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Introduction The individual dose estimation to organs at risk has known important evolution last years, with new tools whose permits to obtain histogram dose-volume. However, dose reconstruction based on retrospective epidemiology studies are often realized dozens of years after initial radiotherapy, based sometimes on non-exhaustive data, both on patient anatomy as the beams. The aim is to establish the link between the missing data rate and the uncertainties induced on out-of-field dose by the non-exhaustivity of the data. Methods and materials Statistics are used for evaluating the missing data rate in patient radiotherapy files from french, british, Italian and dutch cohorts. The around twenty variables contributing to the patient anatomy modelisation and dose calculation are evaluated. Statistics methods (multiples imputation) are used to complete the missing data. For uncertainties dose calculation, the formalism defined in TRS 384 is applied, variances are deducted from the statistical study. Results The primary results indicate that, according to the considered parameter, missing data rate is very inconstant and strongly linked to the year of treatment and the institution. The dose uncertainties induced is very linked to the considered parameter. Conclusion The results of the study should allow a better knowledge of the uncertainties in retrospective dose estimations used for long term studies of effects of radiotherapy.

Objectives: To examine what patients do when they have a prescription with a dosage where tablets must be split. Methods: Interviews were performed at 12 pharmacies across Sweden with pharmacy customers who had prescriptions with a dosage meaning that the tablets have to be divided to give the prescribed individual dose. Key findings: Of the 436 pharmacy customers interviewed, 255 (58.5%) reported they divided the tablets without tools and 162 (37.2%) used tools, the most common was a knife. Only few used a tablet splitter. Almost every third patient (31.4%) stated they had problems to divide the tablets. Conclusions: Patients’ difficulties in splitting tablets are common, but seem to be overlooked. Pharmacists should be permitted to adjust dispensing to a strength corresponding to the prescribed dosage level, price policies with flat prices need to be revised to eliminate economic incentives to prescribe dosages with split tablets and a computerised decision support should be developed signalling when there is a suitable strength for the prescribed individual dose.

Chromosome aberrations induced by radiation have been used for the purpose of dosimetry for a long time. Translocations are especially useful for retrospective dosimetry, since they are assumed to be stable. The method of chromosome painting (FISH) has facilitated objective scoring of aberrations considerably. Translocation frequencies, obtained by FISH, for retrospective dosimetry rely on the main assumptions of neutral selection value and that the distribution of aberrations over the chromosomes is a known function of the DNA content of the chromosomes. Data scrutinising the two above-mentioned assumptions indicate deviations from both. Other factors potentially causing problems for retrospective dosimetry, such as inter-individual variations in background and induction patterns, are discussed. Finally, a brief analysis of the statistical power of dosimetry studies shows that establishing low doses (approximately 0.25 Gy) with good precision requires a great effort, which is probably unrealistic for individual dose estimates in epidemiological studies.

A preliminary radiological dose assessment of equipment decontamination, subsurface disposal, landspreading, equipment smelting, and equipment burial was conducted to address concerns regarding the presence of naturally occurring radioactive materials (NORM) in production waste streams. The assessment estimated maximum individual dose equivalents for workers and the general public. Sensitivity analyses of certain input parameters also were conducted. On the basis of this assessment, it is concluded that (1) regulations requiring workers to wear respiratory protection during equipment cleaning operations are likely to result in lower worker doses, (2) underground injection and downhole encapsulation of NORM wastes present a negligible risk to the general public, and (3) potential doses to workers and the general public related to smelting NORM-contaminated equipment can be controlled by limiting the contamination level of the initial feed. It is recommended that (1) NORM wastes be further characterized to improve studies of potential radiological doses; (2) states be encouraged to permit subsurface disposal of NORM more readily, provided further assessments support this study; results; (3) further assessment of landspreading NORM wastes be conducted; and (4) the political, economic, sociological, and nonradiological issues related to smelting NORM-contaminated equipment be studied to fully examine the feasibility of this disposal option.

The Nuclear Energy Agency of the Organisation for Economic Cooperation and Development has set up an information system on occupational exposure (ISOE) received at nuclear power stations throughout the world. The third annual report produced by NEA on the data held on ISOE has recently been published. Data from 16 countries are included in the report, mainly from OECD countries, but some non-OECD countries are included through membership of IAEA, which is a co-sponsor of ISOE. The 1993 data are analysed and trends are given for the period 1969 to the end of 1993. At the end of 1993, data for 339 reactors were included in the database, which represents 78% of the operating reactors in the world. About half of these supplied data directly to ISOE, and other data for the report were obtained from annual reports produced by the utilities. The data are well presented, mainly in tabular and graphical form. The ISOE information system consists of three databases: NEA 1, NEA 2 and NEA 3. NEA 1 contains radiological data in the form of collective dose, and individual dose distributions, which can be analysed by country or type of reactor; these data are the main source of information for this report. However, only collective dose is analysed in the report and not individual dose data. NEA 2 includes information on dose control techniques and work management, whereas NEA 3 contains details of specific operations and experience gained in radiation protection procedures. All three databases are to be developed further. The total collective dose from all reactors in 1993 was 585 man Sv, which was 6% less than in 1992. This fall is a continuation of a steady reduction since the mid-1980s, there being a maximum of 913 man Sv in 1983. That peak was mainly caused by back-fitting work in PWR reactors required after the Three Mile Island incident. In recent years also, increased emphasis on dose minimisation has gradually reduced the annual collective dose. The collective dose per unit power generated in 1993 was 0.32 man Sv per Tw h; this is the lowest value achieved in any year for utilities on the database. The report gives other analyses such as average outage period for refuelling: Finland was lowest with an average of 2 to 3 weeks and Japan was the highest at around 20 weeks. The penultimate chapter gives brief reports from each participating country on the principal events that affected the collective dose in 1993, and shows how multifarious are the influences on this quantity from various plant operations. These national reports also demonstrate how universal is the drive towards minimising occupational exposure.

