zamani, M.; Kasesaz, Y.; Khalafi, H.; Pooya, S. M. Hosseini

    Boron Neutron Capture Therapy (BNCT) is used for treatment of many diseases, including brain tumors, in many medical centers. In this method, a target area (e.g., head of patient) is irradiated by some optimized and suitable neutron fields such as research nuclear reactors. Aiming at protection of healthy tissues which are located in the vicinity of irradiated tissue, and based on the ALARA principle, it is required to prevent unnecessary exposure of these vital organs. In this study, by using numerical simulation method (MCNP4C Code), the absorbed dose in target tissue and the equiavalent dose in different sensitive tissues of a patiant treated by BNCT, are calculated. For this purpose, we have used the parameters of MIRD Standard Phantom. Equiavelent dose in 11 sensitive organs, located in the vicinity of target, and total equivalent dose in whole body, have been calculated. The results show that the absorbed dose in tumor and normal tissue of brain equal to 30.35 Gy and 0.19 Gy, respectively. Also, total equivalent dose in 11 sensitive organs, other than tumor and normal tissue of brain, is equal to 14 mGy. The maximum equivalent doses in organs, other than brain and tumor, appear to the tissues of lungs and thyroid and are equal to 7.35 mSv and 3.00 mSv, respectively.

  7. Peer Review for EPA’s Proposed Approaches to Inform the Derivation of a Maximum Contaminant Level Goal for Perchlorate in Drinking Water

    EPA Science Inventory

    EPA is developing approaches to inform the derivation of a Maximum Contaminant Level Goal (MCLG) for perchlorate in drinking water under the Safe Drinking Water Act. EPA previously conducted an independent, external, scientific peer review of the draft biologically-based dose-res...

  8. VirtualDose: a software for reporting organ doses from CT for adult and pediatric patients

    NASA Astrophysics Data System (ADS)

    Ding, Aiping; Gao, Yiming; Liu, Haikuan; Caracappa, Peter F.; Long, Daniel J.; Bolch, Wesley E.; Liu, Bob; Xu, X. George

    2015-07-01

    This paper describes the development and testing of VirtualDose—a software for reporting organ doses for adult and pediatric patients who undergo x-ray computed tomography (CT) examinations. The software is based on a comprehensive database of organ doses derived from Monte Carlo (MC) simulations involving a library of 25 anatomically realistic phantoms that represent patients of different ages, body sizes, body masses, and pregnant stages. Models of GE Lightspeed Pro 16 and Siemens SOMATOM Sensation 16 scanners were carefully validated for use in MC dose calculations. The software framework is designed with the ‘software as a service (SaaS)’ delivery concept under which multiple clients can access the web-based interface simultaneously from any computer without having to install software locally. The RESTful web service API also allows a third-party picture archiving and communication system software package to seamlessly integrate with VirtualDose’s functions. Software testing showed that VirtualDose was compatible with numerous operating systems including Windows, Linux, Apple OS X, and mobile and portable devices. The organ doses from VirtualDose were compared against those reported by CT-Expo and ImPACT—two dosimetry tools that were based on the stylized pediatric and adult patient models that were known to be anatomically simple. The organ doses reported by VirtualDose differed from those reported by CT-Expo and ImPACT by as much as 300% in some of the patient models. These results confirm the conclusion from past studies that differences in anatomical realism offered by stylized and voxel phantoms have caused significant discrepancies in CT dose estimations.

  9. Calibration of entrance dose measurement for an in vivo dosimetry programme.

    PubMed

    Ding, W; Patterson, W; Tremethick, L; Joseph, D

    1995-11-01

    An increasing number of cancer treatment centres are using in vivo dosimetry as a quality assurance tool for verifying dosimetry as either the entrance or exit surface of the patient undergoing external beam radiotherapy. Equipment is usually limited to either thermoluminescent dosimeters (TLD) or semiconductor detectors such as p-type diodes. The semiconductor detector is more popular than the TLD due to the major advantage of real time analysis of the actual dose delivered. If a discrepancy is observed between the calculated and the measured entrance dose, it is possible to eliminate several likely sources of errors by immediately verifying all treatment parameters. Five Scanditronix EDP-10 p-type diodes were investigated to determine their calibration and relevant correction factors for entrance dose measurements using a Victoreen White Water-RW3 tissue equivalent phantom and a 6 MV photon beam from a Varian Clinac 2100C linear accelerator. Correction factors were determined for individual diodes for the following parameters: source to surface distance (SSD), collimator size, wedge, plate (tray) and temperature. The directional dependence of diode response was also investigated. The SSD correction factor (CSSD) was found to increase by approximately 3% over the range of SSD from 80 to 130 cm. The correction factor for collimator size (Cfield) also varied by approximately 3% between 5 x 5 and 40 x 40 cm2. The wedge correction factor (Cwedge) and plate correction factor (Cplate) were found to be a function of collimator size. Over the range of measurement, these factors varied by a maximum of 1 and 1.5%, respectively. The Cplate variation between the solid and the drilled plates under the same irradiation conditions was a maximum of 2.4%. The diode sensitivity demonstrated an increase with temperature. A maximum of 2.5% variation for the directional dependence of diode response was observed for angle of +/- 60 degrees. In conclusion, in vivo dosimetry is an

  10. Dose optimization of contrast-enhanced carotid MR angiography.

    PubMed

    Unterweger, M; Froehlich, J M; Kubik-Huch, R A; Seifert, B; Birrer, M; Huber, T; Otto, R

    2005-09-01

    The purpose of this work was to compare the diagnostic performance of a single-contrast or a double-contrast dose of carotid contrast-enhanced MR angiography (MRA). One-hundred nineteen patients (mean age 65+/-14.4 years) underwent carotid contrast-enhanced MRA with a standardized protocol (repetition time/echo 3.73 ms/1.38 ms, flip-angle 25 degrees, acquisition-time 19 s, voxel size 1.2 x 1.2 x 0.9 mm3) on a 1.5-T scanner (Sonata, Siemens-Medical-Systems) using a neck phased-array coil. Contrast agent was administered intravenously at a rate of 3.0 ml/s, either as a single dose (n=57; 0.1 mmol/kg body weight) or as a double dose (n=62; 0.2 mmol/kg body weight) of meglumine gadoterate (0.5 M/l), followed by 30 ml saline. Qualitative image analysis was performed on maximum intensity projections using a five-point scale. Signal intensities were measured at three different vascular levels on both sides to assess the contrast-to-noise ratios (CNRs). Image quality was rated as good or excellent in all cases. A double dose did not influence the efficacy of carotid enhancement (CNR single dose 69.12+/-19.8; CNR double dose 70.01+/-20.7; p = 0.81) compared with a single dose. In both dose groups the mean CNRs were inversely related to bodyweight, despite adjusted contrast volumes (p=0.0005). Double-dose contrast-enhanced carotid MRA is not superior to single-dose MRA, as overall diagnostic performance and quantitative contrast enhancement are equal. Being more cost-efficient, a single-dose administration of contrast agent is recommended for MRA of the carotid arteries.

