A review of some epidemiological studies on cancer risk from low-dose radiation or other carcinogenic agents

It is extremely difficult to assess cancer risks accurately due to health effects of low-dose radiation exposure or other carcinogens based on epidemiological studies. For the detection of minute increases of the risk at low-level exposure, most of epidemiological studies lack statistical power, and they involve various complicated confounding factors. This paper reports on a literature survey of epidemiological studies published since 2000 on cancer risks associated with low-dose radiation and other carcinogens to gather major epidemiological data. Integrated risk indices were derived from those data by using, where possible, statistical models. Regarding risk assessment of low-dose radiation exposure, it is important to lower the degree of uncertainty arising from risk estimation. Risk assessment of low-dose radiation exposure could be scientific evidence when uncertainty is considered in comparing carcinogenic risks of radiation with those of other carcinogens.     

Proposal for a patient database on cardiac interventional exposures for epidemiological studies

Relatively high organ doses absorbed by patients in interventional cardiology suggest the opportunity to define these patients as a cohort to be followed forward in time in an epidemiological study of the cancer risks associated with exposure to low-dose ionising radiation. In this paper, the UNSCEAR 2000 Report risk estimates for the most exposed organs/tissues in cardiac interventional procedures are reviewed, as well as the critical features of such an epidemiological study that is anticipated to have an intrinsically low statistical power because of the low levels of risk and possible confounding factors. To overcome these limitations, data collected in different institutions can be combined provided that a common design and conduct are used for dose assessment. A minimum dataset to be collected on a patient basis is proposed that can be implemented routinely in most facilities. This data should be linked to the local patient information system in order to retrieve all the exposures of a given patient.     

Growth curve analysis of tumourigenesis using cellular level cancer model

It is known that carcinogenesis by low-dose radiation will start from DNA damage by ionising radiation. After the long time period, these very small effects will appear on a cellular scale by accumulation of various intracellular biological responses and finally grow to the tumour with clonal expansion of cancer cell. Thus, the biological radiation effects are phenomena with a very wide scale from DNA damage (10(-9) m, 10(-6) s) to the tumour (10(-3) m, 10(5) s); so the risk estimation of low-dose radiation is difficult to study by the experiments. To overcome these difficult situations at low-dose radiation effects' problems, it is good to study the process of carcinogenesis using a biologically based mathematical model. This study's cellular-scale mathematical model of tumourigenesis and some results of the statistical calculations about the tumour growth as presented in the work.     

Validated biomarker responses influence medical surveillance of individuals exposed to genotoxic agents.

There is currently a vast armamentarium of biomarkers for evaluating human exposures to environmental carcinogens, the effects of such exposures and/or susceptibility to disease outcome. Before application, however, these biomarkers require validation in terms of truly reflecting what is claimed. Transitional epidemiological studies bridge the gap between laboratory and field. In a transitional study, a biomarker response is the dependent variable being evaluated, while the intended measure, i.e. exposure effect or susceptibility, is the independent variable. Once validated, biomarker responses provide valuable data for use in making human health risk assessments and as guides for individual medical surveillance programmes. An analysis of medical decision-making illustrates how biomarker responses that increase the relative risk of subsequent disease occurrence change the 'pre-test likelihood' of having the disease, thereby influencing interpretation of medical diagnostic tests and even the choice of tests to be performed. This argues that an individual's response using salidated biomarkers should be made part of the medical record.     

Radiation dose vs. image quality for low-dose CT protocols of the head for maxillofacial surgery and oral implant planning

The goal of this study was to determine the acquisition parameters for a low-dose multi-slice CT protocol and to compare the effective dose and the image quality of this low-dose protocol with the image quality of a clinical multi-slice CT protocol, routinely used for visualisation of the head. The low-dose protocol was derived from a clinical multi-slice CT protocol by lowering mA s and kV and increasing the pitch. The low-dose protocol yielded a dose reduction from 1.5 to 0.18 mSv for a multi-slice CT scan of the whole head, whereas noise in the low-dose CT images was increased. For bone segmentation, noise could be reduced by use of a non-linear edge preserving smoothing filter. Tests on ESP and skull phantom indicated that the accuracy of the measurements on low-dose CT is acceptable for image-based planning of maxillofacial and oral implant surgery, reducing the dose by a factor of 8.     