Population and individual radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1992. Fifty-year dose commitments for a 1-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teenager, and adult) residing between 2 and 80 km from each of 72 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is an estimate of individual doses, which are compared with 10 CFR Part 50, Appendix I, design objectives. The total collective dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 3.7 person-rem to a low of 0.0015 person-rem for the sites with plants in operation and producing power during the year. The arithmetic mean was 0.66 person-rem. The total population dose for all sites was estimated at 47 person-rem for the 130-million people considered at risk. The individual dose commitments estimated for all sites were below the 10 CFR 50, Appendix I, design objectives.

Recent proposals for a new U.S. standard for high-level waste disposal would limit the average dose to individuals in the vicinity surrounding a geologic repository. This would be a new approach to protecting the public from environmental releases of radioactivity. Heretofore, criteria adopted for geologic disposal have limited the reasonable maximum exposure to a future hypothetical individual. Here we present quantitative analyses of the relation between maximum exposure and vicinity-average exposure, resulting from future human use of ground water contaminated by radioactive releases from a repository.Estimating the vicinity-average exposure would require postulates and guesses of location and habits of future people. Exposure probabilities postulated by others show that proposed dose limit to the vicinity-average individual would be a far more lenient standard than the traditional dose limit to reasonably maximally exposed individuals. The proposed vicinity-average dose limit would allow far greater concentrations of contaminants in ground water than would be allowed by normal standards of ground water protection. A safety standard that limits vicinity-average exposure should also include limits on maximum exposure.

Population and individual radiation dose commitments have been estimated from reported radionuclide releases from commercial power reactors operating during 1991. Fifty-year dose commitments for a one-year exposure from both liquid and atmospheric releases were calculated for four population groups (infant, child, teenager and adult) residing between 2 and 80 km from each of 72 reactor sites. This report tabulates the results of these calculations, showing the dose commitments for both water and airborne pathways for each age group and organ. Also included for each of the sites is an estimate of individual doses which are compared with 10 CFR Part 50, Appendix 1 design objectives. The total collective dose commitments (from both liquid and airborne pathways) for each site ranged from a high of 22 person-rem to a low of 0.002 person-rem for the sites with plants in operation and producing power during the year. The arithmetic mean was 1.2 person-rem. The total population dose for all sites was estimated at 88 person-rem for the 130 million people considered at risk. The individual dose commitments estimated for all sites were below the Appendix 1 design objectives.

The hedonic valence of the interoceptive stimuli associated with a wide range of cocaine doses administered by either SC or intraperitoneal injections was assessed in rats. Ninety-six male Sprague-Dawley rats were randomly assigned to different dose- and route-of-administration dependent groups (n = 8/group) and conditioned in a place learning task. During half of the conditioning trials, rats received either SC or intraperitoneal injections of saline or an individual dose of cocaine from 0.32 to 32 mg/kg (10 groups, 0.5 log common log unit increments), and were immediately placed in the initially nonpreferred compartment of a straight alley-way place-conditioning chamber. Prior to the other conditioning trials, rats received equivalent volumes of saline injections via the same routes of administration and were immediately placed in the initially preferred compartment. Two additional control groups received saline injections on both sides. Each rat received eight conditioning trials (four on each side). Significant conditioned place approach was produced by both SC- and IP-injected cocaine. However, the IP route of cocaine administration required a dose of 10 mg/kg cocaine to elicit a conditioned place approach, whereas a 0.32 mg/kg SC cocaine injection produced a CPP. Saline injections alone did not change the initial preference scores, and conditioned place aversions were not produced by any cocaine dose. The results of the present study demonstrate the relative safety of SC cocaine administration in the rat and a behavioral potency difference between these two routes of administration relative to the hedonic valence of the associated subjective states.

This report analyzes the radionuclide dose impact of the PUREX process waste stream. The radionuclide ingestion and inhalation pathways are analyzed. Two spent fuel assemblies processed in the Separation facilities are analyzed, the Mark 31A and Mark 31B. The individual radionuclide significance to dose is evaluated in terms of dose percentage. Comparing the radionuclide individual dose value allows the determination of those radionuclides whose dose impact is significant. The results of this analysis demonstrate that a limited number of radionuclides contribute 1% or more to the total dose and that the major contributor to the sludge source dose is strontium. The results obtained permit reducing the list of radionuclides to be considered in the development of source terms to support the High Level Waste Safety Analysis Report.

Individual dose measurements in highly contaminated areas in the Brjansk region of Russia are presented. The measurement programme comprised 285 persons living in six different villages, with contamination levels ranging from 0.8 to 2.3 MBq.m −2 of 137 Cs. The measurements were performed in the month of September in the years 1990, 1991 and 1992, with three participating dosimetry laboratories. Mean monthly dose values between 148 and 287 μSv were recorded, including a natural background contribution of 60 μSv. Not unexpectedly, people with outdoor occupations living in wooden houses received the highest doses. The most heavily contaminated vilIages were also most effectively decontaminated. The effect of this is clearly reflected in the dose data

An EXCEL{reg_sign} spreadsheet has been developed that, when combined with the PC version of XOQDOQ, will generate estimates of maximum individual dose from routine atmospheric releases of radionuclides. The spreadsheet, MAXINE, utilizes a variety of atmospheric dispersion factors to calculate radiation dose as recommended by the US Nuclear Regulatory Commission in Regulatory Guide 1.109 [USNRC 1977a]. The methodology suggested herein includes use of both the MAXINE spreadsheet and the PC version of XOQDOQ.

