Cancer mortality among atomic bomb survivors exposed as children

Objectives

To compare cancer mortality among A-bomb survivors exposed as children with cancer mortality among an unexposed control group (the entire population of Japan, JPCG).

Methods

The subjects were the Hiroshima and Nagasaki A-bomb survivor groups (0–14 years of age in 1945) reported in life span study report 12 (follow-up years were from 1950 to 1990), and a control group consisting of the JPCG. We estimated the expected number of deaths due to all causes and cancers of various causes among the exposed survivors who died in the follow-up interval, if they had died with the same mortality as the JPCG (0–14 years of age in 1945). We calculated the standardized mortality ratio (SMR) of A-bomb survivors in comparison with the JPCG.

Results

SMRs were significantly higher in exposed boys overall for all deaths, all cancers, leukemia, and liver cancer, and for exposed girls overall for all cancers, solid cancers, liver cancer, and breast cancer. In boys, SMRs were significantly higher for all deaths and liver cancer even in those exposed to very low doses, and for all cancers, solid cancers, and liver cancer in those exposed to low doses. In girls, SMRs were significantly higher for liver cancer and uterine cancer in those exposed to low doses, and for leukemia, solid cancers, stomach cancer, and breast cancer in those exposed to high doses.

Conclusions

We calculated the SMRs for the A-bomb survivors versus JPCG in childhood and compared them with a true non-exposed group. A notable result was that SMRs in boys exposed to low doses were significantly higher for solid cancer.     

Reanalysis of cancer mortality in Japanese A-bomb survivors exposed to low doses of radiation: bootstrap and simulation methods

Background

The International Commission on Radiological Protection (ICRP) recommended annual occupational dose limit is 20 mSv. Cancer mortality in Japanese A-bomb survivors exposed to less than 20 mSv external radiation in 1945 was analysed previously, using a latency model with non-linear dose response. Questions were raised regarding statistical inference with this model.

Methods

Cancers with over 100 deaths in the 0 - 20 mSv subcohort of the 1950-1990 Life Span Study are analysed with Poisson regression models incorporating latency, allowing linear and non-linear dose response. Bootstrap percentile and Bias-corrected accelerated (BCa) methods and simulation of the Likelihood Ratio Test lead to Confidence Intervals for Excess Relative Risk (ERR) and tests against the linear model.

Results

The linear model shows significant large, positive values of ERR for liver and urinary cancers at latencies from 37 - 43 years. Dose response below 20 mSv is strongly non-linear at the optimal latencies for the stomach (11.89 years), liver (36.9), lung (13.6), leukaemia (23.66), and pancreas (11.86) and across broad latency ranges. Confidence Intervals for ERR are comparable using Bootstrap and Likelihood Ratio Test methods and BCa 95% Confidence Intervals are strictly positive across latency ranges for all 5 cancers. Similar risk estimates for 10 mSv (lagged dose) are obtained from the 0 - 20 mSv and 5 - 500 mSv data for the stomach, liver, lung and leukaemia. Dose response for the latter 3 cancers is significantly non-linear in the 5 - 500 mSv range.

Conclusion

Liver and urinary cancer mortality risk is significantly raised using a latency model with linear dose response. A non-linear model is strongly superior for the stomach, liver, lung, pancreas and leukaemia. Bootstrap and Likelihood-based confidence intervals are broadly comparable and ERR is strictly positive by bootstrap methods for all 5 cancers. Except for the pancreas, similar estimates of latency and risk from 10 mSv are obtained from the 0 - 20 mSv and 5 - 500 mSv subcohorts. Large and significant cancer risks for Japanese survivors exposed to less than 20 mSv external radiation from the atomic bombs in 1945 cast doubt on the ICRP recommended annual occupational dose limit.     