The use of animal models for predicting the potential chronic effects of highly toxic chemicals

The acute effects of highly toxic chemicals in man and animals are often blatantly obvious. However, the data obtained from experimental investigation of the chronic effects of toxic chemicals often correlate poorly with epidemiological findings following exposure of the population to these chemicals in the field. The reasons for this discrepancy between experimental and epidemiological observations are numerous and complex. The areas of erroneous predictions resulting from errors in data extrapolation, inaccurate statistical methods, environmental variables and a lack of standard operating procedures may account for some of the lack of correlation between experimental findings and the in-field situation. Epidemiological studies may not give a true assessment of the impact of a chemical on the population as a whole.     

Role of high-dose exposure in transmission hot zones as a driver of SARS-CoV-2 dynamics

Epidemiological data about SARS-CoV-2 spread indicate that the virus is not transmitted uniformly in the population. The transmission tends to be more effective in select settings that involve exposure to relatively high viral dose, such as in crowded indoor settings, assisted living facilities, prisons or food processing plants. To explore the effect on infection dynamics, we describe a new mathematical model where transmission can occur (i) in the community at large, characterized by low-dose exposure and mostly mild disease, and (ii) in so-called transmission hot zones, characterized by high-dose exposure that can be associated with more severe disease. The model yields different types of epidemiological dynamics, depending on the relative importance of hot zone and community transmission. Interesting dynamics occur if the rate of virus release/deposition from severely infected people is larger than that of mildly infected individuals. Under this assumption, we find that successful infection spread can hinge upon high-dose hot zone transmission, yet the majority of infections are predicted to occur in the community at large with mild disease. In this regime, residual hot zone transmission can account for continued virus spread during community lockdowns, and the suppression of hot zones after community interventions are relaxed can cause a prolonged lack of infection resurgence following the reopening of society. This gives rise to the notion that targeted interventions specifically reducing virus transmission in the hot zones have the potential to suppress overall infection spread, including in the community at large. Epidemiological trends in the USA and Europe are interpreted in light of this model.     

The Genetic Heterogeneity among Different Mouse Strains Impacts the Lung Injury Potential of Multiwalled Carbon Nanotubes

Genetic variation constitutes an important variable impacting the susceptibility to inhalable toxic substances and air pollutants, as reflected by epidemiological studies in humans and differences among animal strains. While multiwalled carbon nanotubes (MWCNTs) are capable of causing lung fibrosis in rodents, it is unclear to what extent the genetic variation in different mouse strains influence the outcome. Four inbred mouse strains, including C57Bl/6, Balb/c, NOD/ShiLtJ, and A/J, to test the pro‐fibrogenic effects of a library of MWCNTs in vitro and in vivo are chosen. Ex vivo analysis of IL‐1β production in bone marrow‐derived macrophages (BMDMs) as molecular initiating event (MIE) is performed. The order of cytokine production (Balb/c > A/J > C57Bl/6 > NOD/ShiLtJ) in BMDMs is also duplicated during assessment of IL‐1β production in the bronchoalveolar lavage fluid of the same mouse strains 40 h after oropharyngeal instillation of a representative MWCNT. Animal test after 21 d also confirms a similar hierarchy in TGF‐β1 production and collagen deposition in the lung. Statistical analysis confirms a correlation between IL‐1β production in BMDM and the lung fibrosis. All considered, these data demonstrate that genetic background indeed plays a major role in determining the pro‐fibrogenic response to MWCNTs in the lung.     

Studies on possibility for alleviation of lifestyle diseases by low-dose irradiation or radon inhalation

Our previous studies showed the possibility that activation of the antioxidative function alleviates various oxidative damages, which are related to lifestyle diseases. Results showed that, low-dose X-ray irradiation activated superoxide dismutase and inhibits oedema following ischaemia-reperfusion. To alleviate ischaemia-reperfusion injury with transplantation, the changes of the antioxidative function in liver graft using low-dose X-ray irradiation immediately after exenteration were examined. Results showed that liver grafts activate the antioxidative function as a result of irradiation. In addition, radon inhalation enhances the antioxidative function in some organs, and alleviates alcohol-induced oxidative damage of mouse liver. Moreover, in order to determine the most effective condition of radon inhalation, mice inhaled radon before or after carbon tetrachloride (CCl(4)) administration. Results showed that radon inhalation alleviates CCl(4)-induced hepatopathy, especially prior inhalation. It is highly possible that adequate activation of antioxidative functions induced by low-dose irradiation can contribute to preventing or reducing oxidative damages, which are related to lifestyle diseases.     