Dear Sir I would like to thank Dr Dalgleish for his letter and his interest in our work. The recently published medical and dental guidance notes [1] provide advice on dealing with patients who die following the administration of a radioactive substance. The guidance notes deal with cremation of radioactive patients and provide limits above which special precautions (and advice from the radiation protection advisor) may be required. For Sr-89 special precautions are required once the administered activity exceeds 200 MBq. In 1989 an assessment of the radiological impact of cremating a corpse containing up to 500 MBq of Sr-89 was undertaken by the NRPB. The results were published by the Institute of Physical Sciences in Medicine [2] and are also discussed in Mountford's `Exposure of critical groups to nuclear medicine patients' [3]. Cremation of one corpse contaminated at a reference level of 500 MBq resulted in a maximum individual dose equivalent to an adult member of the public of less than 0.1 µSv (mostly from inhalation). A skin dose of less than 2 µSv would be expected in conditions of moderate rain (mostly from direct deposition on the skin). A crematorium worker would receive a maximum individual effective dose equivalent of about 0.3 µSv from inhalation and 0.4 µSv from ingestion. The maximum doses to an adult members of the public scattering contaminated ashes are unknown but are extremely unlikely to exceed those calculated for the crematorium worker per cremation. The maximum dose equivalents to a child or infant who may come into contact with the ash shortly after being scattered is similarly unknown and subject to considerable uncertainty. Pessimistic estimates based on a reference intake (1 mg) are greatest for an infant ingesting ash inadvertently (3 µSv). It was noted that although a person may be exposed to an atmospheric discharge of Sr-89 on more than one occasion, direct exposure to contaminated ash is very unlikely to occur more than once. The conclusion was that the levels of dose likely to be encountered in practice should be of no cause for concern. I have contacted the Environment Agency for guidance on this matter and received the following advice: The medical and dental guidance notes state that RPAs should advise on the safety of cremation of corpses containing therapeutic doses of radionuclides. The Environment Agency has no direct role in this and RSA93 is unlikely to be an issue in considering the corpse (after removal of implants). However, where an RPA identifies that a potentially significant hazard could arise from the ashes after cremations, they might want to discuss it with the Agency. We would like to acknowledge the advice provided by Mark Singleton and Cathy Griffiths in formulating this response. Yours faithfully

The offsite individual residing at the SRS boundary location of maximum exposure (maximum individual) received a dose from SRS atmospheric releases in 1992 of 0.10 mrem. Tritium oxide releases were responsible for more than 90% of the atmospheric dose. Ninety-nine percent of the atmospheric dose is accounted for with the inclusion of I-129, U-235, Pu-238 and Pu-239. The 50-mile population received a collective dose of 6.4 person-rem from 1992 releases. Atmospheric radiation dose is dominated by the inhalation and vegetation consumption pathways. The maximum dose received by an offsite individual as a result of SRS liquid releases in 1992 was 0.13 mrem. This dose is dominated by Cs-137 that is accumulated in Savannah River fish and tritium in drinking water. More than 99% of the maximum individual dose from liquid releases results from Cs-137, tritium, Sr-90, and Pu-239. The population dose from liquid releases in 1992 was 2.5 person-rem. The major exposure pathway to the population is drinking water. Radiation dose to the general public from operations at the Savannah River Site continues to be a very small fraction of the natural background dose. A resident of the CSRA receives about 300 mrem per year from background radiation. The populationmore » within 50-miles of the SRS (620,000) and at the downstream water treatment facilities (65,000), therefore, receives a natural background population dose of approximately 200,000 person-rem.« less

This report summarizes the occupational radiation exposure information that has been reported to the NRC`s Radiation Exposure Information Reporting System (REIRS) by nuclear power facilities and certain other categories of NRC licensees during the years 1969 through 1992. The bulk of the data presented in the report was obtained from annual radiation exposure reports submitted in accordance with the requirements of 10CFR20.407 and the technical specifications of nuclear power plants. Data on workers terminating their employment at certain NRC licensed facilities were obtained from reports submitted pursuant to 10CFR20.408. The 1992 annual reports submitted by about 364 licensees indicated that approximately 204,365 individuals were monitored, 183,927 of whom were monitored by nuclear power facilities. They incurred an average individual dose of 0.16 rem (cSv) and an average measurable dose of about 0.30 (cSv). Termination radiation exposure reports were analyzed to reveal that about 74,566 individuals completed their employment with one or more of the 364 covered licensees during 1992. Some 71,846 of these individuals terminated from power reactor facilities, and about 9,724 of them were considered to be transient workers who received an average dose of 0.50 rem (cSv).

Tegafur (Sunfural-S), as masked compound of a 5-fluorouracil derivative, was administered orally as a maintenance chemotherapeutic agent at a dose of 600 mg/day in 98 cases of head and neck epithelial cancer. The effectiveness of the drug was evaluated by a statistical method involving two formulae: individual dose intensity (IDI) and relative performance (RP). When comparing patients rated above a reference IDI value of 1.0 with those rated below 1.0, it was not possible to predict patient survival or tumor-free rates. In contrast, the value of the RP did show such a correlation. These findings support the effectiveness of Tegafur as a maintenance chemotherapeutic treatment for head and neck cancer patients.

