Estimating human cancer risk from the results of animal experiments: relationship between mechanism and dose-rate and dose.

Experimental animals are often used as surrogate models in estimating human cancer risk from environmental agents when adequate epidemiological data are not available. Studies in experimental animals have usually evaluated the effects of exposure to single substances; however, humans receive combinations of exposures, to both initiators and promoters of carcinogenesis. Exposure to several agents may modify the carcinogenic process of one of them. For many agents, the relationship between dose and carcinogenic response depends on both dose-rate and cumulative dose. For a given total dose, dose-rate may affect carcinogenic potency both qualitatively (target organ) and quantitatively. The effects of dose-rate are a function of total dose, species, and most importantly, the mechanism by which the agent exerts its carcinogenic effect. Prediction of the effects of different dose-rates of potentially carcinogenic agents can be based on knowledge of its mechanism of action.     

Radiation cancer risk at different dose rates: new dose-rate effectiveness factors derived from revised A-bomb radiation dosimetry data and non-tumor doses

The dose rate of atomic bomb (A-bomb) radiation to the survivors has still remained unclear, although the dose–response data of A-bomb cancers has been taken as a standard in estimating the cancer risk of radiation and the dose and dose-rate effectiveness factor (DDREF). Since the applicability of the currently used DDREF of 2 derived from A-bomb data is limited in a narrow dose-rate range, 0.25-75 Gy/min as estimated from analysis of DS86 dosimetry data in the present study, a non-tumor dose (D_nt) was applied in an attempt to gain a more universal dose-rate effectiveness factor (DREF), where D_nt is an empirical parameter defined as the highest dose at which no statistically significant tumor increase is observed above the control level and its magnitude depends on the dose rate. The new DREF values were expressed as a function of the dose rate at four exposure categories, i.e. partial body low LET, whole body low linear energy transfer (LET), partial body high LET and whole body high LET and provided a value of 14 for environmental level radiation at a dose rate of 10⁻⁹ Gy/min for whole body low LET.     

光子外照射周围剂量当量与空气比释动能转换系数的实验研究

为执行国际辐射单位与测量委员会（ Ｉ Ｃ Ｒ Ｕ） 的建议，在光子外照射环境和个人剂量监测中使用实用量，研究周围剂量当量 Ｈ（１０） 与空气比释动能 Ｋａ 之间的转换系数。方法是用直径３０ｃｍ 的聚乙烯球代替 Ｉ Ｃ Ｒ Ｕ 球，利用热释光探测器测量球表面与球内深度１０ｍ ｍ 处两位置的空气比释动能，经过一些必要的修正，将测量结果转化为 Ｉ Ｃ Ｒ Ｕ 球内的剂量值。在 Ｉ Ｓ Ｏ４０３７ 规范的窄谱 Ｘ 射线和１３７ Ｃｓ 、６０ Ｃｏ γ射线准平行束照射条件下，测量了 Ｈ（１０）／ Ｋａ 的值，分析了测量中不确定度的来源及其大小，转换系数的总不确定度为３２ ％ 。本文还与有关文献报道结果作了比较和分析。表明测量结果与理论计算值在误差范围内一致，转换因子可用于环境监测仪和个人剂量计的刻度。     

New condensed pyrroles of potential biological interest syntheses and structure-activity relationship studies

The Pyrrole derivatives Ia-d were prepared and utilized for the preparation of pyrrolo[2,3-d]pyrimidine derivatives IIa-c, III, IVa-e, V and VIIIa-c; pyrrolo[3,2-e]tetrazolo[1,5-c]pyrimidine VI and pyrrolo[4,3e][1,2,4]triazolo[1,5-c]pyrimidine derivative derivatives VIIa-c. These some newly synthesized compounds were examined for their in vitro antimicrobial activity and in vivo anti-inflammatory. Result indicated that these compounds showed promising anti-inflammatory activity in comparison to ibuprofen (the standard anti-inflammatory drug). The structure-activity relationships (SAR) and anti-inflammatory activities of these compounds are also discussed in this paper.     