日本原子弹爆炸幸存者辐射致癌效应及其干扰因素的研究进展

日本辐射效应研究基金会(RERF)在对1958—1998年原子弹爆炸幸存者（原爆幸存者）实体癌发生率研究的基础上,增加了11年（1999—2009年）的随访结果,对原爆幸存者50年（1958—2009年）实体癌发生率进行深入研究,考虑性别、吸烟、饮酒、BMI以及医疗暴露等因素的影响,对实体癌的放射风险估计值进行更新,并在研究过程中发现了性别特异性的剂量反应、暴露年龄与癌症发生率的关系等新问题,为下一步的研究提供了指导方向。     

Cancer risk at low doses of ionizing radiation: artificial neural networks inference from atomic bomb survivors

Cancer risk at low doses of ionizing radiation remains poorly defined because of ambiguity in the quantitative link to doses below 0.2 Sv in atomic bomb survivors in Hiroshima and Nagasaki arising from limitations in the statistical power and information available on overall radiation dose. To deal with these difficulties, a novel nonparametric statistics based on the ‘integrate-and-fire’ algorithm of artificial neural networks was developed and tested in cancer databases established by the Radiation Effects Research Foundation. The analysis revealed unique features at low doses that could not be accounted for by nominal exposure dose, including (i) the presence of a threshold that varied with organ, gender and age at exposure, and (ii) a small but significant bumping increase in cancer risk at low doses in Nagasaki that probably reflects internal exposure to ²³⁹Pu. The threshold was distinct from the canonical definition of zero effect in that it was manifested as negative excess relative risk, or suppression of background cancer rates. Such a unique tissue response at low doses of radiation exposure has been implicated in the context of the molecular basis of radiation–environment interplay in favor of recently emerging experimental evidence on DNA double-strand break repair pathway choice and its epigenetic memory by histone marking.     

低强度超短波电磁辐射对机体的影响

目的　调查超短波作业环境 (170MHz)对职业接触人员神经功能、血清酶和免疫功能的影响。方法　询问职业接触人员主诉症状并进行脑血流图检测和神经行为核心测试组合试验 ,检测血清酶和免疫球蛋白。结果　现场超短波电场强度在天线发射方向 0°角 10m内和 135°角 2 0m内超过国家标准 (5V m)。接触组神经系统主诉症状如头痛、头晕和健忘等发生率明显高于对照组 ,差异有显著性 (P <0 .0 1) ;接触组工作后脑血流图上升时间 [左侧 (0 .15 5 3± 0 .0 5 79)s、右侧 (0 .15 4 1±0 .0 5 92 )s]明显比工作前 [左侧 (0 .10 4 4± 0 .0 30 2 )s、右侧 (0 .10 32± 0 .0 30 4 )s]或对照组 [左侧(0 .1185± 0 .0 5 6 8)s、右侧 (0 .1177± 0 .0 5 75 )s]延长 ,差异均有显著性 (P <0 .0 1)。神经行为功能测试结果表明 ,接触组工作后数字译码、数字跨度和目标追踪下降明显。接触组工作后丙氨酸转氨酶(ALT)变化不明显 ,天冬氨酸转氨酶 (AST)、碱性磷酸酶 (ALP)、乳酸脱氢酶 (LDH)均明显升高。接触组工作后IgA浓度变化不明显 ,IgM和IgG浓度升高 ,尤以IgG水平升高明显。结论　低强度超短波电磁辐射对职业暴露人员神经系统功能有影响 ,并可引起部分血清酶活力和免疫球蛋白浓度升高。     

Delayed effects of A-bomb radiation: a review of recent mortality rates and risk estimates for five-year survivors.

A review of published data relating to A-bomb survivors has led to the conclusion that since they were based on the mortality experiences of five year survivors estimates of radiation effects should have been controlled for two opposing forces-namely, selective survival of exceptionally fit individuals during the period of heavy acute mortality and residual disabilities. Both effects were dose-related and beyond question, and the disabilities probably included the effects of incomplete repair of bone marrow damage. Therefore, in addition to differences between high and low dose being largely obliterated, there was probably distortion of cancer effects. The two opposing forces are clearly the reason why the change from the high mortality rates of 1945-6 to the low rates of the 1950s was not accompanied by a change from a position to a negative association with dose, and imperviousness to the residual disabilities is probably the reason why sudden deaths of previously healthy individuals (exemplified by suicides) were an exception to this rule. Finally, impairment of bone marrow function probably accounts for the early epidemic of myeloid leukaemia; the apparent absence of other cancers at this time, and the relatively high dose-related death rates for blood diseases other than leukaemia.     