Abstract 1416 Introduction: A population pharmacokinetic (PK) model of a recombinant FVIII (rFVIII) was established on ADVATE® (Antihemophilic Factor (Recombinant), Plasma/Albumin-Free Method) studies in pediatric and adult patients with hemophilia A. The objective of this analysis was to evaluate the effect of reduced PK sampling time points on the estimated PK parameters in the population PK model. Patients and Methods: Plasma FVIII activity PK data were collected for 3 ADVATE® clinical trials in previously treated patients: 184 full PK data sets (11 time points) for 100 adults/adolescents, aged 10 to 65 years, and from 52 reduced sample PK data sets (5 time points) for 52 children, aged 1 to 6 years. A population PK analysis was conducted on a two-compartment structure model and the covariate effect of age and weight was explored. Four reduced sampling scenarios from the full 10 post-infusion sampling time points, were investigated: 1) Reduced to 4 (1 hr, 9 hr, 24 hr, and 48 hr), 2) Reduced to 3 (6 hr, 24 hr, and 48 hr), 3) Reduced to 2 (6 hr and 24 hr), and 4) Reduced to 1 sampling time points (24 hr post-infusion). After applying the reduced sampling on a random 10% of sampling set at a time in the population PK model, the differences in model estimates and individual PK estimates between full and reduced sampling, were evaluated. Results: The two-compartment population PK model adequately described the data. Clearance (CL) was significantly correlated with age and body weight and central volume of distribution was also related with body weight. Absolute deviations (%) from the estimates using full PK sampling in the Individual PK estimates (CL, Vss, and Half-life) using each of the reduced sampling time points were showed in the below table. Conclusions: It appears that PK parameters estimated using population PK model are robust to reduced sampling time points. Accurate measurement of PK on reduced samples gives patients and clinicians the opportunity to design treatment regimens that are better tailored to individuals. Disclosures: Oh: Baxter: Employment. Björkman:Baxter: Consultancy; Octapharma: Consultancy. Schroth:Baxter: Employment. Fritsch:Baxter: Employment. Collins:NovoNordisk: Consultancy, Honoraria, The EACH2 registry was funded by Novonordisk; Baxter Healthcare: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Fischer:Baxter: Consultancy; NovoNordisk: Consultancy. Blanchette:Bayer: Consultancy; Baxter: Research Support. Casey:Baxter: Employment. Spotts:Baxter: Employment. Ewenstein:Baxter Bioscience: Employment.

Purpose One of the main benefits in making Pre Treatment verification based on volumetric dose data is that the acceptance criteria can be based in part on clinical significance, rather than on a pure percentage dose error. Higher importance can be thus given to the dose errors in specified regions of interest Since 2006, the Delta4 array dosimeter included an option to reconstruct 3D dose distributions and DVHs. The current methodology uses TPS data in a unique way and is very accurate. The limitation however is that the TPS dose data on the sub‐beam level are required, which may not be available from the VMAT or TomoTherapy TPS. In this work, FAST‐3D, a new, TPS‐independent, method to calculate 3D dose distribution implemented in the Delta4software was validated. Method and Materials FAST‐3D does not require the TPS dose‐data for 3D dose reconstruction. However it requires accurate dose measurement per control point. This is readily available with the Delta4 system, whose unique feature is discrimination between individual dose pulses, as opposed to a common but less accurate solution of integration over pre‐set time intervals. Results The 3D method based on TPS data proved to be accurate (2%, 2mm] and useful for assessing the clinical significance of a dose discrepancy. The new FAST‐3D method is completely independent of TPS data and can be used even if the calculated dose data on the sub‐beam level are missing. It is not quite as accurate as the TPS‐method, but still in five of six cases studied, the Gamma analysis passing rates were > 99% at the (3%, 3mm] error level. Conclusion Utilizing the FAST‐3D method when the full TPS data are not available will in most cases result in measured data reconstructed in 3D agreeing well with the calculations. Research sponsored by ScandiDos Corporation

This Software Development Plan (SDP) outlines all software activities required to obtain functional environmental accumulation and individual dose codes for the Hanford Environmental Dose Reconstruction (HEDR) project. The modeling activities addressed use the output of the air transport-code HATCHET to compute radionuclide concentrations in environmental pathways, and continue on through calculations of dose for individuals. The Hanford Environmental Dose Reconstruction (HEDR) Project has a deliverable in the June 1993 time frame to be able to start computing doses to individuals from nuclear-related activities on the Hanford Site during and following World War II. The CIDER code will compute doses and their uncertainties for individuals living in the contaminated environment computed by DESCARTES. The projected size of the code is 3000 lines.

As part of the Hanford Environmental Dose Reconstruction (HEDR) Project, Battelle, Pacific Northwest Laboratories reviewed literature and data on radionuclide concentrations and distribution in the water, sediment, and biota of the Columbia River and adjacent coastal areas. Over 600 documents were reviewed including Hanford reports, reports by offsite agencies, journal articles, and graduate theses. Radionuclide concentration data were used in preliminary estimates of individual dose for the period 1964 through 1966. This report summarizes the literature and database reviews and the results of the preliminary dose estimates.

As part of the Hanford Environmental Dose Reconstruction (HEDR) Project, Battelle, Pacific Northwest Laboratories reviewed literature and data on radionuclide concentrations and distribution in the water, sediment, and biota of the Columbia River and adjacent coastal areas. Over 600 documents were reviewed including Hanford reports, reports by offsite agencies, journal articles, and graduate theses. Radionuclide concentration data were used in preliminary estimates of individual dose for the period 1964 through 1966. This report summarizes the literature and database reviews and the results of the preliminary dose estimates.

Preliminary radiation doses were estimated and reported during Phase I of the Hanford Environmental Dose Reconstruction (HEDR) Project. As the project has progressed, additional information regarding the magnitude and timing of past radioactive releases has been developed, and the general scope of the required calculations has been enhanced. The overall HEDR computational model for computing doses attributable to atmospheric releases from Hanford Site operations is called HEDRIC (Hanford Environmental Dose Reconstruction Integrated Codes). It consists of four interrelated models: source term, atmospheric transport, environmental accumulation, and individual dose. The source term and atmospheric transport models are documented elsewhere. This report describes the initial implementation of the design specifications for the environmental accumulation model and computer code, called DESCARTES (Dynamic EStimates of Concentrations and Accumulated Radionuclides in Terrestrial Environments), and the individual dose model and computer code, called CIDER (Calculation of Individual Doses from Environmental Radionuclides). The computations required of these models and the design specifications for their codes were documented in Napier et al. (1992). Revisions to the original specifications and the basis for modeling decisions are explained. This report is not the final code documentation but gives the status of the model and code development to date. Final code documentation is scheduled to be completed in FY 1994 following additional code upgrades and refinements. The user's guide included in this report describes the operation of the environmental accumulation and individual dose codes and associated pre- and post-processor programs. A programmer's guide describes the logical structure of the programs and their input and output files.

