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C K Ross

Publications and source records attributed to C K Ross.

At least 19 recordsLinked to original sources
PubMed2004

Commissioning of an NRC-type sealed water calorimeter at METAS using 60Co gamma-rays.

As part of a collaborative project between the National Research Council of Canada (NRC) and the Swiss Federal Office of Metrology and Accreditation (METAS), a sealed water calorimeter was built at NRC and transferred to METAS. The calorimeter is operated at 4 degrees C and uses two thermistor probes in a sealed glass vessel containing high-purity water to measure the radiation-induced temperature rise. The various correction factors have been evaluated and the estimated standard uncertainty on the absorbed dose to water is 0.41%. An extensive set of measurements using 60Co gamma-rays was carried out at NRC and two ionization chambers were calibrated against the absorbed dose determined calorimetrically. The chambers were also calibrated against the NRC standard for absorbed dose. After transferring the calorimeter to METAS, a similar set of measurements was carried out using their 60Co beam and the same two ionization chambers were calibrated against the absorbed dose to water established at METAS. The discrepancy between the three sets of calibration coefficients was smaller than the estimated standard uncertainty of 0.47% on the ratio of any pair of calibration coefficients.

Calibration↗
PubMed2003

The response of lif thermoluminescence dosemeters to photon beams in the energy range from 30 kV x rays to 60Co gamma rays.

The energy response of standard (TLD-100) and high-sensitivity (TLD-100H) LiF thermoluminescence dosemeters (TLDs) has been studied for photon beams with mean energies from about 25 keV to 1100 keV. Canadian primary standards for air kerma were used to establish the air kerma rates for each of the photon beams. TLDs were mounted in a PMMA holder and the air kerma response was measured as a function of energy. The EGSnrc Monte Carlo code was used to model the TLD holder and calculate the absorbed dose to the TLD chip per unit air kerma for each beam. The measured and calculated results were combined to obtain the intrinsic dose response of the TLD chip. Broadly, our results are consistent with existing data, which show a marked difference in the energy dependence of the two materials. However, the precision of our measurements (standard uncertainty of about 0.6%) has permitted the identification of features that have not been noted before. In particular, the energy dependence of the two materials is quite different in the important energy region delimited by 137Cs and 60Co gamma rays.

Calibration↗
PubMed2002

The effect of wall thickness on the response of a spherical ionization chamber.

Air-filled ionization chambers are used widely for radiation dosimetry. For some applications it is important to know the effect on the chamber response of photon attenuation and scattering in the chamber walls. Traditionally, the wall effect is determined by measuring the chamber response as a function of wall thickness and extrapolating linearly to zero thickness. We have constructed a spherical graphite chamber with variable wall thickness. The change in the chamber response with wall thickness has been measured in a 137Cs gamma-ray beam. Our data show that the change in response is not linear with wall thickness, in agreement with the theoretical prediction of Bielajew (1990 Med. Phys. 17 583-7). A linear versus non-linear extrapolation of the measured data to zero wall thickness leads to a difference of almost 1% in the estimate of the wall correction factor, Kw. The value of Kw obtained using the non-linear extrapolation is in good agreement with the result obtained using Monte Carlo techniques.

Algorithms↗
PubMed2000

Comparison of measured and Monte Carlo calculated dose distributions from the NRC linac.

We have benchmarked photon beam simulations with the EGS4 user code BEAM [Rogers et al., Med. Phys. 22, 503-524 (1995)] by comparing calculated and measured relative ionization distributions in water from the 10 and 20 MV photon beams of the NRC linac. Unlike previous calculations, the incident electron energy is known independently to 1%, the entire extra-focal radiation is simulated, and electron contamination is accounted for. The full Monte Carlo simulation of the linac includes the electron exit window, target, flattening filter, monitor chambers, collimators, as well as the PMMA walls of the water phantom. Dose distributions are calculated using a modified version of the EGS4 user code DOSXYZ which additionally allows scoring of average energy and energy fluence in the phantom. Dose is converted to ionization by accounting for the (L/rho)water(air) variation in the phantom, calculated in an identical geometry for the realistic beams using a new EGS4 user code, SPRXYZ. The variation of (L/rho)water(air) with depth is a 1.25% correction at 10 MV and a 2% correction at 20 MV. At both energies, the calculated and the measured values of ionization on the central axis in the buildup region agree within 1% of maximum ionization relative to the ionization at 10 cm depth. The agreement is well within statistics elsewhere. The electron contamination contributes 0.35(+/- 0.02) to 1.37(+/- 0.03)% of the maximum dose in the buildup region at 10 MV and 0.26(+/- 0.03) to 3.14(+/- 0.07)% of the maximum dose at 20 MV. The penumbrae at 3 depths in each beam (in g/cm2), 1.99 (dmax, 10 MV only), 3.29 (dmax, 20 MV only), 9.79 and 19.79, agree with ionization chamber measurements to better than 1 mm. Possible causes for the discrepancy between calculations and measurements are analyzed and discussed in detail.