Methods for analyzing combined data from studies of workers exposed to low doses of radiation

Epidemiologic studies of workers exposed occupationally to protracted low doses of radiation provide a direct assessment of health effects resulting from such exposure and thus supplement information provided by studies of populations exposed at high doses of radiation and high dose rates. Analyses based on combined data from several studies can be expected to provide a more thorough assessment of low dose occupational studies and more precise risk estimates than can be obtained from any single study. Statistical methods for conducting such combined analyses are discussed, and different approaches, such as basing analyses on various levels of aggregation of exposure data, are compared and evaluated. Emphasis is given to methods for obtaining risk estimates and confidence limits that can be appropriately compared with estimates that form the basis for current radiation protection standards; these estimates have been obtained through extrapolation from high dose data. Methods are illustrated using combined data on workers at three US Department of Energy facilities: the Hanford Site, Richland, Washington; the Oak Ridge National Laboratory, Oak Ridge, Tennessee; and the Rocky Flats Nuclear Weapons Plant, Denver, Colorado.     

2015—2019年某医院放射人员个人剂量监测结果分析

目的 了解河北省某医院2015—2019年放射工作人员职业外照射剂量水平及动态变化情况,从而评价放射性工作防护情况及放射管理措施的效果,为加强放射人员的管理提供依据。方法 依据现行GBZ 128标准,采集2015—2019年所有放射工作人员连续五年外照射个人剂量监测数据,比较不同年份及不同职业类别（放射岗位）间人均年有效剂量的动态变化和差异水平。结果 2015—2019年人均年有效剂量分别为0.16 mSv/a、0.08 mSv/a、1.25 mSv/a、0.72 mSv/a和0.37 mSv/a,均小于5 mSv/a,低于医院的管理目标值和国家标准的要求;不同年份间比较2017年人均年有效剂量最高,且差异有统计学意义;不同岗位间比较介入放射（2E）和核医学（2C）人均年有效剂量较高,且差异有统计学意义。结论 该院放射工作人员人均年有效剂量处于较低水平,应继续保持现有的放射防护管理和措施;介入放射与核医学放射人员个人剂量较高,是放射防护管理的重点监护对象。     

Ethical,legal and social implications of human genome studies in radiation research: a workshop report for studies on atomic bomb survivors at the Radiation Effects Research Foundation

The Radiation Effects Research Foundation (RERF) is the primary organization in Japan dedicated to studying the health consequences of the Hiroshima and Nagasaki atomic bombings in World War II. In December 2020, RERF held a virtual international workshop on the ethical, legal and social implications (ELSI) of genome studies. In this workshop, the ELSI considerations of future human genome studies on radiation research including atomic bomb survivors and their families were discussed. Since genome sequencing (GS) is now practical and affordable, RERF now plans GS of parents/child trios to examine genetic effects of atomic bomb radiation. As such studies may engender some novel risks and benefits, ethics review and engagement with families (including consent) need to be considered. These include protection of individual privacy, use of samples from deceased prior participants, return of results to the participants, public sharing of genome data and advance science and social welfare. Specifically with regard to social welfare, the results of such studies may have implications for public and government decision-making regarding social benefits of victims and other important questions. Based on these broad-ranging discussions we have developed the following concepts to guide this work: “trust,” “compromise” and “relationship building,” inclusive of the concerned stakeholders, scientific aims and Japanese society at large. We conclude that in order to realize, establish and maintain these concepts, it is essential to put procedures into place to ensure the successful, consensus-based implementation of the RERF studies.     

调强适形放疗技术在非小细胞肺癌寡转移胸部原发灶区域的临床研究

在中国肺癌是恶性肿瘤的首位死亡原因,而非小细胞肺癌是肺癌最常见的组织学类型。寡转移是介于局部原发灶和广泛远处转移之间的过渡阶段,具有器官特异性。近年来许多临床研究表明,非小细胞肺癌寡转移其生物学行为不同于广泛转移的患者,预后相对较好。因此,找到有效方法改善其预后显得至关重要。本文主要探讨调强适形放疗在非小细胞肺癌寡转移治疗中的应用。     

Second primary gastric cancers in a region with an overall high risk of gastric cancer

