2015-2017年惠州市个人剂量异常情况的调查

目的 调查分析2015-2017年惠州市个人剂量异常原因。方法 对单次个人剂量监测结果大于1.25 mSv的人员所在单位发放《职业外照射个人监测达到调查水平剂量核查登记表》,结合电话询问和现场调查,核实剂量异常原因。结果 3年共收回调查表126份,69.84%剂量异常的为非实际受照,实际受照中以反应堆运行、工业探伤等职业类别为主,但单次受照剂量均在20 mSv以下。结论 剂量异常的大多由人为因素引起,应加强放射防护知识培训和监督执法管理力度,提高放射工作人员个人防护意识,同时还应明确调查水平规范调查程序。     

A statistical model for species extrapolation using categorical response data

Predictions of human health risk for single chemicals are often based on animal studies and hence require some sort of adjustment for species differences in toxic susceptibility. In the past, either the animal dose has been divided by an uncertainty factor or the dose has been transformed by a mathematical model into a human equivalent dose. A generalization of the allometric model previously used for carcinogens, the so-called "surface area model," is investigated here for use with graded severity response data for noncarcinogenic systemic toxicity. Statistical methods for estimating one of the model's parameters, the power of body weight, are proposed and tested on simulated and actual toxicity data. Early results indicate reasonable accuracy if data are available for a large number of dose groups.     

Comparative in vitro percutaneous absorption of nonylphenol and nonylphenol ethoxylates (NPE-4 and NPE-9) through human, porcine and rat skin

The purpose of this study was to assess the percutaneous absorption of nonylphenol (NP) and the nonylphenol ethoxylates, NPE-4 and NPE-9, in human, porcine and rat skin. In vitro studies with the NPEs were conducted for 8 h in flowthrough diffusion cells using topical solutions of 0.1, 1.0 and 10% in PEG-400 or 1% in water (NPE-9 only). NP absorption was assessed as a 1% solution in PEG-400. All compounds were 14C ring-labeled and radioactivity in perfusate was monitored over time. Skin deposition was measured at the termination of the experiment. Absorption into perfusate and total penetration (compound absorbed plus compound sequestered in skin) were calculated. Absorption of NPE-4, NPE-9 and NP was similar across all species at less than 1% of the applied dose over 8 h. Penetration was generally below 5% of applied dose, the majority located in the stratum corneum. In all species and for both NPEs, the fraction of dose absorbed was highest for the lowest applied dose. Absorptions expressed as actual mass absorbed over 8 h were similar (approximately 0.3 microg/cm2) across all concentrations. Penetration, but not absorption, was greater from a water vehicle compared to a PEG-400 vehicle, particularly in rat skin. These studies suggest that NP, NPE-4 and NPE-9 were minimally absorbed across skin from all three species. Fractional absorption was concentration-dependent, making the actual absorbed flux constant across all doses.     

A Markov mixed effect regression model for drug compliance

Patient compliance (adherence) with prescribed medication is often erratic, while clinical outcomes are causally linked to actual, rather than nominal medication dosage. We propose here a hierarchical Markov model for patient compliance. At the first stage, conditional upon individual random effects and a set of individual-specific nominal daily dose times, we assume that (i) the subject-specific probability of taking zero, one, or more than one dose associated with a given nominal dose time depends on the value of certain covariates, and on the number of doses associated with the immediate previous time, but is independent of any other previous or future dosing events (the Markov hypothesis); and (ii) the set of ‘errors’ between actual dose times associated with each nominal time is multivariate normally distributed, conditional on covariates and the number of such actual dose times, as in (i). At the second stage, a multivariate normal distribution is assumed for the individual random effects. We fit this model by maximum likelihood to data collected over three months using an electronic system for recording actual dose times in HIV-positive patients assigned to a regimen of zidovudine thrice daily. Beyond its value for describing and quantifying compliance behaviour, as illustrated here, the model may prove useful for explanatory analyses of clinical trials. © 1998 John Wiley & Sons, Ltd.     