  11. An analysis of collegiate band directors' exposure to sound pressure levels

    NASA Astrophysics Data System (ADS)

    Roebuck, Nikole Moore

    Noise-induced hearing loss (NIHL) is a significant but unfortunate common occupational hazard. The purpose of the current study was to measure the magnitude of sound pressure levels generated within a collegiate band room and determine if those sound pressure levels are of a magnitude that exceeds the policy standards and recommendations of the Occupational Safety and Health Administration (OSHA), and the National Institute of Occupational Safety and Health (NIOSH). In addition, reverberation times were measured and analyzed in order to determine the appropriateness of acoustical conditions for the band rehearsal environment. Sound pressure measurements were taken from the rehearsal of seven collegiate marching bands. Single sample t test were conducted to compare the sound pressure levels of all bands to the noise exposure standards of OSHA and NIOSH. Multiple regression analysis were conducted and analyzed in order to determine the effect of the band room's conditions on the sound pressure levels and reverberation times. Time weighted averages (TWA), noise percentage doses, and peak levels were also collected. The mean Leq for all band directors was 90.5 dBA. The total accumulated noise percentage dose for all band directors was 77.6% of the maximum allowable daily noise dose under the OSHA standard. The total calculated TWA for all band directors was 88.2% of the maximum allowable daily noise dose under the OSHA standard. The total accumulated noise percentage dose for all band directors was 152.1% of the maximum allowable daily noise dose under the NIOSH standards, and the total calculated TWA for all band directors was 93dBA of the maximum allowable daily noise dose under the NIOSH standard. Multiple regression analysis revealed that the room volume, the level of acoustical treatment and the mean room reverberation time predicted 80% of the variance in sound pressure levels in this study.

  12. Real-time dose calculation and visualization for the proton therapy of ocular tumours

    NASA Astrophysics Data System (ADS)

    Pfeiffer, Karsten; Bendl, Rolf

    2001-03-01

    A new real-time dose calculation and visualization was developed as part of the new 3D treatment planning tool OCTOPUS for proton therapy of ocular tumours within a national research project together with the Hahn-Meitner Institut Berlin. The implementation resolves the common separation between parameter definition, dose calculation and evaluation and allows a direct examination of the expected dose distribution while adjusting the treatment parameters. The new tool allows the therapist to move the desired dose distribution under visual control in 3D to the appropriate place. The visualization of the resulting dose distribution as a 3D surface model, on any 2D slice or on the surface of specified ocular structures is done automatically when adapting parameters during the planning process. In addition, approximate dose volume histograms may be calculated with little extra time. The dose distribution is calculated and visualized in 200 ms with an accuracy of 6% for the 3D isodose surfaces and 8% for other objects. This paper discusses the advantages and limitations of this new approach.

  13. A quality assurance device for measuring afterloader performance and transit dose for nasobiliary high-dose-rate brachytherapy.

    PubMed

    Deufel, Christopher L; Mullins, John P; Zakhary, Mark J

    2018-05-17

    Nasobiliary high-dose-rate (HDR) brachytherapy has emerged as an effective tool to boost the radiation dose for patients with unresectable perihilar cholangiocarcinoma. This work describes a quality assurance (QA) tool for measuring the HDR afterloader's performance, including the transit dose, when the source wire travels through a tortuous nasobiliary catheter path. The nasobiliary QA device was designed to mimic the anatomical path of a nasobiliary catheter, including the nasal, stomach, duodenum, and bile duct loops. Two of these loops, the duodenum and bile duct loops, have adjustable radii of curvature, resulting in the ability to maximize stress on the source wire in transit. The device was used to measure the performance over time for the HDR afterloader and the differences between intraluminal catheter lots. An upper limit on the transit dose was also measured using radiochromic film and compared with a simple theoretical model. The QA device was capable of detecting performance variations among nasobiliary catheter lots and following radioactive source replacement. The transit dose from a nasobiliary treatment increased by up to one order of magnitude when the source wire encountered higher than normal friction. Three distinct travel speeds of the source wire were observed: 5.2, 17.4, and 54.7 cm/s. The maximum transit dose was 0.3 Gy at a radial distance of 5 mm from a 40.3 kU 192 Ir source. The source wire encounters substantially greater friction when it navigates through the nasobiliary brachytherapy catheter. A QA tool that mimics the nasal, stomach, duodenum, and bile duct loops may be used to evaluate transit dose and the afterloader's performance over time. Copyright © 2018 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

  14. SU-F-P-19: Fetal Dose Estimate for a High-Dose Fluoroscopy Guided Intervention Using Modern Data Tools

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

    Moirano, J

    Purpose: An accurate dose estimate is necessary for effective patient management after a fetal exposure. In the case of a high-dose exposure, it is critical to use all resources available in order to make the most accurate assessment of the fetal dose. This work will demonstrate a methodology for accurate fetal dose estimation using tools that have recently become available in many clinics, and show examples of best practices for collecting data and performing the fetal dose calculation. Methods: A fetal dose estimate calculation was performed using modern data collection tools to determine parameters for the calculation. The reference pointmore » air kerma as displayed by the fluoroscopic system was checked for accuracy. A cumulative dose incidence map and DICOM header mining were used to determine the displayed reference point air kerma. Corrections for attenuation caused by the patient table and pad were measured and applied in order to determine the peak skin dose. The position and depth of the fetus was determined by ultrasound imaging and consultation with a radiologist. The data collected was used to determine a normalized uterus dose from Monte Carlo simulation data. Fetal dose values from this process were compared to other accepted calculation methods. Results: An accurate high-dose fetal dose estimate was made. Comparison to accepted legacy methods were were within 35% of estimated values. Conclusion: Modern data collection and reporting methods ease the process for estimation of fetal dose from interventional fluoroscopy exposures. Many aspects of the calculation can now be quantified rather than estimated, which should allow for a more accurate estimation of fetal dose.« less

  15. 77 FR 5717 - National Organic Program; Proposed Amendment to the National List of Allowed and Prohibited...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-06

    ... Service 7 CFR Part 205 [Document Number AMS-NOP-11-0063; NOP-11-11PR] RIN 0581-AD18 National Organic... address a recommendation submitted to the Secretary of Agriculture (Secretary) by the National Organic... maximum levels currently allowed in organic poultry production after October 1, 2012. This proposed rule...

  16. Escalation to High Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease

    PubMed Central

    Triplett, Brandon M.; Kuttab, Hani I.; Kang, Guolian; Leung, Wing

    2015-01-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those utilized in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial, 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. There was no observed increase in toxicity until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10–100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, while those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (p=0.008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose escalation strategy remains unclear, as outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. PMID:26278046

  17. Use of microdose phenotyping to individualise dosing of patients.

    PubMed

    Hohmann, Nicolas; Haefeli, Walter E; Mikus, Gerd

    2015-09-01

    Administering the right amount of the right drug at the right time is a key mission of clinical medicine. This comprises dose adaptation according to a patient's intrinsic and extrinsic factors influencing drug disposition. Several biomarkers are available for dose adaptation; still, prediction of individual drug disposition may be improved. Phenotyping is the quantification of drug metabolism with probe substrates specific to drug-metabolising enzymes. This allows measurement of baseline metabolism and changes after modulation of drug metabolism. This article explores the concept of phenotyping using pharmacologically ineffective microdoses of probe substrates to obtain information on drug metabolism. Several probe drugs such as midazolam for cytochrome P450 3A have already been used, but validation of other microdosed probe drugs, analytical procedures and drug formulations still face some challenges that have to be overcome. Since microdosed probe drugs have no risk of adverse drug reactions or interference with therapy, more widespread use is possible. This allows drug-drug interaction data to be safely obtained during first-in-man studies, enhancing the clinical safety of human healthy volunteers and patients in clinical trials, and, most importantly, allows determination of the drug-metabolising phenotype in severely ill patients. With harmless probe drugs at hand quantifying drug metabolism and adapting the dose accordingly, a phenotyping-based dosing strategy could become reality, offering the possibility of individualised drug therapy with reduced adverse effects and fewer therapeutic failures.