Cumulative effects assessment: learning from Canadian case studies

Cumulative effects assessment (CEA) for environmental impact assessments are required by some Canadian and American legislation. However, there is confusion concerning exactly what CEA involves. This clarifies the requirements of CEA and illustrates its use in a number of case studies. Practitioners must: identify valued ecosystem components (VECs) affected by the proposed project; determine what other past, present and future human activities have affected or will affect these VECs; predict the impacts on the VECs of the combined activities; and suggest how to manage these cumulative effects.     

The ICRP protection quantities, equivalent and effective dose: their basis and application

Equivalent and effective dose are protection quantities defined by the The International Commission on Radiological Protection (ICRP). They are frequently referred to simply as dose and may be misused. They provide a method for the summation of doses received from external sources and from intakes of radionuclides for comparison with dose limits and constraints, set to limit the risk of cancer and hereditary effects. For the assessment of internal doses, ICRP provides dose coefficients (Sv Bq(-1)) for the ingestion or inhalation of radionuclides by workers and members of the public, including children. Dose coefficients have also been calculated for in utero exposures following maternal intakes and for the transfer of radionuclides in breast milk. In each case, values are given of committed equivalent doses to organs and tissues and committed effective dose. Their calculation involves the use of defined biokinetic and dosimetric models, including the use of reference phantoms representing the human body. Radiation weighting factors are used as a simple representation of the different effectiveness of different radiations in causing stochastic effects at low doses. A single set of tissue weighting factors is used to take account of the contribution of individual organs and tissues to overall detriment from cancer and hereditary effects, despite age- and gender-related differences in estimates of risk and contributions to risk. The results are quantities that are not individual specific but are reference values for protection purposes, relating to doses to phantoms. The ICRP protection quantities are not intended for detailed assessments of dose and risk to individuals. They should not be used in epidemiological analyses or the assessment of the possibility of occurrence and severity of tissue reactions (deterministic effects) at higher doses. Dose coefficients are published as reference values and as such have no associated uncertainty. Assessments of uncertainties may be appropriate in specific analyses of doses and risks and in epidemiological studies.     

The history of radon from a Swedish perspective

Beginning in the 16th century, what was later found to be radon was thought to be causing sickness among miners. During the first decades of the 20th century, exposure to radon was seen as being healthy. During the 1940s, 1950s and 1960s researchers thought that the gamma radiation in residences could produce genetic damage. It was not until approximately 1970 that a quantitative risk estimate for lung cancer could be calculated for miners, and not until the 1990s that a risk estimate could be established based on epidemiological studies on radon in dwellings and lung cancer.     

Nationwide survey on pediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects

A nationwide survey was conducted in Japan on paediatric CT among children of public health and school nurses to examine a possibility for a follow-up study on radiation effects. A survey questionnaire was sent out to 3173 public primary and junior high schools and 317 public health centres during October to December in 2009. According to the collected responses, 410 (16.2 %) children received the CT scans and the total number of CT scans was 585. Most of respondents expressed a high interest in radiation health effects and an intent to participate in the epidemiological study that will follow-up the health conditions of children. This study provides information to discuss the feasibility of the epidemiological study on health effects in children who received CT scans.     

Comparison of ordered structure in buried oxide layers in high-dose, low-dose, and internal-thermal-oxidation separation-by-implanted-oxygen wafers

The ordered SiO₂ in the buried oxide (BOX) layer of high-dose, low-dose, and internal-thermal-oxidation (ITOX) separation-by-implanted-oxygen (SIMOX) wafers was investigated by X-ray diffraction. From the results, it was found that the SiO₂ molecules in the low-dose and ITOX SIMOX wafers are better ordered than those in the high-dose SIMOX wafer and that the ordered structure of the ITOX layer is different from that of the originally formed BOX layer, suggesting that the ITOX layer has a structure similar to that of the ordered SiO₂ in the thermal oxide layer.     

