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.     

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.     

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。     

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     

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     

Complexities of holistic community-based participatory research for a low income, multi-ethnic population exposed to multiple built-environment stressors in Worcester, Massachusetts

Low income, multi-ethnic communities in Main South/Piedmont neighborhoods of Worcester, Massachusetts are exposed to cumulative, chronic built-environment stressors, and have limited capacity to respond, magnifying their vulnerability to adverse health outcomes. “Neighborhood STRENGTH”, our community-based participatory research (CBPR) project, comprised four partners: a youth center; an environmental non-profit; a community-based health center; and a university. Unlike most CBPR projects that are single topic-focused, our ‘holistic’, systems-based project targeted five priorities. The three research-focused/action-oriented components were: (1) participatory monitoring of indoor and outdoor pollution; (2) learning about health needs and concerns of residents through community-based listening sessions; (3) engaging in collaborative survey work, including a household vulnerability survey and an asthma prevalence survey for schoolchildren. The two action-focused/research-informed components were: (4) tackling persistent street trash and illegal dumping strategically; and (5) educating and empowering youth to promote environmental justice. We used a coupled CBPR-capacity building approach to design, vulnerability theory to frame, and mixed methods: quantitative environmental testing and qualitative surveys. Process and outcomes yielded important lessons: vulnerability theory helps frame issues holistically; having several topic-based projects yielded useful information, but was hard to manage and articulate to the public; access to, and engagement with, the target population was very difficult and would have benefited greatly from having representative residents who were paid at the partners’ table. Engagement with residents and conflict burden varied highly across components. Notwithstanding, we built enabling capacity, strengthened our understanding of vulnerability, and are able to share valuable experiential knowledge.     

An application of the challenge assay in boat builders exposed to low levels of styrene--a feasibility study of a possible biomarker for acquired susceptibility.

Sensitivity to carcinogens and susceptibility for malignant diseases may be related to genetic predisposition, e.g. polymorphisms in toxicant-metabolizing enzymes or DNA repair deficiencies. The latter may also be acquired by exposure to substances that interfere with DNA repair processes. Application of the challenge assay to an exposed population may allow scientists to study the interference of DNA repair as an acquired susceptibility phenomenon. The assay was therefore used in a feasibility study to evaluate its application. A group of 14 workers exposed to low levels of styrene (mean < 100 mg/m3 styrene in air; 35 micrograms/l styrene in blood) and a reference of seven controls were investigated for structural chromosomal aberrations using FISH. The rate of exchange-type aberrations per 100 metaphases was 0.14 (95% CI, 0.05-0.31) in controls and 0.22 (95% CI, 0.13-0.36) in exposed workers. The difference is not statistically significant. Interaction with DNA repair was measured in the 14 workers and 2 historical controls using the challenge assay. Exchange-type aberrations per 100 metaphases after X-ray challenge of 1.66 Gy were 13.26 (10.53-16.50) and 16.19 (15.00-17.40) for the controls and exposed, respectively. The difference is statistically significant (p < 0.038). Among the exposed group, the challenge response was also significantly correlated with the cumulative lifetime exposure to styrene (R2 = 0.3996; p < 0.015) but not with the current exposure as measured in blood (R2 = 0.0226; p = 0.700). The challenge responses in the short-term and long-term exposed subgroups were 15.55 (14.23-16.96) and 17.90 (15.64-20.39), respectively, based on sample sizes of 5 and 9, respectively. The difference was not significant. Hence, data from our study are consistent with the hypothesis that long-term exposure to styrene can interfere with DNA repair activities. The lack of statistically significant differences in some of the data may be due to the small sample size and a possible confounding by age in our investigation. Additional data from our ongoing study should clarify this uncertainty.     

Interventions for physical activity promotion applied to the primary healthcare settings for people living in regions of low socioeconomic level: study protocol for a non-randomized controlled trial

Background

Regular physical activity practice has been widely recommended for promoting health, but the physical activity levels remain low in the population. Therefore, the study of interventions to promote physical activity is essential. Objective: To present the methodology of two physical activity interventions from the “Ambiente Ativo” (“Active Environment”) project.

Methods

12-month non-randomized controlled intervention trial. 157 healthy and physically inactive individuals were selected: health education (n = 54) supervised exercise (n = 54) and control (n = 49). Intervention based on health education: a multidisciplinary team of health professionals organized the intervention in group discussions, phone calls, SMS and educational material. Intervention based on supervised exercise program: consisted of offering an exercise program in groups supervised by physical education professionals involving strength, endurance and flexibility exercises. The physical activity level was assessed by the International Physical Activity Questionnaire (long version), physical activities recalls, pedometers and accelerometers over a seven-day period.

Result

This study described two different proposals for promoting physical activity that were applied to adults attended through the public healthcare settings. The participants were living in a region of low socioeconomic level, while respecting the characteristics and organization of the system and its professionals, and also adapting the interventions to the realities of the individuals attended.

Conclusion

Both interventions are applicable in regions of low socioeconomic level, while respecting the social and economic characteristics of each region.

Trial registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT01852981","term_id":"NCT01852981"}}NCT01852981     

Three-fraction CyberKnife radiotherapy for brain metastases in critical areas: referring to the risk evaluating radiation necrosis and the surrounding brain volumes circumscribed with a single dose equivalence of 14 Gy (V14)

The efficacy and toxicity of three-fraction CyberKnife radiotherapy were evaluated in patients with brain metastases in critical areas. One hundred and fifty-nine metastases in 145 patients including tumors >10 cm³ were treated with three-fraction CyberKnife radiotherapy with a median marginal dose of 27 Gy at a median prescribed isodose of 60%. Changes in the neurological manifestations, local tumor control and adverse effects were investigated after treatment. The surrounding brain volumes circumscribed with 23.1 Gy (single dose equivalence of 14 Gy: V14) were measured to evaluate the risk of adverse effects. Neurological manifestations, such as motor weakness, visual disturbances and aphasia improved in 26 of 97 patients (26.8%). Local tumor control was obtained in 137 of 143 metastases (95.8%) during a median follow-up of 7 months. Nine patients had symptomatic edema and three of them (2.1%) required surgical resection because of radiation necrosis. The V14 of these patients was 4.6–31.5 cm³. There were 35 lesions with a V14 of 7 cm³ or more and three of them developed extensive brain edema due to radiation necrosis. None of the patients with a V14 of <7 cm³ exhibited edema requiring an operation. We therefore conclude that a high rate of local tumor control and low rates of complications are obtained after three-fraction CyberKnife radiotherapy for metastases in critical areas. The V14 of the surrounding brain therefore seems to be a useful indicator for the risk evaluation of radiation necrosis in patients with larger metastases.