  18. Toddlers' choice: Yo-Yoing diabetes control or deci-unit insulin dosing?

    PubMed

    Abul-Ainine, Sarah Aa; Abul-Ainine, Ahmad Aa

    2012-02-15

    While the incidence of toddlers' diabetes is soaring, their mainstay insulins were withdrawn, namely the weak 10% or 20% insulin mixtures (WIM), which were injected only once or twice daily. Consequently, toddlers are coerced to use an insulin pump, multi-dose insulin regime (MuDIR), mix or dilute insulins. This paper highlights the difficulties and proposes a simple solution. While an insulin pump is the best available option, it is not readily available for everyone. Mixing insulins is not sufficiently precise in small doses. Although diluting insulin would allow precise dosing and reduce the dose variability secondary to dribbling after injections, it, like insulin mixing, deprives children from using the pen and related child-friendly accessories. In MuDIR, we inject 4-5 small doses of insulin instead of 1-2 daily larger doses of WIM. Thus, on using a half unit (½unit) insulin pen, a dose of 0.5, 1, 1.5 and 2 units are adjusted in steps of 100%, 50%, 33% or 25%; unlike the advisable 5%-20%. This does not easily match the tiny erratic meals of grazing toddlers. Maternal anxiety peaks on watching yo-yoing glycemia. Carers have to accept either persistently high sugar or wild fluctuation. The risks of such poor glycemic pattern are increasingly recognized. Using insulin U20 in a ½unit disposable pen allows deci-unit dosing, with 5%-20% dose-tuning, greater accuracy on delivering small doses and reduction of dose variability from dribbling. Deci-unit dosing may help avoid wide glycemic swings and provide the affordable alternative to insulin pumps for toddlers. Deci-unit pen materializes the Human Rights of Children, a safer and effective treatment.

  19. Flight attendant radiation dose from solar particle events.

    PubMed

    Anderson, Jeri L; Mertens, Christopher J; Grajewski, Barbara; Luo, Lian; Tseng, Chih-Yu; Cassinelli, Rick T

    2014-08-01

    Research has suggested that work as a flight attendant may be related to increased risk for reproductive health effects. Air cabin exposures that may influence reproductive health include radiation dose from galactic cosmic radiation and solar particle events. This paper describes the assessment of radiation dose accrued during solar particle events as part of a reproductive health study of flight attendants. Solar storm data were obtained from the National Oceanic and Atmospheric Administration Space Weather Prediction Center list of solar proton events affecting the Earth environment to ascertain storms relevant to the two study periods (1992-1996 and 1999-2001). Radiation dose from exposure to solar energetic particles was estimated using the NAIRAS model in conjunction with galactic cosmic radiation dose calculated using the CARI-6P computer program. Seven solar particle events were determined to have potential for significant radiation exposure, two in the first study period and five in the second study period, and over-lapped with 24,807 flight segments. Absorbed (and effective) flight segment doses averaged 6.5 μGy (18 μSv) and 3.1 μGy (8.3 μSv) for the first and second study periods, respectively. Maximum doses were as high as 440 μGy (1.2 mSv) and 20 flight segments had doses greater than 190 μGy (0.5 mSv). During solar particle events, a pregnant flight attendant could potentially exceed the equivalent dose limit to the conceptus of 0.5 mSv in a month recommended by the National Council on Radiation Protection and Measurements.

  20. Patient Dose Management: Focus on Practical Actions

    PubMed Central

    2016-01-01

    Medical radiation is a very important part of modern medicine, and should be only used when needed and optimized. Justification and optimization of radiation examinations must be performed. The first step of reduction of medical exposure is to know the radiation dose in currently performed examinations. This review covers radiation units, how various imaging modalities report dose, and the current status of radiation dose reports and legislation. Also, practical tips that can be applied to clinical practice are introduced. Afterwards, the importance of radiology exposure related education is emphasized and the current status of education for medical personal and the public is explained, and appropriate education strategies are suggested. Commonly asked radiation dose related example questions and answers are provided in detail to allow medical personnel to answer patients. Lastly, we talk about computerized programs that can be used in medical facilities for managing patient dose. While patient dose monitoring and management should be used to decrease and optimize overall radiation dose, it should not be used to assess individual cancer risk. One must always remember that medically justified examinations should always be performed, and unneeded examinations should be avoided in the first place. PMID:26908988

  1. Effects of different strength training frequencies on maximum strength, body composition and functional capacity in healthy older individuals.

    PubMed

    Turpela, Mari; Häkkinen, Keijo; Haff, Guy Gregory; Walker, Simon

    2017-11-01

    There is controversy in the literature regarding the dose-response relationship of strength training in healthy older participants. The present study determined training frequency effects on maximum strength, muscle mass and functional capacity over 6months following an initial 3-month preparatory strength training period. One-hundred and six 64-75year old volunteers were randomly assigned to one of four groups; performing strength training one (EX1), two (EX2), or three (EX3) times per week and a non-training control (CON) group. Whole-body strength training was performed using 2-5 sets and 4-12 repetitions per exercise and 7-9 exercises per session. Before and after the intervention, maximum dynamic leg press (1-RM) and isometric knee extensor and plantarflexor strength, body composition and quadriceps cross-sectional area, as well as functional capacity (maximum 7.5m forward and backward walking speed, timed-up-and-go test, loaded 10-stair climb test) were measured. All experimental groups increased leg press 1-RM more than CON (EX1: 3±8%, EX2: 6±6%, EX3: 10±8%, CON: -3±6%, P<0.05) and EX3 improved more than EX1 (P=0.007) at month 9. Compared to CON, EX3 improved in backward walk (P=0.047) and EX1 in timed-up-and-go (P=0.029) tests. No significant changes occurred in body composition. The present study found no evidence that higher training frequency would induce greater benefit to maximum walking speed (i.e. functional capacity) despite a clear dose-response in dynamic 1-RM strength, at least when predominantly using machine weight-training. It appears that beneficial functional capacity improvements can be achieved through low frequency training (i.e. 1-2 times per week) in previously untrained healthy older participants. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Model-Based Dose Selection for Intravaginal Ring Formulations Releasing Anastrozole and Levonorgestrel Intended for the Treatment of Endometriosis Symptoms.

    PubMed

    Reinecke, Isabel; Schultze-Mosgau, Marcus-Hillert; Nave, Rüdiger; Schmitz, Heinz; Ploeger, Bart A

    2017-05-01

    Pharmacokinetics (PK) of anastrozole (ATZ) and levonorgestrel (LNG) released from an intravaginal ring (IVR) intended to treat endometriosis symptoms were characterized, and the exposure-response relationship focusing on the development of large ovarian follicle-like structures was investigated by modeling and simulation to support dose selection for further studies. A population PK analysis and simulations were performed for ATZ and LNG based on clinical phase 1 study data from 66 healthy women. A PK/PD model was developed to predict the probability of a maximum follicle size ≥30 mm and the potential contribution of ATZ beside the known LNG effects. Population PK models for ATZ and LNG were established where the interaction of LNG with sex hormone-binding globulin (SHBG) as well as a stimulating effect of estradiol on SHBG were considered. Furthermore, simulations showed that doses of 40 μg/d LNG combined with 300, 600, or 1050 μg/d ATZ reached anticipated exposure levels for both drugs, facilitating selection of ATZ and LNG doses in the phase 2 dose-finding study. The main driver for the effect on maximum follicle size appears to be unbound LNG exposure. A 50% probability of maximum follicle size ≥30 mm was estimated for 40 μg/d LNG based on the exposure-response analysis. ATZ in the dose range investigated does not increase the risk for ovarian cysts as occurs with LNG at a dose that does not inhibit ovulation. © 2016, The American College of Clinical Pharmacology.

  3. The radial distribution of cosmic rays in the heliosphere at solar maximum

    NASA Astrophysics Data System (ADS)

    McDonald, F. B.; Fujii, Z.; Heikkila, B.; Lal, N.