Evaluation of a national register on occupational exposure to carcinogens: effectiveness in the prevention of occupational cancer, and cancer risks among the exposed workers

OBJECTIVES: The objective of this study was to evaluate the performance and effectiveness of a register of employees exposed to carcinogens (the ASA Register) which has been in operation in Finland since 1979, and to study cancer risks among the notified workers. METHODS: The impact of ASA at workplaces was studied by questionnaires mailed to 1448 work departments, which were notified to ASA in 1996, and to 1033 departments, which departed ASA in 1991-1996. The mailing was responded by 69% of departments. The cancer incidence of 35,138 workers notified to ASA in 1979-1988 was followed up through the files of the Finnish Cancer Register for the period 1980-2003. RESULTS: Changes eliminating or substantially reducing exposure to carcinogens were reported by 73% of departments notified to ASA in 1996. The ASA notification process had directly prompted measures to reduce exposure (8% of cases) or contributed to them (24% of cases). Estimations based on responses of the workplaces suggested that the ASA registration had decreased exposure of 600 workers year(-1) (out of approximately 15,000 notified workers, which is <1% of the employed in Finland), preventing thereby an unknown number of occupational cancers. Other benefits of ASA included the saving of the treatment costs of prevented cancers, the prevention of other health outcomes of carcinogens, improved safety behaviour of exposed workers and avoidance of human suffering among cancer patients and their families. The labour safety authorities had better possibilities to direct their activities against carcinogen exposure. These benefits should be considered against the annual costs, mainly due to 7-8 person-years of work required by tasks related to ASA. The results of the cancer incidence study among notified workers were based on a relatively short follow-up (on average 19 years). The incidence of mesothelioma was significantly increased in the ASA cohort, probably due to exposure to asbestos. CONCLUSIONS: These results suggest that a national exposure register may stimulate preventive measures at workplaces. Partially based on the results of the present study the Finnish Ministry of Social Affairs and Health continues ASA registration.     

剂量沉积方式在食管癌放疗中的差异性研究

目的 研究Monaco计划系统(Monaco Treatment planning system,Monaco TPS)应用不同剂量沉积方式的情况下,对中下段食管癌放射治疗的剂量学影响.方法 选取30例T3N0M0 Ⅱ a期中下段食管癌患者进行实验,使用瑞典医科达公司Monaco 5.11TPS的X射线体素蒙特卡洛(X...     

Marginal estimation for multi-stage models: waiting time distributions and competing risks analyses.

We provide non-parametric estimates of the marginal cumulative distribution of stage occupation times (waiting times) and non-parametric estimates of marginal cumulative incidence function (proportion of persons who leave stage j for stage j' within time t of entering stage j) using right-censored data from a multi-stage model. We allow for stage and path dependent censoring where the censoring hazard for an individual may depend on his or her natural covariate history such as the collection of stages visited before the current stage and their occupation times. Additional external time dependent covariates that may induce dependent censoring can also be incorporated into our estimates, if available. Our approach requires modelling the censoring hazard so that an estimate of the integrated censoring hazard can be used in constructing the estimates of the waiting times distributions. For this purpose, we propose the use of an additive hazard model which results in very flexible (robust) estimates. Examples based on data from burn patients and simulated data with tracking are also provided to demonstrate the performance of our estimators.     

食管癌调强放疗靶区与肺体积比和处方剂量的关系

目的 研究食管癌调强放射治疗中能够做出既定目标的放疗计划时,靶区体积与肺体积比值和处方剂量的关系,从而帮助临床医生根据靶区情况,选择适合的处方剂量.方法 随机选取临床上己进行放射治疗的食管癌患者80例;其中病变范围包括全部食管癌类型,靶区根据ICRU(International Commission Radiologi...     

Cost effectiveness of interventions to promote screening for colorectal cancer: a randomized trial

Objectives

Screening for colorectal cancer is considered cost effective, but is underutilized in the U.S. Information on the efficiency of "tailored interventions" to promote colorectal cancer screening in primary care settings is limited. The paper reports the results of a cost effectiveness analysis that compared a survey-only control group to a Centers for Disease Control (CDC) web-based intervention (screen for life) and to a tailored interactive computer-based intervention.