Effects of insulin on muscle tissue

The anabolic nature of insulin on muscle protein has been recognized since the initial clinical use of insulin therapy in type 1 diabetes about sixty years ago, but the exact mechanism whereby insulin effects muscle protein metabolism in human subjects remains unclear. In particular, the effect of insulin on muscle protein synthesis has been debated. In vitro studies document a stimulatory effect of insulin on muscle protein synthesis, but in vivo results are conflicting. Everything from decreased muscle protein synthesis to increased muscle protein synthesis in response to insulin has been reported. A recent publication suggests that the response of muscle protein synthesis to insulin is dose dependent, and that only supraphysiological dose of insulin stimulate muscle protein synthesis. On the other hand, some studies show a stimulatory effect of insulin in low doses. It is possible to form a more coherent picture of the effect of insulin if the results from various experiments are expressed in the context of the availability of amino acids. In general, insulin stimulated muscle protein synthesis in studies in which intramuscular amino acid availability was maintained or increased regardless of the dose of insulin. In contrast, insulin was ineffective in stimulating muscle protein synthesis when amino acid availability was allowed to drop, irrespective of the dose of insulin. Thus, whereas insulin has a potential stimulatory effect on human muscle protein synthesis, an adequate availability of amino acids is required for that potential to be expressed in an actual increase in the synthetic rate.     

一种核电站事故工况下安全壳内剂量率的估算方法

目的 通过估算冷却剂丧失事故(LOCA)时间内的安全壳内剂量率,推测事故的大小和发展趋势,为防止事故扩大、保护公众辐射安全提供依据。方法 根据国内某核电站安全分析报告及LOCA事故应急演习的实际情况基础上,提出了冷却剂丧失事故工况序列MCNP耦合计算方法,将该计算方法用于LOCA事故实际演习边界条件计算。结果 计算结果与现场事故期间安全壳内γ辐射剂量率监测通道的实际读数比对,数据匹配较好。结论 该计算方法经验证可以用于类似事故工况下安全壳内剂量率的估算,为事故工况下安全壳内的放射性变化情况提供参考。     

Mayak film dosimeter response studies, part iii: application to worker dose assessment

This paper describes the methods used to correct individual dosimeter readings for workers to obtain estimates of worker doses received at the Mayak Production Association (Mayak PA). Film dosimeters were used at Mayak PA for worker monitoring from 1948 until 1992. The method requires a determination of the relationship between the absorbed dose in film emulsion and the dose in air under calibration conditions, which is then extended to exposures in the actual radiation fields of the workplace. Corrections needed to account for actual workplace exposure conditions were determined by modeling with the Monte Carlo radiation transport computer code MCNP. Correction factors were developed to convert from dosimeter reading to a realistic worker dose. The method was applied as a basis for individual dose reconstruction using film dosimeters in realistic photon spectra and geometries at Mayak PA work areas.     

DR实际光野外影像成因的研究

目的:研究DR原始图像光野外的影像成因,减少患者辐射剂量,实现放射防护最优化。方法:分析原始图像光野外影像成因及射线来源,比较指示野与实际射线光野是否一致,外加遮线器以增加遮线器厚度减少漏线,使用自制可调手动遮线器对身体附近射线进行遮挡实验。结果:DR原始图像光野外影像是直射线方向产生的散射线照射到患者后在探测器形成的影像。结论:DR原始图像实际光野外影像是原发射线方向上的散射线照射到患者后,由于探测器(FD)比较灵敏,使患者肢体在探测器实际射线光野外形成的污渍影像,符合散射线"污渍效应"成像。     

精确校准直线加速器的注意事项

直线加速器是肿瘤放射治疗的主要设备,射线剂量大小的准确直接影响肿瘤实际吸收剂量,从面影响放射治疗的效果。因此精确校准直线加速器剂量是非常很需要的。     

Enhanced radiobiological effects at the distal end of a clinical proton beam: in vitro study

In the clinic, the relative biological effectiveness (RBE) value of 1.1 has usually been used in relation to the whole depth of the spread-out Bragg-peak (SOBP) of proton beams. The aim of this study was to confirm the actual biological effect in the SOBP at the very distal end of clinical proton beams using an in vitro cell system. A human salivary gland tumor cell line, HSG, was irradiated with clinical proton beams (accelerated by 190 MeV/u) and examined at different depths in the distal part and the center of the SOBP. Surviving fractions were analyzed with the colony formation assay. Cell survival curves and the survival parameters were obtained by fitting with the linear–quadratic (LQ) model. The RBE at each depth of the proton SOBP compared with that for X-rays was calculated by the biological equivalent dose, and the biological dose distribution was calculated from the RBE and the absorbed dose at each position. Although the physical dose distribution was flat in the SOBP, the RBE values calculated by the equivalent dose were significantly higher (up to 1.56 times) at the distal end than at the center of the SOBP. Additionally, the range of the isoeffective dose was extended beyond the range of the SOBP (up to 4.1 mm). From a clinical point of view, this may cause unexpected side effects to normal tissues at the distal position of the beam. It is important that the beam design and treatment planning take into consideration the biological dose distribution.     