ObjectiveTo compare the incidence rates of gastric cancer among cancer survivors with those in the general population, and estimate the probability of a gastric second primary cancer being diagnosed 10 years after any other first primary cancer.MethodA cohort of first primary cancers (other than gastric) diagnosed in Northern Portugal between 2000 and 2006 (n = 64,648) was followed until 31/12/2012 for gastric second primary cancers. Incidence rates, standardized incidence ratios and the cumulative incidence of gastric second primary cancers were calculated.ResultsOverall, 330 patients developed gastric second primary cancers (21.2% within two months). The incidence rate of gastric second primary cancers was higher within two months of the first primary cancer (standardized incidence ratios: 5.20 in males and 7.89 in females), particularly among survivors of cancers of the oesophagus, colon and rectum, than in the remaining period (standardized incidence ratios: 0.64 in males and 0.74 in females). The 10-year risk of a gastric second primary cancer was 0.6% (males: 0.7%; females: 0.4%).ConclusionThe incidence rate of gastric second primary cancers among cancer survivors was higher than in the general population only soon after the first primary cancer, and lower thereafter. Despite the high mortality, the probability of a gastric second primary cancer within 10-years of the first primary cancer was 0.6%.     

职业受照人群健康检查必检项目漏检原因分析

目的 通过对职业受照人群的健康检查,了解必检项目的实施及漏检情况,分析原因、提供对策,提高健康监护及评价工作质量,更好控制放射工作人员确定性效应的发生,降低随机性效应的发生率,减轻放射工作人员职业性放射损伤。方法 选择2016年青海省不同受照工作人员1116名,包括从事医用普通X射线摄片、CT、介入治疗、核医学、放射治疗和其他非医疗单位辐射设备应用等,对其健康检查资料做统计分析。结果 总体上X射线胸片检查漏检率最高（56.6%）,依次是眼科裂隙灯检查（37.0%）、实验室检查（11.2%）、电生理检查（5.8%）和内科检查（0.3%）;不同工种职业受照人群中：X射线胸片检查漏检率最高是CT室工种人员（84.9%）,眼科裂隙灯检查漏检率最高是放疗人员（51.9%）,实验室检查漏检率最高是核医学人员（14.8%）,电生理检查漏检率最高是CT室人员（9.2%）,内科检查漏检率最低。普放人群中县区级医疗单位漏检率最高（27.1%）,个体诊所医院漏检率较低（11.6%）。结论 健康检查必检项目的漏检,不能全面反映放射人员健康状况,影响判断是否继续进行放射工作,不完整的体检报告直接影响放射场所效果评价工作,直接影响对放射工作人员确定性效应的发生和降低随机性效应的发生率控制。     

介入放射学工作者的放射损伤及防护教育

目前介入放射学技术主要采用X线透视引导下介入操作,且操作时间较长,致使介入放射学工作者受照剂量比传统X线工作者高出数倍。而现行高等医学教育体系未给予放射卫生防护和安全教育充分重视,因此有必要在我国建立起一个以高等医学院校教学为主,职业培训为辅的新的放射卫生防护和安全教育体系。     

Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses

During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4⁺ T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic A. thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses.     

Energy density at a buffet-style lunch differs for adolescents born at high and low risk of obesity

The energy density (ED; kcal/g) of foods, when manipulated in the laboratory, affects short-term energy intake. The aim of this study was to examine if, when given a choice, dietary ED (foods only) and energy intake (expressed as a percentage of subjects' estimated daily energy requirement; EER) at a self-selected, single meal differ for teens born with a different familial predisposition to obesity and as a function of their sex. Subjects (13 males, 17 females) were 12 years of age and born at high risk (HR; n = 15) or low risk (LR; n = 15) for obesity based on maternal pre-pregnancy body mass index (BMI; kg/m²). The buffet meal, served for lunch and consumed ad libitum, consisted of a variety of foods and beverages with a range in ED. HR subjects consumed a more energy-dense meal (foods only) than LR subjects (1.84 vs. 1.42 kcal/g; P = 0.02) and males consumed a more energy-dense meal than females (1.83 vs. 1.43 kcal/g; P = 0.03). Total energy intake, when expressed as a percentage of subjects' daily EER, did not differ between HR and LR subjects (42% vs. 33%; P = 0.16). Males, compared to females, consumed ~ 59% more energy from foods and beverages during the meal (46 vs. 29%; P = 0.008). During a single multi-item lunch meal, teens with a familial predisposition to obesity and males, independent of their obesity risk status, self-selected a more energy-dense meal. Familial risk for obesity, through either genetic or environmental pathways, may facilitate a more energy-dense diet.     