Methods

A randomized controlled trial of people 50 and over, was conducted to test the interventions. The sample was 1224 partcipants 50-70 years of age, recruited from Kelsey-Seybold Clinic, a large multi-specialty clinic in Houston, Texas. Screening status was obtained by medical chart review after a 12-month follow-up period. An "intention to treat" analysis and micro costing from the patient and provider perspectives were used to estimate the costs and effects. Analysis of statistical uncertainty was conducted using nonparametric bootstrapping.

Results

The estimated cost of implementing the web-based intervention was $40 per person and the cost of the tailored intervention was $45 per person. The additional cost per person screened for the web-based intervention compared to no intervention was $2602 and the tailored intervention was no more effective than the web-based strategy.

Conclusions

The tailored intervention was less cost-effective than the web-based intervention for colorectal cancer screening promotion. The web-based intervention was less cost-effective than previous studies of in-reach colorectal cancer screening promotion. Researchers need to continue developing and evaluating the effectiveness and cost-effectiveness of interventions to increase colorectal cancer screening.     

内镜逆行胰胆管造影术（ERCP）中放射工作人员有效剂量估算与分析

目的 通过调查取得ERCP手术的相关参数,模拟ERCP手术过程,借助仿真人体模型、热释光剂量计,测量计算吸收剂量,为估算放射工作人员受照剂量提供基础数据。方法 通过现场调查的ERCP过程的透视时间及摄片帧数,选取实验照射条件进行照射,用仿真人体模型替代放射工作人员,测量吸收剂量。结果 共选取5组实验条件,包括放射工作人员未穿铅衣的L、M、S组和穿铅衣后的M、L剂量组。S组（无铅衣）有效剂量为2.63 μSv,M组（无铅衣）有效剂量为9.38 μSv,M组（有铅衣）有效剂量为0.58 μSv,L组（无铅衣）有效剂量为29.11 μSv,L组（有铅衣）有效剂量为7.48 μSv。结论 放射工作人员有效剂量随着透视时间的增加而增加;穿戴铅衣组别的有效剂量明显低于未穿戴铅衣的组别。虽然在床侧装有铅帘,床旁设有铅屏,但放射工作人员的个人防护用品仍不容忽视。     

Patient-centered, comparative effectiveness of esophageal cancer screening: protocol for a comparative effectiveness research study to inform guidelines for evidence-based approach to screening and surveillance endoscopy

ABSTRACT: BACKGROUND: The comparative effectiveness (CE) of endoscopic screening (versus no screening) for Barrett's esophagus (BE) in patients with GERD symptoms, or among different endoscopic surveillance strategies in patients with BE, for the early detection of esophageal adenocarcinoma (EA) is unknown. Furthermore, it is unclear if patients or providers have or will adopt any of these strategies (screening only, screening and surveillance, vs. none), irrespective of their effectiveness. Endoscopic screening and surveillance is expensive and can be risky. Therefore, it is imperative to establish the CE and acceptability about the risks and outcomes related to these practices to better inform expert recommendations and provider-patient decisions.Methods/ResultsWe propose a mixed methods study which will involve: (1) an analysis of secondary databases (VA and VA-Medicare linked datasets for 2004--09) to examine CE of endoscopic screening and surveillance in an observational study cohort (an estimated 680,000 patients with GERD; 25,000--30,000 with BE; and 3,000 with EA); (2) a structured electronic medical record (EMR) review on a national sample of patients using VA EMRs to verify all EA cases, identify cancer stage, cancer-targeted therapy, and validate the screening and surveillance endoscopy; and (3) qualitative in depth interviews with patients and providers to elicit preferences, norms, and behaviors to explain clinical contexts of these findings and address gaps arising from the CE study. CONCLUSION: This study will compare clinical strategies for detecting and monitoring BE, a pre-cancerous lesion. Additionally, by eliciting acceptability of these strategies for patients and providers, we will be able to propose effective and feasible strategies that are likely to be implemented in routine use. Findings will inform recommendations for clinical practice guidelines. Our innovative approach is consistent with the methodological standards of patient-centered outcomes research, and our findings will offer a significant contribution to the literature on cancer surveillance.Trial RegistrationNot applicable.     