Time-dependent spectral analysis of epidemiological time-series with wavelets.

In the current context of global infectious disease risks, a better understanding of the dynamics of major epidemics is urgently needed. Time-series analysis has appeared as an interesting approach to explore the dynamics of numerous diseases. Classical time-series methods can only be used for stationary time-series (in which the statistical properties do not vary with time). However, epidemiological time-series are typically noisy, complex and strongly non-stationary. Given this specific nature, wavelet analysis appears particularly attractive because it is well suited to the analysis of non-stationary signals. Here, we review the basic properties of the wavelet approach as an appropriate and elegant method for time-series analysis in epidemiological studies. The wavelet decomposition offers several advantages that are discussed in this paper based on epidemiological examples. In particular, the wavelet approach permits analysis of transient relationships between two signals and is especially suitable for gradual change in force by exogenous variables.     

Optimal control of epidemics in metapopulations

Little is known about how best to deploy scarce resources for disease control when epidemics occur in different but interconnected regions. We use a combination of optimal control methods and epidemiological theory for metapopulations to address this problem. We consider what strategy should be used if the objective is to minimize the discounted number of infected individuals during the course of an epidemic. We show, for a system with two interconnected regions and an epidemic in which infected individuals recover and can be reinfected, that equalizing infection in the two regions is the worst possible strategy in minimizing the total level of infection. Treatment should instead be preferentially directed at the region with the lower level of infection, treating the other subpopulation only when there is resource left over. The same strategy holds with preferential treatments of regions with lower levels of infection when quarantine is introduced.     

ENEA extremity dosemeter based on LiF(Mg,Cu,P) to evaluate Hp(3,alpha)

Recent epidemiological studies suggest a rather low-dose threshold (<0.5 Gy) for the induction of a cataract of the eye lens. Some other studies even assume that there is no threshold at all. Therefore, protection measures have to be optimised and current dose limits for the eye lens may be reduced in the future. ICRP Publication 103 on H(p)(d), in §(136), reads that '… a depth d = 3 mm has been proposed for the rare case of monitoring the dose to the lens of the eye. In practice, however, H(p)(3) has rarely been monitored and H(p)(0.07) can be used for the same monitoring purpose… '. As recommended on the EU 'Technical recommendations for monitoring individuals occupationally exposed to external radiation', a test on the ENEA TL extremity dosemeter is herein reported. The results within the actual EU founded Optimization of RAdiation protection for MEDical staff (ORAMED) Project, whose WP2 is aimed at the quantity H(p)(3) and eye lens dosimetry in practice, are taken into account. The paper summarises the main aspects of the study carried out at ENEA-Radiation Protection Institute (Bologna, Italy) to provide practical solutions (in the use and the design) to evaluate the response of the ENEA TL extremity dosemeter in terms of H(p)(3).     

Design and other types of fixation

Design educators often comment on the difficulties that result from a premature commitment by students to a solution to a design problem. Similarly practitioners can find it difficult to move away from an idea they have developed or precedents in a field. In the psychology of problem solving this effect is called functional fixedness or fixation. It is not surprising that these effects should occur in design problem solving. However, while these types of issues have been discussed in the context of design, there has been little systematic evidence available about whether or not and under what conditions design fixation does occur. The paper reviews the results of a series of recent experiments which begin to address these issues. The results of the experiments are examined in terms of what insights they provide into the design process, what implications they have for design education and how they relate to the larger and more general area of human problem solving.     

Case–control analysis in highway safety: Accounting for sites with multiple crashes

There is an increased interest in the use of epidemiological methods in highway safety analysis. The case–control and cohort methods are commonly used in the epidemiological field to identify risk factors and quantify the risk or odds of disease given certain characteristics and factors related to an individual. This same concept can be applied to highway safety where the entity of interest is a roadway segment or intersection (rather than a person) and the risk factors of interest are the operational and geometric characteristics of a given roadway. One criticism of the use of these methods in highway safety is that they have not accounted for the difference between sites with single and multiple crashes. In the medical field, a disease either occurs or it does not; multiple occurrences are generally not an issue. In the highway safety field, it is necessary to evaluate the safety of a given site while accounting for multiple crashes. Otherwise, the analysis may underestimate the safety effects of a given factor.