    2003-08-01

    To obtain a more detailed profile of the radial distribution of galactic (GCRs) and anomalous (ACRs) cosmic rays, a unique time in the 11-year solar activity cycle has been selected - that of solar maximum. At this time of minimum cosmic ray intensity a simple, straight-forward normalization technique has been found that allows the cosmic ray data from IMP 8, Pioneer 10 (P-10) and Voyagers 1 and 2 (V1, V2) to be combined for the solar maxima of cycles 21, 22 and 23. This combined distribution reveals a functional form of the radial gradient that varies as G 0/r with G 0 being constant and relatively small in the inner heliosphere. After a transition region between ˜10 and 20 AU, G 0 increases to a much larger value that remains constant between ˜25 and 82 AU. This implies that at solar maximum the changes that produce the 11-year modulation cycle are mainly occurring in the outer heliosphere between ˜15 AU and the termination shock. These observations are not inconsistent with the concept that Global Merged Interaction. regions (GMIRs) are the principal agent of modulation between solar minimum and solar maximum. There does not appear to be a significant change in the amount of heliosheath modulation occurring between the 1997 solar minimum and the cycle 23 solar maximum.

  4. Low-dose dacarbazine-doxorubicin therapy against intra-abdominal desmoid tumors.

    PubMed

    Yamamoto, Hirofumi; Oshiro, Ryota; Nishimura, Junichi; Uemura, Mamoru; Haraguchi, Naotsugu; Hata, Taishi; Takemasa, Ichiro; Mizushima, Tsunekazu; Sekimoto, Mitsugu; Doki, Yuichiro; Mori, Masaki

    2013-05-01

    Intra-abdominal desmoid tumor is a life-threatening disease. Studies have shown that dacarbazine (DTIC)-doxorubicin (DOX) (D-D) therapy is the most effective treatment. However, myelosuppression is a major problem, and cardiac muscle disorders due to DOX limit the number of administration cycles, whereas it usually requires a long time to achieve tumor shrinkage. To resolve these issues, we introduced low-dose D-D therapy to 3 patients employing 50 mg/m² DOX and 600-700 mg/m² DTIC per cycle, which permits repeated administration cycles up to 10-11 times. Case 1 was a 23-year-old female with a sporadic recurrent mesenterium desmoid tumor located in the pelvis (maximum diameter, 8 cm). Cases 2 and 3 were a 33-year-old female and a 36-year-old male. Both patients had intra-abdominal mesenterium desmoid tumors (maximum diameter 9.6 and 9.0 cm, respectively) that were generated after proctocolectomy due to familial adenomatous polyposis. No severe adverse events occurred during the therapy. With the aid of sulindac and tamoxifen after low-dose D-D therapy, the first two patients achieved a complete response, and the third patient achieved a partial response and awaits further tumor shrinkage. Our experience indicates that low-dose DT-D therapy is a safe and effective regimen for patients with intra-abdominal desmoid tumors.

  5. Radiologic Monitoring of Faculty and Staff in an Electrophysiology Lab Using a Real-Time Dose Monitoring System

    NASA Astrophysics Data System (ADS)

    Chardenet, Kathleen A.

    Purpose: A real-time dose management system was used to determine if radiation exposure levels would decrease when providers were privy to their real-time radiation exposure levels. Six aggregate categories of providers were first blinded (phase 1) and subsequently made aware of their radiation exposure levels during electrophysiology procedures (phase 2). Methods: A primary, quantitative crossover study of faculty and staff working in an electrophysiology lab at the University of Michigan Hospitals setting occurred. Participants in the control group was first blinded in phase 1 to their radiation exposure over an 10-week time period. The same group subsequently became the treatment group in phase 2 when over a second 10-week period real-time exposure levels were made available to them. Power analysis, using a 40% decrease in exposure, was calculated using a variance of radiation exposure equal to the mean radiation exposure with 80% power and alpha = .05. Calculations revealed 102 subjects in each treatment and control group were necessary. Results: Using the mixed effect linear model, a significant decrease in radiation levels occurred in phase 2 as compared to phase 1 for the operator role represented by the combined electrophysiologist-fellow role with a P value of .025. Exposure levels in all other provider groups for phase 1 or 2 failed to reach statistical significance. All dose values were low and well below the US maximum allowable yearly dose of 5,000 mrem per year. Conclusion: A real-time radiation dose monitoring system during electrophysiology procedures may significantly lower occupational radiation exposure in health care workers.

  6. Effect of radiance-to-reflectance transformation and atmosphere removal on maximum likelihood classification accuracy of high-dimensional remote sensing data

    NASA Technical Reports Server (NTRS)

    Hoffbeck, Joseph P.; Landgrebe, David A.

    1994-01-01

    Many analysis algorithms for high-dimensional remote sensing data require that the remotely sensed radiance spectra be transformed to approximate reflectance to allow comparison with a library of laboratory reflectance spectra. In maximum likelihood classification, however, the remotely sensed spectra are compared to training samples, thus a transformation to reflectance may or may not be helpful. The effect of several radiance-to-reflectance transformations on maximum likelihood classification accuracy is investigated in this paper. We show that the empirical line approach, LOWTRAN7, flat-field correction, single spectrum method, and internal average reflectance are all non-singular affine transformations, and that non-singular affine transformations have no effect on discriminant analysis feature extraction and maximum likelihood classification accuracy. (An affine transformation is a linear transformation with an optional offset.) Since the Atmosphere Removal Program (ATREM) and the log residue method are not affine transformations, experiments with Airborne Visible/Infrared Imaging Spectrometer (AVIRIS) data were conducted to determine the effect of these transformations on maximum likelihood classification accuracy. The average classification accuracy of the data transformed by ATREM and the log residue method was slightly less than the accuracy of the original radiance data. Since the radiance-to-reflectance transformations allow direct comparison of remotely sensed spectra with laboratory reflectance spectra, they can be quite useful in labeling the training samples required by maximum likelihood classification, but these transformations have only a slight effect or no effect at all on discriminant analysis and maximum likelihood classification accuracy.

  7. Using quality of life measures in a Phase I clinical trial of noni in patients with advanced cancer to select a Phase II dose.

    PubMed

    Issell, Brian F; Gotay, Carolyn C; Pagano, Ian; Franke, Adrian A

    2009-01-01

    ABSTRACT. The purpose of this study was to determine a maximum tolerated dose of noni in cancer patients and whether an optimal quality of life-sustaining dose could be identified as an alternative way to select a dose for subsequent Phase II efficacy trials. Dose levels started at two capsules twice daily (2 g), the suggested dose for the marketed product, and were escalated by 2 g daily in cohorts of at least five patients until a maximum tolerated dose was found. Patients completed subscales of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 quality of life (physical functioning, pain, and fatigue) the brief fatigue inventory (BFI), questionnaires at baseline and at approximately 4-week intervals. Blood and urine were collected at baseline and at approximately 4-week intervals for measurement of scopoletin. Fifty-one patients were enrolled at seven dose levels. The maximum tolerated dose was six capsules four times daily (12 g). Although no dose-limiting toxicity was found, seven of eight patients at the next level (14 g), withdrew due to the challenges of ingesting so many capsules. There were dose-related differences in self-reported physical functioning and pain and fatigue control. Overall, patients taking three or four capsules four times daily experienced better outcomes than patients taking lower or higher doses. Blood and urinary scopoletin concentrations related to noni dose. We concluded that it is feasible to use quality of life measures to select a Phase II dose. Three or four capsules four times daily (6-8 g) is recommended when controlling fatigue, pain, and maintaining physical function are the efficacies of interest. Scopoletin, a bioactive component of noni fruit extract, is measurable in blood and urine following noni ingestion and can be used to study the pharmacokinetics of noni in cancer patients.

  8. 5 CFR 1600.22 - Maximum contributions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Maximum contributions. 1600.22 Section... ELECTIONS AND CONTRIBUTION ALLOCATIONS Program of Contributions § 1600.22 Maximum contributions. (a) Regular...) FERS percentage limit. The maximum employee contribution from basic pay for a FERS participant for 2005...