Condom effectiveness for reducing transmission of gonorrhea and chlamydia: the importance of assessing partner infection status

This analysis examined the importance of differential exposure to infected partners in epidemiologic studies of latex condom effectiveness for prevention of sexually transmitted infections. Cross-sectional, enrollment visit data were analyzed from Project RESPECT, a trial of counseling interventions conducted at five publicly funded US sexually transmitted disease clinics between 1993 and 1997. The association between consistent condom use in the previous 3 months and prevalent gonorrhea and chlamydia (Gc/Ct) was compared between participants known to have infected partners and participants whose partner infection status was unknown. Among 429 participants with known Gc/Ct exposure, consistent condom use was associated with a significant reduction in prevalent gonorrhea and chlamydia (30% vs. 43%; adjusted prevalence odds ratio = 0.42, 95% confidence interval: 0.18, 0.99). Among 4,314 participants with unknown Gc/Ct exposure, consistent condom use was associated with a lower reduction in prevalent gonorrhea and chlamydia (24% vs. 25%; adjusted prevalence odds ratio = 0.82, 95% confidence interval: 0.66, 1.01). The number of unprotected sex acts was significantly associated with infection when exposure was known (p for trend < 0.01) but not when exposure was unknown (p for trend = 0.73). Restricting analyses to participants with known exposure to infected partners provides a feasible and efficient mechanism for reducing confounding from differential exposure to infected partners in condom effectiveness studies.     

Software for the estimation of foetal radiation dose to patients and staff in diagnostic radiology.

Occasionally, it is clinically necessary to perform a radiological examination(s) on a woman who is known to be pregnant or an examination is performed on a woman who subsequently discovers that she was pregnant at the time. In radiological examinations, especially of the lower abdomen and pelvis area, the foetus is directly irradiated. It is therefore important to be able to determine the absorbed dose to the foetus in diagnostic radiology for pregnant patients as well as the foetal dose from occupational exposure of the pregnant worker. The determination of the absorbed dose to the unborn child in diagnostic radiology is of interest as a basis for risk estimates from medical exposure of the pregnant patient and occupational exposure of the pregnant worker. In this paper we describe a simple computer program, FetDose, which calculates the dose to the foetus from both medical and occupational exposures of the pregnant woman. It also calculates the risks of in utero exposure, compares calculated doses with published data in the literature and provides information on the natural spontaneous risks. The program will be a useful tool for the medical and paramedical personnel who are involved with foetal dose (and hence risks) calculations and counselling of pregnant women who may be concerned about in utero exposure of their foetuses.     

Use of the bioaccumulation factor to screen chemicals for bioaccumulation potential

The fish bioconcentration factor (BCF), as calculated from controlled laboratory tests, is commonly used in chemical management programs to screen chemicals for bioaccumulation potential. The bioaccumulation factor (BAF), as calculated from field-caught fish, is more ecologically relevant because it accounts for dietary, respiratory, and dermal exposures. The BCFBAF? program in the U.S. Environmental Protection Agency's Estimation Programs Interface Suite (EPI Suite? Ver 4.10) screening-level tool includes the Arnot-Gobas quantitative structure-activity relationship model to estimate BAFs for organic chemicals in fish. Bioaccumulation factors can be greater than BCFs, suggesting that using the BAF rather than the BCF for screening bioaccumulation potential could have regulatory and resource implications for chemical assessment programs. To evaluate these potential implications, BCFBAF was used to calculate BAFs and BCFs for 6,034?U.S. high- and medium-production volume chemicals. The results indicate no change in the bioaccumulation rating for 86% of these chemicals, with 3% receiving lower and 11% receiving higher bioaccumulation ratings when using the BAF rather than the BCF. All chemicals that received higher bioaccumulation ratings had log K(OW ) values greater than 4.02, in which a chemical's BAF was more representative of field-based bioaccumulation than its BCF. Similar results were obtained for 374 new chemicals. Screening based on BAFs provides ecologically relevant results without a substantial increase in resources needed for assessments or the number of chemicals screened as being of concern for bioaccumulation potential. Environ. Toxicol. Chem. 2012; 31: 2261-2268. ? 2012 SETAC.