The water level of Par Pond has been lowered over the past several months to reduce the effects in the event of catastrophic dam failure while assessing the condition of the dam and determining if repairs are necessary. In lowering the level of Par Pond, 60 billion liters of water containing low levels of tritium and cesium-137 were discharged to several onsite streams. SRS surface streams flow to the Savannah River. An assessment made to determine the total amount of tritium and Cs-137 discharged and to estimate the consequences to downstream Savannah River users. It is estimated that a total of 160 curies of tritium were displaced from Par Pond to the Savannah River between June 28, 1991 and September 19, 1991. This release could hypothetically result in a maximum individual dose of 3. 2{times}10{sup {minus}4} mrem and a total (80-km and drinking water populations) population dose of 1.4{times}10{sup {minus}2} person-rem. Likewise, a maximum individual dose of 5.0{times}10{sup {minus}2} mrem and a total population dose of 1.7{times}10{sup {minus}1} person- rem are predicted as a result of an estimated 0.21 curies of Cs-137 being discharged from Par Pond to the Savannah River.

Radiological dose to the offsite maximum individual or the 50-mile population is often estimated assuming that operational atmospheric releases originate from the geographical center of the Savannah River Site. Historically, meteorological data collected from instrumentation on the H-Area tower have been utilized to estimate atmospheric dispersion from centrally located ``releases.`` This paper examines the effect on dose predictions using meteorological data from seven onsite towers located at A, C, D, F, H, K, and P areas to describe meteorological conditions at the central release location. Maximum individual dose estimates using both annual and short-term average air concentrations are well within 20% of the mean prediction. Population dose estimates are also within 20% of the mean prediction. Population dose estimates are also within 20% of the mean except for two-hour doses using H-Area meteorological data, which is less than the average estimate by about 30%.

Potential radiation impacts from launch of the Ulysses solar exploration experiment were evaluated using eight postulated accident scenarios. Lifetime individual dose estimates rarely exceeded 1 mrem. Most of the potential health effects would come from inhalation exposures immediately after an accident, rather than from ingestion of contaminated food or water, or from inhalation of resuspended plutonium from contaminated ground. For local Florida accidents (that is, during the first minute after launch), an average source term accident was estimated to cause a total added cancer risk of up to 0.2 deaths. For accidents at later times after launch, a worldwide cancer risk of up to three cases was calculated (with a four in a million probability). Upper bound estimates were calculated to be about 10 times higher.

Literature relevant to the use of benzimidazole-levamisole combinations for the control and prevention of anthelmintic resistance in gastrointestinal nematodes in sheep is reviewed and the likely consequences of such a strategy are considered. It is suggested that while a system of multiple attack involving the simultaneous administration of both compounds, each given at their full recommended individual dose rates, may have limited scope in combatting resistance once it has arisen, as a means of delaying or preventing its emergence in the first place it may be more appropriate. In these latter circumstances, it seems unlikely that the use of a benzimidazole-levamisole mixture would result in a faster build-up of resistance then would the sequential application of either drug on its own, and indeed may greatly delay it.

Editor: We read with interest the article of Dr Mastora and colleagues in the January 2004 of Radiology (1), regarding radiation dose reduction with the use of anatomically adapted online tube current modulation in the evaluation of the thoracic outlet. This method for sparing the dose is of great interest, but the authors’ recommendations may be incomplete to optimize the dose reduction to the lowest acceptable level by following the “ALARA” concept (as low as reasonably achievable) (2). In particular, we observe that the parameters for the standard protocol used in the study are very high with regard to kilovoltage (140 kV) and tube current (140 mAs). When compared with 120 kV, a standard for computed tomographic (CT) chest imaging, a kilovoltage of 140 kV represents an increase of 36% in radiation dose. As a result, the global radiation dose expressed in CT dose index is high (19 mGy for each acquisition), higher than the maximal radiation dose recommended (15.7 mGy) for thoracic CT (3). Thus, it is not surprising that reducing the dose from this high-dose level will not affect image quality for most patients. Of course, one can object that shoulders are highattenuation areas and require higher radiation dose. This is true, but it is also a region where individual variations are important (especially between men and women), so individual adaptation is crucial for optimal sparing dose strategy. Tack et al (4), who evaluated the same sparing system for the thorax and abdomen, concluded that the attenuation-based online tube current modulation does not replace the reduction in tube current presets but should be considered as a supplementary tool to decrease the radiation dose. We fully agree with this conclusion. We noted that the two nice cases used for illustration of this article involved two lightweight women (48 kg each). As noted in the discussion by the authors, it is difficult to measure the real dose absorbed by the patient in clinical routine. It is certain that in lightweight patients, however, the absorption is greater than the CT dose index displayed by the manufacturer, since the absorption rates are calculated with a 32-cm-diameter phantom intended for body imaging. Because of substantial individual differences in body weight, we showed that it was possible to reduce the radiation dose by more than 50% (by using lower kilovoltage—that is, 80 kV instead of 120 kV) without impairment of the image quality for routine thoracic imaging in patients weighing less than 60 kg (5). We did not observe substantial artifacts at the shoulder level in this work, and a higher intravenous contrast due to lower kilovoltage was appreciable for visualization of the supraaortic vessels. In conclusion, this article describes useful quantitative information about a new tool for dose reduction. Even if this article was not an attempt to define an optimal strategy for decreasing the dose in the thoracic outlet evaluation, we emphasize the primary importance of considering the patients’ anatomic parameters when the objective is to decrease the radiation dose without impairment of image quality.

OBJECTIVE: To determined the dose response of insulin resistance (IR) to estrogen in individual patients. STUDY DESIGN: Eighteen subjects meeting inclusion criteria were enrolled, and 9 completed the study. Each subject was treated for 3 months with 0.3, 0.625 and 1.25 mg of conjugated equine estrogens (CEE) in random order, for a total of 9 months of treatment. Fasting serum insulin and glucose levels were obtained. RESULTS: The fasting glucose/insulin ratio and quantitative insulin-sensitivity check index (QUICKI) were calculated. No significant change was noted in either parameter with any dose of CEE in a single subject. CONCLUSION: This was the first study to examine the dose response of IR to estrogen using paired measurements from individuals. IR does not vary in individuals when doses of estrogen are altered.