  9. Analysis and Evaluation of Parameters Determining Maximum Efficiency of Fish Protection

    NASA Astrophysics Data System (ADS)

    Khetsuriani, E. D.; Kostyukov, V. P.; Khetsuriani, T. E.

    2017-11-01

    The article is concerned with experimental research findings. The efficiency of fish fry protection from entering water inlets is the main criterion of any fish protection facility or device. The research was aimed to determine an adequate mathematical model E = f(PCT, Vp, α), where PCT, Vp and α are controlled factors influencing the process of fish fry protection. The result of the processing of experimental data was an adequate regression model. We determined the maximum of fish protection Emax=94,21 and the minimum of optimization function Emin=44,41. As a result of the statistical processing of experimental data we obtained adequate dependences for determining an optimal rotational speed of tip and fish protection efficiency. The analysis of fish protection efficiency dependence E% = f(PCT, Vp, α) allowed the authors to recommend the following optimized operating modes for it: the maximum fish protection efficiency is achieved at the process pressure PCT=3 atm, stream velocity Vp=0,42 m/s and nozzle inclination angle α=47°49’. The stream velocity Vp has the most critical influence on fish protection efficiency. The maximum efficiency of fish protection is obtained at the tip rotational speed of 70.92 rpm.

  10. Use Dose Bricks Concept to Implement Nasopharyngeal Carcinoma Treatment Planning

    PubMed Central

    Wu, Jia-Ming; Yu, Tsan-Jung; Yeh, Shyh-An; Chao, Pei-Ju; Huang, Chih-Jou

    2014-01-01

    Purpose. A “dose bricks” concept has been used to implement nasopharyngeal carcinoma treatment plan; this method specializes particularly in the case with bell shape nasopharyngeal carcinoma case. Materials and Methods. Five noncoplanar fields were used to accomplish the dose bricks technique treatment plan. These five fields include (a) right superior anterior oblique (RSAO), (b) left superior anterior oblique (LSAO), (c) right anterior oblique (RAO), (d) left anterior oblique (LAO), and (e) superior inferior vertex (SIV). Nondivergence collimator central axis planes were used to create different abutting field edge while normal organs were blocked by multileaf collimators in this technique. Results. The resulting 92% isodose curves encompassed the CTV, while maximum dose was about 115%. Approximately 50% volume of parotid glands obtained 10–15% of total dose and 50% volume of brain obtained less than 20% of total dose. Spinal cord receives only 5% from the scatter dose. Conclusions. Compared with IMRT, the expenditure of planning time and costing, “dose bricks” may after all be accepted as an optional implementation in nasopharyngeal carcinoma conformal treatment plan; furthermore, this method also fits the need of other nonhead and neck lesions if organ sparing and noncoplanar technique can be executed. PMID:24967395

  11. In HFREF patients, sacubitril/valsartan, given at relatively low doses, does not lead to increased mortality or hospitalization : A retrospective cohort study.

    PubMed

    De Vecchis, R; Ariano, C; Di Biase, G; Noutsias, M

    2018-03-08

    In heart failure with reduced left ventricular ejection fraction (HFREF) patients, the dosage of sacubitril/valsartan is modulated according to a gradual increase regimen. Nevertheless, if patients exhibit tolerability problems, a provisional reduction of the dose of sacubitril/valsartan or even its interruption are recommended. This study provides estimates of respective proportions of patients receiving minimum or intermediate doses of sacubitril/valsartan. In addition, a comparison was made to detect possible differences regarding all-cause mortality and heart failure hospitalization in patients treated with the recommended optimum dose compared to those receiving submaximum maintenance doses of sacubitril/valsartan. Patients treated with sacubitril/valsartan in addition to beta-blocker and mineralocorticoid receptor blocker were 68. Among them, 20 patients (29.4%), were identified as having clinical features that were contraindications to the administration of sacubitril/valsartan at full dose. The subsequent decision was to maintain an intermediate dose in 11 patients and to reduce the dose to the minimum level allowed, i.e., 24 mg/26 mg twice daily in nine patients. After a median follow-up of 5.25 months, no differences were found concerning the risk of all-cause death by comparing patients treated with reduced versus those subjected to target doses of sacubitril/valsartan (odds ratio [OR] = 1.666; 95% confidence interval [CI] = 0.256-10.823; p = 0.6266). Patients taking reduced doses had a similar risk of heart failure hospitalizations when compared to patients treated with the target dose (OR = 0.789; 95% CI: 0.077-8.0808; p = 1.00). During a median follow-up of 5.25 months, in the group of patients who had proven to be intolerant to the maximum dose of sacubitril/valsartan, use of reduced doses of the drug did not result in increased all-cause mortality or heart failure hospitalization compared to patients treated with

  12. Probabilistic assessment method of the non-monotonic dose-responses-Part I: Methodological approach.

    PubMed

    Chevillotte, Grégoire; Bernard, Audrey; Varret, Clémence; Ballet, Pascal; Bodin, Laurent; Roudot, Alain-Claude

    2017-08-01

    More and more studies aim to characterize non-monotonic dose response curves (NMDRCs). The greatest difficulty is to assess the statistical plausibility of NMDRCs from previously conducted dose response studies. This difficulty is linked to the fact that these studies present (i) few doses tested, (ii) a low sample size per dose, and (iii) the absence of any raw data. In this study, we propose a new methodological approach to probabilistically characterize NMDRCs. The methodology is composed of three main steps: (i) sampling from summary data to cover all the possibilities that may be presented by the responses measured by dose and to obtain a new raw database, (ii) statistical analysis of each sampled dose-response curve to characterize the slopes and their signs, and (iii) characterization of these dose-response curves according to the variation of the sign in the slope. This method allows characterizing all types of dose-response curves and can be applied both to continuous data and to discrete data. The aim of this study is to present the general principle of this probabilistic method which allows to assess the non-monotonic dose responses curves, and to present some results. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Six steps to a successful dose-reduction strategy

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

    Bennett, M.

    1995-03-01

    The increased importance of demonstrating achievement of the ALARA principle has helped produce a proliferation of dose-reduction ideas. Across a company there may be many dose-reduction items being pursued in a variety of areas. However, companies have a limited amount of resource and, therefore, to ensure funding is directed to those items which will produce the most benefit and that all areas apply a common policy, requires the presence of a dose-reduction strategy. Six steps were identified in formulating the dose-reduction strategy for Rolls-Royce and Associates (RRA): (1) collating the ideas; (2) quantitatively evaluating them on a common basis; (3)more » prioritizing the ideas in terms of cost benefit, (4) implementation of the highest priority items; (5) monitoring their success; (6) periodically reviewing the strategy. Inherent in producing the dose-reduction strategy has been a comprehensive dose database and the RRA-developed dose management computer code DOMAIN, which allows prediction of dose rates and dose. The database enabled high task dose items to be identified, assisted in evaluating dose benefits, and monitored dose trends once items had been implemented. The DOMAIN code was used both in quantifying some of the project dose benefits and its results, such as dose contours, used in some of the dose-reduction items themselves. In all, over fifty dose-reduction items were evaluated in the strategy process and the items which will give greatest benefit are being implemented. The strategy has been successful in giving renewed impetus and direction to dose-reduction management.« less

  14. Beyond conventional dose-response curves: Sensorgram comparison in SPR allows single concentration activity and similarity assessment.

    PubMed

    Gassner, C; Karlsson, R; Lipsmeier, F; Moelleken, J

    2018-05-30

    Previously we have introduced two SPR-based assay principles (dual-binding assay and bridging assay), which allow the determination of two out of three possible interaction parameters for bispecific molecules within one assay setup: two individual interactions to both targets, and/or one simultaneous/overall interaction, which potentially reflects the inter-dependency of both individual binding events. However, activity and similarity are determined by comparing report points over a concentration range, which also mirrors the way data is generated by conventional ELISA-based methods So far, binding kinetics have not been specifically considered in generic approaches for activity assessment. Here, we introduce an improved slope-ratio model which, together with a sensorgram comparison based similarity assessment, allows the development of a detailed, USP-conformal ligand binding assay using only a single sample concentration. We compare this novel analysis method to the usual concentration-range approach for both SPR-based assay principles and discuss its impact on data quality and increased sample throughput. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Epidemiologic programs for computers and calculators. A microcomputer program for multiple logistic regression by unconditional and conditional maximum likelihood methods.