Humans↗
PubMed2000

Absorbed-dose beam quality conversion factors for cylindrical chambers in high energy photon beams.

Recent working groups of the AAPM [Almond et al., Med. Phys. 26, 1847 (1999)] and the IAEA (Andreo et al., Draft V.7 of "An International Code of Practice for Dosimetry based on Standards of Absorbed Dose to Water," IAEA, 2000) have described guidelines to base reference dosimetry of high energy photon beams on absorbed dose to water standards. In these protocols use is made of the absorbed-dose beam quality conversion factor, kQ which scales an absorbed-dose calibration factor at the reference quality 60Co to a quality Q, and which is calculated based on state-of-the-art ion chamber theory and data. In this paper we present the measurement and analysis of beam quality conversion factors kQ for cylindrical chambers in high-energy photon beams. At least three chambers of six different types were calibrated against the Canadian primary standard for absorbed dose based on a sealed water calorimeter at 60Co [TPR10(20)=0.572, %dd(10)x=58.4], 10 MV [TPR10(20)=0.682, %dd(10)x=69.6), 20 MV (TPR10(20)=0.758, %dd(10)x= 80.5] and 30 MV [TPR10(20) = 0.794, %dd(10)x= 88.4]. The uncertainty on the calorimetric determination of kQ for a single chamber is typically 0.36% and the overall 1sigma uncertainty on a set of chambers of the same type is typically 0.45%. The maximum deviation between a measured kQ and the TG-51 protocol value is 0.8%. The overall rms deviation between measurement and the TG-51 values, based on 20 chambers at the three energies, is 0.41%. When the effect of a 1 mm PMMA waterproofing sleeve is taken into account in the calculations, the maximum deviation is 1.1% and the overall rms deviation between measurement and calculation 0.48%. When the beam is specified using TPR10(20), and measurements are compared with kQ values calculated using the version of TG-21 with corrected formalism and data, differences are up to 1.6% when no sleeve corrections are taken into account. For the NE2571 and the NE2611A chamber types, for which the most literature data are available, using %dd(10)x, all published data show a spread of 0.4% and 0.6%, respectively, over the entire measurement range, compared to spreads of up to 1.1% for both chambers when the kQ values are expressed as a function of TPR10(20). For the PR06-C chamber no clear preference of beam quality specifier could be identified. When comparing the differences of our kQ measurements and calculations with an analysis in terms of air-kerma protocols with the same underlying calculations but expressed in terms of a compound conversion factor CQ, we observe that a system making use of absorbed-dose calibrations and calculated kQ values, is more accurate than a system based on air-kerma calibrations in combination with calculated CQ (rms deviation of 0.48% versus 0.67%, respectively).

Air↗
PubMed1999

Fricke dosimetry: the difference between G(Fe3+) for 60Co gamma-rays and high-energy x-rays.

A calibration of the Fricke dosimeter is a measurement of epsilon G(Fe3+). Although G(Fe3+) is expected to be approximately energy independent for all low-LET radiation, existing data are not adequate to rule out the possibility of changes of a few per cent with beam quality. When a high-precision Fricke dosimeter, which has been calibrated for one particular low-LET beam quality, is used to measure the absorbed dose for another low-LET beam quality, the accuracy of the absorbed dose measurement is limited by the uncertainty in the value of G(Fe3+). The ratio of G(Fe3+) for high-energy x-rays (20 and 30 MV) to G(Fe3+) for 60Co gamma-rays, G(Fe3+)MV(Co), was measured to be 1.007(+/-0.003) (confidence level of 68%) using two different types of water calorimeter, a stirred-water calorimeter (20 MV) and a sealed-water calorimeter (20, 30 MV). This value is consistent with our calculations based on the LET dependence of G(primary products) and, as well, with published measurements and theoretical treatments of G(Fe3+).