The exploitation of a number of current clinical trials and reports on outcomes after radiation therapy (i.e. breast, head and neck, prostate) in clinical practice reflects many limitations for conventional techniques and dose-fractionation schedules and for “ average ” conclusions. Even after decades of evolution of radiation therapy we still do not know how to optimize treatment for the individual patient and only have “ averages ” and ill-defined “ probabilities ” to guide treatment prescription. Wide clinical and biological heterogeneity within the groups of patients recruited into clinical trials with a few-fold variation in tumour volume within one stage of disease is obvious. Basic radiobiological guidelines concerning average cell killing of uniformly distributed and equally radiosensitive tumour cells arose from elegant but idealistic in vitro experiments and seem to be of uncertain validity. Therefore, we are confronted with more dilemmas than dogmas. Nonlinearity and in homogeneity of human tumour pattern and response to irradiation are discusses. The purpose of this paper is to present and discuss various aspects of non-uniform tumour cell targeted radiotherapy using conformal and dose intensity modulated techniques.

Dr. McDonald errs in his reply to my earlier letter "Researchers Should Talk to Workers," stating that the Amandus et al. [1987] study did not rely on McDonald's exposure estimates. Amandus [1987] states "the eight hour TWA fiber-exposure for jobs was estimated from the short term samples employing a scheme derived by McDonald et al. [1986a,b]." As this sentence indicates, Amandus et al. used Dr. McDonald's formula for the individual dose estimates. While it may be, as Dr. McDonald claims, that the Amandus team decided separately to rely on this exposure estimate, this does not obviate the fact that Amandus et al. did indeed rely on the McDonald et al. exposure scheme. Dr. McDonald's publications make no mention of his "numerous discussions with past and present employees." The only "employee" thanked for assistance in the 1986 study that was the focus of my original letter was Earl D. Lovick, the W.R. Grace Co. plant manager, an accountant by training [McDonald, 1986]. Moreover, in his sworn testimony Lovick said that he reviewed the exposure estimates with top executives at corporate headquarters, none of whom ever worked in the mine or mill. If Dr. McDonald's discussions with employees contributed to his estimates, then he should have cited (and perhaps thanked) them in his original paper. Dr. McDonald's interviews should have revealed a variety of problems with the Company's estimates. One worker, for example, testified that dust samples that were "too heavy to count" were thrown out [Egilman, 2000]. Dr. McDonald's assertion that fiber estimates which included the observations of workers would mean that tremolite was less hazardous than previously thought reveals other problems with his data. For example, Dr. McDonald underreported the occurrence of lung cancer at Libby. He reported 21 cases, but as of 1984, Grace knew of 32 asbestos lung cancers (R.C. Walsh to H.A. Eschenbach, October 18, 1983). The protocol explains why six of those lung cancers were omitted, but that still leaves 26 lung cancers that should have been included in the published papers. Since data on the higher number of lung cancers was available at the time of the study, I am hard-pressed to understand why this was omitted from the published paper. Neither Dr. McDonald nor the Grace Company has made the raw data from the tremolite studies public. Given the number and seriousness of the flaws in the McDonald et al. study, no conclusions about the toxicity of tremolite can be drawn from the Libby studies.

This paper focuses on the effects of mine design features on postclosure risk associated with a nuclear waste repository. Under conditions that enhance the effects of mine features and where the waste package allows high release rates, it was found that point-source repository models can lead to a range of ''limiting-individual'' doses covering several orders of magnitude. If engineered features are included in the models, these predicted doses are substantially lower.

The concentration of radioactive material in air and on the ground surface, released from the normal operation of the Iran-1 and Iran-2 nuclear power plants, is calculated using the AIRDOS computer code. The plants are located in the Halileh site on the coast of the Persian Gulf. These two units are of the Kraftwerk Union standardized PWR type of the 1300 MW class. The time schedule for the first criticality of these two units is mid-1980 and 1981, respectively. The nearest population centre to the site is Bushehr, with a population of ∼62 000, to the north-west and at a distance of about 18 km from the site. The calculation shows that the concentration of radioactive material in air and the ground surface deposition are higher towards the north-west than to any other direction. The annual individual dose rates released from the site are 4.4, 2.3 and 29.8 mrem for the noble gases, aerosols (with half-life longer than 8 days) and radio iodines, respectively.

The preferred dose of netilmicin was determined in each of 39 patients with severe gram-negative sepsis treated at two centres. The dose was based upon the attainment of recommended serum concentrations. Patient age varied from 18 to 87 years (mean 58), estimated creatinine clearance from 20 to 150 ml/min (mean 71), and the preferred dose from 100 to 750 mg/24 h. The dose generated by a nomogram for netilmicin was compared in retrospect with the initial dose assigned to each patient by the clinical microbiologist concerned. With respect to the preferred dose, the nomogram underdosed, on the average, by 40 mg/24 h, and the microbiologists, by 30 mg/24 h. The correlation with the preferred dose was stronger for the nomogram dose (r = 0.66; p less than 0.001, 37 df) than for the microbiologists' dose (r = 0.47; p less than 0.005, 37 df) but there was no significant difference between the two in the frequency with which they predicted the preferred dose to within 50 mg/24 h (nomogram 19/39; microbiologists 16/39). The prescription of a fixed dose of 450 mg/day to all patients would have had a similar success rate (15/39). The performance of the nomogram was better in patients with serum creatinine concentrations of greater than or equal to 100 microM (r = 0.82; p less than 0.001, 13 df; 10/15 within 50 mg/24 h of preferred dose) than in those with creatinine concentrations less than 100 microM (r = 0.55; p less than 0.01, 22 df; 9/24 within 50 mg/24 h of preferred dose).