    PubMed

    Campos-Filho, N; Franco, E L

    1989-02-01

    A frequent procedure in matched case-control studies is to report results from the multivariate unmatched analyses if they do not differ substantially from the ones obtained after conditioning on the matching variables. Although conceptually simple, this rule requires that an extensive series of logistic regression models be evaluated by both the conditional and unconditional maximum likelihood methods. Most computer programs for logistic regression employ only one maximum likelihood method, which requires that the analyses be performed in separate steps. This paper describes a Pascal microcomputer (IBM PC) program that performs multiple logistic regression by both maximum likelihood estimation methods, which obviates the need for switching between programs to obtain relative risk estimates from both matched and unmatched analyses. The program calculates most standard statistics and allows factoring of categorical or continuous variables by two distinct methods of contrast. A built-in, descriptive statistics option allows the user to inspect the distribution of cases and controls across categories of any given variable.

  16. Applications of non-standard maximum likelihood techniques in energy and resource economics

    NASA Astrophysics Data System (ADS)

    Moeltner, Klaus

    Two important types of non-standard maximum likelihood techniques, Simulated Maximum Likelihood (SML) and Pseudo-Maximum Likelihood (PML), have only recently found consideration in the applied economic literature. The objective of this thesis is to demonstrate how these methods can be successfully employed in the analysis of energy and resource models. Chapter I focuses on SML. It constitutes the first application of this technique in the field of energy economics. The framework is as follows: Surveys on the cost of power outages to commercial and industrial customers usually capture multiple observations on the dependent variable for a given firm. The resulting pooled data set is censored and exhibits cross-sectional heterogeneity. We propose a model that addresses these issues by allowing regression coefficients to vary randomly across respondents and by using the Geweke-Hajivassiliou-Keane simulator and Halton sequences to estimate high-order cumulative distribution terms. This adjustment requires the use of SML in the estimation process. Our framework allows for a more comprehensive analysis of outage costs than existing models, which rely on the assumptions of parameter constancy and cross-sectional homogeneity. Our results strongly reject both of these restrictions. The central topic of the second Chapter is the use of PML, a robust estimation technique, in count data analysis of visitor demand for a system of recreation sites. PML has been popular with researchers in this context, since it guards against many types of mis-specification errors. We demonstrate, however, that estimation results will generally be biased even if derived through PML if the recreation model is based on aggregate, or zonal data. To countervail this problem, we propose a zonal model of recreation that captures some of the underlying heterogeneity of individual visitors by incorporating distributional information on per-capita income into the aggregate demand function. This adjustment

  17. 20 CFR 229.48 - Family maximum.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Family maximum. 229.48 Section 229.48... OVERALL MINIMUM GUARANTEE Computation of the Overall Minimum Rate § 229.48 Family maximum. (a) Family... month on one person's earnings record is limited. This limited amount is called the family maximum. The...

  18. 49 CFR 107.329 - Maximum penalties.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... maximum civil penalty is $110,000 if the violation results in death, serious illness or severe injury to... 49 Transportation 2 2012-10-01 2012-10-01 false Maximum penalties. 107.329 Section 107.329... PROGRAM PROCEDURES Enforcement Compliance Orders and Civil Penalties § 107.329 Maximum penalties. (a) A...

  19. 49 CFR 107.329 - Maximum penalties.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... maximum civil penalty is $110,000 if the violation results in death, serious illness or severe injury to... 49 Transportation 2 2010-10-01 2010-10-01 false Maximum penalties. 107.329 Section 107.329... PROGRAM PROCEDURES Enforcement Compliance Orders and Civil Penalties § 107.329 Maximum penalties. (a) A...

  20. 49 CFR 107.329 - Maximum penalties.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... maximum civil penalty is $110,000 if the violation results in death, serious illness or severe injury to... 49 Transportation 2 2011-10-01 2011-10-01 false Maximum penalties. 107.329 Section 107.329... PROGRAM PROCEDURES Enforcement Compliance Orders and Civil Penalties § 107.329 Maximum penalties. (a) A...

  1. A step-up test procedure to find the minimum effective dose.

    PubMed

    Wang, Weizhen; Peng, Jianan

    2015-01-01

    It is of great interest to find the minimum effective dose (MED) in dose-response studies. A sequence of decreasing null hypotheses to find the MED is formulated under the assumption of nondecreasing dose response means. A step-up multiple test procedure that controls the familywise error rate (FWER) is constructed based on the maximum likelihood estimators for the monotone normal means. When the MED is equal to one, the proposed test is uniformly more powerful than Hsu and Berger's test (1999). Also, a simulation study shows a substantial power improvement for the proposed test over four competitors. Three R-codes are provided in Supplemental Materials for this article. Go to the publishers online edition of Journal of Biopharmaceutical Statistics to view the files.

  2. Reduced Radiation Dose with Model-based Iterative Reconstruction versus Standard Dose with Adaptive Statistical Iterative Reconstruction in Abdominal CT for Diagnosis of Acute Renal Colic.

    PubMed

    Fontarensky, Mikael; Alfidja, Agaïcha; Perignon, Renan; Schoenig, Arnaud; Perrier, Christophe; Mulliez, Aurélien; Guy, Laurent; Boyer, Louis

    2015-07-01

    To evaluate the accuracy of reduced-dose abdominal computed tomographic (CT) imaging by using a new generation model-based iterative reconstruction (MBIR) to diagnose acute renal colic compared with a standard-dose abdominal CT with 50% adaptive statistical iterative reconstruction (ASIR). This institutional review board-approved prospective study included 118 patients with symptoms of acute renal colic who underwent the following two successive CT examinations: standard-dose ASIR 50% and reduced-dose MBIR. Two radiologists independently reviewed both CT examinations for presence or absence of renal calculi, differential diagnoses, and associated abnormalities. The imaging findings, radiation dose estimates, and image quality of the two CT reconstruction methods were compared. Concordance was evaluated by κ coefficient, and descriptive statistics and t test were used for statistical analysis. Intraobserver correlation was 100% for the diagnosis of renal calculi (κ = 1). Renal calculus (τ = 98.7%; κ = 0.97) and obstructive upper urinary tract disease (τ = 98.16%; κ = 0.95) were detected, and differential or alternative diagnosis was performed (τ = 98.87% κ = 0.95). MBIR allowed a dose reduction of 84% versus standard-dose ASIR 50% (mean volume CT dose index, 1.7 mGy ± 0.8 [standard deviation] vs 10.9 mGy ± 4.6; mean size-specific dose estimate, 2.2 mGy ± 0.7 vs 13.7 mGy ± 3.9; P < .001) without a conspicuous deterioration in image quality (reduced-dose MBIR vs ASIR 50% mean scores, 3.83 ± 0.49 vs 3.92 ± 0.27, respectively; P = .32) or increase in noise (reduced-dose MBIR vs ASIR 50% mean, respectively, 18.36 HU ± 2.53 vs 17.40 HU ± 3.42). Its main drawback remains the long time required for reconstruction (mean, 40 minutes). A reduced-dose protocol with MBIR allowed a dose reduction of 84% without increasing noise and without an conspicuous deterioration in image quality in patients suspected of having renal colic.

  3. Dose finding study of granisetron in patients receiving high-dose cisplatin chemotherapy. The Granisetron Study Group.

    PubMed Central

    Riviere, A.