应用Geant4模拟EBT3胶片的能量响应和质子射程测量

目的 计算EBT3胶片吸收剂量的能量依赖性，展示EBT3胶片测量质子吸收剂量时的误差。方法 在临床光子和质子能量照射范围内逐步增加射线束能量，应用Geant4计算EBT3胶片吸收剂量与同体积水吸收剂量的差异，并与理论结果进行比对。结果 对于光子和质子来说，EBT3胶片吸收剂量能量依赖性与理论结果一致的分界线分别为100 keV和11 MeV；光子和质子能量高于相应值时EBT3胶片能量依赖性与理论结果保持一致，低于相应值时EBT3胶片能量依赖性与理论结果无关；计算EBT3胶片测量质子布拉格峰和50%剂量点与实际位置的差异，最大误差小于1%。结论 对较高能量区间内的质子和光子来说，EBT3胶片吸收剂量能量依赖性可忽略；对低能量区间的质子和光子，EBT3胶片吸收剂量能量依赖性差异较大，应给予重点关注。EBT3胶片测量的质子布拉格峰和50%剂量点与实际位置基本一致。     

呼吸运动对胸腹部肿瘤照射剂量分布的影响

目的：研究放疗中呼吸运动对胸腹部肿瘤照射时靶区实际剂量分布的影响。方法：在不同组织运动幅度下，分别用自动呼吸运动模拟机带慢感光胶片行伽玛刀单靶点模拟照射。获得靶区实际剂量分布图。以得出“靶体积大小修正因子”（Fv）进行比较。结果：呼吸运动对靶区实际剂量分布有影响；呼吸运动幅度越大，剂量分布面积越大。射野最大剂量值越小；运动幅度小于射野半高宽时，高剂量区为椭圆形，且椭圆的短轴方向与运动方向相同；当运动幅度大于射野半高宽时，高刺量区被拉长，变为椭圆的长轴方向与运动方向相同；呼吸运动幅度越大，Fv值越大。结论：放疗中必须根据患者呼吸运动幅度大小。修正临床靶区和靶区内剂量。确保放疗质量。     

用儿童药物利用指数评价儿科用药剂量合理性

合理用药是指根据患者的临床治疗需要进行给药,且药物给予剂量以及使用疗程应符合患者的实际情况,患者所负担的药物费用对患者自身病情以及社会均价有所值。儿科用药剂量的不合理主要表现对患儿进行相应诊断后,给予的单次用药剂量或单日用药剂量偏多或偏少。在进行治疗时,应遵循疗效确切、无不良反应或较少不良反应、服用方式较为方便易操作以及价格相对合理的药物为原则．根据患儿的年龄以及患儿实际病情采用适合的给药途径,考虑患儿的体质、疾病种类、药物敏感度等综合情况进行给药剂量的判断,并根据患儿的病情变化及时调整给药剂量。     

Investigation of magnetic nanoparticles for the rapid extraction and assay of alpha-emitting radionuclides from urine: demonstration of a novel radiobioassay method