A committee of the Health Council of the Netherlands has developed a system of activity concentration limits in order to control the radiation dose coming from building materials. For each building material two limits have been calculated: one based on an upper bound for the additional individual dose equivalent and one based on an unconditionally acceptable additional dose equivalent for parts of the population.

The biliary excretion and organ distribution of mercury was investigated in male rats which received mercuric chloride (HgCl2) (0.65 mg/kg Hg2+) or methylmercury chloride (MeHgCl) (2 mg/kg Hg) i.p. and 48 h later the same compound i.v. Mercury was labelled with 203Hg either in the first or second injection. In controls saline was substituted for unlabelled mercury. In one experiment rats pretreated with HgCl2 were given Me203HgCl 48 h later. The biliary excretion and organ distribution of 203Hg were not influenced by the injection of cold MeHgCl given before or after Me203HgCl or by HgCl2 given 48 h after 203HgCl2. HgCl2 given 48 h before the injection of 203HgCl2 or Me203HgCl significantly decreased biliary excretion of 203Hg despite increased 203Hg levels in blood and liver.

While monitoring the thenar EMG response to ulnar nerve stimulation, the authors gave either 105, 150, 210, or 300 micrograms/kg of atracurium to 60 patients. The maximal neuromuscular responses were plotted on a log-probit paper. The individual second dose required to produce 95% neuromuscular block (NMB) was estimated from a graph drawn on the paper. The maximal response following this second dose was then plotted. The mean maximal response following the second atracurium dose was 95.5% (SD range, 92.6-97.4%) NMB. The two dose-response points thus acquired resulted in the individual two-dose dose-response curve. The ED50 and ED95 and slope of the two-dose dose-response curve were compared with the single-dose dose-response curve. The average ED50 and ED95 determined by the two-dose and the single-dose techniques were nearly identical [160 micrograms/kg (SD range, 126-201 micrograms/kg) vs. 164 micrograms/kg (SD range, 150-179 micrograms/kg) and 302 micrograms/kg (SD range, 251-363 micrograms/kg) vs. 336 micrograms/kg (SD range, 274-411 micrograms/kg) respectively]. Also, the slopes of the curves were similar [6.2 (SD range, 5.2-7.2) vs. 5.4 (SD range, 4.5-6.4) probit/log]. It is therefore possible to construct an individual dose-response curve for atracurium within 7-9 min and to determine individual pharmacodynamic characteristics of atracurium from this curve.

New advice from the National Radiological Protection Board gives a range of monetary values for the unit collective dose, depending in part on the annual individual dose. In this paper the special factors in medical radiodiagnosis are described and a valuation for the man-sievert in this field is suggested. The harm to children from ionising radiation may be appreciably larger than in adults, and a different value for children and in obstetrics is suggested.

A single, rapid intravenous injection of tobramycin in doses of 1.5 mg/kg or 80 mg administered to subjects with normal renal function produced a wide range of concentrations in serum. Serum concentrations peaked at greater than 20mug/ml in one third of the subjects, but these peaks were transitory. At 6 hr the serum levels were less than 2 mug/ml in all but one subject and were less than 0.1 mug/ml in 50% of the subjects. A dosage interval of 6 hr with a total dosage of 6 mg/kg per day is recommended. The variation in individual dose responses emphasizes the need for monitoring of levels of tobramycin in serum during treatment. Serum concentrations of 4-6 mug/ml 1 hr after injection can be considered indicative of adequate therapy. Levels in serum 6 hr after administration should also be monitored, particularly in the elderly. No immediate or delayed toxic effects were observed after intravenous injection of tobramycin.

Interaction from several agents, i.e., a greater or smaller effects than expected from the sum of the individual effects can be of essentially two types: a) The agents could act in parallel on the same target, and a term depending on the doses of the agents involved would have to be added to the individual dose effect relationships (parergic interaction). b) The agents could act at different points in the chain of events leading to the observed effect, and the action of the second agent, the promotor, would be, at least in part, contingent on the action of the first inducer agent so that the dose effect relationships are linked in a multiplicative manner (metergic interaction). The dose effect surfaces for interaction depend on the type of dose effect relationship of the individual agents. Formulas are given for the general cases and are exemplified in graphs. Typical isobolic diagrams are also illustrated. These formulas may be adapted to experimental data by means of non-linear regression or maximum-likelihood analysis.

Radionuclides released from the Chernobyl accident have been dispersed throughout the Northern Hemisphere. Values are collected here of the estimates so far provided of the resultant radiation exposures in countries. The collective effective dose equivalent commitment is of the order of 800,000 man Sv. Average individual dose commitments outside the USSR range up to 4 mSv, which is approximately twice the normal annual dose from natural background radiation. The estimated average doses in countries decrease in a regular fashion with distances from the accident site.

During the test operations of JPDR-II (BWR), cracks were detected at primary pipe nozzle, and the inspections were made over about 2.5 years.In this report, the procedures such as shielding and removal of fuels which were taken to reduce radiation exposure during the inspections are summarized and the cost-benefit analysis of the shieldings were attempted to determine whether the optimum shieldings were made or not.The radiation doses was measured to be about 62 man·rem for 420 workers and the maximum individual dose was 1.3rem. The average cost to reduce exposures at various working areas was calculated approximately 1.4×105yen/man-rem.Especially, the provisional shielding at under core area reduced 61 man-rem and its reduction cost was 8.9×106 yen. Assuming that the economic and social detriment cost is 1, 000$/man-rem, it seems that the optimum shielding were taken, although the optimum conditions shifted depending on the economic and social detriment cost which cannot be simply determined. It was found that the optimum conditions depended on the order of combination of the provisional shields.