Calibration↗
PubMed1999

Development and sensitivity to visual impairment of the Low Vision Functional Status Evaluation (LVFSE).

BACKGROUND: Functional limitation because of visual impairment is one of the most important measures of low vision rehabilitation outcome because it represents the true impact of visual impairment upon the daily lives of individuals. The Low Vision Functional Status Evaluation (LVFSE) was designed to evaluate functional limitation because of visual impairment using both observed and self-reported performance on daily activities. METHODS: Performance on 27 daily activities was evaluated for 155 visually impaired subjects. Subjects also provided ratings of task difficulty. RESULTS: Correlations between observed performance and visual acuity, contrast sensitivity, and visual field loss severity were moderate, r = -0.60 to r = 0.34. Correlations between self-reported task performance difficulty and measures of visual clinical state were weaker, r = -0.44 to r = 0.21. CONCLUSIONS: The LVFSE shows promise as a sensitive measure of low vision-related functional status but more work is needed to refine the measure.

Activities of Daily Living↗
PubMed1998

Continuous and discontinuous changes in the unit cell of HIV-1 reverse transcriptase crystals on dehydration.

A crystal form of HIV-1 reverse transcriptase (RT) complexed with inhibitors showed diffraction to a high-resolution limit of 3.7 A. Instability in the unit-cell dimensions of these crystals was observed during soaking experiments, but the range of this variability and consequent change in lattice order was revealed by a chance observation of dehydration. Deliberately induced dehydration results in crystals having a variety of unit cells, the best-ordered of which show diffraction to a minimum Bragg spacing of 2.2 A. In order to understand the molecular basis for this phenomenon, the initial observation of dehydration, the data sets from dehydrated crystals, the crystal packing and the domain conformation of RT are analysed in detail here. This analysis reveals that the crystals undergo remarkable changes following a variety of possible dehydration pathways: some changes occur gradually whilst others are abrupt and require significant domain rearrangements. Comparison of domain arrangements in different crystal forms gives insight into the flexibility of RT which, in turn, may reflect the internal motions allowing this therapeutically important enzyme to fulfill its biological function.

Crystallization↗
PubMed1998

3'-Azido-3'-deoxythymidine drug resistance mutations in HIV-1 reverse transcriptase can induce long range conformational changes.

HIV reverse transcriptase (RT) is one of the main targets for the action of anti-AIDS drugs. Many of these drugs [e.g., 3'-azido-3'-deoxythymidine (AZT) and 2',3'-dideoxyinosine (ddI)] are analogues of the nucleoside substrates used by the HIV RT. One of the main problems in anti-HIV therapy is the selection of a mutant virus with reduced drug sensitivity. Drug resistance in HIV is generated for nucleoside analogue inhibitors by mutations in HIV RT. However, most of these mutations are situated some distance from the polymerase active site, giving rise to questions concerning the mechanism of resistance. To understand the possible structural bases for this, the crystal structures of AZT- and ddI-resistant RTs have been determined. For the ddI-resistant RT with a mutation at residue 74, no significant conformational changes were observed for the p66 subunit. In contrast, for the AZT-resistant RT (RTMC) bearing four mutations, two of these (at 215 and 219) give rise to a conformational change that propagates to the active site aspartate residues. Thus, these drug resistance mutations produce an effect at the RT polymerase site mediated simply by the protein. It is likely that such long-range effects could represent a common mechanism for generating drug resistance in other systems.

Binding Sites↗
PubMed1997

Unique features in the structure of the complex between HIV-1 reverse transcriptase and the bis(heteroaryl)piperazine (BHAP) U-90152 explain resistance mutations for this nonnucleoside inhibitor.