In the event of an accidental or intentional release of radionuclides into a populated area, massive numbers of people may require radiobioassay screening as triage for dose-reduction therapy or identification for longer-term follow-up. If the event released significant levels of beta- or alpha-emitting radionuclides, in vivo assays would be ineffective. Therefore, highly efficient and rapid analytical methods for radionuclide detection from submitted spot urine samples (≤50 mL) would be required. At present, the quantitative determination of alpha-emitting radionuclides from urine samples is highly labor intensive and requires significant time to prepare and analyze samples. Sorbent materials that provide effective collection and enable rapid assay could significantly streamline the radioanalytical process. The authors have demonstrated the use of magnetic nanoparticles as a novel method of extracting media for four alpha-emitting radionuclides of concern (polonium, radium, uranium and americium) from chemically-unmodified and pH-2 human urine. Herein, the initial experimental sorption results are presented along with a novel method that uses magnetic nanoparticles to extract radionuclides from unmodified human urine and then collect the magnetic field-induced particles for subsequent alpha-counting-source preparation. Additionally, a versatile human dose model is constructed that determines the detector count times required to estimate dose at specific protective-action thresholds. The model provides a means to assess a method's detection capabilities and uses fundamental health physics parameters and actual experimental data as core variables. The modeling shows that, with effective sorbent materials, rapid screening for alpha-emitters is possible with a 50-mL urine sample collected within 1 wk of exposure/intake.     

Estimating Human Exposures to Environmental Pollutants: Availability and Utility of Existing Databases

Information about human exposures to environmental agents is a crucial component of informed decisions about protection of public health. Results from an inventory of exposure-related databases are used to examine the value of exposure information for risk assessment, risk management, surveillance of status and trends, and epidemiologic studies. Findings indicate that current and future exposure-related databases should include (1) standardized procedures for the collection, storage, analysis, and reporting of data; (2) an enhanced ability to compare data over time, i.e., conduct comparison studies of “old” and “new” methods; (3) mechanisms for coordination and cooperation among public and private-sector organizations with respect to the design, maintenance, exchange, and review of information systems; (4) measurements of actual exposures and dose for relevant human populations; and (5) data collection, storage, and retrieval methods that permit easy manipulation of information for both model building and testing.     

Incorporation of gantry angle correction for 3D dose prediction in intensity-modulated radiation therapy

Pretreatment dose verification with beam-by-beam analysis for intensity-modulated radiation therapy (IMRT) is commonly performed with a gantry angle of 0° using a 2D diode detector array. Any changes in multileaf collimator (MLC) position between the actual treatment gantry angle and 0° may result in deviations from the planned dose. We evaluated the effects of MLC positioning errors between the actual treatment gantry angles and nominal gantry angles. A gantry angle correction (GAC) factor was generated by performing a non-gap test at various gantry angles using an electronic portal imaging device (EPID). To convert pixel intensity to dose at the MLC abutment positions, a non-gap test was performed using an EPID and a film at 0° gantry angle. We then assessed the correlations between pixel intensities and doses. Beam-by-beam analyses for 15 prostate IMRT cases as patient-specific quality assurance were performed with a 2D diode detector array at 0° gantry angle to determine the relative dose error for each beam. The resulting relative dose error with or without GAC was added back to the original dose grid for each beam. We compared the predicted dose distributions with or without GAC for film measurements to validate GAC effects. A gamma pass rate with a tolerance of 2%/2 mm was used to evaluate these dose distributions. The gamma pass rate with GAC was higher than that without GAC (P = 0.01). The predicted dose distribution improved with GAC, although the dosimetric effect to a patient was minimal.     

Conflicting views on chemical carcinogenesis arising from the design and evaluation of rodent carcinogenicity studies

Conflicting views have been expressed frequently on assessments of human cancer risk of environmental agents based on animal carcinogenicity data; this is primarily because of uncertainties associated with extrapolations of toxicologic findings from studies in experimental animals to human circumstances. Underlying these uncertainties are issues related to how experiments are designed, how rigorously hypotheses are tested, and to what extent assertions extend beyond actual findings. National and international health agencies regard carcinogenicity findings in well-conducted experimental animal studies as evidence of potential carcinogenic risk to humans. Controversies arise when both positive and negative carcinogenicity data exist for a specific agent or when incomplete mechanistic data suggest a possible species difference in response. Issues of experimental design and evaluation that might contribute to disparate results are addressed in this article. To serve as reliable sources of data for the evaluation of the carcinogenic potential of environmental agents, experimental studies must include a) animal models that are sensitive to the end points under investigation; b) detailed characterization of the agent and the administered doses; c) challenging doses and durations of exposure (at least 2 years for rats and mice); d) sufficient numbers of animals per dose group to be capable of detecting a true effect; e) multiple dose groups to allow characterization of dose-response relationships, f) complete and peer-reviewed histopathologic evaluations; and g) pairwise comparisons and analyses of trends based on survival-adjusted tumor incidence. Pharmacokinetic models and mechanistic hypotheses may provide insights into the biological behavior of the agent; however, they must be adequately tested before being used to evaluate human cancer risk.     