Sweden introduced limits and gave recommendations for decreasing the indoor radon daughter concentrations in 1980. The resulting experiences are summarized. From 1979 to 1987, measurements were carried out by the local authorities in about 58,000 out of 3.9 million homes in Sweden, and 5,300 homes were found to have levels exceeding the limit for existing houses, or 400 Bq/m{sup 3} of equilibrium equivalent concentration of radon (EER). This may be about 13% of the estimated 40,000 homes with levels exceeding 400 Bq/m{sup 3}. Very high levels, up to 28,000 Bq/m{sup 3}, have been found. According to the local authorities, in one third of the homes found with levels exceeding the limit (1921 homes) certain reconstruction and other measures have been taken in order to decrease the levels. In reality, measures have been carried out in more houses. The methods depend on the radon source. The average reductions found for respective methods are reported. The local authorities can require a check of the radon daughter concentrations in newly built houses when they suspect that the concentrations exceed the limit of 70 Bq/m{sup 3}. In 11% of the measured homes built during 1981 to 1985, the levels were above the limit formore » newly built houses. In 1.4% of these houses, the limit for existing houses, 400 Bq/m{sup 3}, had been exceeded. The strategy to decrease both the collective dose to the population and the individual dose is discussed.« less

Healthy adult subjects were given oral sustained-release (SR) aminophylline tablets 225 mg 12-hourly (n = 12) or 450 mg 12-hourly (n = 6) for 5 doses, and all were given aminophylline 225 mg intravenously on a separate occasion to determine individual kinetic parameters. The mean plasma theophylline half-life ( 1 1/2) from the intravenous study was 5.8 hr (SD +/- 1.9). During the 12 hr after the fifth dose of SR aminophylline, the maximum and minimum mean (SD) plasma theophylline levels were 9.7 (3.2) mug/ml and 4.9 (2.0) mug/ml for the 225-mg dose, and 21.1 (2.2) mug/ml and 11.6 (4.4) mug/ml for the 450-mg dose. Side effects were generally mild in the low-dose study, but in the high-dose study 3 subjects reported headache and 1 was withdrawn after 3 doses. Two subjects also noted nausea, and 3 reported insomnia and anxiety in the high-dose study. It was concluded that there was a considerable range of doses needed to achieve adequate plasma levels, and that the formulation studied was capable of producing reasonably stable and satisfactory plasma theophylline levels once individual dose requirements had been established.

On-off fluctuations have been studied in twenty patients with Parkinson's disease on long-term levodopa treatment. The pattern of fluctuations was related to the timing of oral levodopa ingestion in all patients. 'Predictable' fluctuators were characterized by fewer daily doses taken at longer intervals than 'unpredictable' fluctuators in whom individual dose responses tended to overlap. Most patients at least once a day experienced an unexplained failure of an oral dose to take effect. Administration of levodopa by intravenous infusion at a constant rate brought about a dramatic extension in the duration of mobility and reduced the frequency of fluctuations compared with oral therapy; apomorphine consistently reversed off phases when administered shortly after their onset, whereas lisuride was less often effective. We conclude that the development of a sustained-release formulation of levodopa would lead to improved control of the response fluctuations seen with conventional levodopa preparations.

A 0.1% aqueous solution of a preparation consisting of a selected fraction of the sodium salts of the total fatty acids of hydnocarpus oil was injected intravenously into 6 normal albino rabbits over a period of approximately one year. Injections were given at biweekly intervals into the marginal ear veins. The individual dose was calculated upon the basis of 0.0166 gm. of the sodium hydnocarpate preparation per kilo of body weight, and ranged from 0.022 gm. to 0.03 gm. (0.22 cc. to 0.3 cc. of the aqueous solution). Each animal received a total of 101 injections.During the period of observation no clinically detectable reactions to the drug occurred in any of the rabbits. At the end of this time 2 animals died, one on the day following the last injection and the other 3 days after injection. The remaining 4 animals were killed 5 days following completion of treatment. The chief pathological findings were limited to the liver and kidneys with the exception of the 2 rabbits that died. In one of these there ...

Summary 1. Treatment of oxyuriasis was undertaken in three institutionalized groups. 2. In the home J. C. 38 per cent of the individuals (23 girls and 35 boys) were found infected with Enterobius vermicularis. Rigid hygienic measures were carried out over a period of six weeks, but a 13 per cent increase in incidence occurred. 3. In the home H. H. 97 per cent of 122 boys, and in the home P. E. 81 per cent of 26 girls were found infected. Treatment of the infected boys and girls with Seal-Ins coated gentian violet medicinal in varying dosages resulted in a cure of approximately 90 per cent. 4. The untoward symptoms of gentian violet medication were not serious. Vomiting, although prevalent, was noted infrequently per individual dose; however, it was found to occur more frequently in females than in males. 5. The difference between the cure of the individual with gentian violet and the eradication of the infection in an institution is emphasized.

In 55 patients 430 thrombelastographic studies after 305 heparin injections revealed that a more complete and more rapid reduction of the over-all coagulability of the blood is obtained by a subcutaneous injection of 40 per cent heparin once every 24 hours than that obtained with prothrombin-depressing agents. The individual dose, by the thrombelastographic technic, is between 3.5 and 4.5 mg./Kg. Further clinical studies are indicated with use of simple laboratory control technics, such as recalcification time.

During recent years schemes of radiotherapy incorporating multiple treatments in one day have been introduced into the clinic. These can lead to a reduction in the overall duration of treatment (accelerated fractionation), an increase in the number of fractions in the same overall time (hyperfractionation), or a combination of both (Fowler, 1984). Two to five treatments have been given each day from Monday to Friday for 1, 2 or more weeks (Svoboda, 1978; Van der Schueren et al, 1985; Wang, 1985). It has usually been found necessary to reduce the individual dose increment from the conventional 1.8–2 Gy to between 1 Gy and 1.6 Gy but, even then, immediate reactions have prevented most workers from achieving a satisfactory total dose without interruption. Commonly, a split-course technique is employed with a rest period of 2–4 weeks to allow normal tissue reactions to settle before further radiotherapy is given. Retrospective comparisons in head and neck cancer have given improved results (Wang, 1985) but ra...