The viral reverse transcriptase (RT) provides an attractive target in the search for anti-HIV therapies. The nonnucleoside inhibitors (NNIs) are a diverse set of compounds (usually HIV-1 specific) that function by distorting the polymerase active site upon binding in a nearby pocket. Despite being potent and of generally low toxicity, their clinical use has been limited by rapid selection for resistant viral populations. The 2.65-A resolution structure of the complex between HIV-1 RT and the bis(heteroaryl)piperazine (BHAP) NNI, 1-(5-methanesulfonamido-1H-indol-2-yl-carbonyl)-4- [3-(1-methyl-ethylamino) pyridinyl] piperazine (U-90152), reveals the inhibitor conformation and bound water molecules. The bulky U-90152 molecule occupies the same pocket as other NNIs, but the complex is stabilized quite differently, in particular by hydrogen bonding to the main chain of Lys-103 and extensive hydrophobic contacts with Pro-236. These interactions rationalize observed resistance mutations, notably Pro-236-Leu, which occurs characteristically for BHAPs. When bound, part of U-90152 protrudes into the solvent creating a channel between Pro-236 and the polypeptide segments 225-226 and 105-106, giving the first clear evidence of the entry mode for NNIs. The structure allows prediction of binding modes for related inhibitors [(altrylamino)piperidine-BHAPs] and suggests changes to U-90152, such as the addition of a 6 amino group to the pyridine ring, which may make binding more resilient to mutations in the RT. The observation of novel hydrogen bonding to the protein main chain may provide lessons for the improvement of quite different inhibitors.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Effect of folate deficiency and folate and B12 excess on memory functioning in young chicks.

The results of this series of experiments with chicks trained on a single trial, passive avoidance task, demonstrate that methotrexate-induced folate deficiency, and excess levels of folate and B12 lead to amnesia in these subjects. The amnesia appears only after 50 min following learning, leaving the earlier processing stages of memory formation unaffected. The application of methotrexate resulted in disruption of righting reflex in a dose dependent manner, however the ataxia did not appear to be the cause of the memory deficit. The deficit in memory induced by methotrexate-induced folate deficiency could be ameliorated with methionine. These studies suggest that cellular processes involving folate metabolism may play an important role in the memory formation of the young chick and that the observed disruption of memory may well occur due to its affect on protein synthesis mediated by alterations in methionine metabolism.

Animals↗
PubMed1996

Water calorimetry for radiation dosimetry.

Calorimetry has a long history as a technique for establishing the absorbed dose, and graphite calorimetry has often been used to establish absorbed dose standards for use in radiation therapy. However, a conversion process is necessary to convert from dose to graphite to dose to water, which is the quantity of clinical interest. In order to more directly measure the dose to water, considerable effort has been devoted in the last fifteen years to the development of water calorimetry. This article reviews these developments and summarizes the present status of water calorimetry. Absorbed dose standards based on water calorimetry and with a relative standard uncertainty of 0.5-1% now seem achievable.

Calorimetry↗
PubMed1995

A comparative study of seven measures of patient satisfaction.

The acceptability of satisfaction as a quality indicator is qualified by several well known measurement problems. This study examines the variability in satisfaction evaluations related to different measurement methods and the effect of response biases on reported satisfaction. Satisfaction evaluations using seven different, commonly used measures of patient satisfaction were obtained from the same sample of respondents. The seven measures were: 1) a global measure of satisfaction using a visual analogue scale; 2) a multidimensional measure of satisfaction based on the Patient Satisfaction Questionnaire using an evaluation response format (poor, fair, good, very good, excellent); 3) a two-item overall evaluation of quality using the evaluation response format; 4) a six-item attitude measure of general satisfaction using a five-point Likert agree-disagree response format; 5) a four-item attitude measure of satisfaction with physician, using the agree-disagree response format; 6) a four-item measure of behavioral intention; and 7) willingness-to-pay in dollars. The percentage of favorable evaluations of care ranged from 63% to 82% across six of the seven measures. Willingness-to-pay does not appear to be a valid measure of satisfaction. Correlations were highest between measures with similar response formats. Although an oppositional response bias was not found, a very substantial acquiescent response bias was detected. Acquiescence reduced the internal consistency of three multiple-item measures, the general and physician attitude and behavioral intention measures, to levels unacceptable even for group comparisons. Between highly and nonacquiescent respondents, levels of satisfaction were somewhat lower for the multidimensional measure of satisfaction and significantly lower for the two attitude satisfaction measures. Highly acquiescent respondents were older, less well educated, and in poorer health than nonacquiescent subjects. Results of satisfaction evaluations dependent on the measurement method used, and unreliability of measurement may be a significant problem in satisfaction measurement, especially for the oldest and most ill patients.

Adult↗
PubMed1994

Crystals of HIV-1 reverse transcriptase diffracting to 2.2 A resolution.