Occupational exposure to low concentrations of carbon disulfide as a risk factor for hypercholesterolaemia

Objective: The objective of this study was to investigate the effect of occupational exposure to carbon disulfide (CS₂) concentrations below threshold limit value (TLV)-time-weighted average (TWA) (31 mg/m³) on total cholesterol, blood pressure and the prevalence of coronary heart disease (CHD). Methods: A cross-sectional study involving 141 viscose rayon workers (64 men), and 141 age- and gender-matched controls without occupational contact with noxious chemicals, was carried out. The probability for CHD was determined by means of the WHO questionnaire and was 12-lead electrocardiography-coded using Minnesota criteria. Blood pressure was measured by the standardized method of the WHO and blood was examined for total cholesterol. A cumulative exposure index (CS₂ index) was calculated for each worker by multiplying the number of years held in a particular job, by the CS₂ concentrations in that job-environment. According to the CS₂ index, the exposed workers were distributed into two groups: group 1 (CS₂ index <100) and group 2 (CS₂ index ≥100). Results: Depending on the job and specific work place the CS₂ concentrations were between 1 and 30 mg/m³. Cholesterol levels were significantly higher in the exposed group (4.9 ± 0.7) compared with the controls (4.6 ± 0.7). Adjustment for age, smoking, body-mass index (BMI) and gender showed the significant effect of the CS₂ index on the total cholesterol (P < 0.001). The prevalence of hypercholesterolaemia was significantly higher in the exposed group (42.6%), compared with the controls (26.2%); odds ratio (OR) (adjusted for potential confounders) was 2.56, 95% CI 1.47–4.46. Logistic regression showed a significantly increased risk for elevated cholesterol in group 2 (OR 5.52; 95% CI 2.81–10.83). No significant effect of CS₂ index on blood pressure and CHD prevalence was found. Conclusions: The results of our study show that occupational exposure to CS₂ concentrations below 31 mg/m³ and a CS₂ index >100 may increase total cholesterol. Our results imply that even the CS₂ concentrations below TLV-TWA may produce morbid changes, and suggest the mechanism of the effect of CS₂, leading to lipid metabolism disturbances and acceleration of atherosclerosis. Received: 1 February 2000 / Accepted: 24 June 2000     

预约就诊在高危儿随访门诊中的作用

【目的】 观察规范预约随访管理就诊在高危儿随访门诊中对其随访率及随防效果中的促进作用,为该制度的推广应用提供依据。 【对象】 按照自愿原则,选择2009年5月-2010年4月在本院新生儿科住院并建档的、自愿参加预约就诊的4 755例高危儿入选预约组,选择同期住院并建档的按原常规就诊的2 929例高危儿作为对照组。 【方法】 对预约组进行有计划的预约随诊时间,并通过出院宣教,专科护士电话预约、现场预约、医院预约网络平台等形式预约随诊。对照组按照常规无预约随访就诊。 【结果】 预约随访管理1年来,初次随访率达到82.72%,增长了26.99％,一年随访率达到了63.4％,增长了30.82％,经处理差异有统计学意义(P<0.001)。通过就诊时间的预约,患儿的非医疗等候时间由原来的(18.965±20.048) min,明显缩短到(6.125±8.048) min。 【结论】 有计划的预约高危儿随诊时间,可缩短等候时间,提高高危儿的随访率及随防效果。     

Study of some erythrocyte and serum enzyme activities in workers exposed to low ozone concentrations for a long time

Summary In 22 subjects exposed during work to ozone concentrations ranging from 0.160 to 0.290 ppm, the following enzyme activities were measured at the end of a normal work shift: AchE, G-6-PDh, PK in erythrocytes, LDH and alfa HBDH in serum.AchE of erythrocytes and serum LDH and alfa HBDH were determined also after three weeks of nonexposure to ozone.LDH and alfa HBDH activities decreased at the second determination; the difference between the two determinations was statistically significant (P<0.001).The results indicate that an exposure to 0.2 ppm of ozone, if prolonged in time, may affect the air-blood barrier and possibly cause alteration of some serum enzyme activities.Concentrations of ozone around 0.2 ppm should therefore be avoided in urban and industrial areas.Abbreviations AchE Acetylcholinesterase in erythrocytes - G-6-PDh Glucose-6-phosphate dehydrogenase in erythrocytes - PK Pyruvate kinase in erythrocytes - LDH Lactate dehydrogenase in serum - alfa HBDH alfa Hydroxybutyrate dehydrogenase in serum