    1994-01-01

    The efficacy and safety of three different doses of granisetron (2 micrograms kg-1, group A; 10 micrograms kg-1, group B; 40 micrograms kg-1, group C) were compared in a randomised, double-blind study of 157 patients due to receive high-dose cisplatin therapy (mean dose > 97 mg m-2). In each group, up to two 3 mg rescue doses of granisetron were allowed if more than mild nausea or vomiting occurred. In group A 30.8%, in group B 61.5% and in group C 67.9% of patients were complete responders (i.e. no vomiting or nothing worse than mild nausea) during the first 24 h. These differences are significant between groups A and B, and A and C. There were no statistically significant differences in any efficacy variable between the 10 micrograms kg-1 and 40 micrograms kg-1 groups, although in each case the trend favoured the higher dose. Additional rescue doses resulted in resolved or improved symptoms in 95.3% for the first rescue dose and 93.3% for the second. Over the 7 days of the study, 82.7%, 82.7% and 86.8% of patients in groups A, B and C respectively were treated with granisetron alone. Headache was the most common side-effect, reported by 9.6% of patients; the majority of headaches were mild. There was no difference between the treatment groups regarding the adverse event rate. We concluded that prophylactic doses of 10 or 40 micrograms kg-1 lead to a safe and satisfactory degree of control of nausea and vomiting induced by high-dose cisplatin. PMID:8180032

  4. 34 CFR 674.12 - Loan maximums.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false Loan maximums. 674.12 Section 674.12 Education..., DEPARTMENT OF EDUCATION FEDERAL PERKINS LOAN PROGRAM General Provisions § 674.12 Loan maximums. (a) The maximum annual amount of Federal Perkins Loans and NDSLs an eligible student may borrow is— (1) $5,500 for...

  5. 49 CFR 190.223 - Maximum penalties.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 3 2010-10-01 2010-10-01 false Maximum penalties. 190.223 Section 190.223... PROCEDURES Enforcement Civil Penalties § 190.223 Maximum penalties. (a) Any person who is determined to have... except that the maximum civil penalty may not exceed $1,000,000 for any related series of violations. (b...

  6. 14 CFR 1261.102 - Maximum amount.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Maximum amount. 1261.102 Section 1261.102...) Employees' Personal Property Claims § 1261.102 Maximum amount. From October 1, 1982, to October 30, 1988, the maximum amount that may be paid under the Military Personnel and Civilian Employees' Claim Act of...

  7. RADIANCE: An automated, enterprise-wide solution for archiving and reporting CT radiation dose estimates.

    PubMed

    Cook, Tessa S; Zimmerman, Stefan L; Steingall, Scott R; Maidment, Andrew D A; Kim, Woojin; Boonn, William W

    2011-01-01

    There is growing interest in the ability to monitor, track, and report exposure to radiation from medical imaging. Historically, however, dose information has been stored on an image-based dose sheet, an arrangement that precludes widespread indexing. Although scanner manufacturers are beginning to include dose-related parameters in the Digital Imaging and Communications in Medicine (DICOM) headers of imaging studies, there remains a vast repository of retrospective computed tomographic (CT) data with image-based dose sheets. Consequently, it is difficult for imaging centers to monitor their dose estimates or participate in the American College of Radiology (ACR) Dose Index Registry. An automated extraction software pipeline known as Radiation Dose Intelligent Analytics for CT Examinations (RADIANCE) has been designed that quickly and accurately parses CT dose sheets to extract and archive dose-related parameters. Optical character recognition of information in the dose sheet leads to creation of a text file, which along with the DICOM study header is parsed to extract dose-related data. The data are then stored in a relational database that can be queried for dose monitoring and report creation. RADIANCE allows efficient dose analysis of CT examinations and more effective education of technologists, radiologists, and referring physicians regarding patient exposure to radiation at CT. RADIANCE also allows compliance with the ACR's dose reporting guidelines and greater awareness of patient radiation dose, ultimately resulting in improved patient care and treatment.

  8. 20 CFR 211.14 - Maximum creditable compensation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Maximum creditable compensation. 211.14... CREDITABLE RAILROAD COMPENSATION § 211.14 Maximum creditable compensation. Maximum creditable compensation for calendar years after 1984 is the maximum annual taxable wage base defined in section 3231(e)(2)(B...

  9. CORRELATION OF LOCAL FAILURE WITH MEASURES OF DOSE INSUFFICIENCY IN THE HIGH-DOSE SINGLE-FRACTION TREATMENT OF BONY METASTASES

    PubMed Central

    Lovelock, D. Michael; Zhang, Zhigang; Jackson, Andrew; Keam, Jennifer; Bekelman, Justin; Bilsky, Mark; Lis, Eric; Yamada, Yoshiya

    2011-01-01

    Purpose In the setting of high-dose single-fraction image-guided radiotherapy of spine metastases, the delivered dose is hypothesized to be a significant factor in local control. We investigated the dependence of local control on measures of dose insufficiency. Methods and Materials The minimum doses received by the hottest 100%, 98%, and 95% (Dmin, D98, and D95) of the gross target volume (GTV) were computed for 91 consecutively treated lesions observed in 79 patients. Prescribed doses of 18–24 Gy were delivered in a single fraction. The spinal cord and cauda equina were constrained to a maximum dose of 12–14 Gy and 16 Gy, respectively. A rank-sum test was used to assess the differences between radiographic local failure and local control. Results With a median follow-up of 18 months, seven local failures have occurred. The distributions of GTV Dmin, D98, and D95 for treatments resulting in local failure were found to be statistically different from the corresponding distributions of the patient group as a whole. Taking no account of histology, p values calculated for Dmin, D98, and D95 were 0.004, 0.012, and 0.031, respectively. No correlations between local failure and target volume or between local failure and anatomic location were found. Conclusions The results indicate that Dmin, D98, and D95 may be important risk factors for local failure. No local failures in any histology were observed when Dmin was >15 Gy, suggesting that this metric may be an important predictor of local control. PMID:20350795

  10. 33 CFR 401.29 - Maximum draft.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Maximum draft. 401.29 Section 401... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.29 Maximum draft. (a) The draft...) The draft of a vessel shall not, in any case, exceed 79.2 dm or the maximum permissible draft...

  11. 33 CFR 401.29 - Maximum draft.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Maximum draft. 401.29 Section 401... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.29 Maximum draft. (a) The draft...) The draft of a vessel shall not, in any case, exceed 79.2 dm or the maximum permissible draft...

  12. 33 CFR 401.29 - Maximum draft.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Maximum draft. 401.29 Section 401... TRANSPORTATION SEAWAY REGULATIONS AND RULES Regulations Seaway Navigation § 401.29 Maximum draft. (a) The draft...) The draft of a vessel shall not, in any case, exceed 79.2 dm or the maximum permissible draft...

  13. Retention of ion-implanted-xenon in olivine: Dependence on implantation dose

    NASA Technical Reports Server (NTRS)

    Melcher, C. L.; Tombrello, T. A.; Burnett, D. S.

    1982-01-01

    The diffusion of Xe in olivine, a major mineral in both meteorites and lunar samples, was studied. Xe ions were implanted at 200 keV into single-crystal synthetic-forsterite targets and the depth profiles were measured by alpha particle backscattering before and after annealing for 1 hour at temperatures up to 1500 C. The fraction of implanted Xe retained following annealing was strongly dependent on the implantation dose. Maximum retention of 100% occurred for an implantion dose of 3 x 10 to the 15th power Xe ions/sq cm. Retention was less at lower doses, with (approximately more than or = 50% loss at one hundred trillion Xe ions/sq cm. Taking the diffusion coefficient at this dose as a lower limit, the minimum activation energy necessary for Xe retention in a 10 micrometer layer for ten million years was calculated as a function of metamorphic temperature.