Application of in vitro biotransformation data and pharmacokinetic modeling to risk assessment

The adverse biological effects of toxic substances are dependent upon the exposure concentration and the duration of exposure. Pharmacokinetic models can quantitatively relate the external concentration of a toxicant in the environment to the internal dose of the toxicant in the target tissues of an exposed organism. The exposure concentration of a toxic substance is usually not the same as the concentration of the active form of the toxicant that reaches the target tissues following absorption, distribution, and biotransformation of the parent toxicant. Biotransformation modulates the biological activity of chemicals through bioactivation and detoxication pathways. Many toxicants require biotransformation to exert their adverse biological effects. Considerable species differences in biotransformation and other pharmacokinetic processes can make extrapolation of toxicity data from laboratory animals to humans problematic. Additionally, interindividual differences in biotransformation among human populations with diverse genetics and lifestyles can lead to considerable variability in the bioactivation of toxic chemicals. Compartmental pharmacokinetic models of animals and humans are needed to understand the quantitative relationships between chemical exposure and target tissue dose as well as animal to human differences and interindividual differences in human populations. The data-based compartmental pharmacokinetic models widely used in clinical pharmacology have little utility for human health risk assessment because they cannot extrapolate across dose route or species. Physiologically based pharmacokinetic (PBPK) models allow such extrapolations because they are based on anatomy, physiology, and biochemistry. In PBPK models, the compartments represent organs or groups of organs and the flows between compartments are actual blood flows. The concentration of a toxicant in a target tissue is a function of the solubility of the toxicant in blood and tissues (partition coefficients), blood flow into the tissue, metabolism of the toxicant in the tissue, and blood flow out of the tissue. The appropriate degree of biochemical detail can be added to the PBPK models as needed. Comparison of model simulations with experimental data provides a means of hypothesis testing and model refinement. In vitro biotransformation data from studies with isolated liver cells or subcellular fractions from animals or humans can be extrapolated to the intact organism based upon protein content or cell number. In vitro biotransformation studies with human liver preparations can provide quantitative data on human interindividual differences in chemical bioactivation. These in vitro data must be integrated into physiological models to understand the true impact of interindividual differences in chemical biotransformation on the target organ bioactivation of chemical contaminants in air and drinking water.     

利用前剂量技术进行辐射事故剂量重建的研究

目的 为估算无个人剂量监测资料时的事故剂量及流行病学研究中的剂量重建提供可行的方法。方法 用事故现场可获得的陶性材料(红砖)为样品,提取其中的石英颗粒,利用前剂量热释光技术进行模拟照射的剂量估算,并与实际照射量进行比较。结果 利用前剂量技术进行模拟照射的剂量估算具有较高的准确性。结论 初步建立了一种以事故现场材料为样品的剂量重建方法,并对影响测量的主要因素进行了讨论。     

机械误差对相邻野衔接处的剂量影响

目的：定性的探讨放射治疗机的机械误差对相邻野衔接处剂量的影响。方法：假定患者的相邻野设计采用半野衔接技术,相邻野相交方向的实际位置与数字指示之间有±1．0mm的误差,利用三维治疗计划系统和胶片剂量仪模拟分析这种误差对实际剂量分布的影响。结果：理论上,用半野衔接技术可以非常好的解决相邻野的剂量衔接问题。而在实际放疗中,如果由于机械误差造成相邻野在衔接部分有重叠区,在辐射野的重叠区,剂量分布会比治疗计划预期高出约10％之多;如果由于机械误差造成相邻野在衔接部分有留空区,在辐射野的留空区,剂量分布会比治疗计划预期低约10％。结论：本研究表明尽管在物理技术方面做了很好的质量保证,但体外照射治疗机很小的机械误差（±1．0mm）也会造成相邻野衔接处的剂量分布与治疗计划有很大的差异。而且机械误差是系统误差,影响疗程总量,对靶区和危及器官的累积物理剂量和生物等效剂量有很大的影响,而这种剂量分布的改变很难为医技人员所掌握控制。因此,在设计治疗计划时,应该尽量避免使用相邻野。