Reverse transcriptase (RT) from the human immunodeficiency virus type 1 has been crystallized in four closely related forms, the best of which diffract X-rays to 2.2 A resolution. The RT was crystallized as a complex with a non-nucleoside inhibitor, either nevirapine or a nevirapine analogue. Crystals grew from 6% PEG 3400 buffered at pH 5. These were of space group P2(1)2(1)2(1) with unit cell parameters a = 147 A, b = 112 A, c = 79 A (form A), with one RT heterodimer in the asymmetric unit. Changes in unit cell parameters and degree of crystalline order were observed on soaking pregrown crystals in various solutions, giving three further sets of unit cells. These were a = 143 A, b = 112, A, c = 79 A (form B), a = 141 A, b = 111 A, c = 73 A (form C), a = 143 A, b = 117 A, c = 66.5 A (form D). The last two forms diffract X-rays to 2.2 A resolution. Structure determinations of these latter crystal forms of RT should give a detailed atomic model for this therapeutically important drug target.

Crystallography, X-Ray↗
PubMed1994

A simple magnetic spectrometer for radiotherapy electron beams.

A small, lightweight, single-focusing magnetic spectrometer was designed, assembled, and tested for analysis of electron beams from radiotherapy electron linacs. The objective was to develop a low cost, simple device that could be easily replicated in other medical centers, and to demonstrate the practicality of individual electron counting for precise analysis of electron spectra. Two methods of spectroscopy have been developed. One method consists of counting electrons individually as a function of magnetic field setting. Electrons are deflected through 90 degrees in the magnetic spectrometer, through an exit slit, and into a scintillation detector. A second method consists of recording the complete spectrum of electron energies from the accelerator on a strip of film at a single magnetic field setting. A critical design element is the 10-cm long collimator for electrons entering the magnet gap, with defining apertures and scraper slits. The spectrometer's cleanliness of transmission, energy calibration, and resolution were all tested at 10 and 16 MeV using the nearly monoenergetic electron beam of the accelerator at the National Research Council of Canada (NRCC). These accelerator tests, and also Monte Carlo trajectory simulations, both show that contamination of the transmitted spectrum due to scattered or knock-on electrons is negligible. Low-energy characteristics were tested using a 90Sr + 90Y beta-particle source. The energy calibration of the 90 degree spectrometer mode was based on mapping the magnetic field and also electron trajectory computer simulations. That calibration agrees with the NRCC's own calibrated scale to 0.8% for the single-particle counting method and to 1.3% for the film method. The energy resolution was measured to be 2% at 10 MeV, which is adequate for radiotherapy linac measurements. The acceptance half angle is 0.5 degrees or less, depending on the aperture size, which is adequate for electron angular distribution measurements within the forward cone of the electron beam. Used with film, the spectrometer is a simple, accurate, and highly transportable device for measuring radiotherapy electron energy spectra.

Biophysical Phenomena↗
PubMed1994

The survival of aerobic and anoxic human glioma and melanoma cells after irradiation at ultrahigh and clinical dose rates.

This in vitro study was undertaken to determine if ultrahigh dose rates could improve the radiation response of human tumors. Two cell lines, human glioma (U-87 MG), which is radioresistant, and human melanoma (HT-144), which is radiosensitive, were irradiated at ultrahigh and high dose rates under aerobic and anoxic conditions to determine if their oxygen enhancement ratios are modified by dose rate. In fact, the survival curves, and hence the oxygen enhancement ratios, were found to be independent of the dose rate. The oxygen enhancement ratio for glioma cells irradiated in plateau phase was 2.8 (+/- 0.3). The oxygen enhancement ratio was 2.7 (+/- 0.4) for melanoma cells in plateau phase and 2.8 (+/- 0.3) in exponential phase. These results indicate that there is no advantage in treating these tumors using ultrahigh dose rates instead of conventional dose rates.

Cell Hypoxia↗
PubMed1993

Two-stage cell shrinkage and the OER for radiation-induced apoptosis of rat thymocytes.

Suspensions of rat thymocytes were given 0.09-100 Gy using 60Co gamma-rays. The radiation-induced changes in the thymocytes were examined from minutes to hours post-irradiation using electron microscopy, agarose gel electrophoresis, staining and Coulter Counter sizing. Sizing by Coulter Counter showed, for the first time, that thymocytes which undergo apoptosis shrink in two distinct stages, first by a sudden decrease from an original volume of 99 microns 3 to a volume of 76 microns 3, followed by a gradual decrease to 57 microns 3 over the space of a few hours. The oxygen enhancement ratio for apoptosis was measured to be about 3.5, similar to the value for reproductive death for many mammalian cells.

Animals↗