  14. ALL-PATHWAYS DOSE ANALYSIS FOR THE PORTSMOUTH ON-SITE WASTE DISPOSAL FACILITY

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

    Smith, F.; Phifer, M.

    A Portsmouth On-Site Waste Disposal Facility (OSWDF) All-Pathways analysis has been conducted that considers the radiological impacts to a resident farmer. It is assumed that the resident farmer utilizes a farm pond contaminated by the OSWDF to irrigate a garden and pasture and water livestock from which food for the resident farmer is obtained, and that the farmer utilizes groundwater from the Berea sandstone aquifer for domestic purposes (i.e. drinking water and showering). As described by FBP 2014b the Hydrologic Evaluation of Landfill Performance (HELP) model (Schroeder et al. 1994) and the Surface Transport Over Multiple Phases (STOMP) model (Whitemore » and Oostrom 2000, 2006) were used to model the flow and transport from the OSWDF to the Points of Assessment (POAs) associated with the 680-ft elevation sandstone layer (680 SSL) and the Berea sandstone aquifer. From this modeling the activity concentrations radionuclides were projected over time at the POAs. The activity concentrations were utilized as input to a GoldSimTM (GTG 2010) dose model, described herein, in order to project the dose to a resident farmer over time. A base case and five sensitivity cases were analyzed. The sensitivity cases included an evaluation of the impacts of using a conservative inventory, an uncased well to the Berea sandstone aquifer, a low waste zone uranium distribution coefficient (Kd), different transfer factors, and reference person exposure parameters (i.e. at 95 percentile). The maximum base case dose within the 1,000 year assessment period was projected to be 1.5E-14 mrem/yr, and the maximum base case dose at any time less than 10,000 years was projected to be 0.002 mrem/yr. The maximum projected dose of any sensitivity case was approximately 2.6 mrem/yr associated with the use of an uncased well to the Berea sandstone aquifer. This sensitivity case is considered very unlikely because it assumes leakage from the location of greatest concentration in the 680 SSL in to

  15. Escalation to High-Dose Defibrotide in Patients with Hepatic Veno-Occlusive Disease.

    PubMed

    Triplett, Brandon M; Kuttab, Hani I; Kang, Guolian; Leung, Wing

    2015-12-01

    Hepatic veno-occlusive disease (VOD) is a serious complication of high-dose chemotherapy regimens, such as those used in hematopoietic cell transplantation recipients. Defibrotide is considered a safe and effective treatment when dosed at 25 mg/kg/day. However, patients who develop VOD still have increased mortality despite the use of defibrotide. Data are limited on the use of doses above 60 mg/kg/day for persistent VOD. In this prospective clinical trial 34 patients received escalating doses of defibrotide. For patients with persistent VOD despite doses of 60 mg/kg/day, doses were increased to a maximum of 110 mg/kg/day. Increased toxicity was not observed until doses rose beyond 100 mg/kg/day. Patients receiving doses between 10 and 100 mg/kg/day experienced an average of 3 bleeding episodes per 100 days of treatment, whereas those receiving doses >100 mg/kg/day experienced 13.2 bleeding episodes per 100 days (P = .008). Moreover, dose reductions due to toxicity were needed at doses of 110 mg/kg/day more often than at lower doses. Defibrotide may be safely escalated to doses well above the current standard without an increase in bleeding risk. However, the efficacy of this dose-escalation strategy remains unclear, because outcomes were similar to published cohorts of patients receiving standard doses of defibrotide for VOD. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  16. 24 CFR 941.306 - Maximum project cost.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 4 2012-04-01 2012-04-01 false Maximum project cost. 941.306... DEVELOPMENT PUBLIC HOUSING DEVELOPMENT Application and Proposal § 941.306 Maximum project cost. (a) Calculation of maximum project cost. The maximum project cost represents the total amount of public housing...

  17. 24 CFR 941.306 - Maximum project cost.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 24 Housing and Urban Development 4 2013-04-01 2013-04-01 false Maximum project cost. 941.306... DEVELOPMENT PUBLIC HOUSING DEVELOPMENT Application and Proposal § 941.306 Maximum project cost. (a) Calculation of maximum project cost. The maximum project cost represents the total amount of public housing...

  18. 20 CFR 226.51 - Maximum monthly amount.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 1 2010-04-01 2010-04-01 false Maximum monthly amount. 226.51 Section 226.51... EMPLOYEE, SPOUSE, AND DIVORCED SPOUSE ANNUITIES Railroad Retirement Family Maximum § 226.51 Maximum monthly amount. The railroad retirement family maximum is equal to an employee's “final average monthly...

  19. Low-dose thiopurine with allopurinol co-therapy overcomes thiopurine intolerance and allows thiopurine continuation in inflammatory bowel disease.

    PubMed

    Vasudevan, Abhinav; Beswick, Lauren; Friedman, Antony B; Moltzen, Alicia; Haridy, James; Raghunath, Ajay; Sparrow, Miles; van Langenberg, Daniel

    2018-02-10

    To assess the utility and tolerability of thiopurine-allopurinol co-therapy in inflammatory bowel disease (IBD) patients with intolerance to thiopurine monotherapy. A retrospective observational study assessed cases of thiopurine intolerance then switched to thiopurine allopurinol co-therapy between 2011 and 2015 at two centres. Indications for switch, dosing and subsequent clinical outcomes (including thiopurine persistence) were recorded. Of 767 patients on thiopurines for IBD, 89 (12%) were switched to co-therapy for intolerance. 64/89 (72%) had Crohn's disease, 38 (43%) were males, median age at switch was 40y (range 17-78), median IBD duration 6y (0-29). Median follow-up was 1.9y (0-5). Reasons for switching to co-therapy included fatigue (37%), hepatotoxicity (23%), nausea (23%), arthralgia (10%), headache (12%) and hypersensitivity reaction (4%). Overall, 66 (74%) patients remained on co-therapy until most recent review and achieved a clinical response. High rates of overcoming intolerance (62-100%) occurred with co-therapy for all reasons above, although fatigue was less amenable to switching than non-fatigue indications (62% vs 91%, p = <0.001). Of 34 patients not escalated to biologics with endoscopic data, 15 were in remission (44%) at most recent review. Low-dose thiopurine combined with allopurinol appears safe and effective in overcoming intolerances to thiopurine monotherapy in many cases. Copyright © 2018. Published by Elsevier Ltd.

  20. Using machine learning to model dose-response relationships.

    PubMed

    Linden, Ariel; Yarnold, Paul R; Nallamothu, Brahmajee K

    2016-12-01

    Establishing the relationship between various doses of an exposure and a response variable is integral to many studies in health care. Linear parametric models, widely used for estimating dose-response relationships, have several limitations. This paper employs the optimal discriminant analysis (ODA) machine-learning algorithm to determine the degree to which exposure dose can be distinguished based on the distribution of the response variable. By framing the dose-response relationship as a classification problem, machine learning can provide the same functionality as conventional models, but can additionally make individual-level predictions, which may be helpful in practical applications like establishing responsiveness to prescribed drug regimens. Using data from a study measuring the responses of blood flow in the forearm to the intra-arterial administration of isoproterenol (separately for 9 black and 13 white men, and pooled), we compare the results estimated from a generalized estimating equations (GEE) model with those estimated using ODA. Generalized estimating equations and ODA both identified many statistically significant dose-response relationships, separately by race and for pooled data. Post hoc comparisons between doses indicated ODA (based on exact P values) was consistently more conservative than GEE (based on estimated P values). Compared with ODA, GEE produced twice as many instances of paradoxical confounding (findings from analysis of pooled data that are inconsistent with findings from analyses stratified by race). Given its unique advantages and greater analytic flexibility, maximum-accuracy machine-learning methods like ODA should be considered as the primary analytic approach in dose-response applications. © 2016 John Wiley & Sons, Ltd.